Cushing's syndrome: Pg.6

Rapid quantitativemeasurement of calprotectinPg.28Weekly news updates on www.cli-online.com | Dec. 2008 - Jan. 2009 | Volume 32 | Issue 8Cushing’s syndrome:late-night salivary cortisol measurementPg.6Also in this issue :Colorectal cancer update Pg. 10 | Nanoparticles in diagnostics Pg. 12 | Communicable disease control Pg. 16Fully automated ELISA systemPg.31Clinical chemistry analyserfor small to medium labsPg.32New!Post-a-comment on featurearticles: see inside andgo to www.cli-online.comComments onthis article?If you have comments,additional data, alternativepoints of view or simply questionsregarding the above article,please feel free to post them atwww.cli-online.com/comment/...

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Comments onthis article?www.cli-online.com/comment/...ContentsFRONT COVERRapid quantitativemeasurement of calprotectinPg.28Fully automated ELISA systemPg.31Clinical chemistry analyserfor small to medium labsPg.32Weekly news updates on www.cli-online.com | Dec. 2008 - Jan. 2009 | Volume 32 | Issue 8Cushing’s syndrome:late-night salivary cortisol measurementPg.6Also in this issue :Colorectal cancer update Pg. 10 | Nanoparticles in diagnostics Pg. 12 | Communicable disease control Pg. 16New!Post-a-comment on featurearticles: see inside andgo to www.cli-online.comFeature articles[6-8] Diagnosis of Cushing’s syndrome using late-nightsalivary cortisol measurement[10-11] Colorectal cancer update:some novel strategies for in vitroscreening and diagnosis[12-15] Nanoparticles for molecular diagnosis and therapy[16-18] Outbreaks of communicable disease: nationalsurveillance and lab investigation[19-21] Exogenous endocrine-disrupting compounds[26] Accurate determination of chlorideby coulometric titrationRegular features[3] Editor’s letter[8] Book review[23-24] News in brief[25] Industry newsEndogenous Cushing’s syndrome,defined as the excess secretion ofcortisol from the adrenal glands,is very challenging to diagnose.However, even mild elevationsin the level of this hormone canhave adverse health effects. Thefront cover depicts the adrenalglands, which secrete cortisolin response to stimulation byadrenocorticotropic hormoneproduced by the pituitary gland.Graphic Design by StudioPress Communication, BrusselsWe’ve gotyou coveredEasy to interpret rapid tests forinfectious diseasesAt Inverness Medical, we believe rapid diagnosis andtreatment is crucial to reducing the spread of infectionand improving recovery rates, especially amongst themost vulnerable.Around 40 million people worldwide are now livingwith HIV/AIDS 1 , as a result increases have been seen inassociated diseases which need early detection andtreatment to improve survival rates and quality of life.The broad range of rapid tests from Inverness Medicalnot only includes tests for HIV, but also products keyin aiding the diagnosis of associated diseases, such asthe sexually transmitted HSV-2 virus and TB in TB/HIVco-infected patients.Malaria, Dengue Fever and Filariasis are among otherdiseases identifiable within the Inverness Medical range.WE givE you ansWErs, fast ...Check out our range of products atwww.invmed.com or email us onprofessionaldiagnostics@invmed.com[27-33] Product news[34] Calendar of eventsFree subscription for clinical lab professionalsClinical lab professionals are entitled to receive CLI for the next12 months completely free of charge. To begin a new subscriptionor to continue your existing free subscription go towww.cli-online.comClick on Free Subscription and follow instructionsPriory Business Park, Bedford, MK44 3UP, UKADGEN06v1 ©2008 Inverness Medical. All rights reserved. 1World Health Organisation www.who.int/en - July 2008www.cli-online.com & search 24087

– Issue N°8 – Dec. 2008 - Jan. 2009 6EndocrinologyDisease focusCushing’s syndrome: diagnosis usinglate-night salivary cortisol measurementThe diagnosis of endogenous hypercortisolism – Cushing’s syndrome – isvery challenging, and historically standard tests such as urine free cortisoland low-dose dexamethasone suppression are not optimal. It has becomeclear that late-night (2300-2400 hr) salivary cortisol is simple to measureand has a high sensitivity and specificity for Cushing’s syndrome.by Dr H. RaffEndogenous Cushing’s syndrome is definedas excess secretion of cortisol from the adrenalgland. It is caused by either autonomous,ACTH-independent secretion of cortisol fromthe adrenal gland (e.g. adrenal adenoma) orsecretion of ACTH from pituitary (Cushing’sdisease) or non-pituitary (ectopic ACTH)sources [1]. With the awareness that even mildelevations in cortisol secretion (sub-clinicalCushing’s syndrome) may have adverse healtheffects, the need for simple and accurate screeningtests for Cushing’s syndrome have becomevital. The standard tests to screen for Cushing’ssyndrome include 24-hour urine free cortisoland the low-dose dexamethasone suppressiontest. Both of these tests have inherent shortcomings,and can be difficult to execute, particularlywhen screening the increasing populationof patients with the Cushing’s phenotype(e.g. obesity, hypertension, depression).One of the first abnormalities during thedevelopment of Cushing’s syndrome is a failureto reach the circadian nadir in cortisolsecretion late at night. This was first exploitedas a diagnostic test by studying patients inclinical research centres and obtaining a midnight,sleeping serum cortisol measurementafter several days of admission. This is notpractical, feasible, or cost-effective for manyclinicians. Since salivary cortisol is in equilibriumwith the biologically active, serum freecortisol (that is, cortisol not bound to plasmaproteins) and saliva is easy to obtain in a nonstressfulway, the measurement of late-nightsalivary cortisol has become a well-acceptedand highly recommended screening test forCushing’s syndrome [2].for steroids with lower salivary concentrations(e.g. oestrogen, 17-hydroxyprogesterone). Onecan obtain a sufficient sample by spitting orpassively drooling into a tube. However, by farthe simplest and most aesthetically pleasingmethod is to use a simple device consisting ofan absorbent material (e.g. cotton or polyester)and a double-barreled tube.We use the plain, untreated Salivette (Sarstedt,Nümbrecht, Germany, www.sarstedt.com) toobtain saliva samples [Figure 1]. This consistsof a cotton cylinder, an upper tube insert witha small hole in the bottom, and an outer tubeand cap. It is important to use the plain cottontube, rather than the tube treated with citricacid, since low sample pH can adversely affectmany immunoassays. Between 11pm (2300hr) and midnight (2400 hr), usually just beforebedtime at home, the patient removes the cap,chews the cotton cylinder (without suckingon it), places the chewed cylinder back in theupper insert tube and caps the sample. Thereshould be no food intake or tooth brushingin the hour before sampling and, in fact, wesuggest that our patients brush their teethafter the sampling. Also, creams and ointmentscontaining corticosteroids (particularlyhydrocortisone) should be avoided. An alternativesimilar device uses an inert polymercylindrical swab instead of cotton to collectsaliva (www.salimetrics.com).We usually obtain two bedtime samples, normally(but not necessarily), two nights in arow. The sample can then be mailed to thelaboratory or stored in a refrigerator for afew days and transported to the lab where thesample is frozen and saved for analysis. Wedo not usually recommend that the patientsfreeze the samples because (a) many homefreezers are frost-free, and periodically warmthe contents to minimise frost and (b) thesamples would be likely to thaw on the wayto the laboratory. Once the sample is readyto be analysed, it is thawed and centrifuged(we recommend 500 g for 15 min) to wringthe saliva from the cotton tube through thehole in the upper tube insert, and into thebottom of the outer tube. If not previouslyfrozen, the sample can be frozen for storageat this point.Obtaining a saliva sampleObtaining a saliva sample for the measurementof cortisol is extraordinarily simple. Becausethe concentration of cortisol in saliva is reasonablyhigh (>1 nmol/L) and is very stable,the collection method is not as critical as it isFigure 1. A method for collecting saliva for cortisol analysis using the plain, untreated Salivette. Note that theinstructions are recommended by my laboratory and should not be attributed to the manufacturer. The samplecan be frozen after Step 5 or after Step 8, but repeated freeze/thaw should be avoided. Also note that thismethod does not apply to all salivary steroids. Images used with permission from ACL Laboratories (left side)and Sarstedt, Inc (right side).

7– Issue N°8 – Dec. 2008 - Jan. 2009Analytical methodsThe two general approaches that have beentaken to measuring salivary cortisol are directimmunoassays and chromatography/massspectrometry. Each has its inherent strengthsand weaknesses. Manual and automated (platform)immunoassays originally developed forserum cortisol have been modified to increasesensitivity sufficiently to measure salivarycortisol [3]. The disadvantage of these methodsis that they can require a fairly large volumeof sample (e.g. 400-500 µL for duplicatemeasurements). As a result, many laboratorieshave switched to ELISAs specifically developedfor analysis of saliva, which require as little as50 µL for duplicate measurements [4$. Theadvantages of immunoassays are that they areeasy to execute and require little by way ofsophisticated instrumentation. The only majordisadvantage of immunoassays is cross-reactivitywith other corticosteroids – in particular,synthetic steroids like prednisone. As with anymeasurement, there are differences betweenassays, and each laboratory should establishits own reference range using the appropriatepopulation of normal subjects. Recently, aliquid chromatography – tandem mass spectrometry(LC/MS-MS) method has been published[5]. The advantage of this method is itsColor profile: Generic CMYK printer profilespecificity Composite Default for cortisol. screen Ironically, this can be adisadvantage since exogenous or surreptitiousFigure 2. Algorithm for the diagnosis of Cushing’s syndrome. Normal values are those that fall within thereference range defined by the individual laboratories. Abbreviation: UFC, 24 h urinary free cortisol.(From reference [1])synthetic corticosteroid use causing Cushingoidsymptoms will not be detected unlesssynthetic steroids are analysed on each sample.Futhermore, LC/MS-MS requires technicallydemanding and expensive equipment as wellas higher saliva volumes for extraction comparedto ELISAs. In general, immunoassays aresufficient for most samples. In my experience,contamination with synthetic steroids usuallyleads to remarkably elevated concentrations(e.g. >100-200 nmol/L), and these samplescan be analysed by LC/MS-MS if necessary. Itis important to point out that no method canidentify contamination with hydrocortisoneAnno 198677 Elektronika Kft.New products!Research, development, production and sale of Blood Glucose Meters,Urine Chemistry- and Sediment Analyzers. OEM is also available.77 Elektronika Kft.Fehérvári út 98.H-1116 Budapest,HungaryPhone: +36-1-206-1480Fax: +36-1-206-1481E-mail: sales@e77.huWeb: www.e77.huD:\regi-f KULKER\Medica 2008\Hirdetes\CLI 2008\hirdetes 206x132 Arab.cdrWednesday, November 26, 2008 9:27:10 AMLabUMat-2 & UriSed-2Great choice for medium size laboratories Easy operation via colour touch screen Advanced, patent pending detection technique Fast and reliable User friendly, flexible software Minimal maintenance and convenient cleaningFor those, who would like to see The Full Picture Fully Automated Urine Chemistry- and Sediment Analyzer Complete and professional Urine Laboratory in one system Revolutionary new method Whole viewfieldmicroscopic images about sediment Fully automated sample preparation User friendly interface Cost effective operation without any liquid reagentsLabUReader Plus 2High Quality Semi-Automated Urine Chemistry AnalyzerVisit us at Arab Health,Hall 8 (Maktoum Hall), MB11www.cli-online.com & search 24437

– Issue N°8 – Dec. 2008 - Jan. 2009 8Endocrinology(i.e. authentic cortisol) except, perhaps, theevaluation of the ratio of cortisol to cortisonein saliva by LC/MS-MS.Diagnosis of Cushing’s syndromeCushing’s syndrome, particularly when mild, isone of the most difficult endocrine pathologiesto diagnose. This is because the phenotype isvery common and the disease, relatively unusual.However, it has become increasingly clearthat endogenous Cushing’s syndrome is morecommon than previously thought, therebyincreasing the need for a simple but accuratescreening test. Late-night salivary cortisol certainlymeets this criterion. There have beenover 12 studies demonstrating that late-nightsalivary cortisol has a sensitivity and specificityof >90-95% for Cushing’s syndrome [1].Furthermore, this approach is highly effectivein children in whom standard blood samplingand urine collection can be challenging.In our early studies, we compared healthy leansubjects with patients with proven Cushing’ssyndrome (CS) and patients with the phenotypein whom the diagnosis was discountedusing other approaches [6]. Most (>95%) ofthe subjects with Cushing’s syndrome had elevatedlate-night salivary cortisol whereas most(>97%) of the subjects without proven Cushing’ssyndrome had salivary cortisol within thereference range. Two of the false-negative resultswere due to cyclical Cushing’s syndrome withsubsequent elevated salivary cortisol resultswhen the ACTH-secreting tumour was active.It is my impression that false-positive resultsare usually due to proximal stress before thesample is obtained. Therefore, it is important,when sampling at home, that patients sampleon quiet evenings with no alcohol intake.Our current approach for screening and diagnosisof endogenous Cushing’s syndrome is shownin Figure 2. A careful history must be taken toensure that the patient is not using any form ofcorticosteroid therapy (particularly hydrocortisonecream or ointment that can contaminatethe saliva sample). Two late-night (2300-2400hr) salivary cortisol samples are obtained, usuallytwo nights in a row. If both late-night salivarycortisol samples are clearly not elevated, it isunlikely that the patient has Cushing’s syndrome.If the clinical index of suspicion is high, or if thesymptoms worsen, late-night salivary cortisoltesting can be repeated. If both results are clearlyelevated, the diagnosis can be confirmed withcomplementary testing and then appropriatedifferential diagnostic testing performed. If theresults are discordant or only mildly elevated,other testing can be performed and salivary cortisoltesting can be repeated. It is these patientswith mild or inconsistent increases in late-nightsalivary cortisol that are the most challenging,and ongoing research is being carried out toresolve this issue [7].SummaryLate-night salivary cortisol is recommended forthe initial evaluation of patients in whom thediagnosis of endogenous hypercortisolism issuspected. There are now many reference laboratoriesthat offer this testing as well as simpleand cost-effective ELISAs for salivary cortisol.It is hoped that testing for Cushing’s syndromeusing this approach becomes routine in patientswith milder characteristics suggestive of Cushing’ssyndrome, such as proximal muscle weakness,abdominal obesity, polycystic ovary syndrome,hypertension (particularly resistant totherapy), and depression that is resistant tostandard therapy.References1. Carroll T, Raff H, Findling JW. Late-night salivarycortisol measurement in the diagnosis of Cushing’ssyndrome. Nat Clin Pract Endocrinol Metab2008;4:344-50.2. Nieman LK, Biller BM, Findling JW, Newell-PriceJ, Savage MO, Stewart PM, Montori VM. The diagnosisof Cushing’s syndrome: an Endocrine SocietyClinical Practice Guideline. J Clin EndocrinolMetab 2008;93:1526-40.3. Raff H, Raff JL, Findling JW. Late-night salivarycortisol as a screening test for Cushing’s syndrome.J Clin Endocrinol Metab 1998;83:2681-6.4. Raff H, Homar PJ, Skoner DP. New enzymeimmunoassay for salivary cortisol. Clin Chem2003;49:203-4.5. Baid SK, Sinaii N, Wade M, Rubino D, Nieman LK.Radioimmunoassay and tandem mass spectrometrymeasurement of bedtime salivary cortisol levels:a comparison of assays to establish hypercortisolism.J Clin Endocrinol Metab 2007;92:3102-7.6. Raff H. Salivary cortisol: a useful measurementin the diagnosis of Cushing’s syndrome and theevaluation of the hypothalamic-pituitary adrenalaxis. The Endocrinologist 2000; 10: 9-17.7. Kidambi S, Raff H, Findling JW. Limitations ofnocturnal salivary cortisol and urine free cortisolin the diagnosis of mild Cushing’s syndrome. EurJ Endocrinol 2007;157:725-31.The authorHershel Raff Ph.D.,Endocrine Research Laboratory,Aurora St. Luke’s Medical Center,Milwaukee, WI 53215, USADepartment of Medicine,Medical College of Wisconsin,Milwaukee, WI 53215, USAAddress for correspondence:Hershel Raff Ph.D.,EndocrinologySt. Luke’s Physician’s Office Bldg2801 W KK River Pky Suite 245Milwaukee WI 53215, USATel +1 414 649 6411Fax +1 414 649 5747e-mail: hraff@mcw.eduComments on this article?Feel free to post them atwww.cli-online.com/comment/CushingsBook reviewHost-Pathogen Interactions:Methods and ProtocolsEdited by Steffen Rupp and Kai SohnPub. by Humana Press (2009),428pp, e66,95In recent decades, infectiousdiseases, once believedto be fairly contained, havebecome a vital, resurgentfield of research. In thisbook, one of the Methods in Molecular Biologyseries, top experts examine the relationshipbetween the host and the pathogen, crucial to theoutcome of an infection and the establishmentof disease, or the asymptomatic, commensalcolonisation by organisms. The step-by-step laboratorymethods and protocols in this volumestudy host-pathogen interaction, with a focuson fungal, bacterial and parasitic pathogens, ata molecular level in order to reveal the mechanismsof infection and to identify the vulnerabilitiesof the pathogen of interest. Written in thehighly successful Methods in Molecular Biologyseries format, the chapters feature brief subjectintroductions, lists of the necessary materials andreagents, and tips on troubleshooting and avoidingknown pitfalls. Comprehensive and cuttingedge,this book serves as an easy entry point forall those investigating the factors responsible forthe pathogenicity of microorganisms.The ready-to-start protocols established for reliabilityby experts in the field are easy to reproduce,and a comprehensive coverage of themodels of infection and methods for studyingthe major human pathogenic bacteria, fungi andparasites is provided. This book will be invaluablefor infectious disease specialists, pathologistsand molecular biologists.Humana pressTotowa, NJ, USAwww.ihe-online.com & search 24481

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– Issue N°8 – Dec. 2008 - Jan. 2009 10Colorectal cancer updateA simple blood test for colorectal cancerPeople are often reluctant to undergo a routinecolonoscopy to screen for colorectal cancer.However, this is the third most commonlydiagnosed cancer in the Western world, thesecond leading cause of cancer deaths, andeighty-five percent of those who develop colorectalcancer have no initial symptoms or familyhistory of the disease. Colorectal cancer has agood prognosis when detected early. Over 90%of patients diagnosed with stage I colorectalcancer survive for at least five years but fewerthan 10% of patients diagnosed with stage IVcolorectal cancer survive for five years.To convince more people to undergo a potentiallylife-saving colonoscopy, Prof. Nadir Arber,who heads the Integrated Cancer PreventionCentre at the Tel Aviv Souraski Medical Centre,has developed a simple early-warning bloodtest to detect colon cancer. Using biomarkers,it is the first test available that can detect cellsof colon polyps –– the precursors to colon cancer–– in the blood, with a very high degree ofsensitivity and accuracy. Those subjects whoare at high risk of colon cancer can be identifiedvia this minimally invasive test, and canreceive a follow-up colonoscopy to confirmthe findings.The novel test is based on CD24. Immunohistochemistryhad previously confirmedthat increased expression of CD24 is an earlyevent in colorectal cancer carcinogenesis. Itwas expressed in 90.7% of adenomas, the polypsthat convert to colon cancer, and 86.3%of colorectal cancers. Very low expression wasseen in normal epithelium (16.6%). Humancancer cell lines showed growth inhibition inresponse to the antibodies, according to theirexpression levels of CD24 and in dose- andtime-dependent manners.The current test, which is being prepared for marketing,utilises the fact that polyps in the colonsecrete biomarkers, which can be detected in theblood at very low levels. Recent studies show thatthe test can correctly identify adenomas with asuccess rate of more than 80%.http://www.aftau.org/site/News2?page=NewsArticle&id=8025New approach to genetic testingcould halve deaths from inheritedcolorectal cancerProfessor John Hopper, an Australia Fellowof the National Health and Medical ResearchCouncil in the Melbourne School of PopulationHealth, says that changing the approach togenetic screening for cancers in Australia couldeffectively halve deaths caused by an inheritedform of bowel cancer.Current cancer genetic screening programmesare highly focused on breast cancer and typicallybased on family history alone. However studiesin the UK and Australia have now shown thatmost of the women who have been tested hada low chance of carrying a faulty gene whichcauses cancer. Instead he believes that geneticscreening should focus more on testing thetumours of young people who develop cancersto determine if they are caused by an inheritedgenetic fault which might be shared by otherfamily members.In the case of colorectal cancer, about 10 percent are the result of a genetic fault that cannow be detected. Deaths caused by an inheritedform of the disease could effectively be halvedif the tumours of early-onset cancer suffererswere routinely tested for signs of an inheritedgenetic cause. Relatives of the patient could, ifthey wished, also be tested for the same geneticfault. Those who were found to be carriers couldthen receive regular bowel screenings to detectearly signs of any cancers, which would greatlyreduce their chance of dying from the disease.http://blogs.unimelb.edu.au/sph-news/2008/10/14/media-releaseGenomic signature of colorectalcancer may individualise treatmentAbout 150,000 people are diagnosed withcolorectal cancer each year in the UnitedStates and almost 50,000 are expected to dieof the disease in 2008. Up to 30 percent ofpatients diagnosed with early stage colorectalcancer go on to experience recurrencesdespite initial cure with surgery and chemotherapywhen indicated. Conventional methodsof characterising tumours currently relyon pathological information such as tumoursize, lymph node involvement and degreeof metastasis. Such clinical data are used todetermine whether an early stage colorectalcancer patient receives chemotherapy aftersurgery, and if so, what type.However, researchers lead by Katherine Garman,M.D., a gastroenterology fellow at theDuke Institute for Genome Sciences & Policy,USA, have developed a model for predictingrisk of recurrence in early stage colorectal cancerpatients, and have also used the model to predictsensitivity to chemotherapy and targetted therapyregimens. Their findings have importantimplications for individualising therapy.The researchers studied gene expression datafrom 52 samples of early stage colon cancertumours, looking for patterns. Then theycorrelated the gene expression patterns withpatient progress reports to track the recurrenceof cancer. The predictive power ofthe correlations was subsequently tested intwo independent data sets from 55 and 73tumours, respectively.In collaboration with colorectal cancer specialistDavid Hsu, M.D., the researchers then tooktheir study one very significant step further,using the data collected on gene expressionand prognosis, to examine response to severaldifferent types of therapy. They found that thetraditional chemotherapy given to patientswith colon cancer varies considerably in itsability to treat tumours with a high likelihoodof recurrence. Using the gene-expression dataas a guide, they then identified several otherdrugs and tested those drugs in their samples.The drugs chosen were novel targetted therapiesand anti-inflammatory agents that targetcertain cancer cell pathways and had been previouslyshown to alter colorectal cancer biology.Two of the drugs tested seemed to causesignificant changes in tumour biology in a laboratorydish, effectively making a high-recurrence-risktumour into a low-recurrence-risktumour by altering the genetic makeup. Thesetherapies would need to be tested further in aclinical trial.http://www.dukehealth.org/HealthLibrary/News/genomic_signature_of_colon_cancer_may_individualize_treatment

11– Issue N°8 – Dec. 2008 - Jan. 2009Novel marker of colon cancerSeveral molecules have been reported to play animportant role in gastroenterological tumourigenesisand tumour metastasis, but the molecularmechanisms involving tumour developmentand progression still remain unclear incolorectal cancer.Recent research addresses this question. Byusing the combined methods of laser microdissection(LMD), P27-based RNA amplificationand polypeptide analysis, the team evaluateddifferentially expressed genes betweenearly carcinoma and lymph node metastaticpatients. Moreover, they further identified fourdifferentially expressed genes in the progressionof colorectal cancer in another group of 15patients by means of semiquantitative reversetranscribed polymerase chain.Their result indicated that the five gene expressionswere changed in colon carcinoma cellscompared with that of controls. Of the fivegenes, three genes were downregulated and twowere upregulated in invasive submucosal coloncarcinoma compared with non-invasive cases.The results were confirmed at the level of RNAand gene expression. Five genes were furtheridentified as differentially expressed genes inthe majority of cases (> 50%, 25/40) in progressionof colon cancer, and their expression patternswere similar to tumour suppressor genesor oncogenes. These results not only reveal thedifferentially expressed genes in progressionof colon cancer, but also provide informationthat may prove useful for identifying noveldiagnostic and therapeutic targets.http://www.wjgnet.com/1007-9327/14/5887.aspCancer-causing gut bacteria exposedIntestinal cancers occur almost exclusivelyin the colon where billions of bacteria are incontact with the gut surface. For years scientistshave tried to identify links between gutbacteria and subjects at risk of colon cancer.This has been made difficult by the enormouscomplexity of the microbial communitiesin the intestine. Now a team lead byProfessor Mark Huycke, Department of Veterans’Affairs Medical Center in OlklahomaCity, USA, has discovered that a moleculeproduced by a common gut bacterium activatessignalling pathways that are associatedwith cancer cells.Enterococcus faecalis is a normal gut bacterium.Unlike most gut bacteria, it can survive usingtwo different types of metabolism: respirationand fermentation. When the bacteria usefermentation they release by-products, one ofwhich is a superoxide that can damage DNAand may play a role in the formation of colontumours.The team found that 42 genes in epithelialcells in the gut are involved in the regulationof the cell cycle, cell death and signalling Thesecells could be rapidly affected when E. faecalisswitches to fermentation.http://www.sgm.ac.uk/news/releases/JMM.1008.MH.1.cfmwww.cli-online.com & search 24297

– Issue N°8 – Dec. 2008 - Jan. 2009 12 NanotechnologyLab technologyNanoparticles for moleculardiagnostics and therapyMultifunctional nanoparticles, which incorporate diagnostic (quantum dots,magnetic, metallic, polymeric and silica nanoparticles) and/or therapeutic(magnetic and metallic nanoparticles) properties, are in the process ofdevelopment. This review focuses on dye-doped silica nanoparticles and goldbasednanomaterials, which have been widely investigated by our group forbioanalytical purposes in molecular diagnostics and cancer therapy. A summarydescribes their main properties, as well as some recent relevant applications.by Dr S. Bamrungsap, Dr Y-F. Huang, Dr M. Carmen Estevez and Dr W. TanNanotechnology, which has received considerableattention in advanced biomedical scienceover the past decade, refers to the applied scienceinvolved with materials in the sub-100nanometre range. With dimensions similar tobiomacromolecules, nanoparticles can be engineeredto have specific or multiple functionsand can be used for investigating and pursuingan in-depth understanding of the mechanismsinvolved in biochemical processes. The uniquecharacteristics of particles in the nanometrerange, such as high surface-to-volume ratio orsize-dependent optical and magnetic properties,are drastically different from those of theirbulk materials and hold promise in the clinicalfield for disease diagnosis and therapeutics[1-4]. The successful transfer of nanotechnologyinto biological systems has been made feasibleby combining the intrinsic properties ofnanoparticles with immobilisation of specificligands, such as proteins and oligonucleotides,on the surface for specific recognition. Thus,the development of multifunctional nanoparticles,which incorporate diagnostic (quantumdots, magnetic, metallic, polymeric and silicananoparticles) and/or therapeutic (magneticand metallic nanoparticles) properties, as wellas specific targeting capability by surface modificationwith biomolecules, is a continuoustopic of research [5-10]. In this review, we willmainly focus on a discussion of dye-doped silicananoparticles and gold-based nanomaterials,which have been widely investigated by ourgroup for bioanalytical purposes in moleculardiagnostics and cancer therapy. A summarydescribing their main properties, as well assome recent relevant applications, is also given[Figure 1 and 2].Dye-doped silica nanoparticlesThe attractive properties of dye-doped silicananoparticles have accelerated their use inbioanalysis. Specifically, their physically andchemically inert surface can protect trappedfluorescent dyes from the oxygenic environment,whereas the silanol surface allows foran easy and versatile chemical modificationwith various functional groups. There aretwo major approaches for the synthesis ofdye-doped silica nanoparticles. One is reversemicroemulsion, which is primarily used forthe incorporation of hydrophilic inorganicdyes. In this water-in-oil (W/O) microemulsionsystem, water nanodroplets are formedin the bulk oil phase which acts as confinedmedia or nanoreactors for discrete nanoparticleformation. Positively charged dye molecules,such as ruthenium complexes, can besuccessfully encapsulated in the negativelyANPBNP-PEG-BiotinSABiotin-target cRNAProbe DNAcharged silica matrix through strong electrostaticinteractions, resulting in the formationof highly uniform particles with diametersranging from 15 to 200 nm. On the other hand,the Stöber method is based on the formationof particles by the hydrolysis of the silica precursor(e.g., tetraethylorthosilicate, TEOS) inethanolic media containing water and ammoniaas the basic catalyst. This method is highlyefficient for the entrapment of more hydrophobicmolecules and has been modified byadding different organosilanes with appropriatefunctional groups (i.e., amine-containingsilane agents, such as 3-aminopropyltriethoxysilane,APTES), which can be linked with dyemolecules, allowing the incorporation of covalentlycoupled molecules to the silica matrix.Thus, these particles make excellent multifunctionalfluorescent probes for ultrasensitivedetection in bioanalytical and biomedicalareas because of 1) their extraordinary brightness,which is provided by the entrapment ofhundreds, or even thousands, of dye moleculesinside their matrix and 2) their extremelyhigh stability which is conferred by the silicashell, thus avoiding photobleaching andphotodegradation of the dyes.Fluorescent silica NPs have been used forthe development of an ultrasensitive DNATarget cellsDye-Doped Silica NP Dyed or Magnetic NP Protein Antibody DNA CellsControl cellsFigure 1. Schematic representation of various diagnostic applications of dye-doped silica nanoparticles (NPs): (a)nanoparticle-based labelling for DNA microarray technology, (b) multiplex bacteria detection using antibody-conjugatedmulticoloured dye-doped silica nanoparticles, (c) multiple cancer cell detection through stepwise extraction and labellingof target cells from a cell mixture by magnetic-core silica nanoparticles (MNPs) and fluorescent dye-doped silicananoparticles (FNPs), respectively. Reproduced with permission from [12, 14, 16]. ©2008 American Chemical Society.CMNP1MNP2MNP3FNP1FNP2FNP3

– Issue N°8 – Dec. 2008 - Jan. 2009 14Nanotechnologyhybridisation assay [11]. The sandwich assaydesign was based on the immobilsation of twodifferent DNA capture sequences, one onto aglass surface and the other one attached todye-doped silica nanoparticles. The unlabelledtarget DNA sequence was complementaryto both capture sequences. After specificDNA hybridisation onto the solid surface,and with the subsequently added NPs, anenhanced fluorescent signal could then bemonitored and quantified. Because of theeffective surface modification, only minimalnonspecific binding of the NPs onto the glasssurface with no aggregation of nanoparticleswas observed. Furthermore, the NPs haveproved to be effective as luminescent probesin commercial microarray systems, such asAffymetrix GeneChips [12]. In an AffymetrixGeneChips system, multiple probes homologousto different regions of target RNA aredesigned and immobilised on the arrays. Thebiotinylated cRNA is then hybridised to theGeneChips. After hybridisation, the arraysare washed and stained with Ruby dyedopednanoparticles [Figure 1a]. Thus, bytheir simplified staining procedure, higherphotobleaching threshold, and enhancedfluorescent signal allowing a concentrationdetection limit of 50 fM, nanoparticleshave been found to be superior to the traditionalprotein Streptavidin-Phycoerythin(SA-PE) approach.These probes have also been used for thedetection of whole living entities, such asbacteria and cancer cells. For instance, a simple,rapid, and sensitive fluorescence-basedimmunoassay has been developed using bioconjugatedsilica nanoparticles for the detectionof single E. coli O157:H7 [13]. Antibodiesagainst single E. coli O157:H7 wereconjugated to dye-doped silica nanoparticlesto form nanoparticle-antibody complexeswhich could specifically bind to the antigensexpressed on the E. coli O157:H7 surface.The high signal intensity, together with thepresence of a high number of antigens on thetarget bacteria surface which are available forspecific recognition, provided an extremelystrong fluorescent signal allowing single bacterialcell detection within 20 minutes. Moreover,accurate enumeration of 1-400 bacterialcells in 1 g of spiked ground beef sample wasdemonstrated with the methodology developed.Furthermore, the ability to encapsulatenot only one type of dye, but also a combinationof fluorophores, all of which undergoefficient energy transfer, resulted in differentnanoparticles with tunable final emissionusing a single excitation source, whichopens the door to multiplexing analysis.Thus, by using three different NPs encapsulatingdifferent ratios of three different dyes,simultaneous analyses of three different bacteriawere conducted by immobilising specific anddistinctive antibodies to each one [14] [Figure 1b].On the other hand, in the area of early diagnostics,there is a continuing need for effectiveand sensitive methodologies which allowaccurate detection of disease in the earlystages. In this context, ultrasensitive detectionof low concentrations of abnormal cellsis required. A recently developed and straightforwardapproach to this problem combineddye-doped silica nanoparticles and magneticcore-silica shell nanoparticles for the collectionand detection of cancer cells [15]. Bothtypes of NPs were conjugated to specificaptamers, which were selected for the specificdetection of leukaemia cancer cells. Thisprotocol involved the selective extraction andseparation of the target cancer cells using theaptamer-conjugated magnetic nanoparticles(AMNPs) under the application of an externalmagnetic field. Then, the correspondingaptamer-conjugated fluorescent nanoparticles(AFNPs) were used for cellular detection.As a consequence of the high brightness of thesilica NPs, an extremely low detection limit ofapproximately 250 cells was achieved, with awide dynamic range covering more than twoorders of magnitude using pure samples. Theassay was fast (less than 30 minutes) and easy,compared with other methodologies, such asPCR-based assays or immunophenotyping.Since it worked in a similar manner in morecomplex matrices, such as serum and wholeblood, the effectiveness of the initial extractionstep was firmly established. Moreover, amultiple successive extraction of three differenttypes of cancer cells has been further performedby using three different dye-dopednanoparticles [16] [Figure 1c]. Overall, theseANP AgglutinationAGNPAptamerfindings clearly demonstrate the high potentialof nanoparticles for ultrasensitive detectionof bacterial pathogens and cells in theclinical, environmental and food fields.Gold-based nanoparticlesSuch fascinating features as ease of synthesisand surface functionalisation with thiolcontainingmolecules, non-cytotoxicity, highbiocompatibility, as well as broad-based opticalproperties, make gold-based nanoparticlesstill another attractive nanomaterial and oneof the most studied in the bioanalytical field.Gold nanoparticles with tunable size (~0.8 - 60nm in diameter) and narrow size distribution(± 10% in deviation) can be synthesised byphysical methods, including photochemistry,sonochemistry and radiolysis, and by chemicalmethods, including reduction of HAuCl 4,microemulsion and seeding growth. Owing tothe quantum size effect, gold nanoparticles possessstrong surface plasmon resonance (SPR)bands in the visible wavelength range. TheirSPR frequencies are also strongly influencedby the interparticle distance. When the goldnanoparticles in solution are in close proximitywith others, their overall change in surfaceplasmon is translated into absorption spectrashifts resulting in a change in sample colour. Inpast years, this characteristic has been exploitedto develop various techniques for selectivecolourimetric detection of ions, genes, proteinsand saccharides. It has also been recentlyapplied to the direct detection of cancer cells[17] by conjugating specific aptamers onto thesurface of the gold nanoparticles. Once the goldnanoparticle-aptamer complexes selectivelybind and assemble around the target cells, theaggregation of gold nanoparticles causes a redshift of absorption spectra, resulting in a noticeablecolour change in solution [Figure 2a]. TheFigure 2. Schematic representation of diagnostic and therapeutic applications of gold-based nanoparticles: (a)aptamer-gold nanoparticle (AGNP) colorimetric assay, b) aptamer-conjugated nanorods (NRs) for photothermal therapy.Reproduced with permission from [17]. ©2008 American Chemical Society.BCellsAu-Ag NRTargetControlTarget cellsControl cells

15– Issue N°8 – Dec. 2008 - Jan. 2009results can be observed with thenaked eye without sophisticatedand expensive instrumentationand can also be quantified usingconventional UV-visible spectrometers.The assay performedwell in complex matrices, such asserum samples, and showed excellentsensitivity and selectivity forthe target cells in the complex system,with low nonspecific bindingin control cells.By changing the shape of goldnanoparticles from spheres toelongated rods, another SPR bandat a longer wavelength arises fromthe plasmon oscillation of electronsalong the longitudinal axis.This longitudinal SPR band canbe shifted into the near-infraredregion (NIR) by an increase in thenanorod aspect ratio, which is theratio of length to diameter. It hasbeen demonstrated that multimetallicnanocomposites, such asgold-silver nanorods, also possesssharper and stronger longitudinalSPR bands, as well as higher molarabsorptivity, than spherical goldnanoparticles or gold nanorods.Thus, gold-silver nanorods areconsidered attractive candidatesfor photothermal therapy as a consequenceof their excellent absorptionin the near infrared (NIR)range and their high efficiency inconverting light energy to localheat. Recently, we reported the useof aptamer-conjugated gold-silvernanorods for specific target cell recognitionand photothermal therapy[18]. Highly specific aptamersselected against leukaemia cancercells were conjugated on the nanorodsurface through thiol linkage.The aptamer-nanorod conjugatesexhibited excellent specific recognitionof both suspension- andadherent-targeted cells. Our nanorodsexhibited high molar absorptivityby utilising only 8.5×10 4 W/m 2 laser exposure to induce 93%cell death as compared to goldnanoshells or gold nanorods whichrequired 1×10 5 ~ 1×10 10 W/m 2 oflaser irradiation. Moreover, resultsdemonstrated that about 50% oftarget (CEM) cells were severelydamaged after laser exposure,while 87% of control (NB-4) cellsstill remained intact in suspensioncell mixture [Figure 2b].ConclusionsNanobiotechnology has becomean attractive and promisingresearch area with potentialapplication in many diversifiedfields, and it has played a particularlyimportant role in biomedicine.Nanoparticles have emergedas promising nanoplatforms forefficient diagnostics and therapeuticsby merging the characteristicproperties they possess at thenanometre scale with the feasibleimmobilisation of specific ligandson the surface. Therefore, theyhave become ideal candidates formolecularly sensitive detection,highly efficient contrast agentsfor molecular imaging, as wellas carriers for targeted drug andgene delivery, and therapeuticalreagents for targeted photothermaltherapy. Nonetheless, a betterfundamental understanding ofthe behaviour of nanomaterialsin biological systems needs to beaddressed, as well as the engineeringof novel nanoparticles, whichcan overcome the drawbacksrelated to currently developednanomaterials, including nonspecificbinding, aggregation, toxicityand biodistribution.AcknowledgementsThis work was supported by NIHNCI grant and by State of FloridaCenter for NanoBiosensors. S. B.acknowledges financial supportfrom The Royal Thai Government,Thailand. M.-C.E acknowledgesfinancial support from the Departamentd’Universitats, Recercai Societat de la Informació de laGeneralitat de Catalunya, Spain.References1. Kim KY. Nanomedicine (NY, US)2007; 3: 103-110.2. Huang X et al. Nanomedicine (London,UK) 2007; 2: 681-693.3. Goya GF et al. Current Nanoscience2008; 4: 1-16.4. Heath JR et al. Ann Rev Med 2008;59: 251-265.5. Katz E and Willner I. Angew ChemInt Ed 2004; 43: 6042-6108.6. Akira I et al. J Biosci Bioeng 2005;100: 1-11.7. Azzazy HME et al. Clin Chem 2006;52: 1238-1246.8. Pinaud F et al. Biomaterials 2006;27: 1679-1687.9. Bhattacharya R and Mukherjee P.Adv Drug Deliver Rev 2008; 60:1289-1306.10. Jain KK. Clin Chem 2007; 53:2002-2009.11. Zhao X et al. J Am Chem Soc 2003;125: 11474-11475.12. Wang L et al. Bioconj Chem 2007;18: 610-613.13. Zhao Z et al. Proc Natl Acad SciUSA 2004; 101: 15027-15032.14. Wang L et al. Bioconj Chem 2007;18: 297-301.15. Herr JK et al. Anal Chem 2006; 78:2918-2924.16. Smith JE et al. Anal Chem 2007; 79:3075-3082.17. Medley CD et al. Anal Chem 2008;80: 1067-1072.18. Huang YF et al. Langmuir 2008;accepted.The authorsSuwussa Bamrungsap, Yu-FenHuang, M.- Carmen Estevez andWeihong TanCenter for Research at the Bio/Nano Interface,Department of Chemistry andPhysiology and FunctionalGenomics,Shands Cancer Center and UFGenetics Institute,University of Florida,Gainesville,Florida, 32611-7200,USAFeel free to post them atParalens ad 101mmx178updated 25/11/08 15:54 Page 1www.cli-online.com/comment/nanotechnology_diagnosticswww.qbceurope.comFast Accurate Detection and quantification ofMalaria and TuberculosisParaLens• Detects Malaria, Tuberculosis,Trypanosomes and otherblood-borne parasites.• Identifies the need for and themost appropriate treatment• Accurate species detection• 40 times more sensitive than athick film• Converts any microscope into alow-cost fluorescent microscope• Use in the laboratory or the field• Now easily transportable in thenew carrying case formatAlso available:Exhibiting at ArabLab 2009QBC STAR POC SystemStand 442QBC AUTOREAD PlusSeeking distributors in Africa, Europe and the Middle EastA Division of Woodley Equipment Company LtdTel: +44 (0)1204 460446Fax: +44 (0)1204 692198Email: sales@qbceurope.comComments onthis article?LOCOMOTIVE HOUSE . LOCOMOTIVE INDUSTRIAL ESTATE . HORWICH . BOLTON . BL6 5UE . U.K.www.cli-online.com & search 23972

– Issue N°8 – Dec. 2008 - Jan. 2009 16MicrobiologyOutbreaks of communicable disease:national surveillance and lab investigationOutbreaks of communicable disease may attract theattention of the public, politicians and the press for threereasons: the occurrence and magnitude of seeminglyavoidable deaths, the need to investigate causes forany delay in recognition and intervention, and theopportunity for, and public interest in, apportioningresponsibility and claims for legal compensation.by Dr A. PearsonThe impact of outbreaks of communicabledisease on the publichealth of western populationsremains undiminished in spiteof the advancements in medicaltreatment. In the Middle Agesthere was bubonic plague, thenthe white plague of tuberculosisdominated public health prioritiesthroughout the 19 th century.In the early 20 th century more peopledied in an influenza outbreakthan were killed in the First WorldWar. During the Second WorldWar, there were concerns about,and investigations into, the potentialuse of bacteria and viruses asbiological warfare agents capableof promulgating epidemics ofcommunicable disease.The 1950s saw the widespreadreduction, and in many westerncountries the virtual control, ofvaccine-preventable disease, forexample, diphtheria. The worldwideeradication of smallpoxthen led some countries to scaledown their investment in publichealth provision, epidemiologicalexpertise and investment inresearch and development inthe epidemiology of communicabledisease. During the 1980sHIV/AIDS emerged as a worldpandemic, and tuberculosis reemergedas a global public healththreat; the possibility of eradicatingtuberculosis had been an earliergoal considered by the WHOfollowing the success achievedwith the global eradicationof smallpox.Sir Donald Acheson, speakingduring a discussion on theFigure 2. Laboratory reports of gastroenteritis in England, 1977 - 2000.‘Decline and Rise of PublicHealth in the 1980s and 1990s’,remarked that on his appointmentas UK Chief MedicalOfficer, both HIV/AIDS and BSE(Bovine Spongiform Encephalopathy)required UK Governmentintervention and actionto address widespread publicBox 1. Exceedance reports: approach used by the UK HPA.concern and fear.He commented further that:“The renaissance of public healthhad other roots . . . . . Within a fewweeks of my arrival in Whitehallin 1983, a calamitous outbreak ofsalmonellosis occurred in a mentalhospital in Yorkshire. The factthat this had happened in Stanley• A regression model applied to weekly data by week of report• Poisson model adjusted for excess variation (over dispersion).• Model allows for secular trend by including a covariate for timewhen significant.• Model accommodates seasonality by using data from comparableweeks (+/-3 weeks) in previous 5 years.• Past outbreaks are down weighted by giving less weight to datapoints well above the expected values.• False positive rate (false alarms) stabilised using a transformationwhen calculating the threshold so they are the same for rare andcommon infections.• Completely automated• O = observed count for the current week• E = expected count from the statistical model• U = upper threshold (upper 99.5% prediction interval), valuesabove this are flagged• X = (O-E)/(U-E)Figure 1. Dates of admission for all cases with respiratory illness at the StaffordGeneral Hospital, UK, 1985.• All organisms with X>1 are ranked by the size of X and listed.Box 2. The exceedance score.

17– Issue N°8 – Dec. 2008 - Jan. 2009Figure 3. Example of exceedance report detection of a Salmonella enteritidisphage type 8 outbreak.Royd Hospital, an institutionunder Government managementwithin the NHS, and that therewere several hundred cases andmore than 50 fatalities, created ascandal, and resulted in the setting up of a public inquiry thatidentified serious deficiencies inpublic health organisation. Thatwas the first public enquiry. . . Ifthat weren’t enough to bring theimportance of public health toevery house in the land, an outbreakof legionellosis occurredin a newly constructed hospitalin Stafford, again resulting inmany fatalities, which underlinedthe point once again [Figure1]. There was a second publicinquiry that was extremelycritical of public health . . . .After these two tragedies came a4500040000Number of C. difficile reports350003000025000200001500010000500001990199119921993199419952007 data are provisional1996199719981999Year20002001200220032004200520062007Figure 4. Voluntary laboratory reporting of C. difficile: the national surveillance systemthat provides an early warning system for changing patterns of communicable disease.www.cli-online.com & search 24314

– Issue N°8 – Dec. 2008 - Jan. 2009 18Microbiologyrecommendation in 1986 to setup an inquiry into the future ofthe public health function undermy chairmanship”.“One further outbreak of infectiousdisease helped sustain themomentum for the revival ofpublic health. This was the Farleyinfant food epidemic, in whicha number of babies became illand died throughout Britain.It turned out that the commonfactor was an infant foodinfected with Salmonella ealing,but this seemed unlikely as thishad only been found in seagulldroppings, so there was greatscepticism. But then, in the end,the mystery was solved, becausethe bacterium was found in thewater tank in the Farley infantfood factory and the tank hadbeen contaminated by seagulldroppings . . . . .”Figure 6. C. difficile laboratory reporting.O'ConnorHollingsworthLeemingRussmannMasseyTicehurstSnellO'Connorvan den BergHollingsworthLeemingCombinedFigure 5. Voluntary reporting of Staphylococcal aureus bacteraemia: evolution of the national outbreak of MRSA bloodstream infections.By the late 1980s salmonellosisand gastroenteric infections dueto Campylobacter were at epidemic0 .05 .1 .15 .2 .25 .3 .35 .4 .45 .5 .55 .6 .65 .7 .75 .8 .85 .9 .95 1sensitivityFigure 7. Meta-analysis of ELISA tests: sensitivity.levels [Figure 2] in England.This lead the then UK Secretaryof State to comment on thenational concern as to the extentof Salmonella in British poultryflocks. National surveillance oflaboratory diagnosed infectionsand exceedance analysis [Box1 and 2, Figure 3] were by thistime well established within theEnglish public health laboratoryservice (PHLS). This service useda national network of over 50PHLS laboratories and a voluntaryelectronic reporting systemfrom over 160 NHS laboratories.During the 1990s the epidemicof food poisoning was addressedby extensive investigations oflocal and national outbreaks bythe PHLS, the veterinary serviceand the newly created FoodsStandards Agency. The results areevident from the reductions seenin Figure 2.No sooner did national surveillancesignal the success of thesemeasures than the same voluntarylaboratory reporting systemsrevealed two new national outbreaksin the English NHS: thatof MRSA bacteraemia and C. difficileinfection, both apparentlyincreasing in hospital patients aswell as, to a lesser extent, in thegeneral population [Figures 4 and5]. Precise measurement of theseoutbreaks is dependent on theascertainment and reporting ofcases. Figures 5 and 6 summarisetwo major factors affecting thedetection and reporting of communicabledisease. Firstly only asmall proportion of the cases ofdiarrhoea caused by C.difficile inthe community will be tested andreported [Figure 6]. Secondlya meta analysis of the sensitivityof the test systems currentlyused to detect and report C. difficileindicates that between 10%and 15% of cases may not beidentified [Figure 7].Hence the future development ofany national reporting and earlywarning systems for outbreaks ofcommunicable disease requiresappropriate levels of authenticationof the processes and surveillancesystem in place for eachtype of bacterial or viral agentunder investigation.The authorDr Andrew Pearson,Consultant epidemiologist,Deputy Head of HealthcareAssociated Infections andAntimicrobial ResistanceDepartment,Health Protection Agency,Colindale,UKComments onthis article?Feel free to post them atwww.cli-online.com/comment/Outbreak control

Endocrinology19– Issue N°8 – Dec. 2008 - Jan. 2009Exogenous endocrine-disrupting compoundsEvery year a plethora of new chemicals of unknown toxicity are releasedinto the environment. Recently, considerable attention has been focused onendocrine-disrupting compounds (EDCs), which constitute a wide group ofenvironmental pollutants that at very low concentrations are able to mimic orantagonise the effects of endogenous hormones (oestrogens and androgens),or disrupt synthesis and metabolism of endogenous hormones and hormonereceptors. Studies have linked endocrine disruptors to adverse biologicaleffects in animals, giving rise to concerns that low-level exposure might causesimilar effects in humans. Because of this, the detection of endocrine disruptersis an important area of research in environmental and medical fields.by Dr R. Gupta and Prof. A. KumarWhat are endocrine disrupters?Endocrine disrupters are defined as exogenoussubstances that alter functions of theendocrine system and consequently causeadverse health effects in a living organismor its progeny. These compounds are alsoknown as hormone mimickers, oestrogenmimickers and xeno-oestrogens, and theyaffect the reproductive and immune systemsas well as the endocrine system. The effectsof exposure to endocrine disrupters early inlife are permanent and irreversible. Endocrinedisrupters interfere with the functioningof the endocrine system in at least threepossible ways: by mimicking the action of anaturally-produced hormone, such as oestrogenor testosterone, and thereby initiatingsimilar chemical pathways in the body; byblocking the receptors in cells receiving thesehormones (hormone receptors), thereby preventingthe action of normal hormones; andby affecting the synthesis, transport, metabolismand excretion of hormones, thus alteringthe concentrations of natural hormones.They may have enormous consequences forwildlife and human populations becausethey directly affect reproduction and thusevolutionary fitness.Environmental endocrine disruptersAny chemical compounds with the potentialto interfere with the function of endocrinesystems are called endocrine-disrupting compounds(EDCs). These exogenous compoundsinterfere with the production, release, transport,metabolism, binding, action or eliminationof natural hormones in the body responsiblefor the maintenance of homeostasis and theregulation of developmental processes. EDCsare both naturally occurring and man-madecompounds present in the environment. EDCs.Natural HormoneOestrogenProgesteroneTestosteronePhytoestrogenFigure 1. Environmental endocrine disrupters.include natural hormones such as phyto-oestrogens(fungal metabolite-derived oestrogen)as well as synthetic hormones, pesticides, industrialchemicals, compounds used in the plasticsindustry (phthalates), pharmaceutical products(contraceptives) and consumer products, andother industrial by-products and pollutants.There are different sources of endocrine disruptersin the environment, namely water, air andsoil. Many endocrine disruptors in the environmentare termed persistent organic pollutants(POPs); these accumulate in fat, so the highestexposures result from eating fatty foods and fishfrom contaminated water. Exposure to endocrinedisruptors also results from agriculturalusage and run off, as well as from industrial,pulp mill and municipal effluents. Figure 1summarises the various endocrine disrupterspresent in the environment.Endocrine disruption in humansEndocrine disrupters and their possible impacton human health is becoming an importantarea of research in environmental engineering.The endocrine system is a complex associationof body organs and tissues, whose actionsare coordinated by chemical messengers (hormones),which control sexual reproduction,growth, development and behaviour. If thesemessages are disrupted by hormone-mimickingchemicals, then the systems receiving theENDOCRINE DISTRUPTERSSynthetically producedhormoneOral contraceptivedrugs(Estradiol,diethylstilbesteroletc.)Man made substancesMan made chemicalsPesticidesIndustrial chemicalsProducts associatedwith plasticsOrdinary householdproductsHeavy metalsmessages will be impaired. A long list of conditionscan result from hormone disruption,including cancer, birth defects, stunted growth,diminished sperm count, reduced reproductiveorgans, endometriosis (a painful disease ofmenstrual tissues), ectopic (tubal) pregnancies,reproductive failure, damage to the immunesystem, loss of muscle tone, weakened reflexes,impaired short-term memory, decreased abilityto pay attention, lowered intelligence and violentbehaviour. In humans, the consequencesfor the reproductive tract of both males andfemales from prenatal exposure to the drugdiethylstilbesterol (DES) are well known, anddevelopmental neurological problems have been

– Issue N°8 – Dec. 2008 - Jan. 2009 20 Endocrinologyidentified in children exposed to polychlorinatedbiphenyls (PCBs) and/or polychlorinateddibenzofurans (PCDFs). In addition, reports ofa decline in the quality and quantity of spermproduction in humans and increases in breast,prostate and testicular cancers have increasedglobal concern concerning remediation of theenvironment to remove EDCs [1,2]. Therefore,several research activities have been initiated tobetter understand the issue of endocrine disrupters,including potential health effects andthe development of a suitable detection system.The effects of the most potent endocrinedisrupters are shown in Table 1.Molecular imprintedpolymer-based detectionsystems for endocrine disruptersThe monitoring of environmental endocrinedisrupters is very important for the protectionof human health. Several conventional methodscan be used, such as solid phase extraction(SPE), high performance liquid chromatography(HPLC) and gas chromatographic-mass spectrometry(GC-MS), commonly used for theseparation and detection of endocrine disruptorsfrom environmental water samples.These conventional methods are expensive,time consuming and require that the samplebe treated prior to analysis. Biological methodsinclude ELISA, oestrogen and androgenreceptor binding bioassays and fish vitellogenin(VTG) induction bioassays. VTG isa serum phospholipoglycoprotein precursorto the egg yolk proteins of oviparous vertebratesand is potentially an ideal biomarkerfor environmental ooestrogens. Highly sensitivecell-based assays are also currently availablefor testing endocrine disrupters whosetoxic effects are mediated through the arylhydrocarbon receptor (AhR). Ah receptormediation has high relevance to vertebrateorganisms, including humans, but little relevanceto invertebrate organisms that lack theAh receptor. All these bioassays are limitedin that they do not have a broad applicationS.No. EDCs Sources Category Structure Effects1. Benzopyrene found in coal Polycyclica. BAP is a mutagenic and(BAP) tar, in aromaticprocarcinogen, causes genetic damageautomobile hydrocarbonsin lung cells that is identical to theexhaust fumes (PAHs)damage observed in the DNA of mostand tobaccomalignant lung tumours.smoke2. Atrazine Chemicallysynthesised,used inagricultural,ground water anddrinking water3. Bisphenol A(BPA)4. 1,1-dichloro-2,2-bis(pchlorophenyl)ethylene(DDE)5. Diethylstilbisterol(DES)Used asmonomer inproduction ofpolycarbonateplastic andepoxy resins,Suspectedchemical inplastic bottlesand cansAgriculture runoff, bioaccumulatesin foodchain, presentmeasurableamount inserumChemicallysynthesised,from municipaleffluentherbicidecurrently inuseIndustrialchemicalMetaboliteof insecticideDDTNonsteroidalsyntheticoestrogenTable 1. List of the most potent EDCs and their effects.HOClHONHNMeClNCH 3CH 3CCl 2NMeNHa. Atrazine inhibits photosynthesisand other metabolic processes inplants.b. Caused hormone disruption inhumans as well as in fish andamphibians.a. Exposure to BPA in the uterusraises the risk of certain cancers,hampers fertility and can causechildhood behavioural problems suchas hyperactivitya. Act as an androgen antagonist, highmaternal level can affect thedevelopment of male offspring.b. Disrupts the oestrogen-androgenbalance regulating the growth ofhormone-dependent breast cancer cellsa. Women prescribed DES whilepregnant are at a modestly increasedrisk for breast cancer.b. Women exposed to DES beforebirth (in the uterus), known as DESdaughters, are at an increased risk forclear cell adenocarcinoma (CCA) ofthe vagina and cervix, reproductivetract structural differences, pregnancycomplications, infertility and autoimmunedisorders.c. Men exposed to DES before birth(in the uterus), known as DES sons,are at an increased risk for noncancerousepididymal cysts and autoimmunedisorders.d. DES can also cause feminisation ofthe male foetus, as DES undergoesmetabolic epoxidation, and the epoxideproduct has affinity towards theoestrogen receptors.across invertebrate and vertebrate groups, anddo not enable cost-effective and rapid in situanalysis [3-5].Use of biosensorsBiosensors provide an attractive alternative tolaboratory-based analytical methods and canallow online monitoring of toxic pollutantsin the environment without any labelling andpreparatory purification steps. In recent years,great efforts have been invested in the developmentof biosensors, which are analyticaltools consisting of biologically active material(bioselector/recognition element) used in closeconjunction with a device (transducer) thatwill convert a biochemical signal into a quantifiableelectrical signal. For selective recognitionof analytes of interest, the bioselector maybe proteins, enzymes, antibodies and cells etc.Compared with biologicals receptors, molecularlyimprinted materials can be potentially utilisedin cases where no recognising biomoleculeis available. Mostly endocrine disrupters do notyet have recognising biomolecules available.The generation of antibodies against endocrinedisrupters, and their use as the recognitionelements of biosensors, require tedious workthat is unsuitable for field analysis. Molecularimprinting technology is a valid alternativeto the molecular recognition systems used inbiological systems, such as those activated byantibodies. Molecular imprinted polymers(MIPs) appear to offer a better alternative toexpensive and labile biorecognition elementsfor the detection of EDCs. In addition theirlong-term stability makes them suitable forwaste water applications. By using noncovalentimprinting, there is no restriction to the choiceof the analyte. Even small molecules withoutany functionality can be detected with highpredetermined selectivity and high affinity.Molecular imprinted polymersThe principle underlying molecular imprintingis the assembly of a cross-linked polymermatrix around a template; when the templateis removed, recognition sites are created whichare complementary to the template. Conventionally,SPE cartridges are used for isolationpurposes. Imprinted polymers can also beused for isolation and screening of EDCs. Severalstudies have reported molecular imprintingof endocrine disrupters and used MIPsin the column as online pretreatment devicesfor the isolation of other structurally relatedchemicals with oestrogenic activity fromcontaminated water, coupled with analyticalinstruments such as HPLC, MS and liquidchromatography [6,7].Lack of selectivity and low recovery of the analyteare the most common problem encounteredwith SPE cartridges; these problems can

21– Issue N°8 – Dec. 2008 - Jan. 2009Figure 2. Representation of molecularimprinting.be overcome by coupling MIPwith SPE. In reports in the literature,the MIPs were mostlyderived from organic polymers.Recently, inorganic polymers arebeing increasingly used for synthesisof MIPs. Sol–gel imprintingis also a newly emerging fieldin area of molecular imprintingas synthesis of sol-gel materials isstraightforward and particularlyuseful for the sensor applications.Further, the availability of a rangeof pure functional monomersand organically modified silaneprecursors (ORMOSILS) makestheir use in molecular imprintingmore attractive [8]. The imprintingof various molecules in a silicatematrix formed by the sol-gelmethod has been attempted ina number of studies. Han et al[9] prepared a new molecularlyimprinted amino-functionalisedsilica gel sorbent with bindingsites situated at the surface forthe template pentachlorophenol(PCP), by a surface imprintingtechnique in combination with asol–gel process, and applied it toan on-line selective SPE coupledwith HPLC for the determinationof trace PCP in water samples.PCP is used as a general herbicidein agriculture and as an insecticidefor termite control in the preservationof wood. Use of inorganicpolymer sol-gel is preferable tousing organic polymers for sensingapplications. Another importantcomponent of the biosensoris the transducer, which monitorsthe reaction between bioselectorand analyte. Among various physicaltransducers including electrochemical,optical and peizoelectricor calorimetricaltransducers,mass sensitive devices such as surfaceacoustic wave (SAW), quartzcrystal microbalance (QCM) andsurface plasmon resonance (SPR)are becoming popular for sensingapplications. Sol-gel molecularimprinting provides an easyapproach for polymerising a sensitivelayer of the recognition elementdirectly over these devices.However, while sol-gel basedMIPs have found several analyticalapplications they have still notbeen much explored for endocrinedisrupter analysis. In conclusion,sol-gel molecular imprintedpolymer-based detection systemswill surely be effectively used forendocrine disrupter analysis in thenear future.References1. Nicolopoulou-Stamati P, PitsosMA. Human Reproduction Update2001;7:323-30.2. Longnecker MP, Klebanoff MA,Brock JW, Zhou H, Gray KA, NeedhamLL, Wilcox AJ. Am J Epidemiol2002;155:313-22.3. Heppell SA, Denslow ND, FolmarLC, Sullivan CV. Environm. HealthPerspect 1995;103:9-15.4. Helaleh Murad IH, Takabayashi Y,Fujii S, Korenaga T. Anal Chim Acta2001;428:227-34.5. Willemsen P, Scippo M-L, Kausel G,Figueroa J, Maghuin-Rogister Guy,Martial J, Muller M. Anal BioanalChem 2004;378:655-63.6. Watabe Y, Hosoya K, Tanaka N,Kondo T, Morita M, Kubo T. AnalBioanal Chem 2005;381:1193-98.7. Bravo JC, Garcinuño RM, FernándezP, Durand JS. Anal BioanalChem 2007;388:1039-45.8. Gupta R, Kumar A. Lab International22: 10-14.9. Han D-M, Fang G-Z, Yan X-P. JChromatogr A 2005;1100:131–36.The authorsDr Radha Gupta,Professor Ashok Kumar,Department of Biological Sciences& Bioengineering,Indian Institute ofTechnology-Kanpur,Kanpur-208016, Uttar Pradesh,Indiae-mail: ashokkum@iitk.ac.inComments onthis article?Feel free to post them atwww.cli-online.com/comment/EDCsSerum Free Light Chain Analysis (plus Hevylite)This 312 page latest (5th) edition of the book written by Prof A.R. Bradwellincludes exciting new information on renal applications of serum free light chain(FLC) assays, new case studies and an introduction to the new Hevylite assays dueto be launched mid-2009. New renal disease applications are the rapid identificationof those myeloma patients at risk from renal failure plus an exciting newtherapeutic intervention using a novel protein-leaking dialysis filter to removeserum FLCs which, early evidence shows, can contribute to many patients withmyeloma kidney becoming independent of kidney dialysis. Hevylite is a novelrange of assays for quantification of immunoglobulin heavy chain/light chainpairs e.g. IgG/kappa and IgG/lambda, which is likely to change the testing ofmonoclonal immunoglobulins when launched in 2009. There are new reportsand updates on current applications of Freelite serum FLC for diagnosis, monitoringand prognosis of a wide range of plasma cell dyscrasia including multiplemyeloma (MM) and AL amyloidosis. An accompanying CD contains a ten slideintroductory seminar (plus a version with a voiceover), a 40 slide PowerPointpresentation and notes, all the figures and tables and a pdf of the complete book.The Binding SiteBirmingham, UKwww.cli-online.com & search 24508NGALEarly diagnosis ofacute kidney injuryKidney TransplantsCardiac surgery•Septic shock• NephrotoxicityContrast media• Therapeutic agentsNGAL Rapid ELISA KitBioPorto Diagnostics A/SGrusbakken 8DK-2820 GentofteDenmarkIVDwww.ngal.comPhone (+45) 4529 0000Fax (+45) 4529 0001E-mail info@bioporto.comWeb www.bioporto.comwww.cli-online.com & search 24045

Less paper fora sustainable worldYour CLi digital edition has arrived!Do you feel concerned about the environmental impact ofthe huge amounts of paper still being used in the vast majorityof businesses, not least the publishing industry?Now there’s something you can do: switch your CLi subscriptionfrom print to digital. Have a peek at Cli’s digital editionon www.cli-online.com. It’s easy to use and you can makeinstant inquiries while browsing through the digital edition ofyour favourite clinical magazine.New!1. Post a comment onlineYou can now post commentsor ask questions regardingfeature articles publishedin CLi on www.cli-online.comusing the link provided in theComments box appearing beloweach article.2. Get in touch directlywith suppliersGo to www.cli-online.com andenter in the search box thei number appearing below eachadvertisement or product newspublished and submit the contactform at the bottom of thenext screen.Ready to switch? Click on Free subscription and Renew andmake sure you select Digital at the top of the registration form.Your next issue of CLi will come automatically into your inbox.And that’s another plus… no more postal delays!THE Magazine for clinical laboratory professionals

News in brief23– Issue N°8 – Dec. 2008 - Jan. 2009Ovarian cancer subtypes aredifferent diseases: implicationsfor biomarker studiesIn a new analysis of tissue biomarkers expressedin ovarian cancer samples, David Huntsmanand his colleagues from Vancouver GeneralHospital, Canada, suggest that substantial differencesexist between ovarian cancer subtypes,which should be reflected in patientmanagement. Although ovarian cancer is notthe most common gynaecological cancer inwomen, the disease contributes a substantialburden of mortality in part because symptomsare nonspecific and the disease presents latein its course.As part of their research, Huntsman and coworkersmeasured expression levels of 21 proteinsin 500 ovarian cancer samples which had beencollected by an ovarian cancer registry servingBritish Columbia, Canada; they then correlatedexpression of these biomarkers with patientsurvival data following standardised treatment.Their analyses studied associations betweenbiomarker expression and survival for all cancersgrouped together, as well as studying thefive major ovarian cancer subtypes separately(high-grade serous, low-grade serous, clear cell,endometrioid, and mucinous carcinomas).Although biomarker expression was stableacross disease stages within a given subtype, theassociations between specific biomarkers anddisease outcome differed substantially betweensubtypes. As a result, the researchers proposethat “our study offers persuasive evidencesupporting the view that ovarian carcinomasubtypes are different diseases.”http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050232Prestigious national award for labtest for allergyScientists who have developed a new techniquethat can test for up to 5,000 different allergensfrom just one drop of blood have received aprestigious national award that encouragesinnovation in healthcare technologies, the DaVinci award in the Breakthrough Technologycategory. This award comes with a £15,000prize to use towards furthering the research.The new basophil-microarray based allergyassay is the idea of researchers at The Universityof Nottingham’s Schools of Pharmacy andBiosciences, in collaboration with colleagues inthe Centre for Respiratory Research at NottinghamCity Hospital, UK. The new technology isa lab-based, in vitro test which mimics humanallergic reactions and could be used as an alternativeto the traditional skin-prick test. It cantest up to 5,000 different food or inhalant allergensthat could cause an allergic reaction in apatient and the researchers are hoping it couldalso be developed as a diagnostic tool for parasiticinfections. Tiny dots of allergen moleculesare added to paper on a glass slide and a dropof the patient’s blood is added before the slideis incubated with the cells causing the symptomsof allergy. Cellular activation can then beanalysed to discover which of the allergens areprompting the release of histamine and otherchemicals indicative of allergic reaction in thepatient’s blood.www.davinci-net.orgResearchers discover howmosquitoes avoid succumbing toviruses they transmitMosquitoes can transmit the viruses that causeWest Nile fever, dengue fever, or yellow feverwithout appearing to be affected. An assistantprofessor of entomology at Virginia Tech,USA, Kevin M. Myles, has now elucidatedthe mechanism by which mosquitoes avoidsuccubing to the infection.The mediators that balance the interactionsbetween mosquito and virus are virusderivedshort-interfering RNAs (viRNAs),which are generated by the mosquito’simmune response to infection. If the mosquitois unable to cut up the virus genomeinto viRNAs, an otherwise invisible infectionbecomes fatal for both the mosquito and thevirus. The virus must submit, to some extent,to the mosquito’s antiviral response in orderto complete its life cycle and be transmittedback to a vertebrate host.The researchers used the arthropod-bornevirus Sindbis, a model virus for a wide varietyof mosquito-transmitted viruses, such aschikungunya and eastern equine encephalitis,both of which cause serious diseasesin humans. They infected Aedes aegypti, animportant mosuito vector of yellow fever anddengue. In response, the mosquito immunesystem generated viRNAs, which make up10 percent or more of total cellular smallRNAs. The researchers then altered the Sindbisgenome so that it would carry a proteinknown to suppress the ability of a cell to cutup virus genomes into viRNAs.The research also represents the first applicationof next generation high-throughputsequencing to characterise small RNAs frommosquitoes infected with an arbovirus.The discovery provides a potential method forcontrolling mosquito-borne diseases by upsettingthe balance so that the virus kills the mosquito.Additional research will be required todetermine how to manipulate the mosquitoes’immune response towards this end.http://www.pnas.org/content/early/2008/12/01/0803408105.abstractWorking toward the visionof ‘an AIDS-free Africa throughan effective vaccine’A recent article describes the African AIDSVaccine Programme (AAVP), which was establishedin 2000. The AAVP is a network of AfricanHIV vaccine stakeholders, led by Africansacross the continent, with a vision of “an AIDSfreeAfrica through an effective vaccine.”Pontiano Kaleebu from the Uganda VirusResearch Institute, Entebbe, Uganda, and colleaguesdescribe what AAVP is, what it does,and the network’s impact, successes and challengesto date. The authors say that AAVP supportsand represents the diverse African communitiesinvolved in HIV vaccine research anddevelopment, and is an important unified voicefor African stakeholders.http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050236

– Issue N°8 – Dec. 2008 - Jan. 2009 24News in briefHypersensitivity reactions to thequadrivalent HPV vaccine rareHypersensitivity reactions to the quadrivalentHPV vaccine (4vHPV, Gardasil) are uncommonand most schoolgirls can tolerate subsequentdoses, finds the first evaluation of thequadrivalent HPV vaccine.In Australia, from April 2007, all girls aged 12received the 4vHPV vaccine as part of a nationalsecondary school immunisation programme.Some components of the vaccine such as aluminiumsalts and yeast have previously beenassociated with hypersensitivity reactions.Reports of some adverse events followed theschool vaccination programme.Dr Sharon Choo and colleagues from Australiadescribe the results of clinical evaluation, skintests, and vaccine challenge in 25 schoolgirlswith suspected hypersensitivity to 4vHPV aftermore than 380,000 vaccine doses were administeredin schools in Victoria and South Australia.Thirty-five schoolgirls with suspectedhypersensitivity reactions including urticaria(hives), generalised rash, angioedema (swellingof subcutaneous tissues) and anaphylaxis werereported to specialised immunisation servicesand 25 agreed to be referred to paediatricallergy centres for further evaluation.A detailed account of the reactions was notedincluding previous doses of the vaccine, timeand severity of reaction, and previous clinicalhistory. Skin prick tests of the quadrivalent andbivalent HPV vaccines were carried out, andvaccine challenges were administered intramuscularly.The school-girls were followed-upby telephone one week after the subsequentdose and any adverse events were recorded.The researchers report that 19 girls had skintesting of the quadrivalent vaccine and all werenegative. Seventeen of the 18 girls subsequentlychallenged with the quadrivalent vaccine toleratedfurther doses. One reported limited urticaria(hives) four hours after the vaccine wasgiven. Only three of the 25 evaluated schoolgirlshad probable hypersensitivity to the quadrivalentvaccine, and the authors conclude thattrue hypersensitivity is uncommon. They pointout that suspected hypersensitivity reactionssuch as hives are often “idiosyncratic” and donot increase the risk of adverse reactions insubsequent vaccinations.The authors recommend that girls with suspectedhypersensitivity to the quadrivalentvaccine should be evaluated before receivingmore doses, and call for research into themechanisms of hypersensitivity to the vaccine.http://www.bmj.com/cgi/content/full/337/dec02_2/a2642Interferon needed to enable cells toovercome repeated virus infectionsScientists at UT Southwestern Medical Center,USA, have determined that the immune-systemprotein interferon plays a key role in enablingthe immune system to defend against repeatedinfections of the same virus. The findings havepotential application in the development of moreeffective vaccines and anti-viral therapies.Typically, when a person is infected with avirus, a massive number of T cells are generated,which kill the infected cells. CD4+ T cellscoordinate the actions of other cells at the siteof infection. Once the infection has cleared,most of the T cells also die, leaving behind asmall pool of central memory cells that areprimed to overcome that particular type ofvirus infection. When a virus or bacteriuminfects a human, the infected cells also secretecytokines, including the cytokine interferonalpha. Although it was known that interferonalpha prevented viruses from multiplying andspreading, the role interferon played in creatingmemory cells was not previously known.In the current study, the UT Southwesternresearchers show that both interferon alpha andanother signalling protein, namely IL-12, areneeded to induce the creation of memory cells.They found that interferon and IL-12 together promotethe creation of a special set of cells that thensecrete another signalling protein, IL-2. These IL-2-secreting cells remain in the body and facilitatesubsequent infections with the same virus.http://www.utsouthwestern.edu/home/news/index.htmlAdropin secreted by mouse liverafter a fatty mealResearchers lead by Andrew Butler, PenningtonBiomedical Research Center, Louisiana StateUniversity, USA have found that in mice theliver produces a protein, namely adropin,which rises in response to high-fat foods andfalls after fasting. This protein appears toplay a role in controlling the activity of othermetabolic genes, particularly those involvedin the production of lipids from carbohydrates.Studies of the protein in obese animalssuggest that it also plays a role in insulinresponse and in preventing the accumulationof fat in the liver (a condition knownas nonalcoholic fatty liver disease). The newresults suggest that treatments designed todeliver adropin or otherwise boost its levelsin humans may hold promise for the treatmentof obesity and associated metabolicdisorders, including fatty liver disease andtype 2 diabetes.http://www.cell.com/cell-metabolism/fulltext/S1550-4131(08)00352-5Holographic method could be usedfor lab-on-a-chip technologiesResearchers at PurdueUniversity, USA,have developed atechnique that uses alaser and hologramsto precisely positionnumerous tinyparticles within seconds,representinga potential new toolto analyse biologicalsamples. The technique,called rapidelectrokinetic patterning,is a potentialalternative toexisting technologiesbecause the patterns can be more quickly andeasily changed.The device consists of two parallel electrodes,50 micrometres apart, made of indium tinoxide. A liquid sample containing fluorescentbeads was injected between the two electrodes,a laser in the near infrared range of the spectrumwas shone through one of the transparentelectrodes, and a small electrical voltagewas applied between the two electrodes. Theparticles in the liquid sample automaticallymove to the location of the light and assumethe shape of the hologram, so the methodcould be used to move particles and moleculesto specific locations, and also to create tinyelectronic or mechanical features. The lightheats up the liquid sample slightly, changingits density and electrical properties. Theelectric field applied to the plates acts on thesealtered properties, causing the heated sampleto circulate, which allows the particles to bepositioned in the circulating liquid by movingthe laser light.http://ecommons.cornell.edu/handle/1813/11399

industry news25– Issue N°8 – Dec. 2008 - Jan. 2009Oxoid Infection Control Team of theYear Awards open for entryOxoid, part of Thermo Fisher Scientific Inc.,and a world-leading microbiology brand, ispleased to announce that the 2008/2009 OxoidInfection Control Team of the Year Awardsare now open for entry. With a first prize of£5,000, and 2nd and 3rd prizes of £1,000 and£500, respectively, the awards are designedto recognise and reward the dedicated teamsof infection control microbiologists, nursesand doctors.Entries must be submitted by 13 th February2009. They should be in English and between1,800 and 2,500 words long, in the form ofa report. Otherwise, there is no prescribedformat for an entry, allowing entrants theflexibility to present their entry in a mannerthat best suits the content. The main activitiesdescribed should have taken place since1 st January 2008.Entries can be emailed tooxoid.awards@thermofisher.com or faxed to+44 1256 329728. Guidelines on how to enterthe competition and the registration formscan be downloaded from: www.oxoid.com/UK/blue/awards/infection_control_awards.asp?c=UK&lang=ENEppendorf Young InvestigatorAward 2008The 2008 Eppendorf Young InvestigatorAward is the 14 th research prize conferred bythe Hamburg biotech company to honouroutstanding work in biomedical research inEurope. With this award, Eppendorf sponsorsyoung European scientists up to age of 35.Dr Simon Boulton of the London ResearchInstitute (Clare Hall Laboratories, SouthMimms, Hertfordshire) won this year’sEppendorf Young Investigator Award for hisgroundbreaking work on SPAR1, a newlydiscovered helicase. SPAR1 plays an important,controlling role in the repair of doublestrandedDNA breaks by HRC (homologousrecombination). Mice with deactivatedSPAR1 will die of dramatic genome instabilityafter 11 days. The reason appears to be aderegulation of homologous recombinationdue to missing SPAR1. Such mechanismsalso play an important role, for example, inthe development of certain tumours. Basedon a detailed insight into this SPAR1 function,therapeutic approaches to combat specifictumours have already been developed. Aprospective therapeutic drug is already beingtested clinically.Dr Simon Boulton received the prize duringa gala dinner attended by guests from thescientific community and related industry.German innovation for HIV/AIDSdiagnostics used 2.5 million timesin 2008The German biotech company Partec isexpanding its global leadership in specialisedHIV monitoring and AIDS patient follow-updiagnostics for developing and emerging countries.In 2008, 2.5 million patient tests wereperformed with the portable, robust and highlyaffordable CyFlow system, which is already supportingmore than one million people livingwith HIV/AIDS. Due to introduction of thisinnovative system, the average cost of e160 peryear per patient could be reduced by a factor 20to e8. The CyFlow instruments are being successfullyused in nearly all Sub-Saharan Africancountries. Furthermore, the technique is beingapplied in Asia, Latin America, Europe and theU.S. In December 2008, the thousandth CyFlowsystem will be installed since its introductionat the XVI th International AIDS Conference inBarcelona inJuly 2002.By precisely measuring the CD4 T-lymphocyteconcentration from blood samples, the systemdelivers accurate information aboutthe immune status of HIV/AIDS patients,necessary as basis for anti-retroviral therapy.Partec award for NGO projectsApproximately 33 million people worldwideare living with HIV/AIDS. More than95% of them reside in developing countries,especially in Africa and Asia. On World AidsDay on 1 st December, Partec announced a globalaward for NGO projects active in the fightagainst HIV/AIDS. The award winner will besupported for one year, free of charge, withthe necessary diagnostics from Partec. Applicantsmust submit a detailed project description,including a statement explaining whytheir project should be chosen, by 31st March2009. Applications should be sent by e-mailto worldaidsday@partec.com or by fax to +493581 874670. Further information is availableat www.partec.com/worldaidsday.Olympus signs agreement withThermo Fisher Scientific foropen-track automationOlympus Life Science Europa has signed anagreement with Thermo Fisher Scientific foropen-track automation for clinical laboratories.The new product offering will complementexisting Olympus Lab Automation products,including the OLA2500 peri-analyticalautomation system. The agreement betweenthe companies will allow laboratory professionalsto consolidate Olympus AU-seriesclinical chemistry and immunoassay analysers,including various third-party analysers.The open track-based system will offer mediumto large sized hospital and private laboratoriesflexibility and access to additional test capabilities.It will also allow customers to consolidateand automate sample processing procedures,such as decapping, centrifugation, aliquoting,recapping and storage/retrieval, currentlyin development.The agreement gives Olympus the right to distributeThermo Fisher’s TC Automation productline, a fully featured, track-based laboratoryautomation product line, in Europe. Olympuswill handle sales and marketing and provideprimary level service and support of theautomation products.Key benefits of laboratory automation includemore efficient sample management, improvedlaboratory services and shortened turnaroundtimes. By automating the main pre-analyticalsteps, such as centrifugation, decapping, aliquotingand sorting, TC Automation helpsto manage current and future workloads; itinterfaces with Olympus systems plus a wideselection of third-party instruments.

– Issue N°8 – Dec. 2008 - Jan. 2009 26Measuring chlorideAccurate determination of chloride bycoulometric titrationThe laboratory measurement of chloride ion concentration has becomeincreasingly important in many fields, such as the quality management,food, beverage and industrial sectors, as well as in clinical laboratories. Itis important to measure chloride ions in body fluids since, together withsodium and potassium ions, they play a vital role in maintaining normalwater distribution between cells, plasma and interstitial fluid through theeffect they exert on the osmotic pressure.The most frequently used methods for measuring chloride are based onion selective electrodes (ISE) or photometric technologies. However suchapproaches have limitations, especially when used outside normal conditions,and can be problematic, particularly with very low sample volumesof less than 20 µL. In addition, most classical chloride-measuring instrumentsare also capable of measuring several other parameters which, inpractice, many laboratories do not need, thus creating an unnecessary costburden. In all such cases a coulometric titrator is preferable.TheoryThe traditional way of measuring chloride in liquids is by the Volhardchloride titration method. This is carried out by first of all adding a known,excess amount of silver nitrate solution to the solution to be assayed.A precipitate of silver chloride is formed:Ag + + Cl - → AgCl ↓Ferric iron (III) is then added as an indicator and the solution is titratedwith potassium thiocyanate solution. As long as there are free excess silverions (the concentration of which depends on the amount of chloride ionsin the original solution), the silver reacts with the thiocyanate ions to forma silver thiocyanate precipitate:Ag + + SCN - → AgSCN↓The solution remains pale yellow. However, when all the silver ions havereacted with the thiocyanate, the first excess of thiocyanate reacts withIron(III) to form an easily detected dark red complex:Fe 3+ + SCN - → [FeSCN] 2+ ↑The concentration of chloride ions in the original solution can then be calculatedby subtracting the mole amount of excess silver ions having reacted withthe thiocyanate from the total mole amount of silver nitrate originally added.Modern chloride titrators measurethe amount of chloride in asample directly, and are based onthe principle of coulometric titrationusing an end point determinedby measuring the currentbetween two silver electrodes. Themain difference compared withthe classical Volhard method isthat the acid buffer in the sampledoes not originally contain silverions. Instead, these are generatedFigure 1. Schemtic diagram of the coulometricthrough oxidation at the silvercontaininganode. This is achievedtitration method for Cl- determination.by passing a generator current through the system. The silver ion concentrationcan be kept constant, under the control of the indicator electrodes.When chloride is added, a precipitate of silver chloride is formed, causingthe indicator current to decrease. This, in turn, results in an increased generationof silver ions from the anode to bring the silver ion concentrationback to its original level before the chloride-induced precipitation. Thisprocess of generating fresh silver ions continues until all the chloride isprecipitated. The concentration of chloride in the original solution canthen simply be determined by measuring the length of time during whichthe silver-generating current flowed.Modern chloridometer instrumentTo meet the the current and future need for chloridedeterminations, a modern, cutting-edge digitalinstrument, the FKGO chloridometer [Figure 2]carries out the process described above preciselyand automatically under tight electronic control.The instrument has an easy, intuitive user interfacewith a modern touch screen and multi-languageuser prompts, which lead the operator through theentire measurement process. The nominal samplevolume is 20 µL, thus making the instrument suitableeven for the analysis of sweat samples in thediagnosis of cystic fibrosis. However, the sampleFigure 2. The FKGOChloridometer.volume is not fixed and can be adapted to suit otherassay requirements, e.g. those in industrial labs. Theinstrument comes factory-calibrated so manualcalibration by lab personnel is not needed. Another feature is the optionaldot-matrix printer, which provides a hard copy printout of the results. Thismeans that copying thermal print-outs for long-term storage, which is necessaryin many other measuring devices, is avoided. For computer-aided dataevaluation and digital data storage a serial interface (RS-232) is available.ConclusionThe FKGO Chloridometer meets all the needs a laboratory may require ofa modern, accurate chloride titrator. The touch-screen, dot-matrix printerand the RS-232 interface of the chloridometer makes the life of laboratorystaff easier and more convenient, without any sacrifice in data quality.www.cli-online.com & search 24301Gonotech GMBHBerlin, Germanywww.cli-online.com & search 24464

Is it possible for one system tohandle all these different samples?The VERSANT kPCR Molecular System * puts the power to processthe largest variety of sample types right in the palm of your hand.Siemens now offers an advanced real-time molecular testing solution designed to meet your currentand future demands. Imagine one platform that handles the widest range of sample types. Plusautomated sample extraction technology provides more accurate results and maximum versatility.Get your hands on the VERSANT® kPCR Molecular System * today: www.siemens.com/diagnostics-versatilityAnswers for life.A91DX-9021-A1-4A00www.cli-online.com & search 24510© 2008 Siemens Healthcare Diagnostics Inc. All rights reserved.VERSANT is a trademark of Siemens Healthcare Diagnostics Inc.*Not available for sale in the U.S.

– Issue N°8 – Dec. 2008 - Jan. 2009 28Product NewsELISA kit for Fetuin ASerum fetuin-A, also known as alpha-2-HSglycoprotein (AHSG ), is a regulator of calciummetabolism and osteogenesis, and a potentinhibitor of systemic vascular calcification.Research has shown that low fetuin A levelsmay be associated with a higher cardiovascularmortality in patients with end stage renaldisease. An ultra-sensitive ELISA method formeasuring fetuin-A in serum is now available.This assay format allows measurementin samples after a single dilution, a departurefrom earlier methods which required extensivesample dilution series prior to analysis.The simplified dilutions are not limited tothe samples. The kit also includes ready-tousestandards, avoiding the need for dilutinga standard curve from one stock standard.These modifications save technician time andresources, while reducing the opportunity tointroduce errors. The standard range is sufficientlysensitive to detect suppressed fetuin-Alevels, for example, in individuals with EndStage Renal Disease (ESRD), and total assaytime is less than three hours.ALPCO DiagnosticsSalem, NH, USAwww.cli-online.com & search 24506Homocysteine reagent for automatedchemistry analysersWhen elevated amounts of homocysteineaccumulate in the blood,arterial vessels may be damaged.The resulting inflammation mayeventually cause blockage ofblood flow to the heart.Recent studies are yielding evidencethat elevated blood levelsof homocysteine have a predictivevalue for risk of coronaryartery disease similar to that of elevated cholesterollevels. Recent evidence has also relatedelevated blood levels of homocysteine to therisk of miscarriage and birth defects.Pointe Scientific has introduced a two partliquid stable Homocysteine assay for measurementof homocysteine on clinical chemistryanalysers. The assay has excellent correlationwith immunoassay and HPLC, yields rapidresults, and is standardised to NIST SRM 1955“Homocysteine Standards Reference Material.”Instrument applications are availableupon request.Pointe ScientificCanton, MI, USAwww.cli-online.com & search 24505Portable binocular microscopesuitable for resource-poor settingsE x c l u s i v e l ydesigned andmanufacturedin Germanywith resourcepoorsettingsalso in mind,CyScope Plusis a new lineof LED fluorescentandt r ansmittedlight binocularmicroscopes.These cost-effective microscopes can be batteryoperated for field work, and an automatic batterycharger is included. The weight of around3kg, as well as the rugged carrying case, facilitatetransportation to the field, ideal for malariaand TB field testing in the developing countriesof Africa, Asia and Latin America. VariousLEDs and filter sets can be selected, includinghigh power UV (365nm) Nichia LED, royalblue (455nm), blue (470nm) and green (510nm). The microscopes also feature a threefoldrevolving nosepiece, 20x, 40x and 100x oilimmersion objectives and separate adjustmentof LED light intensity. A USB CCD cameraadapter with image capture PC software is alsoavailable for use with these microscopes.Partec GmbHGörlitz, Germanywww.cli-online.com & search 24507Rapid test for quantitativemeasurement of calprotectinCalprotectin, a calcium-binding S100 proteinreleased mainly by neutrophils, is a reliable, sensitiveand specific marker for bowel inflammation,but is not elevated in functional disorderssuch as Irritable Bowel Syndrome (IBS). Thesensitive Quantum Blue Calprotectin RapidTest utilises a lateral flow cartridge and a userfriendlyReader System to distinguish betweenthose patients who require a colonoscopy forfurther diagnosis of Inflammatory Bowel Disease(IBD), and those patients who have IBSand for whom a colonoscopy is unnecessary.The test is both simple and rapid. Once thetest cartridge isinserted into thetray in the reader,stool extract followedby chasebuffer is added tothe sample loadingport on thecartridge. Thetimer function onthe reader is thenstarted, the tray is closed, and the cartridge isscanned. The result, given as mg of calprotectinper g stool, can be read on the reader screenafter 12 minutes.Buhlmann Laboratories AGBasel, Switzerlandwww.cli-online.com & search 24485High-throughput genotyping systemA new analysis system to enable rapid, easy andcost-effective high-sample-throughput genotypingstudies, the TaqMan OpenArray genotypingsystem provides life scientists with theease-of-use, accuracy and reproducibility ofApplied Biosystems’ TaqMan SNP genotypingassays and TaqMan DME assays in a flexibleformat. This system expands the potentialuses of TaqMan technology across a widerange of genotyping applications, providing anextremely fast, high-sample-throughput validationand screening tool. Studies that associategenotypes with complex diseases, ethnicancestry and drug-treatment response shouldbenefit from the use of this system.Researchers using this integrated platform canexperience an end-to-end genotyping workflowof less than eight hours, enabling them toanalyse thousands to tens of thousands of samplesin days, in contrast to weeks or months, onalternative genotyping platforms. SNP genotypingstudies can also be performed in a costeffectivemanner, as the system delivers a lowercost per genotype, coupled with a workflowrequiring a minimal amount of user interaction.The system includes an instrument platform,reagents and consumables, as well as theTaqMan OpenArray genotyping instrumentplatform, and plates that are pre-loaded withpre-designed or custom TaqMan SNP genotypingor drug metabolising enzyme (DME)assays. A comprehensive line of more than 4.5million individual pre-designed TaqMan SNPgenotyping assays, custom TaqMan SNP genotypingassays, or TaqMan DME genotypingassays for detecting polymorphisms in the drugmetabolism enzyme genes are available.Applied BiosystemsCarlsbad, CA, USAwww.cli-online.com & search 24497

Product News29– Issue N°8 – Dec. 2008 - Jan. 2009Two plate ELISA processorand validated assaysThe DS2 is a “state-of-the-art” ELISA processorwith features often only found on highercapacity ELISA platforms. The system is idealfor clinical, hospital or reference laboratorieswishing to automate time-consuming manualELISA and is designed to offer true “walkaway”capability as well as being a cost effectivesolution for laboratories with specialty orlower throughput assay requirements. Importantly,all Binding Site assays for use on the DS2have been fully validated and the optimisedassay protocols and settings ensure a high levelof assay performance.The capability to perform assays requiringdifferent incubation temperatures is ideal foranalysis of a wide range of ELISAs includingautoimmune and infectious disease assays. Inaddition, the compact design is ideally suitedfor laboratories where space is a premium.The binding siteBirmingham, UKwww.cli-online.com & search 24502Bead-based immunoassays formetabolic disease-related analytesFlowCytomix bead-based immunoassays formultiple analyte detection are now available forthe quantitative detection of analytes related tometabolic disease research. Human Adiponectin,Leptin, Resistin, CRP, MPO, OPG, PAI-1,NGF, TNF-alpha, sTNF-R and many moreinflammatory cytokines and chemokines canbe quantified simultaneously in cell culturesupernatants, serum and plasma. Followingthe convenient protocol, only two incubationsteps have to be performed. The assay can beperformed in a filter plate, which is includedwith the kit. Alternatively, a protocol for handlingin tubes is also provided. The FlowCytomixtechnology is designed to assay up to20 analytes simultaneously using only 25µL ofsample. Researchers may choose from a varietyof predesigned Multiplex Kits or create customcombinations. The assays can be run on mostcommercially available single or dual laser flowcytometers. The easy-to-use analysis software iscomplementary, and can be downloaded fromwww.bendermedsystems.com/software_downloadalong with sample raw data for variousMultiplex Kits.Bender MedSystems GmbHVienna, Austria.www.cli-online.com & search 24503Fluorescent dyes conjugatedto antibodiesBright, photostable and with little background,DyLight fluorescent dyes conjugated to antibodiesare available. The detection level ofany fluorophore-antibody conjugate dependson brightness and photostability of the dye,antibody activity, specificity and cross-reactivity,as well as the optimum number of molesof dye per antibody. For each of these dyes amolar saturation curve vs fluorescence intensity,antibody activity, background level and/or other parameters have been established tooptimise the level of antibody detection andminimise background.The fluorescent dyes are highly water solubleand remain fluorescent from pH 4 to pH9. Over 250 secondary antibodies, as well aspurified immunoglobulins, streptavidin, antidigoxin,anti-FITC and anti-biotin are offered.Many secondary antibodies are extensivelyadsorbed to ensure minimal cross-reactivityto other species for multiple labeling protocolsand for minimal background due to crossreactivitywith host Ig on tissues and cells.Four DyLight fluorescent dyes, which coverthe most commonly used excitation sources,as well as filter sets from green to far-red emissions,are already available. Fluorescent dyesemitting in the blue and infra-red are currentlyundergoing testing.Jackson ImmunoResearch Europe LtdNewmarket, Suffolk, UKwww.cli-online.com & search 24504Introducing CRP andhsCRP for Point-of-Care.We are actively seekingDistributors and Partners.For more info visit:www.lifeassays.comwww.cli-online.com & search 24118www.cli-online.com & search 24303HAVE YOU RENEWED YOURFREE SUBSCRIPTION ?www.cli-online.com

– Issue N°8 – Dec. 2008 - Jan. 2009 30Product NewsRapid test systemBased on theReaScan readertogether withReaLink Bluetoothwirelesstechnology,ReaMobilesoftware, andwith proprietaryimmunochromatographytechnology,the ReaMobileDiagnostic TestSystem is a versatile system for quantitativeand qualitative applications in clinical chemistry,virology and microbiology. The systemis designed to provide diagnostic POC resultsquickly and easily. Quantitative diagnosticresults are displayed and printed in easy-toreadnumbers. Qualitative diagnostic resultsare displayed as positive or negative, eliminatingthe need for visual interpretation of thetest lines. ReaScan tests for Strep A, CRP andhs-CRP are the newest tests using the system,with more tests to come soon.ReagenaToivola, Finlandwww.cli-online.com & search 24500Rapid and effective testing fordrugs of abuseA compact system for detecting drugs ofabuse by analysing saliva, the Dräger DrugTest5000 it is also extremely simple and hygienicto use. Furthermore, modern data managementcapabilities ensure sample documentationis easy to create. The system is capableof detecting even minute traces of addictivewww.cli-online.com & search 24302drugs in saliva within minutes, so that aquick check on whether a patient has consumeddrugs of abuse and to which class theybelong can be carried out, making it particularlyuseful prior to admission to the emergencyward. As a preliminary test, the systemanalyses the samples for traces of opiates,cocaine, cannabinoids and amphetamines,as well as designer drugs and sedatives fromthe group of benzodiazepines. The results forfive of the drug classes are available after justfive minutes, while the test for cannabinoidsis completed after ten. This not only makesit possible to exclude drug abuse quickly, italso helps to reduce the number of cost- andtime-intensive laboratory blood tests.The system comprises two main components:the analyser and the drug test kit. After theprotective cap has been removed from thesaliva test collector, a sample is taken fromthe patient’s mouth. As soon as sufficientsaliva has been gathered in the test kit foranalysis, the built-in indicator turns blue.The operator then places the test cassetteinto the analyser, which displays whetherthe result is “positive” or “negative” for everydrug class on its colour display. Acoustic signalssupport and inform the operator duringthe entire procedure. Due to its simpleoperation, the system is far more discreet andhygienic for both patients and operators thanurine-based sample collection; the healthrisks associated with handling body fluidsare minimised. In addition, controlling theentire sample collection procedure is mucheasier, virtually eliminating the possibility ofmanipulation.The analyser saves the number, course andresults of up to 500 tests. It also documentsoperator and instrument errors. If immediatedocumentation of protocols is required,the system can be linked to a portable printerusing an infrared interface.Drägerwerk AG and CoLubeck, Germanywww.cli-online.com & search 24501Batch analysis mode for flowcytometry softwareUsing the latest version of VenturiOne flowcytometry data analysis software (v3), up to 400files can be fully analysed concurrently in lessthan ten seconds. This speed is a direct resultof the patent pending multi-processor technologythat lies at the heart of the concept. In additionto performing such rapid batch analyses,the latest version of the software also producessignificantly enhanced reports, generated fromwithin the software itself. Being able to handleup to 400 files at one time makes the new versionideal for analysing data generated from multiple96-well formats, right up to 384 well plates. Furthermore,its inherent flexibility and simplicityof set-up means it can handle the vast majorityof a laboratory’s routine workload.As standard, the new software works in backgroundcalculation mode, which means thatfiles are analysed as soon as they are selected.This considerably speeds up the time to resultwhilst removing the need to select all therequired files before each run commences.However, when larger data files need to be analysed,for example in rare event detection, thebackground mode can be switched off. Thisallows files to be analysed sequentially, therebyavoiding any delays in reporting. There is alsoscope to modify protocols on the fly. Usersnow have the time to perform numerous ‘whatif’ analyses on their data to help them identifyclassifier populations and outcomes theywould otherwise have missed had they reliedon standard flow cytometry analysis protocols,running on slower software packages.Once the data has been analysed, it can bepresented in easy-to-interpret graphics usingthe newly enhanced report capabilities. Sincethese are incorporated into the new software,there is no need to export the data to a standalonereporting package. In addition, thisversion is highly intuitive and easy to learnby anyone used to modern office tools.The company plans to continue to enhanceits VenturiOne software, and all users willreceive free upgrades introduced within12 months of purchase.Applied CytometrySheffield, Yorks, UKwww.cli-online.com & search 24499

Product News31– Issue N°8 – Dec. 2008 - Jan. 2009Fully automated ELISA systemThe first open, fully automated, multi-test andmulti-batch immunoassay system, Trituruscan perform a variety of different tests on agroup of samples and process several batchessimultaneously. Offering complete automationof ELISA without changing the laboratory‘snormal workflow routine, the flexibilityof the system ensures maximum performancein laboratories with a complex work load,involving a large number of samples anddifferent groups of tests. All the steps of anymicroplate ELISA assay are carried out by thesystem, including sample dilution, reagentdispensing, washing, reading and calculationof results. The system can be programmedfor all the stages in any ELISA micro-well testand can perform up to eight different testsper batch on a given sample or on a group ofsamples (e.g.,TORCH profile, EBV profile). Itis also possible to schedule several consecutivegroups of tests independently:new workbatches can be loaded while other batchesare being processed. In addition, a bi-directionalhost communication and on-line connectionfor data management and reportingis enabled.Grifols International SABarcelona, Spain.www.cli-online.com & search 24486Rapid test for faecal occult bloodExtending a range of diagnostic tests for gastrointestinaldiseases, the ColonView Hb and Hb/Hp quicktests are intended to aid early diagnosis and preventionof colorectal cancer. These tests can be used forsimple and cost-effective identification of patientswith faecal occult blood, which is a well-knownmarker for colorectal cancer and pre-cancerouslarge adenomas. Testing can also give informationon other possible disease of the gastrointestinaltract that are associated with bleeding.ColonView Hb test detects human haemoglobin(Hb) from red blood cells, and ColonView Hb/Hp test detects haemoglobin/haptoglobin complex(Hb/Hp). These immunological tests specificallydetect human faecal occult blood, so testingdoes not require a special diet on the days beforeor during sample collection. Patients can collectfaecal samples at home on three consecutive daysin a convenient and simple way, and forward thesamples to the laboratory for single-step testing.Screening for faecal occult blood has been foundto improve early detection of colorectal cancer inmany studies. These sensitive and specific testsare well suited for screening programmes andfor testing of patients in hospitals, doctors’ practicesand occupational health centres. Patientswho may benefit from this are those sufferingfrom dyspepsia, and people over 50 years of ageas part of routine health checks.Biohit LtdHelsinki, Finlandwww.cli-online.com & search 24487Rapid diagnosis of vaginal infectionUntil now accurate diagnosisof vaginal infectionhas been a lengthyand expensive process,and such infections arefrequently improperlydiagnosed and treated,leading to pain, discomfortand conditionsthat continue to worsenrather than improve. Forinstance, in the absenceof an immediate diagnosis, doctors often prescribea barrage of treatments, including antibiotics, whichmay be useless or even counter-productive. If thepatient is suffering from candidiasis, which is a yeastinfection, not only will some medications not help,but they may actually exacerbate the condition.In pregnant women bacterial vaginosis has beenassociated with adverse pregnancy outcomes,including premature rupture of the membranes,preterm labour, low birth weight, intra-amnioticinfection, postpartum endometritis and post-caesareanlesion infection. In addition surgery performedin the presence of such infection can havedire consequences.Based on world-proven Ion Mobility Spectrometry(IMS) technology, the VGTest can rapidly diagnosewhether an infection is present, and identifythe type of infection, allowing for immediate andeffective treatment. The device is simple and quickto operate, requiring just the taking of a samplewhich is then placed in the VGTest device. Withinjust one minute, one of four lights will flash, indicatingwhether an infection is indeed present, andif so, classifying it as bacterial vaginosis, candidiasisor trichomoniasis.3QBDArad, Israelwww.cli-online.com & search 24488www.cli-online.com & search 24164

– Issue N°8 – Dec. 2008 - Jan. 2009 32Product NewsClinical chemistry analyser for smallto medium laboratoriesBuilding on the success of its predecessor theAU400, which has sold 4000 units globally,the new AU480 clinical chemistry analyserminimises sample volume requirements andfeatures new intuitive GUI and master curvecalibration. It also maintains the company’sreputation for precision, reliability and lowmaintenance with superior spot photometertechnology and long-life ISE electrodes.The instrument is the ideal main analyser forsmall to medium-sized laboratories due to itsthroughput of up to 800 tests per hour withISE and it is simultaneously programmablefor 63 different analytes. It can also be used asa special chemistry or STAT analyser in largelaboratories. The new intuitive Graphic UserInterface (GUI), standardised to the AU680,as well as the touch-screen monitor make theAU480 extremely user-friendly. User-definablesoftware options, such as auto rerun via rackhandler and true reflex testing, further expanduser convenience.The analyser only requires minimal samplevolumes; high precision micro-sampling as lowas 1 µL makes the new system ideal for paediatrictesting. Computer controlled sampleand reagent dispensing, in combination withclot detection and crash prevention, are additionalsafety features of the analyser, resultingin unique system reliability.More than 120 different Olympus SystemReagent (OSR) applications are available forthe instrument, which are specially designedto match the requirements and features ofthe analyser platform for optimum performance.Additionally, all reagents are barcoded,with master curve calibration established forsome parameters via 2D barcodes, to maximiseproductivity in the laboratory.The analyser is able to hold up to 80 primaryand secondary tubes in parallel. Different tubesizes may be mixed within the linear racksand can be loaded continuously. Serum indices(haemolysis, icterus, lipaemia) are alsoautomatically checked.Olympus life sciences Europa GmbHHamburg, Germanywww.cli-online.com & search 24489Energy saving osmometers with3-point calibrationBecause of improvedswitching regulators,the power consumptionof two osmometers/cryometershas been noticeablyreduced. For theosmometer type 6with manual freezinginitiation, energy savingwill be 18%: theinstrument requires18 W in normal, ready mode and 27 W duringan average measuring cycle. With the osmometertype 15, energy saving will be 12%, with32 W required in normal, ready mode and 39W with an average measuring cycle. This is animportant contribution towards reducing alaboratory’s costs, especially if instruments runthe whole day in ready mode. Because powerconsumption is lower, it is possible to use asmaller and quieter air fan for cooling. Thisreduces noise pollution.All models have a 3-point push button calibrationfor 0, 300 and 900 mosm/kg H 2O whichare standard, an automatic measuring valuedetection and storage, and a back lighted LCdisplaywith user guiding and error messages,enabling the easy and safe use of the unit.In addition, the automatic osmometer type 15provides a value memory for the last 100 measurements,with date and time of measuring, aswell as data interfaces for PC, printer and scannerfor sample numbers as standard features.Löser MeSStechnikBerlin, Germanywww.cli-online.com & search 24490GC-MS systemServing a wide range of applications in clinicalanalysis or other complex sample type analyses,the new multidimensional MDGC-2010 systemwas particularly designed for the transfer of coelutingpeaks to a second column (“cut”) andmakes quantitation very easy. The instrumentrepresents the renaissance of the multidimensionalGC method. It applies the well-knownDeans Switch technology, but in a totally differentway than in the past. Using different restrictors,the pressure at the end of the first columnalways remains constant, whether or not a cut isused. The user may thus perform as many cuts asrequired without any shifts of retention time andwith excellent precision of the retention times.This allows for easy method development. Justthree steps are needed to set up a multidimensionalmethod, i.e. the standard should be runonce, the cut times should be defined graphicallyusing the specially developed MDGCsolutionsoftware, and the sample can then be run.Quantitation of co-eluting peaks is very easy. Acalibration curve can be run using the cut timeswith a standard sample. Calibration curves arecalculated in a conventional way by integrationof the peaks in the chromatogram from thesecond column. All operation parameters formultidimensional chromatography are controlledvia the system’s software. All conventionalGC detectors as well as the extremely sensitiveand fast GCMS-QP2010 series instruments canbe used for detection, making the system evenmore powerful.Shimadzu Europa GmbHDuisburg, Germanywww.cli-online.com & search 24391Bottle top dispensorResponding to currentneeds, the Microlit bottletop dispensor is a uniquecombination of affordablepricing and highperformance. The simpledesign together witha variety of useful featuresfacilitates all routinedispensing needs.The plunger movementis smooth and effortless.Each instrument comeswith four adapters to fitmost laboratory reagentbottles. The safety discharge system reduces therisk of accidentaldispensing and the nozzle cap prevents anyunwanted drops landing on the work space. Theinstrument is fully autoclavable at 121 °C , 15psi,and whilst there is no need for disassembling theinstrument for autoclaving, it is easy to disassemblefor cleaning and servicing. Five modelsare available, with adjustable volumes rangingfrom 0.25mL to 60mL. High precision and accuracyis ensured through several stages of strictquality checks during the manufacturing process.Each instrument is individually calibrated inaccordance with ISO 8655 standards and comeswith an individual calibration certificate.MicrolitLucknow, Indiawww.cli-online.com & search 24498

Product News33– Issue N°8 – Dec. 2008 - Jan. 2009Range of tests for influenza virustypes A and BInfluenza virusinfections peakin the wintermonths andremain a majorhealth concern.The diagnosticchallengeis exacerbatedby the fact thatsymptoms ofviral respiratoryinfectionssuch as influenza, respiratory syncytial virusand adenovirus are often difficult to differentiatefrom those caused by other pathogens,such as bacteria or fungi. Since antiviral therapeuticsare being more commonly used, rapididentification of the causative agent is increasinglyimportant to allow the correct treatmentoption to be determined.Rapid diagnosis of Influenza A or B virusinfections plays an important role in patientmanagement, influencing the use of antiviraltherapy and enabling effective managementand control of outbreaks. The Xpect Flu A&Btest detects and differentiates influenza typesA and B directly from nose and throat swabsand provides a clearly visible result that is easilyinterpreted in just 20 minutes. No specialisedequipment or expertise is required. The simplicityof the test makes it ideal for use in laboratoriesof any size or in a near patient setting,allowing medical professionals to test patientsquickly in surgeries, community hospitals andcare homes.The IMAGEN influenza virus A and B test isa qualitative direct immunofluorescence testfor the detection and differentiation of influenzaA virus and influenza B virus in clinicalspecimens or for the confirmation and differentiationof influenza virus A and B in cell cultures.Monoclonal antibodies, specific to eitherinfluenza virus type A or B, are conjugated tofluorescein isothiocyanate (FITC). These areused in a one-step, direct immunofluorescencetechnique. Specimens are incubated withthe FITC conjugated antibody reagents for 15minutes. The stained areas are mounted andviewed microscopically using epifluorescenceillumination. If either influenza virus types Aor B virus is present, the corresponding reagentproduces a characteristic bright apple greenfluorescence within the cytoplasm and nucleusof the cells, which contrasts with the redbackground staining of uninfected cells.Oxoid LtdBasingstoke, Hants, UKwww.cli-online.com & search 24482Electromagnetic instrument compatiblewith PCR tubes and microscope slidesDeveloped forusers working withmagnetic particlesin the laboratory,the In Vitro MagneticField GeneratorMFG-1000is an electromagneticinstrumentfor generating astrong high-frequencyalternatingmagnetic fieldin an inserted sample container. The instrumentuses PCR tubes and/or microscope slidesas disposable sample containers, and is idealfor cellular and DNA studies in biochemicaland medical applications. Other researchapplications involve the use of magnetic nanoparticles,tissues, cells, bacteria, viruses and biologicalfluids (such as blood). The instrument isCE-approved and already available.European Institute of Science ABLund, Swedenwww.cli-online.com & search 24483Electrochemical detector systemProviding the options necessary for performingpulsed amperometric detection and cyclicvoltammetry for maximum flexibility, theCoulochem III ECD system delivers excellentamperometric and coulometric performanceThe highly sensitive, electrochemical detectoris ideal for use in either methods developmentor for routine applications requiringhigh-sensitivity detection of a single ora small group of analytes. For HPLC clinicalresearch applications, a number of importantclinically relevant cancer, cardiovascularand osteoporosis markers can be readilyand accurately measured in serum, plasmaor urine by electrochemical detection usingthe specificity, selectivity and sensitivity ofthis system.ESA Analytical LtdAylesbury, Bucks, UKwww.cli-online.com & search 24350www.cli-online.com & search 24359

– Issue N°8 – Dec. 2008 - Jan. 2009 34www.cli-online.com & search 24263New!The simple and easyCLI online reader service.To receive prompt product informationand communicate directly with suppliers1.2.3.Go to www.cli-online.comEnter in the search box the numberappearing below the advertisement orproduct news item and click searchFill in and submit the contact formappearing on screen below theadvertisement or product description100 Rue des Palais, 1030 BrusselsTel. +32 2 240 26 11Fax +32 2 240 27 78www.cli-online.comManaging EditorsFrances Bushrod, Ph. D.f.bushrod@panglobal.beAlan Barclay, Ph. D.EditorRuth Knowles, BSc.PublisherBernard Léger, M.D.Advertising SalesManagerAstrid Wydouwa.wydouw@panglobal.bePublishing AssistantAnna HyrkasSales & ProductionCoordinatorJennifer ChristophersExhibition CoordinatorShirley WaringCirculation ManagerArthur LégerList RentalAstrid WydouwWebmasterDamien Noël de BurlinCalendar of eventsJanuary 26-29, 2009Arab HealthDubai, United Arab EmiratesIIR Middle EastTel. +971 4 3365161Fax +971 4 3364021e-mail: Mustafa.Iqbal@iirme.comwww.arabhealthonline.comFebruary 17, 2009Food Allergy: a global perspectiveWelwyn Garden City, UKEurosciconTel. +44 870 199 7315Fax +44 709 211 4307e-mail: enquiries@euroscicon.comwww.regonline.co.uk/food09March 12-15, 2009KIMES 2009 - 25th Korea InternationalMedical & Hospital Equipment ShowCoex, Seoul, KoreaKorea E & Ex Inc.Tel. +82 2 551 0102Fax +82 2 551 0103e-mail: kimes@kimes.krwww.kimes.krApril 1-3, 200913th SE Asian Healthcare & PharmaShow 2009Kuala Lumpur, MalaysiaABC ExhibitionsTel. +45 62 21 79 12Fax +45 62 20 23 37e-mail: bhullar@abcex.comwww.abcex.comApril 18-21, 2009CMEF Spring 2009Shenzen, ChinaReed Sinopharm ExhibitionsTel. +86 10 62028899Fax +86 10 82022922http://en.cmef.com.cnApril 24, 2009Improving Immunohistochemistry – 09Welwyn Garden City, UKEurosciconTel. +44 870 199 7315Fax +44 709 211 4307e-mail: enquiries@euroscicon.comwww.regonline.co.uk/IHC09May 16-19, 2009ECCMID - European Congress of ClinicalMicrobiology and Infectious diseasesHelsinki, FinlandTel. +41 61 686 7711Fax +41 61 686 77 88e-mail: info@akm.chwww.escmid.org/eccmid2009May 18-21, 2009Focus 2009Liverpool, UKThe Association for Clinical BiochemistryTel: +44 141 434 1500Fax +44 141 434 1519e-mail: focus2009@meetingmakers.co.ukwww.focus-acb.org.ukMay 22, 2009The Global Public Health implicationsof Tropical Diseases ResearchWelwyn Garden City, UKEurosciconTel. +44 870 199 7315Fax +44 709 211 4307e-mail: enquiries@euroscicon.comwww.regonline.co.uk/tropical09June 2-5, 2009Hospitalar 2009São Paulo, Brazilwww.hospitalar.com/inglesJune 7-11, 2009EuroMedLab 2009Innsbruck, AustriaTel. +39 02 66802323Fax +39 02 6686699www.innsbruck2009.orgJuly 7-11, 20092009 AACC Annual MeetingChicago, IL, USAAACC InternationalTel: +1 800 892 1400Fax +1 202 887 5093www.aacc.org/events/2009amDates and descriptions of futureevents have been obtained fromofficial industrial sources.CLi cannot be held responsible forerrors, changes or cancellations.

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Imagine ... innovating the scienceof histopathologyDedicated to HistopathologySakura Finetek, again, improves thelaboratory. By offering productsto automate manual proceduresand smoothen the workflow, thehistotechnologists can easily completethe other activities required and eliminatepotential risks. As the innovative companyin histopathology, Sakura Finetek is continuouslylooking for possibilities to improve the laboratory...and succeeds in offering solutions for the problemsfound in the histopathology laboratory.Sakura Finetek offers you the only concept to achieve:• An efficient, manageable, continuous workflow• Same day results by real reduction of turn-around time• Higher productivity resulting in a higher morale• Consistent high quality; sample by sample• Improved health and safety standards in your laboratoryFirst we un derstand.Then we innovate.Sakura Finetek Europe B.V.The NetherlandsPhone: +31 71 589 83 00Fax: +31 71 589 84 88Sakura@sakura.euwww.sakura.euwww.cli-online.com & search 2427508_009_SFE_5500_add-xSeriesA&P_D1 1 04-11-2008 16:15:29