The Contribution of cocoa additive to cigarette smoking addiction

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Page 82 of 207 RIVM report 650270002 Histamine significant increase in brain histamine levels after 20 minutes. This increase in the brain histamine levels seems to be a direct result of brain histamine release due to ethanol or acetaldehyde metabolism in the body. The effect of ethanol on brain histamine levels may have important implications in view of the fact that both histamine and ethanol influence diuresis, EEG activity, and thermoregulation in the body (51). The plasma histamine concentrations after oral food challenges in 13 patients who were positive to food antigen-specific IgE, increased significantly. No significant change in plasma histamine concentrations was observed after the challenges in the controls. The results confirmed the strong connection between food allergy and the elevation of plasma histamine concentration. Therefore, plasma histamine concentration following food challenges might be a useful marker in the detection of food allergy (52). Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate (SCG ) was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways (53). However, another study showed that histamine did not increase the absorption of tracer chromium-51 labelled EDTA, which was instilled into one nasal cavity for 15 minutes, with a nasal pool-device (total volume 14 ml). The present data agree with previous observations in guinea pig tracheobronchial airways, where histamine and other exudative agents did not increase the mucosal absorption of solutes from the airway lumen. The data in the mentioned study suggest that the potent protein systems of blood plasma can transverse the endothelial-epithelial linings and operate on the surface of the airway mucosa without compromising its integrity as a barrier to luminal material (54). Normal CFW mice, when exposed to tobacco smoke, showed a significantly increased susceptibility to the lethal effects of histamine. The LD50 for mice subjected to smoke was 45 mg/kg of histamine, whereas in normal CFW mice the LD50 was 1,100 mg/kg. Injecting the mice with isoproterenol markedly diminished the histamine susceptibility of tobacco smoke. Normal CFW mice, as well as sham control mice, exhibited an epinephrine-induced hyperglycemia, whereas the blood glucose values for smoked mice given epinephrine were essentially the same as those for sham mice given only saline. This observation indicates that tobacco smoke may contain a component, which causes an autonomic imbalance, hence rendering the mice more susceptible to histamine. This tobacco smoke-induced allergy is probably related to a blockade of adrenergic receptors and not to an immunologic phenomenon (55). Both S-(-)- and R-(+)-nicotine enantiomers are inhibitors of histamine N taumethylation activity in guinea-pig pulmonary alveolar macrophage cultures, exhibiting IC50 values of 7 and 8 µM, respectively. S-(-)-Nicotine is not biotransformed under the conditions of the experiment, however, R-(+)-nicotine
RIVM report 650270002 Page 83 of 207 Histamine undergoes significant N-methylation to produce N-methylnicotinium ion. S-(-)- Nicotine appears to inhibit the N-methylation of its optical antipode by the alveolar nicotine N-methyltransferase. The results indicate that a contributing factor in the toxicology of cigarette smoke inhalation may be due to the inhibition of pulmonary metabolism of histamine by nicotine (56). In vitro studies with rat intestines showed that the potentiation of histamine toxicity by putrefactive amines, such as cadaverine, results from the inhibition of histamine metabolism which leads to increased uptake of unmetabolized histamine (57). The airway response to histamine has been shown to be related to the 24 hour urinary excretion of sodium. To assess whether this relation is likely to represent a direct causal association a randomised double blind crossover trial of slow sodium (80 mmol/day) was compared with placebo in 36 subjects having a low sodium diet. The dose of histamine causing a 20% fall in FEV1 (PD20) was 1.51 doubling doses lower when the men were taking sodium than when they were taking placebo (p less than 0.05). On the basis of PD10 values, the difference in men was 1.66 doubling doses of histamine (p less than 0.05). There was no corresponding effect in women. Regressing PD10 against urinary excretion of electrolytes with data from the two occasions during the trial and the measurements made before the trial showed a significant association with sodium excretion after allowance had been made for any effect associated with potassium or creatinine excretion, the latter being a marker of the completeness of the urine collection. Again there was no corresponding effect among women. These findings are compatible with the differences in regional mortality data for England and Wales, which show a relation between asthma mortality and regional per person purchases of table salt for men but not for women (58). Critical assessment Chemical (see critical assessment of the general section) The free amino group is a potential group to react with aldehydes and ketones and with monoaminooxydase (MOA); a base group, i.e. a potential group to react with acids. The ring nitrogen atoms: The extra pairs of electrons are involved in the pi-cloud of the ring and are not available for sharing with acids. Substitution reactions may occur in which the stabilized ring is retained. In vivo Histamine level in the body is increased either by mediators (at food allergy) or by inhibition of the histamine metabolism (by nicotine or putrefactive amines). Increased sodium intake seems to increase the hyperresponsiveness to histamine reactions in asthmatic men. It is unclear whether histamine increases the permeability of the respiratory mucosa to other compounds. Conclusion Chemical Especially the free amino group has the potential of a reactive site.
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