Theoretical QSAR study on carcinogenic potency of N-nitrosamines

A mechanistic QSAR study on N-nitrosamines (NA) was performed with the aid of the semiempirical MINDO/3 method. Both the chemical reactivity and the transport in biological medium were taken into account. The parent NA molecules and their first reaction intermediates in the metabolic activation pathway were examined for possible determinants of the relative carcinogenic potency. The correlations found support the previous suggestions concerning the metabolic C alpha radical hydroxylation of NA. The role of transport properties in the early stage of NA biotransformation was also demonstrated.     

Innervation of the sheep adrenal cortex: an immunohistochemical study with rat corticotrophin-releasing factor antiserum

Using indirect immunohistochemistry and an antiserum raised against rat corticotrophin-releasing factor (CRF) we have outlined an asymmetric network of cells and varicose fibers in sheep adrenal cortex. This network was not associated with the larger splanchnic nerves, but was occasionally found in small bundles or with blood vessels; in most instances fibers were found weaving independently through cortical parenchyma. A plexus of fibers was found in the zona reticularis, with a few fibers ramifying into adjacent medulla. Uni or bipolar cells were found throughout the cortex, with the greatest frequency at the corticomedullary junction; a multipolar-type cell was also found in this area. Staining of varicose structures and most cells was abolished by incubation with excess rat CRF 1-41, but not by ovine CRF or a range of other peptides. Though the immunoreactive species has not as yet been identified, it may thus share homology with sequences present in rat but not ovine CRF.     

Drug-induced bronchial asthma

In any case of acute bronchoconstriction the possibility of an adverse reaction to a drug should be considered. In many of such side reactions no allergic mechanism can be detected. Therefore, they are included into the category of pseudoallergic reactions (PAR). The clinically most important form of drug-induced bronchial asthma, analgesics asthma, belongs to this PAR group. A further risk for asthmatics are intravenous applications of contrast-media for roentgenography which in about 15% induce a severe, sometimes life-threatening pseudo-allergic adverse reaction. In asthmatics, the application of any beta-receptor blocking agents and also the use of parasympathicotonic eye drops for treatment of glaucoma are contraindicated. Paradoxical bronchial constriction following application of antiasthmatics are preponderantly caused by locally irritative actions, less frequently by genuine allergic phenomena or additive intolerance. The most reliable prophylaxis against drug-induced bronchial asthma consists in strong avoidance of all derivatives possibly capable to trigger any intolerance. A respective warning should entered into the emergency passport.     

Effects of hypertension and antihypertensive drugs on cardiovascular complications in the elderly

The role of hypertension and antihypertensive drugs in cardiovascular complications was evaluated in 380 elderly people living in the Tokyo Metropolitan Gerontology Center. The subjects were classified into four groups according to the presence or absence of hypertension and their antihypertensive treatment, and followed up prospectively for 5 years from 1979 to 1984. The average age of each group was 74 to 76 years. Cerebrovascular disease was observed in 19.3% of male hypertensives and 10.1% of male normotensives (p = 0.078). The drug treated group revealed no cerebral hemorrhage and less cerebral infarction. This tendency was not observed in females. Ischemic heart disease was prevalent in the drug treated group (10.9% vs 4.5%, p = 0.023) irrespective of blood pressure level. Risk factors such as body mass index, skinfold thickness, serum cholesterol, albumin, creatinine, blood urea nitrogen and uric acid at entry were elevated in the drug treated group. Diuretics were used in 92% of the drug treated group; in 53% as monotherapy and in 39% as combination therapy with other antihypertensive agents. The metabolic effect of diuretics may increase the incidence of ischemic heart disease in the elderly. We might conclude that hypertension in the aged accelerates cerebrovascular complications, and that antihypertensive treatment is effective even in this group. However, the wide use of diuretics could increase the incidence of ischemic heart disease. Careful selection of antihypertensive drugs as well as dose adjustment are needed in the treatment of elderly hypertensives.