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Male Wistar albino rats were fed for 21 days on a diet in which fat (12%) was included either as fresh corn oil, malonaldehyde content = 0.11+/-0.05 micro microg/g (control) or thermally oxidized corn oil, malonaldehyde content = 0.20+/-0.03 microg/g (experimental) and the tissue levels of lipid peroxides in six organs-namely, liver, kidney, brain, heart, lungs and testes-were determined. Of the organs studied, significantly (P < 0.1) higher concentrations of lipid peroxides were observed only in the liver and kidney of the experimental rats. In the course of the feeding, the experimental rats showed significantly (P < 0.1) lower gains in body weights as well as higher relative liver weights than the control rats.

The sulfones are the drug of choice in the treatment of leprosy, with dapsone as the clear favorite. The major route for dapsone metabolism leading to its inactivation and excretion is via acetylation by hepatic N-acetyl transferase (NAT), as is the case with isoniazid (INH) and sulfamethazine (SMZ). The enzyme is known to exhibit genetic polymorphism. The object of the present study is mainly to determine the incidence of acetylator phenotype in a population of leprosy patients with a view to evaluating the degree of association, if any, between phenotype and the disease. Obviously a knowledge of the incidence of the phenotypes may provide a valuable contribution to the institution of more rational and successful therapy. In the normal or control subjects, as well as in the leprosy patients, the frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum samples are bimodal, and this indicates the existence of a genetic polymorphism. Based on the bimodality, individuals were classified as either "rapid" or "slow" acetylators, and the incidence of the slow acetylator phenotype of about 51% was observed in the leprosy population. This gives a relatively high incidence of the allele controlling the slow acetylator (q = 0.73). Although there is evidence that the mean percentage of SMZ acetylated in leprosy patients of the slow acetylator phenotype is significantly higher than that observed for the same phenotype in the controls (t = 4.86, P less than 0.02), statistical analyses show that there is no association between the slow acetylator phenotype and the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Sulfamethazine (syn, sulfadimidine) is inactivated by conversion to its N-acetyl derivative. Individuals are phenotyped as either "rapid" or "slow" acetylators. We have tested the validity of this theory in a Nigerian population. The frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum were found to be bimodal, indicating the existence of a genetic polymorphism as observed by earlier workers. A plot of the percentage of the drug acetylated in serum against that in urine of the same individual results in a satisfactory separation of the rapid and slow acetylator phenotypes. An incidence of the slow acetylator phenotype of 41% was observed in the Nigerian population tested. How this observation fits into the hypothesis that the slow frequency of the allele increases from the Arctic Circle toward the Equator is discussed.

A method for determining plasma paroxonase activity using an auto-analyser is described. Frequency distributions for British and Indian subjects show bimodality. A study of 40 British families confirms the presence of a genetic polymorphism with regard to plasma paroxonase activity. Two phenotypes can be defined, controlled by two alleles at one autosomal locus. The frequency of the low activity phenotype is less in the Indian population than in the British population. Malay, Chinese, and African subjects fail to show obvious bimodality.

Trehalase is an enzyme which hydrolyzes the disaccharide trehalose, yielding glucose. It is widespread in nature and found in various human tissues as well as in human plasma. The synthesis and degradation of its substrate trehalose have been considered as being implicated in carbohydrate transport mechanisms. Trehalase activity has been examined in both normal subjects and diabetic patients. In the normal subjects, the frequency histogram of the enzyme activity is bimodal, indicating the existence of genetic polymorphism. The proposed model of a single autosomal locus with two alleles has been verified, with 27% of the population tested belonging to the "low-activity" phenotype and 73% being of the "high-activity" phenotype. Males have higher mean plasma trehalase activity than females. Apparently, the reverse appears to be the case in the diabetic subjects. The mean value for all nondiabetics and that of diabetics were computed and the difference was found to be statistically significant (F = 7.02, N1 = 3, N2 = 56, P less than 0.01). An experiment showed that neither the abnormally high concentration of glucose in diabetics nor any other constituent of the diabetic plasma caused an increase in plasma trehalase activity (t = 0.0724, P greater than 0.10). A Woolf and Haldane test to determine association of diabetes mellitus and plasma trehalase phenotype indicated a highly significant association with the high-activity phenotype (chi 2 = 18.5350, P less than 0.01). Thus the inference is that people with high plasma trehalase activity are more prone to develop diabetes mellitus than people with low enzyme activity.

Thirty-eight healthy white British Caucasian subjects were hydroxylator phenotyped with sparteine and acetylator phenotyped with sulphadimidine. The results showed that there was no significant difference in the mean sparteine metabolic ratio between eight rapid acetylator extensive hydroxylators and 27 slow acetylator extensive hydroxylators.

A complex segregation analysis of acid phosphatase activity in 50 British families showed that the essential features of the acid phosphatase polymorphism, i.e., a major gene with three alleles, is retrieved by using the biallelic mixed model. The estimates of gene frequency and displacement obtained from segregation analysis were in agreement with those obtained from electrophoretic studies. In addition, there was evidence for a multifactorial component.

1. Gel-filtration of an extract from the liver of the local Hausa goat Capra hircus indicated the presence of two molecular forms of alkaline phosphatase (orthophosphoric monoester phosphohydrolase, E.C. 3.1.3.1.). 2. Cellulose acetate electrophoresis showed that the lower-molecular-weight form had a similar electrophoretic mobility to alpha 2-globulin from goat serum, whereas the higher-molecular-weight form had a similar electrophoretic mobility to gamma-globulin. 3. Only the lower-molecular-weight form was detected on electrophoresis of a liver extract which contained some residual n-butanol used in the extraction procedure, whereas dialysed acetone powder obtained from the liver extract contained both molecular-weight forms. 4. The partially purified enzyme showed maximum activity at pH 9.8, and was stimulated by Mg2+. 5. The enzyme was heat-labile, and was competitively inhibited by phosphate ions but uncompetitively inhibited by L-phenylalanine. 6. These results are discussed in terms of the properties of the enzyme from other sources.

There is an association between exposure to aromatic amines and the development of bladder cancer. Aromatic amines such as are known to occur in tobacco smoke are polymorphically acetylated. One hundred bladder cancer patients have been acetylator phenotyped. Only three of them were non-smokers at the time of diagnosis. This new series, together with four previous series (each with its own control), have been statistically analysed together. The results show a significant association between the slow acetylator phenotype and bladder cancer. The slow acetylator phenotype is associated about 39% more with bladder cancer than is the rapid acetylator phenotype. This association can be interpreted in one of two ways: (1) rapid acetylators may be protected against developing bladder cancer because they are better able to render amines non-carcinogenic by acetylation, or (2) slow acetylators have greater survival with bladder cancer than rapid acetylators. Further evidence will be required to differentiate between these alternatives.

Glutamic oxaloacetic transaminase (EC 2.6.1.1), has been prepared from the liver of Hausa he-goat (Capra hircus). 2. Gel filtration of the liver extract presents evidence of two molecular species of the enzyme; one species (Fraction A) has a specific activity of 280 U/mg protein and the other (Fraction B) has a specific activity of 338 U/mg protein. 3. Fraction A has optimum activity at pH 6.8 and Fraction B is optimally active at pH 5.5. The observed variation in activity with pH variation may be due to ionisation of some group(s) on the enzyme. 4. Characteristic spectral changes typical of INH/GOT interactions at low and high pH values are presented. 5. Typical Dixon's plot indicates a competitive inhibition of the enzyme by INH. Ki and Km of 0.04 and 2.5 mM for Fraction A and Ki and Km of 0.098 and 4.7 mH for Fraction B have been calculated from the data. 6. These results have been discussed in the light of the properties of the enzyme from other sources.