Biochemical and histologic presentations of female Wistar rats administered with different doses of paracetamol/methionine.

This study was carried out to compare the hepatoprotective effect of methionine on paracetamol treated rats at both the peaks of toxicity and absorption. Female Wistar rats were divided into 17 groups consisting of eight rats per group and treated with different doses of paracetamol/methionine (5:1). Each control rat received 5 ml of physiologic saline. The study was terminated at two different end points -the 4th and 16th hours. Results show that rats administered with toxic doses (1000 mg/kg, 3000 mg/kg, 5000 mg/kg BW) of paracetamol exhibited significant increases in the levels of ALT, AST, γ- GT compared with controls. These increases were much higher at the 16th than 4th hour but serum total protein, albumin and globulin were significantly decreased by the end of the 16th hour. Histology results of rats in the 3000 and 5000 mg/kg (by the end of the 16th hour) confirmed hepatic damage, light microscopic evaluation of liver showed remarkable centrilobular necrosis. Moreover, the presence of mononuclear cells in liver section of rats intoxicated with APAP (5000 mg/kg) suggests a possible involvement of inflammatory process which resulted in regurgitation of bilirubin leading to its elevated level as well as increase activity of ALP. The hepatoprotective effect of methionine, on the other hand, was demonstrated in these rats at the 4th and 16th hours, and both results were comparable and therefore not significantly different but elevation in GGT level still persisted. In conclusion, data obtained from this study suggest that these agents may be capable of inducing GGT, although further study is required to establish a possible relationship between methionine and this enzyme in some other animal species.

Effects of methionine containing paracetamol formulation on serum vitamins and trace elements in male rats.

Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a number of pathological conditions. It also alters plasma levels of many vital elements and molecules. This study was designed to identify if the alteration observed for antioxidant vitamins and minerals especially at sub-toxic and toxic levels of exposure in our earlier study of 24-hour exposure period may warrant trace elements supplementation. This was investigated by carrying out a 48-hour study to test the ability of a living organism to restore homeostasis of these vital molecules and elements. The levels of antioxidant minerals and vitamins were estimated in the serum samples obtained from adult male Wistar rats exposed to paracetamol tablets. At 100 mg\kg BW (body weight) vitamin A, niacin, riboflavin, selenium and manganese were not significantly different from the control group. Moreover at 350 mg\kg, all these indices except zinc were not significantly different in the exposed group compared with controls whereas at 1000 mg\kg level of exposure manganese, selenium and vitamin E were not significantly decreased at the end of 48 hours of exposure but copper, niacin and vitamin A were significantly increased in the exposed group compared with the controls. These results suggest that with time the body may be capable of bringing about restoration of the levels of some of these elements\vitamins. This was more evident at 350 mg\kg level of exposure than a higher dose of 1000 mg\kg level.

High cadmium / zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer.

Tobacco smoke may be one of the most common sources of cadmium (Cd) in the general population, particularly in the rising population of smokers in developing countries. Although a relationship between both cigarette smoking and environmental Cd contamination with prostate cancer exist, the mechanisms are unclear. Most prospective cohort studies found a positive association between current smoking and a fatal cancer of the prostate. We investigated the interaction between zinc and cadmium and the potential risk of prostate cancer in smokers. Serum cadmium level was significantly (P < 0.001) higher in smokers compared with non-smokers, the level in smokers was three-fold that in non-smokers. In contrast zinc was significantly (P < 0.001) reduced in smokers compared with non-smokers. Unlike Zn, Cu was significantly (P < 0.05) higher in smokers than in non-smokers. Iron (Fe) though higher in smokers was not significantly different. Zinc: cadmium ratio was very significantly (P < 0.001) reduced, implying high cadmium: zinc ratio. This ratio was 4.5-fold the level in non-smokers. Total protein, albumin and total globulin levels were all significantly (P < 0.001) reduced in smokers compared with non-smokers respectively. Potassium (K+) was significantly (P < 0.05) higher in smokers than in non-smokers. Magnesium (Mg) was significantly (p < 0.01) reduced in smokers compared to non-smokers. Altered Zn status culminating in high Cd:Zn ratio appears the central factor in smokers; leading to oxidative stress, DNA damage, mutation, impaired DNA repair, P53 expression, angiogenic effect of Cu and impaired vitamin A metabolism. These converge in the risk of the carcinogenic process, suggesting high Cd: Zn ratio as the critical determinant of the risk of prostate cancer in smokers and possibly a biomarker of susceptibility to this environmental disease.

Increased plasma manganese, partially reduced ascorbate, 1 and absence of mitochondrial oxidative stress in type 2 diabetes mellitus: implications for the superoxide uncoupling protein 2 (UCP-2) pathway.

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve beta-cell dysfunction in type 2 diabetes mellitus.

Study processes of first year clinical students of the College Of Medicine, University of Ibadan, Ibadan Nigeria.

Students adopt several learning approaches towards achieving the perceived goal of passing their prescribed examinations. This study was carried out to determine the study processes being used by medical students of the College of Medicine, University of Ibadan on arrival at the Faculty of Clinical Sciences. One hundred and sixty five first year clinical students were studied using the modified 'Biggs' Study Process Questionnaire. Additional questions to identify local factors that would contribute to the learning were also included. There were 143 respondents (87% of the study population). The predominant study pattern among the students was the deep approach (63%). The achieving and superficial approaches were used by 8% and 29% of the students respectively. Additional analysis showed that 68%, 31% and 1% had 'good', 'average' and poor learning capacities respectively. Self interest was the principal reason why the students chose medicine as a career. Most students (76%) preferred lectures to tutorials, and only 30% found out extra information about topics taught frequently. Thirty-nine percent of the study cohort saw their teachers as role models, and 76% intended to travel abroad after graduation. Majority of 1st year clinical students of the College of Medicine, University of Ibadan adopted a deep approach to learning and have a good capacity to learn. However, most do not employ self-directed learning strategies and do not see their teachers as role models. The majority intend to travel abroad upon graduation.

Liver and renal function tests in artisans occupationally exposed to lead in mechanic village in Nnewi, Nigeria.

Additives in petroleum solvents have been reported to have adverse health implications. An evaluation study on some toxicological effects of occupational exposure to petroleum products (especially petrol which contains tetraethyl lead) amongst twenty five occupationally exposed artisans and twenty five graduate students of College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria as controls, was carried out using the following biochemical markers: electrolytes, urea, uric acid, inorganic phosphorus, creatinine, zinc and blood lead, as well as the activities of alanine and aspartate aminotransferases, and alkaline phosphatase. The results showed that occupational exposure of human subjects to lead in petrol increases the concentrations of uric acid (357 +/- 123micro mol/L) and phosphate (1.5 +/- 0.5m mol/L) in exposed subjects compared with unexposed subjects (uric acid 228 +/- 105micro mol/L, phosphate 1.2 +/- 0.41m mol/L; p < 0.01 in both cases). Significantly lower activities were observed for alkaline phosphatase (66 +/- 18.9 iu/L). The activities of alanine aminotransferase (11.4 +/- 4.0 iu/L) and aspartate aminotransferase (15.8 +/- 4.4 iu/L) in occupationally exposed artisans were higher compared with unexposed subjects (alkaline phosphatase = 78 +/- 22.4 iu/L alanine aminotranferase = 6.8 +/- 2.7 iu/L, aspartate aminotranferase = 9.6 +/- 3.5i u+/-L; p < 0.01 in all cases). Occupational exposure of human subjects to lead significantly increased blood lead (59.6 +/- 15.9 microg/dL) and decreased plasma zinc (71.3 +/- 14.4 microg/L) in exposed compared with unexposed subjects (blood lead = 35 +/- 7 microg/dL, zinc = 108.4 +/- 16.9 microg/dL; p < 0.01). The results indicate that occupational exposure to lead in petrol may compromise liver and renal function.