Effects of oral zinc in erythropoietic protoporphyria.
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Biomedical subjects
Publications and source records attributed to C Weinkove.
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A very low calorie formula diet (VLCD) with physician and dietitian support was used to achieve and maintain weight loss in 408 overweight patients, referred by consultants because of concurrent health problems. The patients had failed to lose weight on conventional diets, and their obesity was considered a significant risk factor in their health. Using 330 or 405 kcal formula diets, the mean rate of weight loss in men was 1.87 kg/week and in women 1.27 kg/week. Women sustained the dieting process over longer periods, with a time to maximum weight loss of 5-72 weeks (mean 24) compared to the achievement in men of 4-40 weeks (mean 12.5). Sixteen per cent of the patients dropped out in the first 3 weeks. Of the remaining 84 per cent, weight loss to within 80-100 per cent BMI 25 (target weight) was achieved by 53 per cent men and 46 per cent women who had completed more than 5 weeks dieting. Women were more complaint than men at weight maintenance follow-up and 58 per cent of the start group were observed for more than 50 weeks (50-164), only 10 per cent experiencing weight regain of 20-70 per cent. Physician support was required to adjust medication in patients attending. Complications of obesity were remarkably improved after weight loss.
Severe hypernatraemia in a hospital population should be an avoidable problem. We have looked at its causes and incidence over one year and have shown that serious hypernatraemia (serum sodium greater than 160 mmol/l) as a manifestation of severe dehydration is associated with a high morbidity and mortality. Failure to maintain adequate fluid intake, intentional or unintentional, was the most frequent cause. Nursing and medical staff must be made more aware of this problem and encouraged to initiate early treatment of dehydration.
A 42 year old heterosexual male with symptomatic human immunodeficiency virus infection presented with a 2-week history of tense blistering skin lesions following azidothymidine therapy. Urinary porphyrin excretion confirmed the diagnosis of porphyria cutanea tarda. The blisters resolved following the withdrawal of the drug but recurred when rechallenged. Three other cases of porphyria cutanea tarda, not associated with azidothymidine, who subsequently developed acquired immunodeficiency syndrome have recently been described. If azidothymidine is not the precipitating agent, it is possible that human immunodeficiency virus itself can impair porphyrin metabolism, leading to the clinical and biochemical features of porphyria cutanea tarda.
Sodium metabisulfite, commonly used to prevent the oxidation of catecholamines during extraction from plasma onto alkaline alumina, does not prevent their subsequent degradation in acetic acid eluates. However, ascorbic acid, a potent antioxidant, is extracted with the catecholamines onto the alumina and prevents such destruction. However, ascorbic acid may interfere with the electrochemical measurement of catecholamines, unless sequential oxidation and reduction are used. Other methods of minimizing catecholamine oxidation in acetic acid eluates include refrigerating at 4 degrees C and capping the sample vials to exclude atmospheric oxygen.
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In the radioenzymatic assay of catecholamines, using catechol-O-methyltransferase, the yield of labelled product is frequently less than the expected value. This has been attributed by some workers to losses during the periodate oxidation of the O-methylated derivatives. Using spectrophotometric methods, we have demonstrated that there is no oxidative demethylation of the methoxycatecholamines during periodate oxidation. In a novel technique designed to determine the specific activity of small quantities of tritiated S-adenosylmethionine, high performance liquid chromatography with electrochemical detection was used to measure the amount of adrenaline formed from unlabelled noradrenaline, in the presence of phenylethanolamine-N-methyltransferase and tritiated S-adenosylmethionine. As well as the real losses occurring during solvent extraction and thin layer chromatography (demonstrated spectrophotometrically), apparent 'loss' of radiolabelled product may be due to the assumption that the value for the specific activity of the tritiated S-adenosylmethionine and the determination of the product's radioactivity are both absolutely accurate, with no allowance being made for the normal and expected experimental errors in such measurements.
Using a modified sensitive and specific radioenzymatic method we have determined the normal range for plasma noradrenaline in healthy, elderly individuals. The effects of tilt on the cardiovascular system and on plasma noradrenaline responses were found to be different compared with healthy young controls. The elderly had higher resting plasma noradrenaline concentrations with an exaggerated response to head-up tilt. In spite of this higher sympathetic drive, the cardiovascular responses in the elderly were attenuated.
The kinetics of enzymatic O-methylation of catecholamines were studied under conditions like those used in the radioenzymatic assay of plasma catecholamines. Inappropriate Michaelis-Menten kinetics and linear approximations of exponential equations were not used. Mathematical analysis indicated the importance of the ratio of methyl donor (S-adenosylmethionine) to substrate (catecholamine) concentration. If the reaction is incomplete, only a large ratio will allow linear approximations between product formed and initial catecholamine concentration. The use of high-concentration internal standards to correct for plasma interference may give erroneous results by reducing this ratio. Accuracy will be improved by ensuring (a) that S-adenosylmethionine is always greatly in excess of catecholamine, (b) that concentrations of added standards are of the same order as for endogenous catecholamine, and (c) that a high activity of enzyme is used, to allow the reaction to reach completion even in the presence of some inhibition.
Alumina is commonly used for the purification and concentration of catecholamines in biological specimens before analysis. Acid eluates of alumina, found to contain high concentrations of Al3+, interfered with O-methylation but not with N-methylation. The chemistry of the catecholamines, supported by kinetic studies, suggest that complex formation between aluminium and the substrate account for the observed inhibition of O-methylation. The addition of desferrioxamine, a metal-chelating agent, to the reaction mixture reversed this inhibition and, by allowing a preliminary alumina extraction, permits the measurement of low concentrations of catecholamines in biological samples.
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A quantitative cytochemical method for the demonstration of 20 alpha-hydroxysteroid dehydrogenase activity (20 alpha-HSD) in the regressing corpora lutea of the adult rat ovary is described. The method employs unfixed tissue sections and relies upon the oxidation of 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OH-P) with nitro blue tetrazolium as the hydrogen acceptor. The enzyme was dependent upon NADP+ for its activity and was inactive when 20 beta-hydroxy-4-pregnen-3-one (20 beta-OH-P) was used as a substrate. The apparent Km values for 20 alpha-OH-P and NADP+ were 3 x 10(-4) M and 2.5 x 10(-5) M respectively. Inhibition of 20 alpha-HSD activity by steroids was demonstrable at pH 8. Androstenedione was by far the most potent inhibitor, followed by progesterone (the product of the enzyme activity) 17 alpha-hydroxyprogesterone, Compound S and 20 beta-OH-P. At pH 6.8, a pH more favourable to the progesterone leads to 20 alpha-OH-P reaction, only progesterone and 17 alpha-hydroxyprogesterone were inhibitory. Testosterone was without demonstrable effect at either pH.
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Young rats were maintained for three weeks on a low-protein diet. These animals developed many of the features of human protein-calorie deficiency, including dextrose intolerance and diminished insulin release. Quantitative histologic and ultrastructural studies showed that malnourished rats had (1) a reduced total pancreatic islet volume, and (2) a preponderance of pale granules in the B cells. It is suggested that pale B granules may contain increased amounts of insulin, which accumulate in the cells because of defective insulin release. The mechanism responsible for this has not been elucidated.
1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.
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