[Preliminary clinical experiences and problems of long-term therapy of diabetes mellitus using 2nd generation sulfonylurea derivatives (glibenclamide)].
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Biomedical subjects
Publications and source records attributed to J Schulze.
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Tobacco-specific nitrosamines are derived from nicotine and related tobacco alkaloids and can be detected in tobacco products as well as in mainstream and sidestream smoke. Two of them, N-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, are strong carcinogens in laboratory animals. Because of its organospecificity for the lung, the latter is considered to be a causative factor in tobacco-related human lung cancer. Upon metabolic activation both nitrosamines give rise to a common reactive intermediate binding to macromolecules such as DNA and haemoglobin and hydrolysing to 4-hydroxy-1-(3-pyridyl)-1-butanone. Because of easy access to large quantities of haemoglobin from blood samples, it is most suitable for biomonitoring human exposure to tobacco-specific nitrosamines. A highly sensitive analytical method for determination of femtogram amounts of 4-hydroxy-1-(3-pyridyl)-1-butanone provides an approach to assess individual exposure to active and passive smoking.
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In non-diabetic persons whose serum triglyceride (TG) concentrations ranged from normal to very high levels, endogenous TG turnover was measured using the radioglycerol method of Farquhar and coworkers. Insulin, FFA, and glucose concentrations were estimated during an oral glucose tolerance test. Stimulated insulin levels were correlated positively to TG concentrations and absolute TG turnover rates, and negatively to fractional TG catabolic rates. FFA concentrations had similar relationships, also in non-insulin-dependent diabetics. A more detailed analysis showed that elevated insulin and FFA levels - as an expression of peripheral insulin resistance - are typical finding in the kind of patients whose fractional TG catabolic rate is low [less than or equal to 0.210 (h-1)], irrespective of actual serum TG concentration. Our data do not suggest a stimulatory role of insulin for TG production.
The nutrient lactose acts as a potential dietary fibre. Depending on the composition of diet, lactose can partially escape from digestion and absorption in the small intestine and is utilised by the colonic microflora. The suggested mechanism, i.e. different rates of enzymatic hydrolysis of the lactose anomers and an influence of food ingredients on lactose mutarotation, seems to be supported by experimental results. The Michaelis constant of the mucosal beta-galactosidase of rats is 14 mmol/l with alpha-lactose and 50 mmol/l with beta-lactose as substrates. During intestinal perfusion of human infants, alpha-lactose is digested at a significantly higher rate than beta-lactose. The mutarotation of lactose is influenced by general acid-base catalysis. Milk formulae containing a high concentration of weak-acid anions, e.g. cow milk which is rich in phosphate and citrate, accelerate mutarotation, but milk formulae with a low content of these anions do not. With these experimental results a mathematical model has been set up simulating lactose digestion in the small intestine of human infants and of rats. The data show that certain dietary components may influence the ratio between lactose anomers, but, surprisingly, they do not influence the amount of digested lactose.
The potential of double-stranded RNA interference (RNAi) technology was studied for down-regulation of gene expression in poplar. A set of vectors was constructed generating RNAs capable of duplex formation of sequences specific for the beta-glucuronidase (GUS) reporter gene system. These gene cassettes are driven by the CaMV-35S promoter. To address the question of gene silencing, we tested the functionality of these vectors, both in transient assays by transforming protoplasts with the RNAi constructs, and in stably transformed GUSexpressing poplar plants. Agrobacterium-mediated transformation of those GUS-expressing plants with a GUS-specific RNAi construct showed a strong down-regulation of the reporter gene. From these results we conclude that RNAi is also functional in poplar.