Browsing by Subject "Metabolism"
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- ItemOpen AccessA study of iron kinetics in normal and abnormal human subjects(1973) French, Terence JohnThe work to be presented in this thesis took pl ace while I was working as a registrar in the department of radio-isotope diagnosis at Groote Schuur Hospital. During this period, I became interested in the ferrokinetic technique for attempting to quantitate normal and abnormal erythropoietis, and the possible development of these techniques so as to allow more accurate quantitation of the data. At the time the study started, the department was offering standard ferrokinetic investigations to aid in the diagnosis of abnormal haematological states. These studies did not, I felt, provide adequate information for the referring clinician, particularly in regard to ineffective erythropoietic activity.
- ItemOpen AccessCase report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation(2015) Abrams, ElaineBackgroundEfavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children.Case presentationFour black African children, between the ages of 4 and 8years presenting between 1 and 20months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60mg/L, 5–15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation.ConclusionEfavirenz toxicity should always be considered in human immunodeficiency virus-infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate.
- ItemOpen AccessGenome-wide DNA methylation in mixed ancestry individuals with diabetes and prediabetes from South Africa(2016) Matsha, Tandi E; Pheiffer, Carmen; Humphries, Stephen E; Gamieldien, Junaid; Erasmus, Rajiv T; Kengne, Andre PAims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings.
- ItemOpen AccessLipoprotein metabolism and its derangements(2003) Marais, DavidThe purpose of this article is to provide the medical practitioner with an understanding of lipids, lipoproteins and their metabolism and disorders. Such an understanding would enhance the assimilation of the sections on clinical assessment and treatment of dyslipoproteinaemia. Lipids may be defined as organic chemicals that are insoluble in water. In the biological context lipids are either carboxylic acids (fatty acids) or sterols, and their derivatives. Lipids are less dense than water and will float spontaneously or under centrifugal force. Cholesterol is the principal sterol in the animal kingdom and promotes the impenetrability of the phospholipid bilayer that constitutes the cell membrane. Additionally cholesterol is found in lipoproteins and in bile and is used to synthesise hormones and bile acids.
- ItemOpen AccessPituitary-gonadal control of creatinine metabolism.(1937) Cheetham, Richard William SpencerThe endocrine in general for a considerable period have been known to exert a humoraal action on the body, controlling its functions to a large extent. These actions have been closely investigated and a clear correlation between the ductless glands have been shown. The interrelation and dependency of the one upon the other, either by inhibition or by stimulation, contribute towards the finer control of the physiology of the body. The studies recorded here are comprised mainly of the dependency of one gland upon another, the relation the normal gland has to protein metabolism, and the alteration in this protein metabolism brought about by alteration in the normal function of one or other of the ductless glands. These features are demonstrated by observing changes in the elimination of creatinine in urine, for this urinary creatinine is regarded as an index of endogenous protein metabolism, and the amount excreted is remarkably constant from day to day.
- ItemOpen AccessStudies in cholestrol metabolism(1958) Lewis, BarryThe biochemistry of the steroids is of unique interest; no other group of relatively simple substances plays so versatile a role in biology. On the one hand are many highly potent steroids occurring in minute quantities e.g. sex hormones, corticosteroids, the vitamins D and the cardiac glycosides. In sharp contrast are certain sterols, exemplified in the animal kingdom by cholesterol - familiar, abundant, easily determined, yet singularly obscure in their physiological significance. In some restricted fields the functions of cholesterol are known. It is a precursor of the adrenocortical hormones (perhaps not an obligatory one ), and is probably important in the biosynthesis of sex hormones too. Present in the skin is 7-dehydrocholesterol, converted to vitamins D by ultraviolet light. Cholesteryl esters are found in large quantities, together with sphingomyelin, in the myelin sheaths of nerve fibres, where these lipids may have an insulating function necessary at least for saltatory conduction.
- ItemOpen AccessThe influence of cadmium on hepatic protein synthesis in the rat(1974) Norton, Kathleen Barbara; Kench, J.ECadmium is a metallic element which is placed between Zn and Hg in Group I IB of the Periodic Table. It is divalent, as are the Group I IA elements Ca and Mg. In order of electropotential, Zn, Cd and Hg fal I below Ca and Mg but above the transition elements, with which they do not have close relationships. They have low melting points so their volatility, as in the case of Pb, is an industrial hazard. Cd has recently received prominence as a cause of environment pollution due to its accumulation in water supplies and crops from Zn mining operations and industrial effluents.
- ItemOpen AccessThe regulation of the serum cholesterol level in man with particular reference to dietary factors(1958) Gordon, HymieFifty years ago, Ignatowski (1908) produced atherosclerotic lesions in rabbits by feeding them with a diet containing meat, milk and eggs. Since then, interest in the diet as a possible atherogenic factor has waxed and waned, but has never been greater than at present. Much of the credit for the present surge of interest is due to the Professor Ancel Keys of the University of Minnesota, who since 1952 has produce considerable evidence relating the development of coronary heart disease and the diet. His epidemiology surveys and his dietary experiments led him to favor the hypothesis which he summarized in the following terms (Keys, 1952).