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Biomedical subjects

S Claxton

Publications and source records attributed to S Claxton.

5 recordsLinked to original sources
PubMed2001

Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy.

Hypertriglyceridemia, peripheral insulin resistance, and trunk adiposity are metabolic complications recently recognized in people infected with human immunodeficiency virus (HIV) and treated with highly active antiretroviral therapy (HAART). These complications may respond favorably to exercise training. Using a paired design, we determined whether 16 wk of weight-lifting exercise increased muscle mass and strength and decreased fasting serum triglycerides and adipose tissue mass in 18 HIV-infected men. The resistance exercise regimen consisted of three upper and four lower body exercises done for 1-1.5 h/day, 4 days/wk for 64 sessions. Dual-energy X-ray absorptiometry indicated that exercise training increased whole body lean mass 1.4 kg (P = 0.005) but did not reduce adipose tissue mass (P = NS). Axial proton-magnetic resonance imaging indicated that thigh muscle cross-sectional area increased 5-7 cm(2) (P < 0.005). Muscle strength increased 23-38% (P < 0.0001) on all exercises. Fasting serum triglycerides were decreased at the end of training (281-204 mg/dl; P = 0.02). These findings imply that resistance exercise training-induced muscle hypertrophy may promote triglyceride clearance from the circulation of hypertriglyceridemic HIV-infected men treated with antiviral therapy.

Adipose Tissue↗
PubMed2000

Export of a misprocessed GPI-anchored protein from the endoplasmic reticulum in vitro in an ATP- and cytosol-dependent manner.

Strict quality control mechanisms within the mammalian endoplasmic reticulum act to prevent misfolded and unprocessed proteins from entering post-endoplasmic reticulum (ER) compartments. Following translocation into the ER lumen via the Sec61p translocon, nascent polypeptide chains fold and are modified in an environment that contains numerous chaperones and other folding mediators. Recently it has emerged that polypeptides failing to acquire the native state are re-exported from the ER to the cytosol for ultimate degradation by the proteasome ubiquitin system, apparently mediated again via Sec61p. Substrates for this degradation pathway include proteins destined to become glycosyl phosphatidylinositol (GPI)-anchored, but which fail to be processed and retain the C-terminal GPI signal peptide. In order to characterise this process we have used a model GPI-anchored mutant protein, prepro mini human placental alkaline phosphatase (PLAP) W179, which cannot be processed efficiently on account of being a poor substrate for the transamidase which cleaves the GPI signal peptide and adds the GPI anchor in a coupled reaction. In vitro transcription, translation and translocation into canine pancreatic microsomes resulted in ER-targeting signal sequence cleavage and formation of prominiPLAP in the ER lumen. We were able to show that prominiPLAPW179 could be exported from the microsomes in a time-dependent manner and that release requires both ATP and cytosol. Export was not supported by GTP, indicating a biochemical distinction from glycopeptide export which we showed recently requires GTP hydrolysis. The process was not affected by redox, unlike several other GPI-anchored model proteins. These data demonstrate that misprocessed proteins can be exported in vitro from mammalian microsomes, facilitating identification of factors involved in this process.

Adenosine Triphosphate↗
PubMed2000

Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time. METHODS: We performed a cross-sectional analysis of whole-body, lumbar spine (L1-L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry. RESULTS: Men receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13-4.23) (P = 0.02). Subjects receiving protease inhibitors had greater central: appendicular adipose tissue ratios than the other two groups (P < 0.0001). There was no relationship between the central: appendicular fat ratio and the lumbar spine or proximal femur bone mineral density t- or z- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART. CONCLUSIONS: Osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.

Absorptiometry, Photon↗
PubMed2000

Refractory amiodarone-associated thyrotoxicosis: an indication for thyroidectomy.

BACKGROUND: Tasmania is an area of endemic iodine deficiency. Amiodarone is a class III anti-arrhythmic drug that is widely used for the management of ventricular and supraventricular tachydysrhythmias. Individuals from areas of endemic iodine deficiency appear more likely to manifest hyperthyroidism following amiodarone therapy, whereas hypothyroidism is a more frequent complication in iodine-replete communities. METHODS: Cases series. The clinical and biochemical response to medical and surgical management of five consecutive Tasmanian patients presenting with severe type-II amiodarone-associated thyrotoxicosis was reviewed. RESULTS: Five patients were identified. Combinations of antithyroid therapy including propylthiouracil, lithium carbonate, dexamethasone and cholestyramine were used. Thyroidectomy was required in two cases (40%) due to severe unremitting thyrotoxicosis despite combined drug regimens. Anaesthesia and total thyroidectomy were undertaken without complication despite the presence of severe hyperthyroidism at the time of surgery. In both cases thyroid histopathology demonstrated degenerative and destructive follicular lesions with multinuclear cell infiltrate and focal fibrosis. CONCLUSION: Amiodarone-associated thyrotoxicosis may be severe and refractory to medical therapy. Despite the potential risks of anaesthesia associated with uncontrolled thyrotoxicosis, thyroidectomy should be considered in the setting of life-threatening thyrotoxicosis.

Acute Disease↗