Dyslipidaemia and dysglycaemia in HIV- infected patients on highly active anti-retroviral therapy in Kumasi Metropolis

Background: Diet and genetic predisposition significantly affect lipid metabolism in the individual. This metabolic effect is further challenged in patients infected with HIV and on HAART. The prolonged use of HAART is associated with lipodystrophy, dyslipidemia, and insulin resistance.Objective: To determine the prevalence of lipid dysregulation and dysglycaemia in HIV infected patients on HAART in the Kumasi metropolis.Methods: This cross sectional study was conducted between October 2009 and June 2010, and 305 HIV-infected patients consisting of 164 patients on HAART for at least six months and 141 HAART-naive patients constituted HIV-positive patients, not on HAART and whose CD4 were not below 320 cell/ml as the control. Data was analyzed using Graph Pad Prism (version 5.0). Unpaired t-test, linear and multivariate regression analyses, was used to predict glucose level from the various parameters. Anthropometric parameters consisting of body weight, waist and hip circumferences, height, bicep and triceps skin fold were measured with a pair of calipers. Lipid profile and fasting blood glucose were determined by enzymatic methods. CD4 counts and hemoglobin were determined.Results: Fasting plasma, glucose (3.81±0.08mmol/l, 4.48±0.17mmol/l), total cholesterol (3.05± 0.0 8mmol/l, 4.54±0.08mmol/l) LDL (2.24±0.07mmol/l, 2.87±0.07mmol/l) and HDL (0.85±0.04mmol/l, 0.97±0.03mmol/l) between the control and case respectively were significantly raised (P< 0.001), though within the physiological range. The significantly increased hip and waist circumferences, waist-to-hip ratio (0.85±0.22, 0.88±0.01) of the control and case correlated with lipodystrophy.Conclusion: HAART was associated with lipodystrohy and, the risk of developing type II diabetes among the HAART experienced group was 5 times higher than the HAART naive group.Keywords: HIV, HAART, non-nucleoside reverse transcriptase inhibitor, nucleoside reverse transcriptase inhibitor, HypertriglyceridemiaAfrican Health Sciences 2013; 13(4): 1107 - 111

Tissue functions mediated by β3-adrenoceptors—findings and challenges

As β3-adrenoceptor agonists metamorphose from experimental tools into therapeutic drugs, it is vital to obtain a comprehensive picture of the cell and tissue functions mediated by this receptor subtype in humans. Human tissues with proven functions and/or a high expression of β3-adrenoceptors include the urinary bladder, the gall bladder, and other parts of the gastrointestinal tract. While several other β3-adrenoceptor functions have been proposed based on results obtained in animals, their relevance to humans remains uncertain. For instance, β3-adrenoceptors perform an important role in thermogenesis and lipolysis in rodent brown and white adipose tissue, respectively, but their role in humans appears less significant. Moreover, the use of tools such as the agonist BRL 37344 and the antagonist SR59230A to demonstrate functional involvement of β3-adrenoceptors may lead in many cases to misleading conclusions as they can also interact with other β-adrenoceptor subtypes or even non-adrenoceptor targets. In conclusion, we propose that many responses attributed to β3-adrenoceptor stimulation may need re-evaluation in the light of the development of more selective tools. Moreover, findings in experimental animals need to be extended to humans in order to better understand the potential additional indications and side effects of the β3-adrenoceptor agonists that are beginning to enter clinical medicine

Clenbuterol-Stimulated Glucose Uptake Activates both GS and GI Pathways through Β2-Adrenoceptor in Mouse Isolated Soleus Muscle

β2-adrenoceptors activated by adrenaline can also couple to both Gs and Gi proteins. The former is associated with an increase in cAMP to illicit the effect of the catecholamine. In the later, β2-AR induces PKA-catalysed phosphorylation of the receptor, which intends couples to Gi, at high concentration. We proposed that, clenbuterol which stimulates glucose uptake at low concentra-tion and inhibits it at high concentration might have identical signalling pathway as adrenaline. Mouse isolated muscles were pre-incubated in flasks containing 3 ml of Krebs-Henseleit Bicar-bonate buffer. After 120 min of pre-incubation, with the appropriate concentration of PTX the muscles were transferred to another incubation flask containing 3 ml of the same buffer and 0.3mCi 2-deoxy[1-14C]glucose containing varying concentrations of adrenaline, clenbuterol or 1nM insulin with or without PTX concentrations of 100ng/ml for adrenaline and clenbuterol and 0.1 or 1.0ng/ml for insulin, or 1M acetylcholine for 45 minutes. Adrenaline stimulated glu-cose uptake in isolated mouse soleus muscle at low concentration (10-10M) and inhibited it at high concentration (10-5M). The effect of the lower concentration was mediated through the β2-AR coupling to the Gs protein and to the Gi protein at high concentration. Similarly, clenbuterol stimulated glucose uptake at lower concentration (10-11M) is mediated through the β2-AR cou-pling to the Gs protein and to the Gi protein at the higher concentration (10-7M). These effects of high concentration of adrenaline and clenbuterol were supported by the fact that 100ng/ml PTX relieved their inhibitory effects. The higher concentration effect of clenbuterol was additionally supported by the fact that, 1M acetylcholine, relieved the inhibitory effect. Keywords: PTX, Pertusis toxin, G-proteins, Guanine nucleotide binding proteins, β-AR, beta adrenoceptor, M2, muscarinic receptor