Cardiac fibroblasts produce leukemia inhibitory factor and endothelin, which combine to induce cardiac myocyte hypertrophy in vitro

Cardiac fibroblasts in culture produce factor(s) that induce hypertrophy of neonatal rat ventricular myocytes in vitro. As in vivo, the myocyte hypertrophy response in culture is characterized by an increase in cell size and contractile protein content, and by the activation of embryonic genes, including the gene for atrial natriuretic peptide. The purpose of this study was to identify the factor(s) produced by fibroblasts that induce myocyte hypertrophy. The fibroblast hypertrophy activity was inhibited using a combination of the endothelin A receptor blocker BQ-123 and an antibody to leukemia inhibitory factor. The individual antagonists each caused a partial inhibition. The mRNAs for both leukemia inhibitory factor and endothelin were detected by RT-PCR analysis and the concentration of both proteins was determined to be approximately 200 pmol/L in the conditioned medium using immunoassays. Purified leukemia inhibitory factor and endothelin each induced distinctive morphological changes in the myocytes. Their combination generated a different morphology similar to that induced by fibroblast conditioned medium. Each factor also induced atrial natriuretic peptide production, but both were required for the myocytes to produce the levels measured after exposure to fibroblast conditioned medium. These results show that hypertrophy activity produced by cardiac fibroblasts in culture is a result of leukemia inhibitory factor and endothelin.     

Chronic withdrawal of a high-palatable obesity-inducing diet completely reverses metabolic and vascular abnormalities associated with dietary-obesity in the rat

Chronic consumption of a high-palatable diet induces obesity and markedly impairs arterial relaxation. We have recently reported that endothelial function is only partially resorted after acute withdrawal of palatable diet. Therefore, this study was designed to investigate the effects of chronic withdrawal of high-palatable obesity-inducing diet on metabolic and vascular function in rats. Wistar rats were fed either standard laboratory chow throughout (controls) or given a highly-palatable diet (diet-fed) for 15 weeks; or fed the diet for 8 weeks and then returned to chow (diet-to-chow) for further 7 weeks before sacrifice. Diet-fed rats had higher body weight, fat mass, liver and heart weight than both chow-fed and diet-to-chow groups (P<0.01 for all). Compared with chow-fed and diet-to-chow groups, diet-fed rats had significantly raised fasting plasma levels of insulin, leptin and triglycerides levels (each +180%; P<0.0001), but not glucose or non-esterified fatty acids. There were no significant differences between any metabolic parameters between chow-fed and diet-to-chow groups. Mesenteric arteries showed no significant differences between any groups in KCl-induced tension generation, while diet-fed groups had significantly higher noradrenaline-induced vasoconstriction than both chow-fed and diet-to-chow groups. Maximum endothelial-dependent vasorelaxation responses to carbamylcholine (CCh) were significantly (by 23%; P<0.001) attenuated in the diet-fed group. This defect was abolished in the diet-to-chow group. There were no significant differences in endothelium-independent vasorelaxation responses to sodium nitroprusside between the three groups. In conclusion, palatable diet induces obesity and metabolic abnormalities as well as a marked endothelial dysfunction. These abnormalities are completely reversed by chronic withdrawal of the obesity-inducing high-palatable diet.     

Dual effect of disopyramide on atrial and atrioventricular conduction and refractory periods.

Disopyramide has been shown in conditions of cholinergic blockade to have a depressant effect upon sinus node automaticity and the atrial refractoriness. It also prolongs atrioventricular conduction and increases atrioventricular refractoriness. These effects may often be masked in vivo by the anticholinergic effects of the drug.     

Sagittal spine shape literacy in the general adult population,assessed by a novel,simple graphical tool

[Purpose] The sagittal shape of the spine is associated with back-pain, balance and quality of life. We developed, evaluated and report the responses of a graphical tool to assess sagittal spine shape knowledge (literacy). [Participants and Methods] Two hundred and fifty adults were randomly assigned, in a cross-sectional crossover study, to free-hand draw and select the “ideal” sagittal spine shape. We evaluated the inter and intra-rater reliability and agreement between tests and the sagittal and lordotic spine literacy between the drawing and selection test versions. [Results] Drawing test inter- and intra-rater agreement was 79% and 80% respectively. Drawing vs. selection agreement was 43%. More participants drew than selected the correct spine (30% vs. 21%) (p<0.001) and lumbar lordosis shape (56% vs. 42%) (p<0.001). Test order did not affect spine shape literacy scores. A significantly poorer literacy trend was observed with spine pain presence (p=0.02). [Conclusion] We developed a reliable method to evaluate spine shape literacy and established that only 21% and 42% of our sample demonstrated correct sagittal spine and lordotic spine shape literacy, respectively. The low literacy scores suggests that consideration of including spine shape literacy in health literacy and self-management programs may be warranted, especially in ageing populations.     

Monocyte/macrophages and their role in HIV neuropathogenesis

Neurological sequelae of human immunodeficiency virus (HIV) infection have been and remain a significant problem. Monocytes and macrophages in humans and monkeys are susceptible to infection by HIV and simian immunodeficiency virus (SIV), and are considered to be a main mechanism by which the central nervous system (CNS) is infected. Within the infected CNS, perivascular macrophages and, in some cases, parenchymal microglia are infected as are multinucleated giant cells when present. While neurons are not themselves directly infected, neuronal damage occurs within the infected CNS. Despite the success of antiretroviral therapy (ART) in limiting virus in plasma to non-detectable levels, neurological deficits persist. This review discusses the continued neurological dysfunctions that persist in the era of ART, focusing on the roles of monocyte and macrophage as targets of continued viral infection and as agents of pathogenesis in what appears to be emergent macrophage-mediated disease resulting from long-term HIV infection of the host. Data discussed include the biology of monocyte/macrophage activation with HIV and SIV infection, traffic of cells into and out of the CNS with infection, macrophage-associated biomarkers of CNS and cardiac disease, the role of antiretroviral therapy on these cells and CNS disease, as well as the need for effective adjunctive therapies targeting monocytes and macrophages.