Crosstalk of cardiomyocytes and fibroblasts in co-cultures.

Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter space relevant for fibrotic cardiac tissue development comprising the following essential processes: (i) adhesion to substrates with varying elasticity, (ii) dynamics of contractile function, and (iii) electromechanical connectivity. By combining electric cell-substrate impedance sensing (ECIS) with conventional optical microscopy, we could measure the impact of fibroblast-cardiomyocyte ratio on the aforementioned parameters in a non-invasive fashion. Adhesion to electrodes was quantified via spreading rates derived from impedance changes, period analysis allowed us to measure contraction dynamics and modulations of the barrier resistance served as a measure of connectivity. In summary, we claim that: (i) a preferred window for substrate elasticity around 7 kPa for low fibroblast content exists, which is shifted to stiffer substrates with increasing fibroblast fractions. (ii) Beat frequency decreases nonlinearly with increasing fraction of fibroblasts, while (iii) the intercellular resistance increases with a maximal functional connectivity at 75% fibroblasts. For the first time, cardiac cell-cell junction density-dependent connectivity in co-cultures of cardiomyocytes and fibroblasts was quantified using ECIS.

Sexual dysfunction associated with protease inhibitor containing highly active antiretroviral treatment.

BACKGROUND: A high proportion of individuals receiving highly active antiretroviral treatment (HAART) complain of sexual dysfunction (SD), encompassing a lack of desire or erectile dysfunction. OBJECTIVE: To determine whether SD was associated with particular components of the HAART regimens and to identify risk factors for the development of SD in patients on HAART. METHODS: A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. A total of 904 individuals currently receiving antiretroviral agents were included in the analyses. RESULTS: A decrease in sexual interest was significantly more frequently reported by subjects (men and women) using HAART containing protease inhibitors (PI) (308/766, 40%), compared with PI-naive patients (22/138, 16%; OR 3.55; 95% CI 2.15--5.89). In addition, a significantly larger number of PI-experienced men reported a decrease in sexual potency (216/628, 34%) compared with PI-naive men (12/99, 12%; OR 2.56; 95% CI 1.33--5.03). In multivariate analyses the following factors were associated with a decrease in sexual interest: a current PI-containing regimen, a history of a PI regimen, symptomatic HIV infection, age and homosexual contact as HIV transmission mode. Factors associated with a decrease in sexual potency were: current use of a PI-containing regimen, symptomatic HIV disease, age and the use of tranquillisers. CONCLUSION: SD appears to be a common side-effect of HAART regimens containing a PI. The potential association between SD and other side-effects of HAART, such as lipodystrophy syndrome and neuropathy, should be investigated further.

Self-reported signs of lipodystrophy by persons living with HIV infection.

OBJECTIVE: To identify risk factors for the development of lipodystrophy in HIV infected patients on highly active antiretroviral therapy. METHODS: A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. Nine hundred and four people receiving antiretrovirals, were included in the analyses. RESULTS: 368 (41%) people reported an increase in abdominal girth since commencing current antiretroviral treatment. Breast enlargement was reported by 106 people (12%). Lipoatrophy signs were reported by approximately one-third of the people: 291 (32%) complained about decrease in facial fat and 300 (33%) reported decrease in buttock fat. One hundred and thirty-one (15%) people reported both lipoatrophy signs and an increase in abdominal girth (mixed lipodystrophy syndrome). In multivariate analysis, the development of the mixed lipodystrophy syndrome was associated with a longer use of indinavir (OR=1.03, 95% CI: 1.00-1.06), ritonavir (OR=1.06, 1.02-1.09) and stavudine (OR=1.05, 1.02-1.08) and also with age, a longer duration of HIV seropositivity and an advanced stage of HIV infection. CONCLUSIONS: This study suggests that multiple factors are associated with the occurrence of lipodystrophy, including the prolonged use of protease inhibitors.