Attenuation of homocysteine-induced endothelial dysfunction by exercise training

Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular disease. Exposure of endothelial cells to elevated levels of homocysteine (HCY) results in decreased availability of nitric oxide (NO) and impaired vascular function, both of which are early events in atherogenesis. Exercise training improves vascular function by increasing endothelial NO production secondary to an increase in the enzyme responsible for its synthesis, endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training would increase endothelial NO production, which would attenuate the endothelial dysfunction associated with HCY exposure. Rats were randomly assigned to either sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of treadmill running at 20–25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks. Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY for 120 min, then exposed to norepinephrine (NE 100 nM) to induce vasoconstriction. Once a stable contraction plateau was achieved, rings were exposed to increasing concentrations of the receptor-mediated endothelium-dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187 (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO₂ (0.1, 1, 10, 100 μM). In addition, eNOS protein content and eNOS enzyme activity were determined. Aortic rings obtained from exercise trained rats demonstrated significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison to aortic rings obtained from SED rats following exposure to HCY. Additionally, exercise training increased aortic eNOS protein content and activity. Our data demonstrate that exercise training improves endothelium-dependent vasorelaxation following HCY exposure and this may be due, at least in part, to elevated levels of eNOS protein and an increase in eNOS activity. These results suggest the possible role exercise may play in attenuating the endothelial dysfunction associated with hyperhomocysteinemia.     

Nitric oxide radical suppresses replication of wild-type dengue 2 viruses in vitro

Nitric oxide is well accepted as one of the defenses for inhibiting viral dissemination. Macrophages and cells in the macrophage lineage are professional nitric oxide producers which sub-serve as target for dengue virus. The interaction between nitric oxide and dengue virus in such target cell is unknown. In this report, the impact of nitric oxide on infectious dengue virus serotype 2 production and RNA replication was investigated in vitro. Primary isolates of dengue virus serotype 2 from dengue patients were replicated in mouse neuroblastoma cells in the presence of an exogenous nitric oxide donor, s-nitroso-N-acethylpennicillamine, SNAP, at the concentration of 50 or 75 or 100 microM. Nitric oxide inhibited viral replication in a dose and a multiplicity of infection dependent manner. Nitric oxide from 50 and 75 microM SNAP delayed and suppressed replication of dengue virus isolates while higher concentration of nitric oxide, 100 microM SNAP, completely inhibited production of infectious particles up to 36 hr study. Twenty-four out of forty tested isolates, 60%, were susceptible to 50 microM SNAP inhibitory effect. The mechanism of inhibition was investigated at the level of RNA synthesis and was found that RNA production was suppressed which correlated to production of the infectious particles. Down-regulation of the RNA synthesis resulted in reduction of protein synthesis which was detected by lower level of NS1 protein synthesis using immunoblotting. In conclusion, nitric oxide from exogenous nitric oxide donor down regulated replication of dengue virus serotype 2 isolates from dengue patients. The suppression was clearly shown at the level of viral RNA and protein synthesis resulting in reduction of viral progenies production. This phenomenon implies that nitric oxide may serve as a defense which diminishes viral load in patients.     

Cleansing lotion containing tamarind fruit pulp extract. II. Study of cumulative irritation effects in human

Background Cleansing lotion containing extract of tamarind fruit pulp was developed to provide skin a lighter effect. Skin irritation may occur due to keratolytic effect of α‐hydroxyl acids (AHA) in the tamarind fruit pulp extract. Objective To assess the cumulative irritation effect of cleansing lotion containing tamarind fruit extract with 2% (w/w) tartaric acid on human skin compared with placebo product and de‐ionized water. Methods The study design was a single‐blinded, randomized side of arm, and controlled study. Three samples, including test product, placebo product, and de‐ionized water, were repeatedly applied on the inner forearm of 15 healthy females (aged 28.3 ± 3.1 years) for 30 min daily for 5 days under semi‐occlusive patch. Skin irritation was measured by using visual scoring and instruments such as Tewameter® and Mexameter®. All measurements were done before application of samples every day from day 1 until day 5. Final measurements were done after the last application for 3 days (day 8). Results The results obtained from the visual scoring scale indicated no irritation signs and symptoms of test product. Mean differences of transepidermal water loss and erythema values between test product and de‐ionized water and between test and placebo products were not statistically significant (P > 0.05). Conclusions These findings indicate a preliminary safety evidence of our developed cleansing lotion containing the natural AHAs and can be used as cumulative evidence for supporting the future home use study of this product in human.