Mitochondrial and lysosomal protective agents ameliorate cytotoxicity and oxidative stress induced by cyclophosphamide and methotrexate in human blood lymphocytes.

Cyclophosphamide (CYP) and methotrexate (MTX) have been evaluated for their ability to induce toxicity in human peripheral blood lymphocytes (PBLs) and the protective role of mitochondrial and lysosomal stabilizing agents. The potential toxicity effects of CYP and MTX were measured in vitro by cellular parameters assays such as cellular viability, reactive oxygen species (ROS) formation, mitochondrial membrane permeability transition (mitochondrial membrane potential (MMP)) collapse, lysosomal membrane damage, intracellular reduced glutathione (GSH), extracellular oxidized glutathione (GSSG), and lipid peroxidation. Separately, human lymphocytes were treated with concentrations of 0.1, 0.2, 0.4, 0.8, and 1.6 ng/mL for CYP and 1, 2, 5, and 10 µg/mL for MTX for 6 h. Statistical evaluations showed that CYP and MTX significantly decreased the cell viability at the three highest concentrations when compared with both the negative and solvent controls. In addition, CYP and MTX were significantly induced ROS formation, MMP collapse, lysosomal membrane damage, lipid peroxidation, and GSH depletion compared with the controls. Mitochondrial and lysosomal protective agents like cyclosporine A and chloroquine, respectively, decreased cytotoxicity and oxidative stress induced by CYP and MTX. The present results indicate that CYP and MTX are toxic to human PBLs and their toxicity could be ameliorated by mitochondrial and lysosomal protective agents.

Rhazes' prescriptions in treatment of gout.

BACKGROUND: Among the diseases that clinicians deal with, few do have a documented medical history that can be traced back to several centuries ago. A careful study of Rhazes' Treatments on Gout reveals a lot about the nature and therapy of gout. METHODS: We managed to study the perceptions about pathogenesis, symptomatology, diagnosis, and treatment of gout that have changed over time. We also discussed some of the past and present fallacies regarding this disease. RESULTS: Rhazes provided a detailed description on the vital role of genetics and the relationship between the development of gout, an indulgent way of living, and tophi at a period of time between 1st and 6th centuries AD. CONCLUSION: This study showed that the findings of Rhazes about treatments of gout were consonant with modern medical theories.

Increased circulating levels of basement-membrane components in patients with abdominal aortic aneurysms--a pilot study.

AIM: The decision for abdominal aortic aneurysm (AAA) repair is based on aneurysm size. However, smaller aneurysms can rupture, while larger ones can remain stable. New variables and markers are needed to better select patients at high rupture risk. The study was done to analyse if AAA patients have increased levels of circulating basement-membrane (BM) fragments. DESIGN: Circulating levels of BM components type IV and XVIII collagen were measured by enzyme-linked immunosorbent assay (ELISA) in 10 patients with AAA, nine patients with peripheral artery disease (PAD) and 10 healthy controls (CON). RESULTS: AAA patients had significantly increased levels of type IV and XVIII collagen compared with CON (134.0 ± 24.8 ng ml(-1) vs. 104.5 ± 16.4 ng ml(-1); p = 0.005 and 149.0 ± 56.9 ng ml(-1) vs. 59.6 ± 8.7 ng ml(-1); p < 0.001, respectively). The PAD patients did not have significantly increased levels of these fragments when compared with CON. In addition, the AAA patients had significantly increased level of type XVIII collagen (149.0 ± 56.9 ng ml(-1) vs. 58.3 ± 25.4 ng/ml(-1); p < 0.01) when compared with the PAD group. CONCLUSION: Based on this preliminary analysis of a small number of subjects, patients with AAA had significantly increased levels of circulating BM components. BM fragments should be studied further to establish their potential role as biomarkers for AAA.

Use of leisure time in cardiovascular patients in Gorgan (south east of Caspian Sea).

The aim of this study was to compare activity patterns and leisure time between matched groups of patients with cardiovascular disease and individuals without a heart disease. The study included 100 patients recruited from those referred to cardiology department of 5th Azar General Hospital of Golestan University of Medical Sciences in Gorgan (South East of Caspian Sea) and 100 matched control subjects during the period 2007-2008. Odds ratios (OR), together with 95% confidence intervals (95% CI), were calculated using logistic regression, as estimates of relative risks. Listening to music OR = 8.800 (95% CI: 2.717-28.499, p<0.05), meditation OR = 6.111 (95% CI; 2.616-14.274, p<0.05) were independent risk factors. Subjects who performed 2 h per week and 2-4 h per week physical activity, the odds ratios were 0.038 (95% CI: 0.012-0.124, p<0.05) and 0.079, (95% CI: 0.024-0.260, p<0.05), respectively. Low physical activity and use of long time relaxation are associated with cardiovascular disease in these patients. Regular participation in physical activity such as walking 2 h per week and 2-4 h per week, are associated with reduced risk of cardiovascular disease. This study suggests the importance of both leisure-time physical activity and sedentary behaviors in the prevention of CVD.

Relaxant effects of different fractions of essential oil from Carum copticum on guinea pig tracheal chains.

In previous studies, the relaxant and anticholinergic (functional antagonism), histamine(H1) inhibitory, and xanthine-like activity effect of Carum copticum have been demonstrated on guinea pig tracheal chains. To investigate the effective component(s) of this plant, responsible for the observed bronchodilatory effect, fractionation of the essential oil from Carum copticum was carried out and the relaxant effects of different fractions were examined in this study. The bronchodilatory effect of different fractions of essential oil from Carum copticum and theophylline in comparison with ethanol was examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 microM methacholine in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 microM propranolol and 1 microM chlorpheniramine (group 3). In addition the relaxant effect of carvacrol was also examined on precontracted tracheal chains of guinea pig by 10 microM methacholine (group 4), (for each group, n = 5). In group 1 experiments, only theophylline and fraction 2 showed significant relaxant effect compared to that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed potent and volume (concentration) dependent relaxant effects comparable to that of theophylline in groups 2 and 3 experiments. The relaxant effects of different volumes of these two fractions were significantly higher than that of ethanol (p < 0.05 to p < 0.002 ). The volumes of fraction 1 showed relatively small relaxant effects in groups 2 and 3 experiments which were not significantly different from that of ethanol. However, the relaxant effect of different volumes of fractions 2 and 3 obtained in group 2 experiments were not significantly different from those of group 3 experiments. The volumes of fraction 4 did not show any relaxant effects. In addition volumes of carvacrol also showed comparable relaxant effect with those of fraction 2 and theophylline which was significantly greater than that of ethanol. These results indicate that the relaxant effect of essential oil from carum copticum is mainly due to its fraction 2 which is presumably carvacrol and to lesser extent due to fraction 3, and their relaxant effects are not due to anticholinergic or beta-adrenegic stimulatory effects.