Strenuous exercise in warm environment is associated with improved microvascular function in sickle cell trait.

PURPOSE: Sickle cell trait is characterized by the presence of both normal and abnormal haemoglobin in red blood cells. The rate of exertional collapse is increased in athletes and military recruits who carry the trait, particularly in stressful environmental conditions. The aim of the present study was to investigate microvascular function and its determinants in response to intense exercise at control and warm environmental temperatures in carriers (AS) and non-carriers (AA) of sickle cell trait. METHODS: Nine AS and 11 AA, all healthy physically active young men, randomly participated in four experimental sessions (rest at 21 °C and 31 °C and cycling at 21 °C and 31 °C). All participants performed three exercises bouts as follows: 18-min submaximal exercise; an incremental test to exhaustion; and three 30-s sprints spaced with 20-s resting intervals. RESULTS: Skin Blood Flow (SkBF) was similar at rest between AA and AS. SkBF for all participants was higher at 31 °C than 21 °C. It was significantly higher in the AS group compared to the AA group immediately after exercise, regardless of the environmental conditions. No significant differences in hemorheological parameters, muscle damage or cardiac injury biomarkers were observed between the two groups. Our data also suggest higher oxidative stress for the AS group, with high superoxide dismutase (P = 0.044 main group effect). CONCLUSION: A specific profile is identified in the AS population, with increased microvascular reactivity after maximal exercise in stressful environment and slight pro-/antioxidant imbalance.

Loss of ovarian estrogens causes only mild deterioration of glucose homeostasis in female ZDF rats preventable by voluntary running exercise.

Studies on normoglycemic ovariectomized Sprague-Dawley rats have provided insights about the effects of estrogen deficiency on insulin resistance in lean individuals. It is not completely clear if subjects with pre-established obesity and insulin resistance are at greater risk of developing type 2 diabetes when ovarian estrogens are no longer secreted, and if physical activity can protect against this susceptibility. Contrasting with their male counterparts, obese and insulin resistant female ZDF (Zucker diabetic fatty) rats do not become hyperglycemic when fed a standard diet. The aim of the study was to evaluate the hypothesis that withdrawal of ovarian estrogens in insulin resistant female ZDF rats would trigger overt hyperglycemia, provided they remain physically inactive. Female ZDF rats underwent either an ovariectomy (OVX) or a simulated surgery (SHAM). Thereafter, OVX rats engaged either in voluntary wheel cage running (OVX-Active), or like the Sham rats, remained sedentary (OVX-Sed) for 6 weeks. Fasting glycemia, insulinemia, and glucose tolerance were not altered in OVX-Sed as compared to SHAM-Sed rats. However, OVX-Sed rats showed altered liver triglyceride and glycogen contents, increased pancreatic insulin content and reduced insulin-stimulated muscle pAKT as compared to SHAM-Sed rats. Physical activity in OVX rats lowered fasting glucose and insulin levels, improved glucose tolerance and insulin-stimulated skeletal muscle glucose uptake as compared to OVX-Sed rats. OVX-induced alterations in pancreatic insulin content and liver glycogen and triglyceride contents were significantly improved by physical activity. Loss of ovarian estrogens did not cause overt hyperglycemia in insulin-resistant female ZDF rats. Physical activity improved glucose homeostasis despite estrogen deficiency.

LDL receptor and Pcsk9 transcripts are decreased in liver of ovariectomized rats: effects of exercise training.

The aim of this study was to determine the effects of ovariectomy in rats on hepatic gene expression of key molecules involved in cholesterol metabolism and to verify if exercise training may play a role in preventing hypercholesterolemia in Ovx rats. Sprague-Dawley rats were ovariectomized (Ovx) or sham-operated (Sham) and were either trained (Tr) on treadmill or kept sedentary (Sed) for 8 weeks. Rats were divided into 5 groups: Sham-Sed, Sham-Tr, Ovx-Sed, Ovx-Tr and Ovx with 17ß-estradiol supplementation (Ovx-E2). Ovx animals had significantly (p<0.05) higher body weight, adiposity, liver total cholesterol (TC) content and hypercholesterolemia compared to Sham rats. In contrast, gene expression of hepatic low-density lipoprotein receptor (LDL-R), LDL receptor-related protein (Lrp1), proprotein convertase subtilisin/kexin type 9 (Pcsk9), sterol regulatory element binding protein 2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-r) were reduced (p<0.05) in Ovx compared to Sham rats. Hepatic mRNA levels of scavenger receptor class B member 1 (SR-B1) and ATP-binding cassette subfamily A member 1 (ABCA1) (hepatic and intestinal) were higher (p<0.05) in Ovx compared to Sham rats. All of these molecular changes were corrected in Ovx-E2. Exercise training, significantly reversed the effect of Ovx on adiposity, plasma triglyceride, TC and mRNA expression of SREBP-2 but had no effect on all other hepatic genes expression. These data indicate that hypercholesterolemia in Ovx rats is associated with a reduction of hepatic LDL-R and Lrp1 gene expression.

Ovariectomy stimulates hepatic fat and cholesterol accumulation in high-fat diet-fed rats.

This study was designed to determine how estrogens withdrawal during a high-fat (HF) diet regimen affects liver triacylglycerol (TAG) and cholesterol accumulation. Female Sprague-Dawley rats were submitted to a HF (42% energy as fat) or a standard (SD) diet for 6 weeks before being either ovariectomized (Ovx) or sham operated (Sham). Thereafter, Ovx and Sham rats were kept on the same diet for another 6 weeks leading to euthanasia. Liver TAG content was increased (p<0.01) in Ovx rats but not by the HF diet alone. However, the combination of HF diet and Ovx resulted in a greater liver TAG accumulation (p<0.06) than that observed in Ovx-SD/SD. Measurement of molecular markers of liver lipid metabolism revealed an increase in transcripts of markers of lipid oxidation (CPT-1 and PGC1; p<0.05) in rats fed the HF diet. This increase was, however, substantially less if HF fed rats were Ovx. Liver total cholesterol levels were increased (p<0.01) only in the Ovx-HF/HF rats while plasma cholesterol levels were increased in Ovx-SD/SD and in SHAM-HF/HF and Ovx-HF/HF rats. Transcripts of molecular markers of cholesterol metabolism suggest that biliary acids synthesis (CYP7a-1) was reduced in Ovx-SD/SD and Sham-HF/HF rats and even more so in Ovx-HF/HF rats. It is concluded that the effects of a HF diet on liver TAG accumulation are especially observed in Ovx rats possibly through a reduction in hepatic lipid oxidation. The combination of Ovx and HF diet also acts synergistically to favor liver cholesterol accumulation.

Evaluation of the in vivo activity of different concentrations of Clerodendrum umbellatum Poir against Schistosoma mansoni infection in mice.

Clerodendrum umbellatum Poir (Verbenaceae) is traditionally used in Cameroon for the treatment of many diseases including intestinal helminthiasis. This study was undertaken to assess the in vivo antischistosomal activity of its leaves aqueous extract on a Schistosoma mansoni mice model and to determine the most effective dose of this extract. Mice showing a patent infection of S. mansoni were daily treated with C. umbellatum leaves aqueous extract at the doses of 40, 80 or 160 mg/kg body weight for 14 days. Seven days after administration of the extract, schistosomicidal activity was evaluated on the liver and spleen weights, faecal eggs releasing, liver egg count and worm burden. Treatment using C. umbellatum leaves aqueous extract resulted in an important reduction in faecal egg output by 75.49% and 85.14% for 80 mg/kg and 160 mg/kg of the extract respectively. These reduction rates did not differ significantly from the 100% obtained in the group of infected mice treated with 100 mg/kg of praziquantel. C. umbellatum leaves aqueous extract was lethal to S. mansoni worm. A 100% reduction rate was recorded in the group of infected mice treated with 160 mg/kg of the extract, as well as in praziquantel-treated mice. An amelioration of the hepatosplenomegaly was noticed in both the extract-treated mice and the praziquantel-treated mice. From these results, we can conclude that C. umbellatum leaves aqueous extract demonstrated schistosomicidal properties in S. mansoni model at doses of at least 80 mg/kg body weight.