Connexin Hemichannel Block Using Orally Delivered Tonabersat Improves Outcomes in Animal Models of Retinal Disease.

Increased Connexin43 hemichannel opening is associated with inflammasome pathway activation and inflammation in a range of pathologies including ocular disorders, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). In this study, the effect on retinal function and morphology of clinically safe doses of orally delivered tonabersat, a small molecule connexin hemichannel blocker, was investigated in the light-damaged retina animal model of dry AMD and in a spontaneous rat model of DR. Clinical parameters (fundus imaging, optical coherence tomography (OCT), and electroretinography) and inflammatory markers (immunohistochemistry for Iba-1 microglial marker, astrocyte marker glial fibrillary acidic protein, and Connexin43 protein expression) were assessed. Tonabersat treatment reduced inflammation in the retina in parallel with preservation of retinal photoreceptor function when assessed up to 3 months post light damage in the dry AMD model. In the DR model, clinical signs, including the presence of aneurysms confirmed using Evans blue dye perfusion, were reduced after daily tonabersat treatment for 2 weeks. Inflammation was also reduced and retinal electrical function restored. Tonabersat regulates assembly of the inflammasome (NLRP3) through Connexin43 hemichannel block, with the potential to reduce inflammation, restore vascular integrity and improve anatomical along with some functional outcomes in retinal disease.

No Differences in Energy Cost of a Predetermined Exercise among Young Overweight/Obese and Undernourished Individuals.

BACKGROUND: Physical activity is an integral part of one's daily life. Obese (Ob) and undernourished (UN) persons are known to underperform physically as compared to normal weight (N) individuals. In this study, we have measured the energy spent to perform a prefixed exercise on treadmill walking and basal heart rate and blood pressure. Body mass index (BMI) and body fat of participating individuals were assessed. Fasting blood sugar and lipid profile were also evaluated. MATERIALS AND METHODS: Eighty-three young individuals (male: 41; female: 42) of medical faculty, Universiti Sultan Zainal Abidin, who volunteered for the study, were recruited. The mean age of the individuals was 19.8 ± 0 years (P < 1.08). The individuals were grouped as N, UN/underweight, and overweight (Ow)/Ob based on BMI. RESULTS: The results of the study revealed that there were no differences in the energy spent on performing the predetermined treadmill walking of 20 min duration among the three groups (a mean of 78 and 70 calories in all male and female subgroups, respectively). The distance covered by the males was 1.6 km while the females covered 1.4 km on treadmill walking in 20 min time. Basal blood pressure and heart rate and fasting blood sugar did not reveal any significant difference among the groups. However, total cholesterol and triglyceride levels were marginally higher in the Ow/Ob groups of male and female individuals as compared to other groups. CONCLUSION: Since the study individuals were very young and competitive by nature and possibly had no major metabolic disturbances, the differences in physical activity performances were not obvious. Possibly, such differences would become apparent only at later stages of life as age advances or when the intensity and duration of exercise are set at higher levels.

Anthropometry and body composition status during Ramadan among higher institution learning centre staffs with different body weight status.

This study was done to observe the anthropometry and body composition changes before, during, and after the holy month of Ramadan. This study was carried out on 46 staff from one of the local universities, which comprised of 14 males and 32 females ranging in age from 25 to 40 years old. There were four sessions done to complete this study, namely, a week before Ramadan (T1), 1st week of Ramadan (T2), 3rd week of Ramadan (T3), and a month after Ramadan (T4). All subjects were assessed according to weight, body circumference, and body composition status. It was found that subjects with different weight status showed a significant reduction in weight (P < 0.01) but no significant reduction in body fat percentage (P < 0.05). The findings suggest that weight reduction does not promise a reduction in body fat. Changes in neck circumference were only found in normal subjects. Hence, it can be said that overweight and obese subjects showed no changes in anthropometry status during Ramadan. No changes in body composition were reported in all three weight groups except for trunk body fat. In conclusion, normal subjects showed significant changes in various anthropometry parameters, but overweight and obese subjects showed no obvious difference.