Paroxetine suppresses recombinant human P2X7 responses

P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part via modulating P2X7 activity and reducing inflammatory responses. In this study, we determined whether common psychoactive drugs could affect recombinant and native human P2X7 responses in vitro. Common antidepressants demonstrated opposing effects on human P2X7-mediated responses; paroxetine inhibited while fluoxetine and clomipramine mildly potentiated ATP-induced dye uptake in HEK-293 cells stably expressing recombinant human P2X7. Paroxetine inhibited dye uptake mediated by human P2X7 in a concentration-dependent manner with an IC50 of 24 μM and significantly reduces ATP-induced inward currents. We confirmed that trifluoperazine hydrochloride suppressed human P2X7 responses (IC50 of 6.4 μM). Both paroxetine and trifluoperazine did not inhibit rodent P2X7 responses, and mutation of a known residue (F 95L) did not alter the effect of either drug, suggesting neither drug binds at this site. Finally, we demonstrate that P2X7-induced IL-1β secretion from lipopolysaccharide (LPS)-primed human CD14+ monocytes was suppressed with trifluoperazine and paroxetine

Health-related physical fitness and weight status in Hong Kong adolescents

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the relation between health-related physical fitness and weight status in Hong Kong adolescents.</p> <p>Methods</p> <p>3,204 students aged 12-18 years participated in the Hong Kong Student Obesity Surveillance (HKSOS) project in 2006-2007. Anthropometric measures (height, weight) and health-related fitness (push-up, sit-up, sit-and-reach, 9-minute run) were assessed. Body mass index (BMI) was computed to classify participants into normal weight, underweight (Grade I, II/III), overweight, and obese groups. The associations of health-related physical fitness with BMI and weight status were examined by partial correlation coefficients and analysis of covariance, respectively.</p> <p>Results</p> <p>More boys than girls were overweight or obese (18.0% vs 8.7%), but more girls than boys were underweight (22.3% vs 16.7%). Boys performed significantly (P < 0.001) better in sit-up (38.8 vs 31.6 times/min) and 9-minute run (1632.1 vs 1353.2 m), but poorer in sit-and-reach (27.4 vs 32.2 cm) than girls. All four physical fitness tests were significantly positively correlated with each other in both sexes, and BMI was only weakly correlated with sit up and sit-and-reach tests in boys. Decreasing performance (P for trend < 0.05) was observed from normal weight to overweight and obese for push-up, sit-up, and 9-minute run in both sexes. From normal weight to Grade I and Grade II/III underweight, decreasing performance (P for trend < 0.05) for sit-up and sit-and-reach in both sexes and for push-up in boys was observed.</p> <p>Conclusions</p> <p>The relations between BMI and health-related physical fitness in adolescents were non-linear. Overweight/obese and underweight adolescents had poorer performance in push-up and sit-up tests than normal weight adolescents. Different aspects of health-related physical fitness may serve as immediate indicators of potential health risks for underweight and overweight adolescents.</p

The pursuit of thinness : an outcome study of anorexia nervosa

INTRODUCTION: Anorexia nervosa (AN) is a growing problem among young female Singaporeans. We studied the demographics and follow-up data of AN patients referred to dietitians for nutritional intervention. METHODS: A retrospective nutritional notes review was done on 94 patients seen from 1992 to 2004. All patients were given nutritional intervention, which included individualised counselling for weight gain, personalised diet plan, correction of poor dietary intake and correction of perception towards healthy eating. We collected data on body mass index (BMI), patient demographics and outcome. RESULTS: 96 percent of the patients were female and 86.2 percent were Chinese. The median BMI at initial consultation was 14.7 kilogramme per square metre (range, 8.6-18.8 kilogramme per square metre). 76 percent were between 13 and 20 years old. 83 percent of the patients came back for follow-up appointments with the dietitians in addition to consultation with the psychiatrist. Overall, there was significant improvement in weight and BMI from an average 37 kg to 41 kg and 14.7 kilogramme per square metre to 16.4 kilogramme per square metre, respectively, between the fi rst and fi nal consultations (p-value is less than 0.001). The average duration of followup was about eight months. Among the patients on follow-up, 68 percent showed improvement with an average weight gain of 6 kg. Patients that improved had more outpatient follow-up sessions with the dietitians (4.2 consultations versus 1.6 consultations; p-value is less than 0.05), lower BMI at presentation (14.2 kilogramme per square metre versus 15.7 kilogramme per square metre; p-value is less than 0.01) and shorter duration of disease at presentation (one year versus three years; p-value is less than 0.05) compared with those who did not improve. Seven patients with the disease for more than two years did not show improvement with follow-up. CONCLUSION: We gained valuable understanding of the AN patients referred to our tertiary hospital for treatment, two-thirds of whom improved with adequate follow-up treatment. Patients that had suffered AN longer before seeking help appeared more resistant to improvement