Skeletal Muscle PGC-1α Is Required for Maintaining an Acute LPS-Induced TNFα Response

Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation. Quadriceps muscles were removed from 10-week old whole body PGC-1α knockout (KO), muscle specific PGC-1α KO (MKO) and muscle-specific PGC-1α overexpression mice (TG), 2 hours after an intraperitoneal injection of either 0.8 µg LPS/g body weight or saline. Basal TNFα mRNA content was lower in skeletal muscle of whole body PGC-1α KO mice and in accordance TG mice showed increased TNFα mRNA and protein level relative to WT, indicating a possible PGC-1α mediated regulation of TNFα. Basal p65 phosphorylation was increased in TG mice possibly explaining the elevated TNFα expression in these mice. Systemically, TG mice had reduced basal plasma TNFα levels compared with WT suggesting a protective effect against systemic low-grade inflammation in these animals. While TG mice reached similar TNFα levels as WT and showed more marked induction in plasma TNFα than WT after LPS injection, MKO PGC-1α mice had a reduced plasma TNFα and skeletal muscle TNFα mRNA response to LPS. In conclusion, the present findings suggest that PGC-1α enhances basal TNFα expression in skeletal muscle and indicate that PGC-1α does not exert anti-inflammatory effects during acute inflammation. Lack of skeletal muscle PGC-1α seems however to impair the acute TNFα response, which may reflect a phenotype more susceptible to infections as also observed in type 2 diabetes patients

Medical genetics in developing countries in the Asia-Pacific region: challenges and opportunities

Advances in genetic and genomic technology changed health-care services rapidly in low and middle income countries (LMICs) in the Asia-Pacific region. While genetic services were initially focused on population-based disease prevention strategies, they have evolved into clinic-based and therapeutics-oriented service. Many LMICs struggled with these noncommunicable diseases and were unprepared for the needs of a clinical genetic service. The emergence of a middle class population, the lack of regulatory oversight, and weak capacity-building in medical genetics expertise and genetic counseling services led to a range of genetic services of variable quality with minimal ethical oversight. Some of the current shortcomings faced include the lack of awareness of cultural values in genetic health care, the variable stages of socioeconomic development and educational background that led to increased demand and abuse of genetics, the role of women in society and the crisis of gender selection, the lack of preventive and care services for genetic and birth defects, the issues of gene ethics in medicine, and the lack of understanding of some religious controversies. These challenges provide opportunities for both developing and developed nations to work together to reduce the inequalities and to ensure a caring, inclusive, ethical, and cost-effective genetic service in the region

Social adaptability and substance abuse: Predictors of depression among hemodialysis patients?

<p>Abstract</p> <p>Background</p> <p>Several aspects linked to social are involved in the onset of depressive feelings. We aimed to find out if social adaptability and substance abuse predict depression among end-stage renal disease (ESRD) patients undergoing hemodialysis (HD).</p> <p>Methods</p> <p>We included 145 ESRD patients undergoing HD. Social adaptability was estimated by the Social Adaptability Index (SAI). Substance abuse was defined according to SAI. We screened for depression by applying the 20-item version of the Center for Epidemiologic Studies Depression Scale. A score ≥ 24 classified the patients as depressed. Comparisons between depressed and non-depressed patients were carried out and logistic regression was performed to test gender, age, total SAI, SAI without the substance abuse item, only the substance abuse score and substance abuse as a categorical variable (yes/no) as predictors of depression.</p> <p>Results</p> <p>There were 36 (24.8%) depressed patients. There were no differences regarding demographic and laboratory data between the depressed and non-depressed patients. Mean SAI among depressed and non-depressed patients was, respectively, 6.1 ± 1.6 vs. 6.2 ± 1.9 (p=0.901). The percentage of patients with or without substance abuse among depressed patients was, respectively, 13.8% vs. 13.9% (p=1.000). Gender, age, total SAI, SAI without the substance abuse item, only the substance abuse score and substance abuse as a categorical variable did not predict depression.</p> <p>Conclusions</p> <p>Social adaptability and substance abuse did not predict depression in HD patients. We propose that aspects related to socioeconomic status not comprised in SAI items should be ruled out as predictors of depression.</p