Expression of TNF-α and Related Signaling Molecules in the Peripheral Blood Mononuclear Cells of Rheumatoid Arthritis Patients

We examined the role of tumor necrosis factor (TNF-α) and its related signaling intermediates leading to apoptosis/proliferation in the peripheral blood mononuclear cells (PBMCs) of RA patients. The constitutive expression of mRNA for TNF-α receptors (TNFR-I and TNFR-II) and the adapter molecules, such as the TNF receptor-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), receptor interacting protein (RIP), and TNF receptor-associated factor 2 (TRAF-2) were analyzed by reverse transcriptase-PCR (RT-PCR) in PBMCs from control and RA cases. PBMCs of RA patients showed a significant increase in TNF-α and TNFR-I expression as compared with that from control subjects along with significantly increased constitutive expression of TRADD, RIP, and TRAF-2 mRNA. There was a decrease in expression of FADD in RA patients, but the difference was not significant as compared to controls. These data suggested enhanced signaling by the TNFR-I-TRADD-RIP-TRAF-2 pathway and suppressed signaling by the TNFR-I-TRADD-FADD pathway in PBMCs of RA patients. However, the regulatory mechanisms for TNF-α induced signaling may not be explained only by these pathways

Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya

The importance of medicinal plants in traditional healthcare practices, providing clues to new areas of research and in biodiversity conservation is now well recognized. However, information on the uses for plants for medicine is lacking from many interior areas of Himalaya. Keeping this in view the present study was initiated in a tribal dominated hinterland of western Himalaya. The study aimed to look into the diversity of plant resources that are used by local people for curing various ailments. Questionnaire surveys, participatory observations and field visits were planned to illicit information on the uses of various plants. It was found that 35 plant species are commonly used by local people for curing various diseases. In most of the cases (45%) under ground part of the plant was used. New medicinal uses of Ranunculus hirtellus and Anemone rupicola are reported from this area. Similarly, preparation of "sik" a traditional recipe served as a nutritious diet to pregnant women is also not documented elsewhere. Implication of developmental activities and changing socio-economic conditions on the traditional knowledge are also discussed

Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner

Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2-/-) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy

Can community action improve equity for maternal health and how does it do so? Research findings from Gujarat, India

BACKGROUND: Efforts to work with civil society to strengthen community participation and action for health are particularly important in Gujarat, India, given that the state has resources and capacity, but faces challenges in ensuring that services reach those most in need. To contribute to the knowledge base on accountability and maternal health, this study examines the equity effects of community action for maternal health led by Non-Government Organizations (NGOs) on facility deliveries. It then examines the underlying implementation processes with implications for strengthening accountability of maternity care across three districts of Gujarat, India. Community action for maternal health entailed NGOs a) working with community collectives to raise awareness about maternal health entitlements, b) supporting community monitoring of outreach government services, and c) facilitating dialogue with government providers and authorities with report cards based on community monitoring of maternal health. METHODS: The study combined qualitative data (project documents and 56 stakeholder interviews thematically analyzed) with quantitative data (2395 women's self-reported receipt of information on entitlements and use of services over 3 years of implementation monitored prospectively through household visits). Multivariable logistic regression examined delivery care seeking and equity. RESULTS: In the marginalised districts, women reported substantial increases in receipt of information of entitlements and utilization of antenatal and delivery care. In the marginalized and wealthier districts, a switch from private facilities to public ones was observed for the most vulnerable. Supportive implementation factors included a) alignment among NGO organizational missions, b) participatory development of project tools, c) repeated capacity building and d) government interest in improving utilization and recognition of NGO contributions. Initial challenges included a) confidence and turnover of volunteers, b) complexity of the monitoring tool and c) scepticism from both communities and providers. CONCLUSION: With capacity and trust building, NGOs supporting community based collectives to monitor health services and engage with health providers and local authorities, over time overcame implementation challenges to strengthen public sector services. These accountability efforts resulted in improvements in utilisation of public sector services and a shift away from private care seeking, particularly for the marginalised