Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets

We report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor alpha-matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with na?ve, allogeneic T cells now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c(+)/CD8a(-) DCs but not to the same extent with CD11c(+)/CD8a(+) DCs. Following coculture with T cells, only BMDCs and CD11c(+)/CD8a(-) DCs and not CD11c(+)/CD8a(+) DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only na?ve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-beta-1 levels with a concomitant reduction in IL-12p40 and interferon-gamma levels from BMDCs and CD11c(+)/CD8a(-) DCs and to a lesser extent, from CD11c(+)/CD8a(+) DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c(+)/CD8a(+) DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.     

The role of IL-1β during human immunodeficiency virus type 1 infection

Interleukin (IL)-1β is a key innate cytokine that is essential for immune activation and promoting the inflammatory process. However, abnormal elevation in IL-1β levels has been associated with unwanted clinical outcomes. IL-1β is the most extensively studied cytokine among the IL-1 family of cytokines and its role in pathology is well established. During the course of human immunodeficiency virus type 1 (HIV-1) infection, the level of this proinflammatory cytokine is increased in different anatomical compartments, particularly in lymphatic tissues, and this elevation is associated with disease progression. The aim of this review is to address the pathological roles play by IL-1β in the light of enhancing HIV-1 replication, driving immune cell depletion, and chronic immune activation. The role of IL-1β in HIV-1 transmission (sexually or vertically ‘from mother-to-child’) will also be discussed. Additionally, the impact of the available antiretroviral therapy regimens on the levels of IL-1β in HIV-1 treated patients is also discussed. Finally, we will provide a glance on how IL-1β could be targeted as a therapeutic strategy.     

Formulation of a single-component kit for the preparation of technetium-99m labelled ethyl cysteinate dimer: biological and clinical evaluation

Ethyl cysteinate dimer (ECD) labelled with reduced technetium-99m has recently been proposed as a promising radiopharmaceutical for brain perfusion imaging. In the present study a single-component kit formulation has been developed, thus simplifying the radiolabelling procedure. A method of analysis by electrophoresis has also been developed, permitting identification of radiochemical impurities in the preparation. ^99mTc-ECD prepared by the single-component kit was further evaluated in primates and humans. The results demonstrated that the complex is stable in vivo, rapidly extracted and retained in the brain tissue for a sufficient time for single-photon emission tomography studies. Therefore the present single-component kit formulation can be proposed as a reliable instant freeze-dried kit for routine preparation of 99-Tc-ECD required for scintigraphic assessment of regional cerebral blood flow.     

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.     

Diagnosis of the multiple effect of selenium nanoparticles decorated by Asteriscus graveolens components in inhibiting HepG2 cell proliferation

Using plant bio-components for Designing green metal nanoparticles was considered as one of the most important methods in nanomedical application field due to their eco-friendly, cheap source, easily obtainable and having a high detection result. In this report, we fabricated eco-friendly engineering and cost-effective technique for green selenium nanoparticles from 0.01 M H₂SeO₃ solution using Asteriscus graveolens leaves extract as reducing and a capping agent at ambient temperature. Spectral techniques have been used to identify the formatted Selenium nanoparticles such as UV–Vis, pH, XPs, FT-IR, XRD, LDS, Z.P, EDS, TEM and AFM spectroscopy, which showed a size of 20 nm with spherical shape. Herein, the multi-effect of decorated Se-NPs surface have been evaluated, firstly on the hemolysis that showed completely hemocompatibility. Cytotoxicity assay showed that Se-NPs have a high selective effect on the HepG2 apoptosis and which proved by phase-contrast microscopy. Furthermore, the effect of nanoparticles on the action of the mechanism internal revealed that Se-NPs significantly and rapidly increased the level of reactive oxygen species and lipid peroxidation, while caused decreased the potential of mitochondrial membrane and glutathione level, which they together responsible on regulating the HepG2 cells fate. Furthermore, Flow cytometry analysis gave high values about S and G2/M phases of cell cycle resulting from Se-NPs effectiveness. In the end, with all the recorded information that has been measured in this study, this report provides a suitable and effective pathway for the green fabrication of Se-NPs decorated by biomolecules having high anticancer inhibited.     

Coverage of private sector community midwife services in rural Punjab,Pakistan: development and demand

Background

In 2007, the Government of Pakistan introduced a new cadre of community midwives (CMWs) to address low skilled birth attendance rates in rural areas; this workforce is located in the private-sector. There are concerns about the effectiveness of the programme for increasing skilled birth attendance as previous experience from private-sector programmes has been sub-optimal. Indonesia first promoted private sector midwifery care, but the initiative failed to provide universal coverage and reduce maternal mortality rates.

Methods

A clustered, stratified survey was conducted in the districts of Jhelum and Layyah, Punjab. A total of 1,457 women who gave birth in the 2 years prior to the survey were interviewed. χ² analyses were performed to assess variation in coverage of maternal health services between the two districts. Logistic regression models were developed to explore whether differentials in coverage between the two districts could be explained by differential levels of development and demand for skilled birth attendance. Mean cost of childbirth care by type of provider was also calculated.

Results

Overall, 7.9% of women surveyed reported a CMW-attended birth. Women in Jhelum were six times more likely to report a CMW-attended birth than women in Layyah. The mean cost of a CMW-attended birth compared favourably with a dai-attended birth. The CMWs were, however, having difficulty garnering community trust. The majority of women, when asked why they had not sought care from their neighbourhood CMW, cited a lack of trust in CMWs’ competency and that they wanted a different provider.

Conclusions

The CMWs have yet to emerge as a significant maternity care provider in rural Punjab. Levels of overall community development determined uptake and hence coverage of CMW care. The CMWs were able to insert themselves into the maternal health marketplace in Jhelum because of an existing demand. A lower demand in Layyah meant there was less ‘space’ for the CMWs to enter the market. To ensure universal coverage, there is a need to revisit the strategy of introducing a new midwifery workforce in the private sector in contexts of low demand and marketing the benefits of skilled birth attendance.

     

Coverage of private sector community midwife services in rural Punjab,Pakistan: development and demand

Background

In 2007, the Government of Pakistan introduced a new cadre of community midwives (CMWs) to address low skilled birth attendance rates in rural areas; this workforce is located in the private-sector. There are concerns about the effectiveness of the programme for increasing skilled birth attendance as previous experience from private-sector programmes has been sub-optimal. Indonesia first promoted private sector midwifery care, but the initiative failed to provide universal coverage and reduce maternal mortality rates.

Methods

A clustered, stratified survey was conducted in the districts of Jhelum and Layyah, Punjab. A total of 1,457 women who gave birth in the 2 years prior to the survey were interviewed. χ² analyses were performed to assess variation in coverage of maternal health services between the two districts. Logistic regression models were developed to explore whether differentials in coverage between the two districts could be explained by differential levels of development and demand for skilled birth attendance. Mean cost of childbirth care by type of provider was also calculated.

Results

Overall, 7.9% of women surveyed reported a CMW-attended birth. Women in Jhelum were six times more likely to report a CMW-attended birth than women in Layyah. The mean cost of a CMW-attended birth compared favourably with a dai-attended birth. The CMWs were, however, having difficulty garnering community trust. The majority of women, when asked why they had not sought care from their neighbourhood CMW, cited a lack of trust in CMWs’ competency and that they wanted a different provider.

Conclusions

The CMWs have yet to emerge as a significant maternity care provider in rural Punjab. Levels of overall community development determined uptake and hence coverage of CMW care. The CMWs were able to insert themselves into the maternal health marketplace in Jhelum because of an existing demand. A lower demand in Layyah meant there was less ‘space’ for the CMWs to enter the market. To ensure universal coverage, there is a need to revisit the strategy of introducing a new midwifery workforce in the private sector in contexts of low demand and marketing the benefits of skilled birth attendance.