206 research outputs found
Recommended from our members
Identifying the effect of public health program on child immunisation in rural Bangladesh
Recommended from our members
Growth, governance and corruption in Bangladesh: a re-assessment
This paper revisits Bangladesh’s ‘double paradox’ – sustained macroeconomic growth despite the poor state of governance and a high level of corruption – by critically reviewing trends in governance and corruption indicators during 1990–2017 vis-à -vis other South Asian countries. In addition, we draw upon data from a purposefully designed survey of manufacturing firms to assess the state of economic governance in the export-oriented ready-made garments (RMG) sector, the country’s main source of foreign exchange and driver of economic growth. Consistent with the country’s poor ranking in a host of indicators of investment climate and corruption perception, in-depth interviews of RMG factory owners confirm the high cost of doing business in various forms. We also find no evidence of growth-mediated improvements in indicators of governance. On the contrary, our review of print media reports suggests a growing governance deficit in the country’s financial sector. We conclude by discussing the implications of our findings for the country’s future growth as well as performance of the RMG sector
Development and release kinetics of a novel formulation of nimesulide prepared by microencapsulation using synthetic polymers
The synthetic polymers and their combinations were employed to retard the release of nimesulide from microcapsules. Microcapsules were prepared in different ratios of Eudragit RL 100 and hydroxy propyl methyl cellulose (HPMC) separately and in combination. All formulations of microcapsules were compressed to tablets. Dissolution of microcapsules and their tablets was performed by USP-apparatus-II in 900 mL borate buffer of pH 8.4 at 37.0 ± 0.5 ºC, at 50 rpm. In vitro kinetics was determined by various models including Zero order, First Order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell. Eudragit showed higher retarding effect over extended period of time on release of drug than HPMC alone or its combination with Eudragit.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Development of in vitro-in vivo correlation for nimesulide loaded ethylcellulose microparticles
A predictive in vitro-invivo correlation (IVIVC) can empower in vitro dissolution as a surrogate for in vivo bioavailability / bioequivalence. IVIVCs can decrease regulatory burden by decreasing the number of biostudies required in support of a drug product. The present study concerns the establishment of in vitro-in vivo correlation for three different sustained release nimesulide loaded ethylcellulose microparticulate formulations (M1, M2 and M3) and conventional tablet (100 mg Nimaran®-Novartis, Pakistan). In vitro dissolution study was conducted in phosphate buffer pH 6.8 stirred at 50 rpm and 37 ± 0.5ºC. A validated HPLC method was adopted to conduct bioavailability studies in young healthy human volunteers. Ultimately IVIVC of prepared microparticles and conventional tablet was established using Wagner-Nelson method. M1 and M2 formulations and Nimaran® exhibited good linear IVIVC (R2 = 0.9220, 0.9124, 0.8728, respectively) as compared to M3 (R2 = 0.9449). The results substantiate the success of this mathematical simulation study encourage researchers to conduct biowaiver studies for other BCS class II drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire
Apilimod Inhibits the Production of IL-12 and IL-23 and Reduces Dendritic Cell Infiltration in Psoriasis
Psoriasis is characterized by hyperplasia of the epidermis and infiltration of leukocytes into both the dermis and epidermis. IL-23, a key cytokine that induces TH17 cells, has been found to play a critical role in the pathogenesis of psoriasis. Apilimod is a small-molecule compound that selectively suppresses synthesis of IL-12 and IL-23. An open-label clinical study of oral administration of apilimod was conducted in patients with psoriasis. Substantial improvements in histology and clinical measurements were observed in patients receiving 70mg QD. The expression of IL-23p19 and IL-12/IL-23p40 in skin lesions was significantly reduced in this dose group, with a simultaneous increase in IL-10 observed. A decrease in the levels of TH1 and TH17 cytokines/chemokines in skin lesions followed these p19 and p40 changes. In parallel, a reduction in skin-infiltrating CD11c+ dendritic cells and CD3+ T cells was seen, with a greater decrease in the CD11c+ population. This was accompanied by increases in T and B cells, and decreases in neutrophils and eosinophils in the periphery. This study demonstrates the immunomodulatory activity of apilimod and provides clinical evidence supporting the inhibition of IL-12/IL-23 synthesis for the treatment of TH1- and TH17-mediated inflammatory diseases
IL-23 plasma level is strongly associated with CMV status and reactivation of CMV in renal transplant recipients
Rapamycin Combined with Anti-CD45RB mAb and IL-10 or with G-CSF Induces Tolerance in a Stringent Mouse Model of Islet Transplantation
Background: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg) cells. Among the various Treg-cell types, Foxp3 +Treg and IL-10-producing T regulatory type 1 (Tr1) cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model). We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. Methodology/Principal Findings: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3 +Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4 +IL-10 +IL-4 - T (i.e., Tr1) cells localized in the spleen. In long-term tolerant mice, only CD4 +IL-10 +IL-4 - T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF); this drug combination promoted tolerance associated with CD4 +IL-10 +IL-4 - T cells. Conclusions/Significance: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces tolerance and such treatment could be readily translatable into the clinic. © 2011 Gagliani et al
Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover
Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL
The SDGs and the empowerment of Bangladeshi women
This chapter describes Bangladesh’s successes with advancing gender equality in the period of the Millennium Development Goals (MDGs), locating their origins in elite commitment to including women in the development process, and in the partnerships and aid that built the state and NGO capacity to reach them. The chapter reflects on the lessons of Bangladesh’s innovative and unexpected advances in the light of the new challenges posed by the Sustainable Development Goals (SDGs), notably those of early marriage and the achievement of decent work. The chapter asks whether contemporary conditions suggest that the elite commitment and state capacity that drove progress on the MDGs are up to meeting the more contentious and complex goals of the SDGs
A Helminth Immunomodulator Exploits Host Signaling Events to Regulate Cytokine Production in Macrophages
Parasitic worms alter their host's immune system to diminish the inflammatory responses directed against them, using very efficient immunomodulating molecules. We have previously shown that the helminth immunomodulator cystatin (AvCystatin) profoundly reduces the progression of inflammatory diseases via modulation of macrophages. Here we elucidate the signaling events in macrophages triggered by AvCystatin. Labeled AvCystatin was predominantly taken up by macrophages and subsequently induced the phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2 and p38. IL-10 expression induced by AvCystatin in macrophages was tyrosine kinase sensitive and dependent on activation of both MAP kinases, in clear contrast to expression of IL-12/23p40. In addition, phosphorylation of the transcription factors CREB and STAT3 was induced by AvCystatin and regulated by phospho-ERK. Chemical inhibition of phosphoinositide 3-kinase (PI3K) reduced AvCystatin-induced cytokine release; however, AKT, the downstream target of PI3K, was not activated following AvCystatin exposure. To characterize signaling elements involved in alteration of the macrophage phenotype we applied mathematical modeling. Experimental testing of the in silico generated hypotheses identified dual specificity phosphatase (DUSP) 1 and 2, as regulators in AvCystatin triggered macrophages in vitro and in vivo. In particular, DUSP1 was subsequently found to be responsible for regulation of ERK- and p38-phosphorylation and controlled the IL-10 expression in macrophages by AvCystatin. Thus, we show that AvCystatin exploits activation and deactivation pathways of MAP kinases to induce regulatory macrophages. This study provides insights into molecular mechanisms of macrophage manipulation by parasites and highlights the utility of mathematical modeling for the elucidation of regulatory circuits of immune cells
- …