Isolation and structures of novel fungal metabolites as chemokine receptor (CCR2) antagonists

The chemokine receptor, CCR2, is predominantly expressed on monocytes/macrophages, and on a subset of memory T cells. It binds to several CC type chemokines of the monocyte chemoattractant protein (MCP) family of which MCP-1 exhibits the highest affinity. CCR2/MCP-1 expression/association in monocyte/macrophage/T cells has been associated with inflammatory processes such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. Neutralization of CCR2 with either a peptide or receptor antagonist results in the prevention of joint swelling in rodent models of arthritis. In this paper, bioassay-guided discovery of CCR2 receptor antagonists derived from natural product extracts are reported. These antagonists belong to two main classes exemplified by bisthiodiketopiperazines and cytochalasins. Six compounds, including emestrin, two new emestrin analogs, and chaetomin represent the first group of compounds. These compounds inhibited the binding of MCP-1 to CCR2 (CHO membrane) with IC50 values of 0.8 to 9 microM and exhibited good activity in a whole cell assay using MCP-1 and human monocytes with IC50's ranging from 4-9 microM. Cytochalasins A and B represented the second group and inhibited the binding activity with IC50 values of 5 and 188 microM, respectively. This is the first report of natural product antagonists of the CCR2 receptor.     

Prevalence of externalizing behavior problems in Sri Lankan preschool children: birth,childhood, and sociodemographic risk factors

Purpose  

There is dearth of epidemiological data on externalizing behavior problems among preschool children in many developing countries. The aim of this study was to examine the prevalence and associated birth, childhood, and sociodemographic factors of externalizing behavior problems among a community sample of preschool children in Sri Lanka.     

A local study of childbearing Bangladeshi women in the UK

OBJECTIVE: to examine the circumstances, experiences and needs of a local sample of low-income, childbearing women of Bangladeshi origin in the UK. DESIGN: qualitative interviews using a semi-structured questionnaire to obtain the interviewees' own accounts of the period around the birth of a baby. SETTING: a deprived area in the City of Leeds in the North of England. PARTICIPANTS: nine women of Bangladeshi origin who were pregnant or had a baby under 1 year of age were interviewed as part of a larger study of the needs and experiences of 52 low-income, childbearing women. The nine women were recruited from a neighbourhood project set up to respond to the needs of Sylheti-speaking women with limited English fluency in the area. FINDINGS: the women's constrained material circumstances limit their access to resources, services and good health. This is related to their limited education, qualifications and English fluency. The lack of an adequate income particularly affects families with new babies. However, their relatively positive experiences of maternity care and benefit claim, compared with women with similar characteristics in other studies, may be related to access to advice, support and concrete help offered by the neighbourhood project. IMPLICATIONS FOR PRACTICE: social and health research, policy and practice might address information and support needs of low-income Bangladeshi women around the birth of a baby, and systematically take forward the idea of providing and evaluating integrated services, language support and advocacy between voluntary and state agencies.     

Evaluation of cross‐linked chitosan microparticles for bone regeneration

The objective of this preliminary study was to evaluate the applying of chitosan (CS)‐based microparticles (MPs) in bone regeneration in vivo. The CS MPs were fabricated using our scale‐up method, as previously described. Mesenchymal stem cells (MSC) were harvested from the femora and tibiae of Dark Agouti (DA) rats and seeded on CS MPs. An in vitro MSCs attachment experiment was conducted by trypsinizing the cells attached to the MPs at 5, 10, 20 and 30 h. Fluorescence images of MSCs attached to the MPs were taken at 24 and 48 h, using a LIVE/DEAD cell assay. The MSC/osteoblasts (OB) seeded on MPs were then cultured in vitro using osteogenic media and implanted into partial thickness bone defects in rat femurs. There were two groups of rats, including experimental animals and controls, for the in vivo studies. The experimental group were implanted with MSC‐seeded MPs and observed at 4 and 8 weeks. The control group of rats did not receive any implant material except the stainless steel plate to support the defect. Four rats per group were used for the study. The femurs were extracted at 4 and 8 weeks post‐implantation and bone formation at the defect site was analysed using radiography, microcomputed tomography (µCT) and histology. Among all groups, a significant increase in bone formation was observed in the experimental group at 8 weeks implantation. The results of this study suggested that CS MPs prove to be a successful biomaterial for bone regeneration. Copyright © 2010 John Wiley & Sons, Ltd.