Bone markers and bone mineral density associates with periodontitis in females with poly-cystic ovarian syndrome.

INTRODUCTION: Studies suggest an association between poly-cystic ovarian syndrome (PCOS) and chronic periodontitis (CP), both being inflammatory conditions. However, insufficient evidence assesses the impact of this inflammation on bone metabolism and bone turnover markers (BTMs). The present study aimed to determine the association between BTMs, bone mineral density (BMD), and clinical periodontal parameters in PCOS women with CP. MATERIALS AND METHODS: Three groups, each with 40 newly diagnosed (1) PCOS+CP, (2) PCOS alone, (3) CP alone, and fourth group (n = 20) systemically and periodontally healthy females aged 18-30 years were included in the study. Full mouth clinical periodontal parameters, C-terminal telopeptides of type I collagen (CTX), bone alkaline phosphatase (ALP), BMD and 25-hydroxyvitamin D (VD) were recorded for all. RESULTS: Low BMD (0.89 ± 0.11 g/cm2), increased CTX levels (2.76 ± 4.64 ng/ml), decreased bone ALP levels (11.09 ± 6.86 ng/ml), higher VD levels (289.02 ± 168.28 nmol/l) and poor clinical periodontal status were observed in PCOS + CP females. BMD-spine showed weak positive correlation with CTX, bone ALP, VD (r = 0.02, r = 0.07, r = 0.15, respectively) in PCOS + CP group. ANCOVA depicted covariates had no confounding effect. Multiple regression model explained 21.0% for BMD-spine and 12.7% for BMD-femur of total variability signifying association with all measured parameters among all groups. CONCLUSION: Enhanced inflammatory thrust by periodontitis increases CTX levels and decreases bone ALP and BMD levels in women with PCOS. Screening PCOS women for periodontal disease and vice versa may have a direct bearing on overall bone health.

Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses.

Integrin alpha4beta1 mediates leukocyte recruitment, activation, mediator release, and apoptosis inhibition, and it plays a central role in inflammatory pathophysiology. High-affinity, selective inhibitors of alpha4beta1, based on the Leu-Asp-Val (LDV) sequence from the alternatively spliced connecting segment-1 (CS-1) peptide of cellular fibronectin, are described that employ a novel N-terminal peptide "cap" strategy. One inhibitor, BIO-1211, was approximately 10(6)-fold more potent than the starting peptide and exhibited tight-binding properties (koff = 1.4 x 10(-4) s-1, KD = 70 pM), a remarkable finding for a noncovalent, small-molecule inhibitor of a protein receptor. BIO-1211 was also 200-fold selective for the activated form of alpha4beta1, and it stimulated expression of ligand-induced epitopes on the integrin beta1 subunit, a property consistent with occupancy of the receptor's ligand-binding site. Pretreatment of allergic sheep with a 3-mg nebulized dose of BIO-1211 inhibited early and late airway responses following antigen challenge and prevented development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.