Zinc and hypoxic preconditioning: a strategy to enhance the functionality and therapeutic potential of bone marrow-derived mesenchymal stem cells.

The therapeutic use of bone marrow mesenchymal stem cells (BM-MSCs) requires a large number of cells (1-100 × 106 cells/kg of body weight). Extensive in vitro growth is limited due to the aging of cultured BM-MSCs which leads to abnormal morphology and senescence. Hypoxia increases BM-MSC proliferation, but the question of whether hypoxia preconditioning is safe for clinical application of BM-MSCs remains to be answered. Zinc is essential for cell proliferation and differentiation, especially for the regulation of DNA synthesis and mitosis. It is a structural constituent of numerous proteins on a molecular level, including transcription factors and enzymes of cellular signaling machinery. All the tissues, fluids, and organs of the human body contain zinc. More than 95% of zinc is intracellular, of which 44% is involved in the transcription of DNA. We investigated the effects of ZnCl2 on proliferation, morphology, migration, population doubling time (PDT), and gene expression of BM-MSCs under hypoxic (1% O2) and normoxic (21% O2) environments. BM-MSCs were preconditioned with optimized concentrations of ZnCl2 under normoxic and hypoxic environments and further examined for morphology by the phase-contrast inverted microscope, cell proliferation by MTT assay, PDT, cell migration ability, and gene expression analysis. Zinc significantly enhanced the proliferation of BM-MSCs, and it decreases PDT under hypoxic and normoxic environments as compared to control cells. Migration of BM-MSCs toward the site of injury increased and expression of HIF1-α significantly decreased under hypoxic conditions as compared to non-treated hypoxic cells and control. At late passages (P9), the morphology of normoxic BM-MSCs was transformed into large, wide, and flat cells, and they became polygonal and lost their communication with other cells. Conversely, zinc-preconditioned BM-MSCs retained their spindle-shaped, fibroblast-like morphology at P9. The expression of proliferative genes was found significantly upregulated, while downregulation of genes OCT4 and CCNA2 was observed in zinc-treated BM-MSCs under both normoxic and hypoxic conditions. ZnCl2 treatment can be used for extensive expansion of BM-MSCs in aged populations to obtain a large number of cells required for systemic administration to produce therapeutic efficacy.

Effect of local probiotic (Lactobacillus reuteri) vs systemic antibiotic therapy as an adjunct to non-surgical periodontal treatment in chronic periodontitis.

AIM: The aim of the present study was to assess and compare the clinical efficacy of local probiotic Lactobacillus reuteri (L. reuteri) and systemic antibiotics as adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis (CP). METHODS: Thirty systemically-healthy participants (15 probiotic and 15 antibiotic), clinically diagnosed with CP, were enrolled. All patients underwent SRP. Adjunctive probiotics were administered twice daily for 3 months, whereas a combination of amoxicillin and metronidazole were given three times daily for 7 days. RESULTS: Intragroup analysis showed statistically-significant improvement in all clinical parameters: plaque index, bleeding on probing, periodontal pocket depth, and clinical attachment level gain at each follow-up visit. However, intergroup comparison of clinical periodontal parameters did not show statistical significance. CONCLUSION: The adjunctive use of L. reuteri and systemic antibiotics along with SRP showed similar improvement in all clinical periodontal parameters. This indicates that both adjunctive therapeutic agents showed similar efficacy in resolving inflammation and improving periodontal outcomes.

Effects of variation in umbilical artery resistive index on placental morphology and birth weight in pregnancy induced hypertension.

BACKGROUND: Pregnancy induced hypertension results from defective trophoblast invasion and increased umbilical artery resistance which in turn results in decreased blood supply to the placenta and hence to the foetus. This arterial resistance varies in different cases of PIH thus causing variable effects on placenta and foetus. The objective of this study was to study the morpho-metric changes in placenta and alterations in birth weight with differences in umbilical artery resistive index in hypertensive pregnancies. METHODS: Ninety pregnant women with pregnancy induced hypertension were selected with gestational age greater than 35 weeks. Doppler ultrasound examinations were carried out to record umbilical artery resistive index (UARI). 2 groups were made on the basis of median values of UARI. Plain ultrasound examination was then carried out to record presentation, site of placentation, grade of maturity, insertion of the cord, cord thickness, placental thickness, vacuolation and amniotic fluid index (AFI). After delivery, foetal birth weight was noted and placentae examined for placental weight, infarcts, number of cotyledons, umbilical cord insertion, cord thickness and placental thickness were noted. Foetoplacental weight ratio was also calculated. RESULTS: Significantly higher UARI was seen in the high-resistance group. Significantly lower values of placental thickness, AFI, birth weight, placental weight and placental thickness, whereas greater number of grade-III maturity, infarcts and marginal cord insertion were noted in the high-resistance group. CONCLUSION: Increased UARI leads to a spectrum of changes in the placenta and also decreased birth weight. Marginal cord insertion causes greater risk of increased UARI.