Chronic inflammation in polycystic ovary syndrome: A case–control study using multiple markers

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and elevated risk of cardiovascular disease and diabetes. Chronic inflammation has been observed in PCOS in several studies but there is also opposing evidence and a dearth of research in Indians. Objective: To estimate chronic inflammation in PCOS and find its relationship with appropriate anthropometric and biochemical parameters. Materials and Methods: Chronic inflammation was assessed in 30 women with PCOS (Group A) and 30 healthy controls (Group B) with highly sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), and platelet microparticles (PMP). In group A, the relationship of chronic inflammation with insulin resistance, waist hip ratio (WHR) serum testosterone, and serum glutamate pyruvate transaminase (SGPT) were examined. Results: In group A, the hsCRP, TNFα, and PMP were significantly elevated compared to group B. However, IL-6 level was similar between the groups. In group A, PMP showed a significant positive correlation with waist-hip ratio and serum testosterone. IL-6 showed a significant positive correlation with insulin sensitivity and significant negative correlation with insulin resistance and serum glutamate pyruvate transaminase. Conclusion: PCOS is associated with chronic inflammation and PMP correlates positively with central adiposity and biochemical hyperandrogenism in women with PCOS. Key words: Polycystic ovary syndrome, Inflammation, C-reactive protein, Interleukin-6, Tumor necrosis factor, Microparticles

Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(I/II) complexes of thiosemicarbazone: special emphasis on their interactions with DNA

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL¹) and X = Br (HL²)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL³) and 4-(p-fluorophenyl)thiosemicarbazone of salicylaldehyde (H₂L⁴) and their copper(I) {[Cu(HL¹)(PPh₃)₂Br]·CH₃CN (1) and [Cu(HL²)(PPh₃)₂Cl]·DMSO (2)} and copper(II) {[(Cu₂L³₂Cl)₂(μ-Cl)₂]·2H₂O (3) and [Cu(L⁴)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1–4) were tested for their ability to exhibit DNA-binding and -cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 10⁴ to 10⁵ M⁻¹. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal

Unraveling the Intricate Molecular Mechanism Between Apoptosis and Autophagy During Cellular Stress

Apoptosis, autophagy and autophagy dependent cell death are important cellular processes with complex and intersecting protein networks; as such, they have been the subjects of intense investigation. Here, we highlight the crucial factors governing the crosstalk between autophagy and apoptosis to describe the mechanisms controlling cell survival and death. We identified the autophagy gene Ulk1 to induce apoptosis by inhibiting the mitochondrial MnSOD enzyme and accentuating the level of mitochondrial reactive oxygen species (ROS). Likely, we found pre-autophagy initiator ATG14 to be interacting with Ulk1 to trigger lipophagy mediated endoplasmic reticulum (ER) stress that induced mitochondrial stress to stimulate apoptosis. Further, we established that cellular stress like serum starvation facilitates anti-apoptotic cIAP1 accumulation in regulating mitophagy through ubiquitination. Moreover, cIAP1-induced mitophagy led to dysfunctional mitochondria resulting in abrogation of mitochondrial oxygen consumption rate that followed to decline in ATP level representing another crucial link between autophagy and apoptosis. We further defined nature of autophagy during cellular stress and serum starvation triggered autophagy doesn’t follow a linear trend when exposed to a prolonged time period of starvation, rather there exists two distinct peaks primary smaller one that arrives at lesser time of stress exposure while the secondary is triggered at a later stage. Protracted cellular stress beyond the secondary peak results in cellular death. Knocking down mTOR disrupts the variation pattern whereas apoptosis gene Bax silencing intensifies the phenomena. The observation highlights that when cells are exposed to stress; an initial primary autophagy peak refluxes certain amount of nutrients in the cell which results in decline of stress for an intermittent period but protracted stress results in a secondary autophagy peak, crossing which the cell is committed to undergo cellular death

Evaluation of results of “Trochanteric Femoral Nailing (TFN) “ in comminuted unstable trochanteric fractures

ABSTRACT:  Background:               In recent years, intramedullary nails for the treatment of comminuted and unstable intertrochanteric hip fractures have gained prominence relative to conventional, sliding hip screws.             The purpose of our study was to evaluate the result of Trochanteric   femoral nailing in comminuted, unstable Trochanteric fracture femur in terms of anatomical restoration and functional outcome.Materials & Methods :             It is a prospective and without control study. Trochanteric femoral nailing has been done in selected 25 patients and they are followed up postoperatively for at least 12 months. Pre-operative and post-operative clinical and radiological parameters are compared accordingly.Results:             Union in all cases. Overall complication rate 12% including some implant related complications. Functional outcome on Harris Hip Score is comparable with standard literature.Conclusions:            For treatment of intertrochanteric hip fractures, particularly with comminuted fracture fragments, an intramedullary devices offer beneficial features in comparison with the extramedullary devices. Further biomechanical and clinical studies are necessary to validate the efficacy of the trochanteric femoral nail, but in our experience this is an improvement over the currently available devices. Level of Evidence-    Level 1 therapeutic study