A comparative study of coagulation profile and platelet indices at term in pre-eclamptic, eclamptic and normal pregnancy along with fetomaternal outcome

Background: Hypertensive disorders of pregnancy is reported to cause about 60-80% of maternal deaths. Platelet indices are biomarkers of platelet activation. Among these platelet indices, mean platelet volume (MPV), and platelet distribution width (PDW), platelet large cell ratio (PLCR) is a group of platelet parameters. When platelets are activated, they become larger in size which causes increased platelet indices such as MPV, PDW and PLCR. So, platelet indices can give an idea of platelet activation. A comparative study of coagulation profile and platelet indices at term in pre-eclamptic, eclamptic and normal pregnancy along with fetomaternal outcome.Methods: This study was carried out in department of obstetrics and gynaecology in collaboration with department of pathology, Rabindranath Tagore Medical College (RNTMC), Udaipur. Cases were selected by systematic random sampling. Bleeding time (BT), clotting time (CT), prothrombin time (PT), mean platelet volume (MPV), platelet distribution width (PDW), and activated partial thromboplastin time (aPTT) to analyse hypertensive disorders in pregnancy (HDP) during the period January 2021 to December 2021.Results: Significant difference was seen in bleeding time (seconds), prothrombin time (seconds), aPTT (seconds) between normal pregnancy as compared to pre-eclampsia and eclampsia. (p value <0.05). Patients’ admission in neonatal intensive care unit (NICU) was significantly higher in eclampsia (p<0.0001) and pre-eclampsia (p<0.0001) as compared to normal pregnancy (66.67%, 43.24% versus 2% respectively).Conclusions: We conclude that coagulation profile like (BT, CT, PT, and aPTT), platelet counts along with platelet indices- MPV, PDW are useful markers, which were significantly raised in patients with preeclampsia and eclampsia. Platelet indices along with coagulation profile emerges as an important, simple, cost effective and effortless tool for predicting severity of pregnancy induced hypertension (PIH).

Comparative study of combination of misoprostol with Foley’s bulb compared with misoprostol alone for termination of second trimester pregnancy

Background: Second trimester abortion is termination of pregnancy in a period from 13 to 28 weeks of gestation. Second trimester losses may be due to maternal factors such as uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth.  Aims and objectives were to compare the efficacy, safety and suitability of combination of misoprostol with intracervical Foley’s catheter v/s misoprostol alone for termination of second trimester pregnancy.Methods: This randomized controlled trial study was conducted on 100 study subjects who passed our inclusion and exclusion criteria. Group A: received misoprostol with intracervical Foley’s catheter. Group B: received misoprostol alone. The groups were compared with respect to the patients’ characteristics, gestational age, indication for termination of pregnancy, rate of complications, etc.Results: Mean value of age (years) of study subjects was 27.12±4.5. Mean induction to delivery time (hours) in P0 was 17.73±6.46 and in P1-P2 was 14.78±4.9 which was significantly higher as compared to ≥P3 (11.46±3.82). (p=0.0004). Mean induction to delivery time (hours) in 14 to 18 weeks was 15.25±5.4 and >18 weeks was 15.02±5.84. (p=0.854). Distribution of side effect between group A and B. (6% vs 20% respectively) (p=0.041).Conclusions: We conclude that intracervical Foley catheter and vaginal misoprostol is a safe and effective method for second trimester abortion as compared to misoprostol alone group with no additional risks.

Bmi1 Is Expressed in Postnatal Myogenic Satellite Cells, Controls Their Maintenance and Plays an Essential Role in Repeated Muscle Regeneration

PMCID: PMC3212532This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sequential alterations in catabolic and anabolic gene expression parallel pathological changes during progression of monoiodoacetate-induced arthritis

Chronic inflammation is one of the major causes of cartilage destruction in osteoarthritis. Here, we systematically analyzed the changes in gene expression associated with the progression of cartilage destruction in monoiodoacetate-induced arthritis (MIA) of the rat knee. Sprague Dawley female rats were given intra-articular injection of monoiodoacetate in the knee. The progression of MIA was monitored macroscopically, microscopically and by micro-computed tomography. Grade 1 damage was observed by day 5 post-monoiodoacetate injection, progressively increasing to Grade 2 by day 9, and to Grade 3-3.5 by day 21. Affymetrix GeneChip was utilized to analyze the transcriptome-wide changes in gene expression, and the expression of salient genes was confirmed by real-time-PCR. Functional networks generated by Ingenuity Pathways Analysis (IPA) from the microarray data correlated the macroscopic/histologic findings with molecular interactions of genes/gene products. Temporal changes in gene expression during the progression of MIA were categorized into five major gene clusters. IPA revealed that Grade 1 damage was associated with upregulation of acute/innate inflammatory responsive genes (Cluster I) and suppression of genes associated with musculoskeletal development and function (Cluster IV). Grade 2 damage was associated with upregulation of chronic inflammatory and immune trafficking genes (Cluster II) and downregulation of genes associated with musculoskeletal disorders (Cluster IV). The Grade 3 to 3.5 cartilage damage was associated with chronic inflammatory and immune adaptation genes (Cluster III). These findings suggest that temporal regulation of discrete gene clusters involving inflammatory mediators, receptors, and proteases may control the progression of cartilage destruction. In this process, IL-1β, TNF-α, IL-15, IL-12, chemokines, and NF-κB act as central nodes of the inflammatory networks, regulating catabolic processes. Simultaneously, upregulation of asporin, and downregulation of TGF-β complex, SOX-9, IGF and CTGF may be central to suppress matrix synthesis and chondrocytic anabolic activities, collectively contributing to the progression of cartilage destruction in MIA

Hemoglobin receptor in Leishmania is a hexokinase located in the flagellar pocket

Hb endocytosis in Leishmania is mediated through a 46-kDa protein located in the flagellar pocket. To understand the nature of the Hb receptor (HbR), we have purified the 46-kDa protein to homogeneity from Leishmania promastigote membrane. Purified HbR specifically binds Hb. The gene for HbR was cloned, and sequence analysis of the full-length HbR gene indicates the presence of hexokinase (HK) signature sequences, ATP-binding domain, and PTS-II motif. Four lines of evidence indicate that HbR in Leishmania is a hexokinase: 1) the recombinant HbR binds Hb, and the Hb-binding domain resides in the N terminus of the protein; 2) recombinant proteins and cell lysate prepared from HbR-overexpressing Leishmania promastigotes show enhanced HK activity in comparison with untransfected cells; 3) immunolocalization studies using antibodies against the N-terminal fragment (Ld-HbR-&#916;C) of Ld-HbR indicate that this protein is located in the flagellar pocket of Leishmania; and 4) binding and uptake of 125I-Hb by Leishmania is significantly inhibited by anti-Ld-HbR-&#916;C antibody and Ld-HbR-&#916;C, respectively. Taken together, these results indicate that HK present in the flagellar pocket of Leishmania is involved in Hb endocytosis

A Role for Non-Covalent SUMO Interaction Motifs in Pc2/CBX4 E3 Activity

Background: Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO is covalently attached to lysines in target proteins via an enzymatic cascade which consists of E1 and E2, SUMO activating and conjugating enzymes. There is also a variable requirement for non-enzymatic E3 adapter like proteins, which can increase the efficiency and specificity of the sumoylation process. In addition to covalent attachment of SUMO to target proteins, specific non-covalent SUMO interaction motifs (SIMs) that are generally short hydrophobic peptide motifs have been identified. Methodology/Principal Findings: Intriguingly, consensus SIMs are present in most SUMO E3s, including the polycomb protein, Pc2/Cbx4. However, a role for SIMs in SUMO E3 activity remains to be shown. We show that Pc2 contains two functional SIMs, both of which contribute to full E3 activity in mammalian cells, and are also required for sumoylation of Pc2 itself. Pc2 forms distinct sub-nuclear foci, termed polycomb bodies, and can recruit partner proteins, such as the corepressor CtBP. We demonstrate that mutation of the SIMs in Pc2 prevents Pc2-dependent CtBP sumoylation, and decreases enrichment of SUMO1 and SUMO2 at polycomb foci. Furthermore, mutational analysis of both SUMO1 and SUMO2 reveals that the SIM-interacting residues of both SUMO isoforms are required for Pc2-mediated sumoylation and localization to polycomb foci

IMECE2008-67924 BIOMECHANICAL DEVICE TOWARDS QUANTITATIVE MASSAGE

ABSTRACT Massage therapies are widely employed for improving and recovering tissue functions and physical activities. It i

Versatile Roles of V-ATPases Accessory Subunit Ac45 in Osteoclast Formation and Function

Vacuolar-type H+-ATPases (V-ATPases) are macromolecular proton pumps that acidify intracellular cargos and deliver protons across the plasma membrane of a variety of specialized cells, including bone-resorbing osteoclasts. Extracellular acidification is crucial for osteoclastic bone resorption, a process that initiates the dissolution of mineralized bone matrix. While the importance of V-ATPases in osteoclastic resorptive function is well-defined, whether V-ATPases facilitate additional aspects of osteoclast function and/or formation remains largely obscure. Here we report that the V-ATPase accessory subunit Ac45 participates in both osteoclast formation and function. Using a siRNA-based approach, we show that targeted suppression of Ac45 impairs intracellular acidification and endocytosis, both are prerequisite for osteoclastic bone resorptive function in vitro. Interestingly, we find that knockdown of Ac45 also attenuates osteoclastogenesis owing to a reduced fusion capacity of osteoclastic precursor cells. Finally, in an effort to gain more detailed insights into the functional role of Ac45 in osteoclasts, we attempted to generate osteoclast-specific Ac45 conditional knockout mice using a Cathepsin K-Cre-LoxP system. Surprisingly, however, insertion of the neomycin cassette in the Ac45-FloxNeo mice resulted in marked disturbances in CNS development and ensuing embryonic lethality thus precluding functional assessment of Ac45 in osteoclasts and peripheral bone tissues. Based on these unexpected findings we propose that, in addition to its canonical function in V-ATPase-mediated acidification, Ac45 plays versatile roles during osteoclast formation and function

Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes

Introduction\ud The importance of mechanical signals in normal and inflamed cartilage is well established. Chondrocytes respond to changes in the levels of proinflammatory cytokines and mechanical signals during inflammation. Cytokines like interleukin (IL)-1β suppress homeostatic mechanisms and inhibit cartilage repair and cell proliferation. However, matrix synthesis and chondrocyte (AC) proliferation are upregulated by the physiological levels of mechanical forces. In this study, we investigated intracellular mechanisms underlying reparative actions of mechanical signals during inflammation.\ud \ud Methods\ud ACs isolated from articular cartilage were exposed to low/physiologic levels of dynamic strain in the presence of IL-1β. The cell extracts were probed for differential activation/inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade. The regulation of gene transcription was examined by real-time polymerase chain reaction.\ud \ud Results\ud Mechanoactivation, but not IL-1β treatment, of ACs initiated integrin-linked kinase activation. Mechanical signals induced activation and subsequent C-Raf-mediated activation of MAP kinases (MEK1/2). However, IL-1β activated B-Raf kinase activity. Dynamic strain did not induce B-Raf activation but instead inhibited IL-1β-induced B-Raf activation. Both mechanical signals and IL-1β induced ERK1/2 phosphorylation but discrete gene expression. ERK1/2 activation by mechanical forces induced SRY-related protein-9 (SOX-9), vascular endothelial cell growth factor (VEGF), and c-Myc mRNA expression and AC proliferation. However, IL-1β did not induce SOX-9, VEGF, and c-Myc gene expression and inhibited AC cell proliferation. More importantly, SOX-9, VEGF, and Myc gene transcription and AC proliferation induced by mechanical signals were sustained in the presence of IL-1β.\ud \ud Conclusions\ud The findings suggest that mechanical signals may sustain their effects in proinflammatory environments by regulating key molecules in the MAP kinase signaling cascade. Furthermore, the findings point to the potential of mechanosignaling in cartilage repair during inflammation

The Protective Antibodies Induced by a Novel Epitope of Human TNF-α Could Suppress the Development of Collagen-Induced Arthritis

Tumor necrosis factor alpha (TNF-α) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-α (hTNF-α) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-α. We performed screening peptide library against anti-hTNF-α antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-α. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80–91 aa) of hTNF-α proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-α biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-α. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-α and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies