Paediatric ovarian torsion: a case report and review of literature

Ovarian torsion is a surgical emergency, can result in ovarian loss, intra-abdominal infection and even death. Paediatric ovarian torsion is a rare condition, requires high clinical suspicion and prompt diagnosis. Diagnosis is a challenge since signs and symptoms are similar to those of other causes of acute abdominal pain such as appendicitis, gastroenteritis, urinary tract infection, renal colic or other conditions of acute abdominal and pelvic pain. Here, authors describe a case of a 4-year-old girl with a presentation of acute abdominal pain, treated empirically elsewhere. After investigations, a provisional diagnosis of ovarian torsion was made and patient was taken up for surgery. Intraoperatively, ovary was found to be necrosed. Detorsion was tried but ovary was unsalvageable. Right sided salpingectomy with oophorectomy was performed. Conservative surgery by laparoscopic detorsion can be tried in cases of ischemia but if necrosis has already set in, then salpingo-oophorectomy has to be performed

Stem Cells in Hypertension

Endothelial dysfunction and vascular remodeling are the hallmarks of pulmonary arterial hypertension (PAH). For PAH treatment, there is a rising demand of Stem cell therapy. Interestingly, research reveals that stem/progenitor cells may have an impact in disease progression and therapy in PAH patients. Clinical trials for stem cell therapy in cardiac cell regeneration for heart repair in PAH patients are now underway. The clinical potential of stem/progenitor cell treatment that offers to PAH patients helps in lesion formation which occurs through regaining of vascular cell activities. Majorly the stem cells which are specifically derived from bone marrow such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and induced pluripotent cells (iPSCs), adipose-derived stem cells (ADSCs), and cardiac stromal cells (CSCs) are among the subtypes that are proved to play a pivotal role in the repair of the heart. But with only MSCs and EPCs, have shown positive outcomes and act as therapeutically efficient in regaining cure for PAH in clinical trials. This chapter also seeks to explain the potential limitations and challenges with most recent achievements in stem/progenitor cell research in PAH

The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair

Diverse internal and external pathologic stimuli can trigger cellular stress response pathways (CSRPs) that are usually counteracted by intrinsic homeostatic machinery, which responds to stress by initiating complex signaling mechanisms to eliminate either the stressor or the damaged cells. There is growing evidence that CSRPs can have context-dependent homeostatic or pathologic functions that may result in tissue fibrosis under persistence of stress. CSRPs can drive intercellular communications through exosomes (trafficking and secretory pathway determinants) secreted in response to stress-induced proteostasis rebalancing. The injured tissue environment upon sensing the stress turns on a precisely orchestrated network of immune responses by regulating cytokine-chemokine production, recruitment of immune cells, and modulating fibrogenic niche and extracellular matrix (ECM) cross-talk during fibrotic pathologies like cardiac fibrosis, liver fibrosis, laryngotracheal stenosis, systemic scleroderma, interstitial lung disease and inflammatory bowel disease. Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins (RBPs) of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation. The paradigm-shift in RNA metabolism associated interactome has begun to offer new therapeutic windows by unravelling the novel RBPs and splicing factors in context of developmental and fibrotic pathways. We would like to review emerging regulatory nodes and their interaction with CSRPs, and tissue remodeling with major focus on cardiac fibrosis, and inflammatory responses underlying upper airway fibrosis

Common Variants of Inflammatory Cytokine Genes Are Associated with Risk of Nephropathy in Type 2 Diabetes among Asian Indians

BACKGROUND: Inflammatory cytokine genes have been proposed as good candidate genes for conferring susceptibility to diabetic nephropathy. In the present study, we examined the combined effect of multiple alleles of pro inflammatory cytokine genes for determining the risk of nephropathy in type 2 diabetic patients. METHODOLOGY/PRINCIPAL FINDINGS: Eight single nucleotide polymorphisms (SNPs) of pro-inflammatory cytokine genes (CCL2, TGFB1, IL8, CCR5, and MMP9) were genotyped in two independently ascertained type 2 diabetic cohorts with (DN) and without nephropathy (DM); consisting of patients from North India (n = 495) and South India (n = 188). Genotyping was carried out using PCR, allele specific oligonucleotide-PCR (ASO-PCR), PCR-RFLP and TaqMan allelic discrimination assays and the gene-gene interaction among genetic variants were determined by multi dimensional reduction (MDR) software. Serum high sensitive CRP (hs-CRP) levels were measured by ELISA. The hs-CRP levels were significantly higher in DN as compared to the DM group (p<0.05). The CCL2, IL8, CCR5 and MMP9 polymorphisms were found to be associated with the risk of diabetic nephropathy. Frequency of CCL2 II, IL8 -251AA, CCR5 59029AA and MMP9 279Gln/Gln genotypes were significantly higher in DN than in DM group (p<0.05) and associated with an increased risk of nephropathy in both North and South Indian cohorts. CCR5 DD and IL8 -251AA genotypes were more prevalent in North Indian DN group only. The co-occurrence of risk associated genotypes (II, -2518GG (CCL2), DD (CCR5) and 279Gln/Gln (MMP9) conferred a tenfold increased risk of nephropathy among type 2 diabetics (p<0.0002). CONCLUSION: The present study highlights that common variants of inflammatory cytokine genes exert a modest effect on risk of DN and a combination of risk alleles confer a substantial increased risk of nephropathy in type 2 diabetes among Asian Indians