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Gurgaon, India

Kalra S.,Bharti Hospital | Vithalani M.,Medisurge Hospital | Gulati G.,Paras Hospitals | Kulkarni C.M.,Shrey Nursing Home | And 5 more authors.
Journal of Association of Physicians of India | Year: 2013

Non-alcoholic fatty liver disease (NAFLD) is a distinct hepatic condition and one of the most common causes of chronic liver disease globally. Prevalence of the disease is estimated to be around 9-32% in the general Indian population, with a higher incidence rate amongst obese and diabetic patients. We conducted this study to determine frequency and risk factors of NAFLD in nonalcoholic Indian type 2 diabetic (T2DM) patients, based on elevated aminotransferase levels, defined as per NHANES III criteria. Out of 924 patients (355 female/569 male), in age group of 25-84 years, enrolled at 189 centers across 101 cities in India, a cohort of 522(56.5%) T2DM patients were identified as having NAFLD. Prevalence of the disease was found to be higher in females (60%) than in males (54.3%) T2DM patients; with prevalence of NAFLD varying from 44.1% in western India to 72.4% in northern states. In our study the prevalence of NAFLD increased with increasing age, with 239(45.8%) identified patients in age group of 25-50 years and 283(54.2%) among those aged 51 years (OR:0.71, 95%CI: 0.54-0.92, p=0.005); with highest prevalence recorded in 61-70 year age group, at 61.8%. The results from the study reinforced the well established clinical association of NAFLD with elements of metabolic syndrome (MetS) including dyslipidemia, hypertension and obesity; as T2DM population with these co-morbid conditions had 38%, 17% and 14% higher risk respectively, for NAFLD. The mean AST and ALT levels were 54.8±36.1 IU/L and 55.6±39.8 IU/L, respectively in NAFLD population and highest in age group of 25-40 years and lowest in 71-84 years age group. Mean ALT levels were found to be higher than mean AST levels across all age groups in identified T2DM NAFLD cohort, with 340(65.3%) patients having elevation of both AST and ALT levels. The results from this study besides demonstrating the prevalence pattern of NAFLD and associated risk factors in Indian T2DM patients, also point out that even mild elevation in aminotransferase levels warrants attention, since it might more often than not point to previously unsuspected liver disease. © JAPI.

Gupta P.,National Brain Research Center | Ghosh S.,National Brain Research Center | Nagarajan A.,National Brain Research Center | Mehta V.S.,Paras Hospitals | Sen E.,National Brain Research Center
Cellular Signalling | Year: 2013

The non-classical HLA class I antigen HLA-G contributes to immune escape mechanisms in glioblastoma multiforme (GBM). We have previously shown that IL-1β-HIF-1α axis connects inflammatory and oncogenic pathways in GBM. In this study, we investigated the role of IL-1β induced inflammation in regulating HLA-G expression. IL-1β increased HLA-G and Toll like receptor 4 (TLR4) expression in a HIF-1α dependent manner. Inhibition of TLR4 signaling abrogated IL-1β induced HLA-G. IL-1β increased HMGB1 expression and its interaction with TLR4. Inhibition of HMGB1 inhibited TLR4 and vice versa suggesting the existence of HMGB1-TLR4 axis in glioma cells. Interestingly, HMGB1 inhibition prevented IL-1β induced HLA-G expression. Elevated levels of HMGB1 and β-defensin 3 were observed in GBM tumors. Importantly, β-defensin-3 prevented IL-1β induced HLA-G, TLR4, HMGB1 expression and release of pro-inflammatory mediators. Our studies indicate that β-defensin-3 abrogates IL-1β induced HLA-G expression by negatively affecting key molecules associated with its regulation. © 2012 Elsevier Inc.

Sharma V.,National Brain Research Center | Dixit D.,National Brain Research Center | Koul N.,National Brain Research Center | Mehta V.S.,Paras Hospitals | Sen E.,National Brain Research Center
Journal of Molecular Medicine | Year: 2011

We observed elevated levels of pro-inflammatory cytokine IL-1β in glioblastoma multiforme tumor samples. Since hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in linking inflammatory and oncogenic pathways, we investigated the effect of IL-1β on HIF-1α expression in glioma cells under normoxia. IL-1β-mediated elevation of HIF-1α transcriptional activity was dependent on Ras-induced NF-κB activation, as IL-1β failed to induce NF-κB and HIF-1α activity in cells transfected with dominant negative RasN17. Increased Ras expression was accompanied by increased phosphorylation of Ras effectors AKT, ERK, JNK, and p38MAPK. While inhibition of these effectors individually failed to block the IL-1β-mediated increase in HIF-1α induction, co-inhibition of both AKT and ERK resulted in a significant decrease in IL-1β-induced HIF-1α activation. Interestingly, IL-1β elevated Wnt-1 expression in a Ras-dependent manner, and small interfering RNA (siRNA)-mediated knockdown of Wnt-1 decreased HIF-1α activity. Although Wnt-1-mediated HIF-1α was independent of the canonical Wnt/β-catenin signaling pathway, it regulated HIF-1α through NF-κB. siRNA-mediated HIF-1α knockdown attenuated elevated IL-1β mRNA levels induced upon IL-1β treatment. This was accompanied by increased interaction of HIF-1α with HIF responsive element on the IL-1β promoter upon IL-1β treatment, under normoxia. Our studies highlights for first time that (1) Ras is a key mediator of IL-1β-induced NF-κB and HIF-1α activation, under normoxia; (2) Wnt-1 regulates IL-1β-mediated HIF-1α induction via NF-κB; (3) Ras and Wnt-1 are intermediaries in the canonical IL-1β-NF-κB signaling pathway downstream of MyD88; and (4) IL-1β-induced HIF-1α drives a HIF-1α-IL-1β autocrine loop to maintain persistently elevated IL-1β level. © 2010 Springer-Verlag.

Sharma V.,VMMC and Safdarjung Hospital | Dogra A.,Paras Hospitals
Journal of Clinical Orthopaedics and Trauma | Year: 2011

Calcaneum the largest tarsal bone accounts for 60% of all tarsal bone injuries and 2% of all fractures. The management of the calcaneal fractures is still a challenge to orthopedic surgeons. The aim of this study was to establish the best treatment, non-surgical or surgical for Sanders type II fractures.It is a prospective study in which a total of 30 patients in age group of 18-60 years were randomized (by envelope) into non-operative (group A) 15 patients and operative (group B) 15 patients. All type II fractures confirmed on CT were included in the study. Patients with any other associated injuries or with any co-morbidity were excluded from this study. The results were evaluated using Bohler's angle, Kerr Atkins, AOFAS, and visual analog scale.In our series, mode of injury was fall from height in 27 (90%) and road traffic accident (RTA) in 3 (10%). There were 21 males and 9 females. The mean Kerr Atkins score in operative group was 66.12 and in conservative group was 60.22. The mean AOFAS in operative group was 72.13 and in conservative group was 71.16. The visual analog scale in operative group was 1.83 and in conservative group was 2.12. The mean follow-up was 28.1 months. Bohler's angle is a good predictor of morbidity and the improvement after surgery was not statistically significant.It was concluded that there is no significant difference in outcome of treatment, surgical or conservative, and results were equivalent in both groups. © 2011 Delhi Orthopedic Association.

Ahmad F.,National Brain Research Center | Ghosh S.,National Brain Research Center | Sinha S.,National Brain Research Center | Joshi S.D.,National Brain Research Center | And 2 more authors.
Molecular and Cellular Biochemistry | Year: 2015

Transforming growth factor (TGF-β) is associated with the progression of glioblastoma multiforme (GBM)—the most malignant of brain tumors. Since there is a structural homology between TGF-β and human chorionic gonadotropin (hCG) and as both TGF-β and hCG-β are known regulators of oxidative stress and survival responses in a variety of tumors, the role of TGF-β in the regulation of hCG-β and its consequences on redox modulation of glioblastoma cells was investigated. A heightened hCG-β level was observed in GBM tumors. TGF-β treatment increased hCG-β expression in glioma cell lines, and this heightened hCG-β was found to regulate redox homeostasis in TGF-β-treated glioma cells, as siRNA-mediated knockdown of hCG-β (i) elevated reactive oxygen species (ROS) generation, (ii) decreased thioredoxin Trx1 expression and thioredoxin reductase (TrxR) activity, and (iii) abrogated expression of TP53-induced glycolysis and apoptosis regulator (TIGAR). Silencing of hCG-β abrogated Smad2/3 levels, suggesting the existence of TGF-β–hCG-β cross-talk in glioma cells. siRNA-mediated inhibition of elevated TIGAR levels in TGF-β-treated glioma cells was accompanied by an increase in ROS levels. As a farnesyltransferase inhibitor, Manumycin is known to induce glioma cell apoptosis in a ROS-dependent manner, and we investigated whether Manumycin could induce apoptosis in TGF-β-treated cells with elevated hCG-β exhibiting ROS-scavenging property. Manumycin-induced apoptosis in TGF-β-treated cells was accompanied by elevated ROS levels and decreased expression of hCG-β, Trx1, Smad2/3, and TIGAR. These findings indicate the existence of a previously unknown TGF-β–hCG-β link that regulates redox homeostasis in glioma cells. © 2014, Springer Science+Business Media New York.

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