Browsing by Author "Srinivas, G"

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    A clinician's dilemma: Sturge-Weber syndrome 'without facial nevus'!!
    (ANNALS OF INDIAN ACADEMY OF NEUROLOGY, 2013) Jagtap, SA; Srinivas, G; Radhakrishnan, A; Harsha, KJ
    Sturge-Weber syndrome (SWS) is a rare, sporadic neurocutaneous syndrome characterized by a classical triad of facial port wine nevus, ipsilateral leptomeningeal angiomatosis (LAM) and glaucoma. The incidence of SWS is 1/50,000 live births, although it is more often underreported. The incidence of SWS without facial nevus is not known, although very few patients without facial nevus have been reported. In these patients, the diagnosis of SWS is made by the findings of computed tomography, magnetic resonance imaging, and histopathology. Here, we report three patients with SWS from our cohort of 28 patients with SWS without facial nevus and discuss their clinical profile and outcome.
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    Calculation error in estimating low HDL in women Response
    (INDIAN JOURNAL OF MEDICAL RESEARCH, 2014) Thankappan, KR; Shah, B; Mathur, P; Sarma, PS; Srinivas, G; Mini, GK; Daivadanam, M; Soman, B; Vasan, RS
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    Containing the first outbreak of COVID-19 in a healthcare setting in India: The sree chitra experience
    (Indian Journal of Public Health., 2020-10) Singh, G; Srinivas, G; Jyothi, EK; Gayatri, LK; Gaitonde, R; Soman, B
    The response to the first health worker case in India and novel strategies adopted in the context of evolving pandemic of COVID-19 is presented here. On the same day of confirmation, institutional COVID cell was established, and contact tracing was started. A total of 184 contacts were identified and quarantined. Hospital services were scaled down, and responsibilities were reassigned. In-house digital platforms were used for daily meetings, contact tracing, line listing, risk stratification, and research. Reverse transcription polymerase chain reaction-based severe acute respiratory syndrome-CoV2 testing facility was established in the institute. All high-risk contacts were given hydroxychloroquine prophylaxis. No secondary cases were found. Hospital preparedness, participatory decision-making through institutional COVID cell, optimal use of in-house digital platforms, and coordination with the state health department and national bodies, including Indian Council of Medical Research, were the supporting factors. Rapidly evolving guidelines, trepidation about the disease, logistic delays, and lack of support systems for people under quarantine were the challenges in the containment exercise.
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    Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents
    (ANNALS OF ONCOLOGY, 2008) Thasni, KA; Rakesh, S; Rojini, G; Ratheeshkumar, T; Srinivas, G; Priya, S
    Background: Cellular response to chemotherapeutic drugs in the absence of BRCA1 either completely or partially had drawn less attention. The present study evaluated whether there is a differential inhibition of cell growth by selected compounds with respect to BRCA1 status in estrogen receptor (ER)-positive ovarian cancer cells. Materials and methods: The BG1 ovarian cancer cells used in the experiments were antisensely blocked with BRCA1 gene. Growth inhibition and apoptotic induction were analyzed to evaluate the cytotoxic effects. Small interfering RNA (SiRNA) transfection, western blot analysis, RT-PCR analysis and molecular modeling were carried out to analyze the estrogen-dependent action of plumbagin. Results: Although we found that all the compounds studied induce apoptosis, the induction was in the order of plumbagin > doxorubicin > tamoxifen > cisplatin. Plumbagin can bind to the active site of ER-alpha. Plumbagin, however, induced ER-alpha 46 kDa truncated isoform, which was found abundantly preempted in the cytoplasm compared with a 66-kDa full-length isoform. The truncated isoform is known to inhibit classical ER-alpha signaling pathways. SiRNA-transfected cells for ER-alpha exhibited lower cytotoxicity upon plumbagin treatment than the control-transfected cells. Conclusion: Taken together, this study indicates that plumbagin has chemotherapeutic potential in BRCA1-mutated/defective ER-positive cancers.
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    Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status
    (EUROPEAN JOURNAL OF PHARMACOLOGY, 2008) Thasni, KAA; Rojini, G; Rakesh, SN; Ratheeshkumar, T; Babu, MS; Srinivas, G; Banerji, A; Srinivas, P
    It has been reported that Breast Cancer Susceptibility gene-1 & 2 (BRCA1 & 2 are potential molecular targets for chemoprevention by isoflavone genistein (4' 5, 7-trihydroxy isoflavone), in breast and prostate cancer cells. It is also known that BRCA1 has inhibitory activity on estrogen receptor-a and genistein's action on cells is mainly through modulation of estrogen receptor activity. The action of genistein with respect to BRCA1 status in ovarian cancer cells has not been reported so far. Therefore in this study, we analyzed the action of genistein on BRCA1 antisense blocked (AS4) and unblocked (NEO) BG-1 ovarian cancer cells. We found that genistein induced comparable cytotoxic effect in both AS4 and NEO cells, but through different pathways. We found that genistein induces caspase 8 dependent apoptotic pathway in NEO cells. Genistein inhibits estrogen receptor-alpha and activates BARD1 in BRCA1 blocked cells and induces estrogen receptor-beta and FAS in presence of BRCA1. It can be concluded that even though there is no difference in the extent of cell death or apoptosis, the molecular mechanism of action of genistein in inducing apoptosis is different in BRCA1 blocked and unblocked cells. This could partially explain the beneficial effects of genistein in both wild type and mutated BRCA1 estrogen receptor positive tumors. (C) 2008 Elsevier B.V. All rights reserved.
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    How can I halt thee? The puzzles involved in autophagic inhibition.
    (Pharmacological Research. 2014, 2014-03) Vinod, V; Padmakrishnan, C J; Vijayan, B; Srinivas, G
    Abstract The strategy for interpreting the role of autophagy on the basis of evidence obtained through autophagic inhibition sounds logical, but is beset with practical constraints. The knock down of autophagy-related (ATG) gene(s) or blockage of class III PI3-Kinase are the most common approaches for inhibiting autophagy. However, during stressful conditions, autophagy may operate in synchrony with other processes such as apoptosis; autophagy-related genes, unlike what their name implies, exert their regulation on apoptosis as well. Knocking down such genes not only blocks autophagy but also renders apoptosis defective, making the interpretation of autophagic roles unreliable. Similarly, class III PI3-Kinase aids in initiating autophagy but it is not a quintessential autophagic regulator. Class III PI3-Kinase also has a role in regulating almost all membrane transport in cells. Blocking it not only inhibits autophagy, but also hampers all the membrane trades, including endosomal transport. The pharmacological inhibitors used to block autophagy by blocking class III PI3-Kinase further compound these limitations with their off-target effects. Knowing the limitations involved in blocking a target or using an autophagy-blocking tool is a prerequisite for designing the experiments meant for analyzing autophagic functions. This review attempts to provide a detailed overview about the practical constraints involved in using autophagic inhibition as a strategy to understand autophagy.
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    MAPT genetic variations are uncommon cause of frontotemporal dementia in south India
    (Neurobiology of Aging, 2013-10) Aswathy, PM; Jairani, PS; Verghese, Joe; Srinivas, G; Mathuranath, PS
    Microtubule-associated protein tau (MAPT) positive neuropathology is the characteristic feature of majority of frontotemporal dementia (FTD) cases, which is due to the mutations or haplotypic variations in the gene encoding MAPT (MAPT). The present study was aimed at determining the frequency of genetic variations in MAPT in a south Indian FTD cohort. The frequency of mutations were determined in 116 FTD, 8 progressive supranuclear palsy (PSP) and 3 corticobasal syndrome (CBS) patients and haplotype diversity were analyzed in a study cohort comprising 116 FTD, 8 PSP, 3 CBS, 194 other dementia groups, 78 mild cognitive impairment (MCI) and 130 cognitively normal individuals and report no pathogenic mutations in FTD/PSP/CBS or haplotypic association with disease risk in FTD or other dementia patients. These findings suggest that there may be other genetic or epigenetic factors contributing to the pathogenesis of FTD in the south Indian population.
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    Mentoring for COVID 19 testing :an exercise in teaching from a National Institute
    (National Journal of Integrated Research in Medicine, Suppl issue. 2020, 2020-11) Raja, K; Srinivas, G; Jyothi, EK
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    Mitochondrial metabolism and function in type 2 diabetic heart ( Project - 5289 )
    (SCTIMST, 2018-06-17) Srinivas, G; Jayakumar, K; Vivek V, Pillai
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    Radiosensitizing effects of plumbagin in cervical cancer cells is through modulation of apoptotic pathway
    (MOLECULAR CARCINOGENESIS, 2008) Nair, S; Nair, RRK; Srinivas, P; Srinivas, G; Pillai, MR
    Radiotherapy is the primary line of cancer treatment for cervical cancer and is known to induce cell death in tumors. Radiotherapy is however limited by the total dose that can be given without damaging normal tissue. Plumbagin, a naturally occurring naphthaquinone, has been reported to have free radical producing properties. Hence we hypothesized that plumbagin could also have properties that could modify effects of radiation on cervical cancer cells. Radiation in combination with plumbagin may thus have treatment augmenting effects. Results from our studies have shown that a lower dose of radiation in combination with plumbagin could induce apoptosis more effectively compared to a higher dose of radiation alone. Plumbagin in combination with 2 Gy of radiation was very effective in inducing apoptosis, when compared to a higher radiation dose of 10 Gy alone. This combination also showed a fivefold increase in the activation of caspase 3 in C33A cells. Activation of effector caspases confirms that the induction of apoptosis by irradiation and plumbagin involves caspase-dependent pathways. Expression of apoptotic regulatory molecules Bcl-2, Bax and Survivin was also modulated by plumbagin in combination with radiation. In summary, this study shows that a combination of plumbagin and radiation augmented cell growth inhibition compared to higher radiation dose alone, thus indicating that plumbagin may be a potential radiosensitizer acting through the induction of apoptosis. (c) 2007 Wiley-Liss, Inc.
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    Risk factor profile for chronic non-communicable diseases: Results of a community-based study in Kerala, India
    (INDIAN JOURNAL OF MEDICAL RESEARCH, 2010)
    Background & objectives: Kerala State is a harbinger of what will happen in future to the rest of India in chronic non-communicable diseases (NCD). We assessed: (i) the burden of NCD risk factors; (h) estimated the relations of behavioural risk factors to socio-demographic correlates, anthropometric risk factors with behavioural risk factors; (iii) evaluated if socio-demographic, behavioural and anthropometric risk factors predicted biochemical risk factors; and (iv) estimated awareness, treatment and adequacy of control of hypertension and diabetes, in Kerala state.Methods: A total of 7449 individuals (51% women) stratified by age group, sex and place of residence were selected and information on behavioural risk factors; tobacco use, diet, physical activity, alcohol use, measured anthropometry, blood pressure was collected. Fasting blood samples were analysed for blood glucose, total cholesterol, high density lipoprotein cholesterol and triglycerides in a sample subset. Using multiple logistic regression models the associations between socio-demographic and anthropometric variables with biochemical risk factors were estimated.Results: The burden of NCD risk factors was high in our sample. Prevalence of behavioural and each of the biochemical risk factors increased with age, adjusting for other factors including sex and the place of residence. The odds ratios relating anthropometric variables to biochemical variables were modest, suggesting that anthropometric variables may not be useful surrogates for biochemical risk factors for population screening purposes.Interpretation & conclusions: In this large study of community-based sample in Kerala, high burden of NCD risk factors was observed, comparable to that in the United States. These data may serve to propel multisectoral efforts to lower the community burden of NCD risk factors in India in general, and in Kerala, in particular.
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    Risk Factor Profile for Chronic Non-communicable Diseases: Results of a Community-Based Study in Kerala, India
    (Indian Journal of Medical Research, 2010) Thankappan, KR; Shah, B; Mathur, P; Sarma, PS; Srinivas, G; Mini, GK; Daivadanam, M; Soman, B; Vasan, RS
    BACKGROUND & OBJECTIVES: Kerala State is a harbinger of what will happen in future to the rest of India in chronic non-communicable diseases (NCD). We assessed: (i) the burden of NCD risk factors; (ii) estimated the relations of behavioural risk factors to socio-demographic correlates, anthropometric risk factors with behavioural risk factors; (iii) evaluated if socio-demographic, behavioural and anthropometric risk factors predicted biochemical risk factors; and (iv) estimated awareness, treatment and adequacy of control of hypertension and diabetes, in Kerala state.METHODS:A total of 7449 individuals (51% women) stratified by age group, sex and place of residence were selected and information on behavioural risk factors; tobacco use, diet, physical activity, alcohol use, measured anthropometry, blood pressure was collected. Fasting blood samples were analysed for blood glucose, total cholesterol, high density lipoprotein cholesterol and triglycerides in a sample subset.Using multiple logistic regression models the associations between socio-demographic and anthropometric variables with biochemical risk factors were estimated.RESULTS: The burden of NCD risk factors was high in our sample. Prevalence of behavioural and each of the biochemical risk factors increased with age, adjusting for other factors including sex and the place of residence. The odds ratios relating anthropometric variables to biochemical variables were modest, suggesting that anthropometric variables may not be useful surrogates for biochemical risk factors for population screening purposes. INTERPRETATION & CONCLUSIONS: In this large study of community-based sample in Kerala, high burden of NCD risk factors was observed, comparable to that in the United States. These data may serve to propel multisectoral efforts to lower the community burden of NCD risk factors in India in general, and in Kerala, in particular.
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    Structure activity relationship of plumbagin in BRCA1 related cancer cells
    (MOLECULAR CARCINOGENESIS, 2013) Thasni, KA; Ratheeshkumar, T; Rojini, G; Sivakumar, KC; Nair, RS; Srinivas, G; Banerji, A; Somasundaram, V; Srinivas, P
    It has been shown earlier that plumbagin, a naturally occurring naphthaquinone has specific anticancer activity in BRCA1 blocked ovarian cancer cells. Plumbagin can induce estrogen dependent cell signaling and apoptosis in BRCA1 blocked ovarian cancer cells. Being a reactive oxygen species (ROS) generator and apoptosis inducing agent, plumbagin has immense potential as a promising anticancer agent. In this study we analyzed whether there would be increased anticancer activity if the positions of the functional groups on plumbagin were altered and further to analyze the detailed molecular mechanism of action of the lead molecule. Methods like MTT assay, apoptosis analysis by flow cytometry, assessment of mitochondrial membrane potential-m, suppression subtractive hybridization, microarray, molecular docking and estrogen receptorDNA binding activity by electrophoresis mobility shift assay (EMSA) were adopted for assessing the anticancer activity. Consequently we found that, plumbagin was the most potent anticancer agent when compared to structurally related compounds. The anti-cancer activities were in the order plumbagin>1,4-naphthaquinone>juglone>lawsone>menadione. Molecular docking studies showed that plumbagin could be well docked in the receptor ligand complex of TRAILDR5 complexes to activate the extrinsic pathway of apoptosis. Since the antiproliferative activity of plumbagin could be reduced by inhibiting ER, we speculated that plumbagin interferes with the binding of ER to ERE and we confirmed this by EMSA. This study clearly indicates that plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells. (c) 2012 Wiley Periodicals, Inc.
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