Browsing by Author "Kartha, CC"

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    1,25-dihydroxyvitamin D-3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D
    (LIFE SCIENCES, 2002)
    Several studies have demonstrated that excess of vitamin D-3 is toxic particularly to vascular tissues. A notable pathological feature is arterial calcification. The nature of the toxic metabolite in hypervitaminosis D and the pathogenesis of arterial calcification are not clearly understood. The present study was undertaken to explore whether arterial calcification is a sequel of increased calcium uptake by arterial smooth muscle mediated by up regulation of vitamin D receptor in the cells in response to elevated circulating levels of vitamin D-3 in serum. The experimental study was performed in 20 New Zealand white female rabbits aged 6 months. Animals in the test group were injected 10,000 IU of cholecalciferol intramuscularly twice a week for one month. Six control animals were given intra-muscular injections of plain cottonseed oil. Animals were sacrificed and aortas were examined for pathological lesions, 1,25-dihyroxyvitamin D-3 (1,25(OH)(2) D-3) receptor levels and Ca-45 uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D-3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D-3 Were elevated. In four of these animals calcification and aneurysmal changes were seen in the aorta. Histological lesions comprised of fragmentation of elastic fibers as well as extensive loss of elastic layers. 1,25(OH)(2) D-3 receptor levels were up regulated and Ca-45 uptake enhanced in aortas of animals which were given excessive vitamin D-3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)(2)D-3 receptor and increased calcium uptake in smooth muscle cells of the arteries. (C) 2002 Elsevier Science Inc. All rights reserved.
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    A promising hybrid vaccine against malignant tertian malaria
    (CURRENT SCIENCE, 1997) Kartha, CC
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    A shot in the leg to treat blocked arteries
    (CURRENT SCIENCE, 1997) Kartha, CC
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    A simple, cost-effective quality assurance model for measurement of lipids in a large epidemiological study
    (NATIONAL MEDICAL JOURNAL OF INDIA, 2008) Lakshmy, R; Gupta, R; Kartha, CC; Malathi, T; Nigam, PK; Akarte, NR; Sampson, U; Borkotoky, S; Doiphode, DN; Arora, U; Prabhakaran, D; Reddy, KS
    Background. Laboratory measurements are an integral part of epidemiological studies in cardiovascular disease. Standardization and quality assurance is of utmost importance in the context of multicentre studies. Methods. We evaluated a simple and cost-effective method of quality assurance for measurement of total cholesterol, high density lipoprotein (HI)L) cholesterol and triglycerides in a study involving 10 centres. Three methods for quality assessment were used for the study that involved measurement of cholesterol, triglycerides and HDL cholesterol and included internal quality control, external quality control and 10% repeat analysis in addition to a uniform standardized protocol developed for the 10 centres. External quality control material was prepared and circulated by the coordinating laboratory. Results. External quality control material was distributed 20 times during the study. The mean variance index suggested a substantial improvement In the performance of participating laboratories over a period of time for cholesterol and triglycerides. This was also evident in the improvement in per cent technical error as a measure of bias and a higher correlation between replicates of samples analysed In the coordinating laboratory and the participating centres for cholesterol, triglycerides and HDL cholesterol. Conclusion. A cost-effective quality assurance model for laboratory measurement using local capacities was developed and implemented in a multicentre epidemiology study. Such a programme would be useful for developing countries where cost-cutting is important.
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    Analyzing sociodemographic factors among blood donors
    (Journal of Emergencies, Trauma and Shock, 2010) Shenga, N; Thankappan, KR; Kartha, CC; Pal, R
    Introduction: Blood transfusion is a fundamental and requisite part of any National Health Service for optimum management of emergency conditions like severe trauma shock and resuscitation with the optimum stock of its different components. The objective of the present study was to analyze the factors of knowledge of prospective blood donors that may influence their perception and awareness about blood donation. Materials and Methods: This population-based cross-sectional study was conducted at Gangtok in the state of Sikkim, India, on 300 subjects of the adult population selected by two-stage cluster sampling. The main outcome variables were the socioeconomic and demographic variables of knowledge of blood donation. By interview technique, using the pre-tested structured close-ended questionnaire, the principal investigator collected the data. Results: In our study population, 46% of the study population was found to have a high knowledge score. The knowledge about blood donation was found to be statistically significant with the occupational status and the education levels, both in the bivariate and in the multivariate analyses. Knowledge about blood donation was not significantly related to age, sex, marital status, religion, community status and per capita monthly family income. Conclusion: The study suggested that the perceptions toward voluntary blood donation could be influenced to a large extent by sociodemographic variables of knowledge among the general population.
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    Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
    (JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2014) Gs, AK; Raj, B; Santhosh, KS; Sanjay, G; Kartha, CC
    Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart failure. Here, we describe a detailed surgical procedure for creating pressure overload and cardiac hypertrophy in rats by constriction of the ascending aorta using a small metallic clip. After anesthesia, the trachea is intubated by inserting a cannula through a half way incision made between two cartilage rings of trachea. Then a skin incision is made at the level of the second intercostal space on the left chest wall and muscle layers are cleared to locate the ascending portion of aorta. The ascending aorta is constricted to 50-60% of its original diameter by application of a small sized titanium clip. Following aortic constriction, the second and third ribs are approximated with prolene sutures. The tracheal cannula is removed once spontaneous breathing was re-established. The animal is allowed to recover on the heating pad by gradually lowering anesthesia. The intensity of pressure overload created by constriction of the ascending aorta is determined by recording the pressure gradient using transthoracic two dimensional Doppler-echocardiography. Overall this protocol is useful to study the remodeling events and contractile properties of the heart during the gradual onset and progression from compensated cardiac hypertrophy to heart failure stage.
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    Association of high sensitive C-reactive protein (hsCRP) with established cardiovascular risk factors in the Indian population
    (Nutrition & Metabolism, 2011) Jeemon, P; Prabhakaran, D; Ramakrishnan, L; Gupta, R; Ahmed, F; Thankappan, KR; Kartha, CC; Chaturvedi, V; Reddy, KS
    INTRODUCTION: Inflammation, the key regulator of C-reactive protein (CRP) synthesis, plays a pivotal role in atherothrombotic cardiovascular disease.METHODS: High sensitivity CRP (hsCRP) analysis was carried out in randomly selected 600 individuals from the sentinel surveillance study in Indian industrial population (SSIP). The hsCRP was measured quantitatively by turbid metric test using kits from SPINREACT, Spain. We analyzed the association between hsCRP and traditional CVD risk factors in this sub-sample.RESULTS: Complete risk factor data and CRP levels were available from 581/600 individuals. One half (51.2%) of the study subjects were males. Mean age of the study group was 39.2 ± 11.2 years. The Pearson correlation coefficients were in the range of 0.12 for SBP (p = 0.004) to 0.55 for BMI (p < 0.001). The linear regression coefficients ranged from 0.01 for SBP, PG and TC (p < 0.001) to 0.55 for logeTAG (p < 0.001) after adjustment for age, sex and education. The mean of logehsCRP significantly increased (P < 0.001) from individuals with ?1 risk factors (-0.50) to individuals with three or more risk factors (0.60). In the multivariate model, the odds ratios for elevated CRP (CRP ? 2.6 mg/dl) were significantly elevated only in females in comparison to males (1.63, 95% CI; 1.02-2.58), overweight individuals in comparison to normal weight individuals (3.90, 95% CI; 2.34-6.44, p < 0.001), and abdominal obese individuals (1.62, 95% CI; 1.02-2.60, p = 0.04) in comparison to non-obese individuals.CONCLUSION: Clinical measurements of adiposity (body mass index and abdominal obesity) correlate well and can be surrogate for systemic inflammatory state of individuals.
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    Association of monocyte chemoattractant protein - 1- 2518 polymorphism with metabolic syndrome in a South Indian cohort
    (Metabolic Syndrome Related Disorders, 2009) Kaur, S; Panicker, SR; James, T; Sarma, PS; Thankappan, KR; Kartha, CC
    BACKGROUND: Previous reports have indicated an association of monocyte chemoattractant protein-1 (MCP-1) with risk factors for atherosclerosis and coronary artery disease (CAD). Because some of these risk factors form components of metabolic syndrome, in the present study, we investigated the association of an important promoter region polymorphism of MCP-1, A-2518G, and its serum levels with metabolic syndrome in a South Indian cohort.METHODS: The study comprised of 126 healthy subjects aged 30-59 years from South India. Subjects were classified on the basis of presence or absence of metabolic syndrome and metabolic syndrome components as per the International Diabetes Federation definition. MCP-1 genotyping was done by polymerase chain reaction restriction fragment-length polymorphism, and serum levels were estimated by enzyme-linked immunosorbent assay. RESULTS: The MCP-1 -2518G allele frequency in the study population was 32.9% and the mean MCP-1 serum levels were 523 +/- 272.3 pg/mL. Subjects with metabolic syndrome showed an increased presence of the MCP-1 -2518G allele in comparison to those without metabolic syndrome (odds ratio [OR] = 5.03, P = 0.02). The association was related to a higher proportion of this allele in subjects with increased waist circumference (OR = 3.78, P = 0.05).CONCLUSIONS:The MCP-1 -2518G allele may be contributing to atherosclerosis and CAD by conferring an increased risk to metabolic syndrome and/or obesity.
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    Cardiomyopathies in the tropics
    (JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2004) Kartha, CC
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    Cerium levels are elevated in the serum of patients with endomyocardial fibrosis (EMF)
    (BIOLOGICAL TRACE ELEMENT RESEARCH, 1997)
    The geochemical hypothesis on endomyocardial fibrosis (EMF) links causation of the disease to increased levels of cerium in the heart. Since cardiac tissues are not easily accessible from patients, we explored whether cerium can be detected in the serum using neutron activation analysis (NAA). Cerium levels in serum of EMF patients were significantly elevated (p < 0.05) compared to controls.
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    Effects of epidermal growth factor on proliferation and migration of cardiosphere-derived cells expanded from adult human heart
    (GROWTH FACTORS, 2010) Rani, KGA; Kartha, CC
    Recent studies have provided evidence that the human heart has an endogenous reserve of cardiac stem cells (CSCs) that can be activated to reconstitute the dead myocardium. Current efforts are now directed towards the identification of factors favoring the growth and expansion of the CSC pool in the heart. Accordingly, in the present study, effects of different growth factors on cardiosphere-derived cells (CDCs), expanded from atrial biopsies from patients undergoing elective coronary artery bypass surgery, were analyzed. CSCs appear to respond to epidermal growth factor (EGF) more efficiently than other widely used growth factors such as vascular endothelial growth factor, insulin-like growth factor, basic fibroblast growth factor, hepatocyte growth factor, transforming growth factor, and platelet-derived growth factor. EGF significantly promoted cardiosphere formation (p < 0.05) and proliferation (p < 0.005), migration (p, 0.0005), and wound healing (p < 0.005) activities of CDCs in comparison to the other growth factors studied. Pretreatment with EGF enhanced the expression of cardiac markers cTN1(+) and MHC(+) in CDCs in comparison to untreated controls.
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    Elevated serum levels of 25-hydroxyvitamin D-3 in outdoor workers of South India
    (CURRENT SCIENCE, 1999) Rajasree, S; Kutty, VR; Sreenivasan, K; Kartha, CC
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    Forkhead box C2 Promoter Variant c.-512C > T Is Associated with Increased Susceptibility to Chronic Venous Diseases
    (PLOS ONE, 2014) Surendran, S; Girijamma, A; Nair, R; Ramegowda, KS; Nair, DH; Thulaseedharan, JV; Lakkappa, RB; Kamalapurkar, G; Kartha, CC
    Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (Fox(2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5' and 3' flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5' flanking region and one in 3' flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4 +/- 1.42 fold increased compared to saphenous veins from 20 normal subjects (p<0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C>T (rs34221227: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers 0114 and Hey2 and downregulation of venous marker COUP-TFIL Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.
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    Forkhead box C2 Promoter Variant c.-512C.T Is Associated with Increased Susceptibility to Chronic Venous Diseases
    (PLoS ONE., 2014-03) Surendran, S; Girijamma, A; Nair, R; Ramegowda, KS; Nair, DH; Jissa, VT; Lakkappa, RB; Kamalapurkar, G; Kartha, CC
    Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 59 and 39 flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 59 flanking region and one in 39 flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 461.42 fold increased compared to saphenous veins from 20 normal subjects (p,0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C.T (rs34221221: C.T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C.T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C.T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.
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    Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain
    (CLINICAL EPIGENETICS, 2016) Thomas, JM; Surendran, S; Abraham, M; Rajavelu, A; Kartha, CC
    Vascular malformations are developmental congenital abnormalities of the vascular system which may involve any segment of the vascular tree such as capillaries, veins, arteries, or lymphatics. Arteriovenous malformations (AVMs) are congenital vascular lesions, initially described as "erectile tumors," characterized by atypical aggregation of dilated arteries and veins. They may occur in any part of the body, including the brain, heart, liver, and skin. Severe clinical manifestations occur only in the brain. There is absence of normal vascular structure at the subarteriolar level and dearth of capillary bed resulting in aberrant arteriovenous shunting. The causative factor and pathogenic mechanisms of AVMs are unknown. Importantly, no marker proteins have been identified for AVM. AVM is a high flow vascular malformation and is considered to develop because of variability in the hemodynamic forces of blood flow. Altered local hemodynamics in the blood vessels can affect cellular metabolism and may trigger epigenetic factors of the endothelial cell. The genes that are recognized to be associated with AVM might be modulated by various epigenetic factors. We propose that AVMs result from a series of changes in the DNA methylation and histone modifications in the genes connected to vascular development. Aberrant epigenetic modifications in the genome of endothelial cells may drive the artery or vein to an aberrant phenotype. This review focuses on the molecular pathways of arterial and venous development and discusses the role of hemodynamic forces in the development of AVM and possible link between hemodynamic forces and epigenetic mechanisms in the pathogenesis of AVM.
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    Geographical distribution of endomyocardial fibrosis in south Kerala
    (INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 1996)
    Background. Endomyocardial fibrosis (EMF) is a chronic heart disease confined to a few geographically specific locations within 15 degrees of the equator. Several aetiological hypotheses exist, among them filarial infection, eosinophilia, and toxic effect of the monazite element cerium from the soil. This study attempts to find out whether the pattern of distribution of EMF in south Kerala in India is consistent with the geochemical hypothesis.Methods. From hospital records we identified all patients from south Kerala who had a confirmed diagnosis of EMF during the period 1978-1994, Our controls were patients from the southern districts diagnosed to have rheumatic heart disease (RHD) during the same period. We traced their residence address to the administrative subunit of taluk, and plotted the distribution of patients with EMF and RHD for each taluk in south Kerala. The taluks were then grouped into areas of high (>4/100 000), medium (2.01-4/100 000), and low (less than or equal to 2/100 000) density in each case.Results. We identified an area of high density of EMF comprising four taluks near the coastline situated within the dis districts of Alapuzha, Kollam, and Pathanamthitta. Two coastal taluks in Kollam and Alapuzha districts are known areas of deposits of monazite elements in the state. Geographical distribution is not related to prevalence of filariasis and eosinophilia.Conclusion. Coexistence of high density of occurrence of EMF and deposits of monazite elements support the geo chemical hypothesis.
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    Levels of cerium in the tissues of rats fed a magnesium-restricted and cerium-adulterated diet
    (BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 1996)
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    Magnesium deficiency and cerium promote fibrogenesis in rat heart
    (BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY, 1996)
    Cerium is a biologically active lanthanide and a major constituent of monazite. The observation that inhalation of particles of cerium causes pneumoconiosis had generated considerable interest in the toxicology of the element (Venugopal and Luckey 1978; Vocatura et al 1983). Cerium tartrate was found to produce cardiac injury and polycythaemia in small animals (Venugopal and Luckey 1978). More recently, tropical endomyocardial fibrosis (EMF), a restrictive cardiomyopathy, was postulated to be the cardiac expression of cerium toxicity in combination with magnesium deficiency (Valiathan et al 1989; Valiathan and Kartha 1990). The postulation was based upon the observation of elevated levels of cerium and depressed levels of magnesium in the cardiac tissue of patients with EMF (Valiathan et al 1989; Valiathan and Kartha 1990). Studies carried out in pursuance of the hypothesis showed that tissue levels of cerium are enhanced in magnesium deficiency (Eapen et al 1996) and that cerium and magnesium deficiency have a synergistic effect on cardiac metabolism (Gunther 1990; Shivakumar and Renuka Nair 1991). Importantly, recent observations on the mode of action of cerium at the molecular level suggested that the element may influence expression of matrix proteins like collagen in the heart and produce fibrosis (Prakash et al 1995; Shivakumar et al 1992). A sequel to these earlier investigations, the present study examined whether chronic ingestion of low doses of cerium would produce cardiac fibrosis in experimental animals. This communication presents evidence that cerium per se or in combination with magnesium deficiency produces subendocardial fibrosis and increase in interstitial cellularity and collagen content in rat heart. It also confirms the earlier observation from this laboratory that magnesium deficiency promotes accumulation of cerium in the cardiac tissue (Eapen el al 1996).