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Biomedical subjects

C C Kartha

Publications and source records attributed to C C Kartha.

At least 19 recordsLinked to original sources
PubMed2002

1,25-dihydroxyvitamin D3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D.

Several studies have demonstrated that excess of vitamin D3 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 D3 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 D3 (1,25(OH)2 D3) receptor levels and 45Ca uptake in smooth muscle cells. Serum samples collected at intervals were assayed for levels of 25-OH-D3 and calcium. The results showed that in animals given injections of cholecalciferol, serum levels of 25-OH-D3 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 D3 receptor levels were up regulated and 45Ca uptake enhanced in aortas of animals which were given excessive vitamin D3. The evidences gathered suggest that excess vitamin D is arteriotoxic and that the vitamin induces arterial calcification through up regulation of 1,25(OH)2D3 receptor and increased calcium uptake in smooth muscle cells of the arteries.

Animals↗
PubMed2001

Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease.

Several lines of evidence point to a possible relationship between vitamin D and cardiovascular disease. Animal experiments and observational studies in humans suggest vitamin D to be arteriotoxic and an association of high intake of vitamin D with increased incidence of ischemic heart disease (IHD). The major source of vitamin D in adults is vitamin D synthesized in the skin through exposure to the sun. In tropical environment there is a possibility of high level of solar exposure and enhanced serum levels of vitamin D in the population. We explored the relation between serum level of 25-hydroxyvitamin D3 and IHD in a case-control study involving 143 patients with either angiographic evidence of coronary artery disease or patients with acute myocardial infarction and 70 controls, all men in the age group of 45-65 years. Fasting blood samples were collected, serum separated and serum levels of 25-hydroxyvitamin D3 was measured by protein binding radioligand assay. Serum levels of cholesterol, triglyceride, calcium, magnesium and inorganic phosphate were also determined. Prevalences of diabetes, hypertension and smoking history were noted. Statistical comparisons of variables between cases and controls were done using chi2-tests. Multivariate logistic regression analysis was done to examine the association of IHD with serum levels of 25-hydroxyvitamin D3 controlling for selected variables. Serum levels of 25-hydroxyvitamin D3, calcium, inorganic phosphate, total cholesterol, low density lipoprotein and triglycerides were elevated in a higher proportion of patients, compared to controls. Serum levels of 25-OH-D3 above 222.5 nmol/l (89 ng/ml) was observed in 59.4% of cases compared to 22.1% in controls (p < 0.001; unadjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 2.62-10.21). When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D3 levels (> or = 222.5 nmol/l, > or = 89 ng/ml) and IHD is 3.18 (95% CI: 1.31-7.73). Given the evidences for the arteriotoxicity of vitamin D, further investigations are warranted to probe whether the elevated serum levels of 25-hydroxyvitamin D3 observed in patients with IHD in a tropical environment has any pathogenic significance.

Aged↗
PubMed1998

Pattern of cardiac fibrosis in rabbits periodically fed a magnesium-restricted diet and administered rare earth chloride through drinking water.

It has been postulated that causation of the tropical cardiomyopathy endomyocardial fibrosis (EMF) is linked to magnesium (Mg) deficiency and cardiac toxicity of the rare earth element cerium (Ce). The aim of the present study was to define the myocardial lesions in rabbits that were fed on Mg-restricted diet (70-80 ppm) periodically and were provided drinking water contaminated with rare earth chloride (1 g/L). Forty New Zealand white rabbits were divided into four groups following a 2 x 2 factorial design. Two groups were periodically fed on Mg-restricted diet with one of them receiving water contaminated with rare earth chloride. The other two groups were continuously fed on Mg-sufficient diet (350-400 ppm) with one of them receiving water contaminated with rare earth chloride. All animals were sacrificed at the end of 6 mo. Cardiac tissues were subjected to histology, elemental analysis (calcium [Ca], Mg, and Ce) and estimation of collagen content and collagen phenotypes. Histological lesions were compared with those of EMF in humans and those of acute Mg deficiency in animals. The results suggest that in rabbits, recurrent episodes of Mg deficiency lead to myocardial fibrosis similar to the pattern observed in human EMF.

Animals↗
PubMed1997

Cerium levels are elevated in the serum of patients with endomyocardial fibrosis (EMF).

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.

Adolescent↗
PubMed1997

Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart.

Magnesium deficiency is known to produce a cardiomyopathy, characterised by myocardial necrosis and fibrosis. As part of the ongoing investigations in this laboratory to establish the biochemical correlates of these histological changes, the present study probed the extent of lipid peroxidation and alterations in collagen metabolism in the heart in rats fed a magnesium-deficient diet for 28, 60 or 80 days. While lipid peroxidation was measured by the thiobarbituric acid reaction, collagen turnover rates and fibroblast proliferation were assessed using [3H]-proline and [3H]-thymidine, respectively. Tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. A 39% increase in the cardiac tissue level of thiobarbituric acid reactive substances was observed on day 60 of deficiency (p < 0.001). A marked drop in collagen deposition rate (59%, p < 0.001%) on day 28 but a significant rise in fractional synthesis rate (12%, p < 0.001) and collagen deposition rate (24%, p < 0.001) on day 60 were observed. A fibroproliferative response in the heart was evident on day 80 but not at earlier time-points. Thus, the present study provides evidence of increased lipid peroxidation and net deposition of collagen in the myocardium in response to dietary deficiency of magnesium. These changes were, however, not directly related to alterations in the tissue levels of Mg. It is suggested that the increase in cardiac collagen synthesis and fibroplasia associated with Mg deficiency may represent reparative fibrogenesis, upon oxidative damage to the cardiac muscle, and is mediated by a mechanism independent of changes in cardiac tissue levels of Mg.

Animals↗
PubMed1996

Levels of cerium in the tissues of rats fed a magnesium-restricted and cerium-adulterated diet.

Cerium, a lanthanide, is the most abundant rare earth element present in monazite and is biologically active. It has been postulated that cerium toxicity in conjunction with magnesium deficiency causes tropical endomyocardial fibrosis, a restrictive human cardiomyopathy (Valiathan et al. 1989; Valiathan and Kartha 1990). Generally, lanthanides are known to be poorly absorbed (Durbin et al. 1956; Evans 1990). The present study was carried out to ascertain whether magnesium deficiency promotes accumulation of cerium in various organs of rats.

Animals↗
PubMed1996

Ultrastructural analysis of the adjacent epithelium of oral squamous cell carcinoma.

Fifteen biopsies of the immediate adjacent epithelium of oral squamous cell carcinoma were examined under light and electron microscopy. Light microscopic examination of one micron thick sections revealed that the majority of lesions (67%) had hyperplastic or mildly dysplastic epithelium while the remaining (33%) had moderate to severe dysplasia. Ultrastructural observations showed that all these lesions had subcellular alterations similar to those seen in frank malignant oral tissue, particularly in the lower half of the epithelium. Important ultrastructural changes observed included bizarre nuclei of basal and lower spinal cells, enlarged and multiple nucleoli, presence of interchromatin and perichromatin granules, loss of desmosomes and marked spongiosis as well as disturbed cellular maturation sequences in the keratinocytes evidenced by abnormal and irregular distribution of maturation markers such as keratohyalin granules and tonofilaments. The present study thus shows the value of electron microscopy in the detection of malignant changes in the adjacent epithelium of oral squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1996

Geographical distribution of endomyocardial fibrosis in south Kerala.

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 (< or = 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 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 geochemical hypothesis.

Adolescent↗
PubMed1996

Response to thymectomy in South Indian patients with myasthenia gravis.

AIMS: The rate of remission among patients with myasthenia gravis (MG) following thymectomy and the predictors of the outcome have revealed vast variation in studies from different geographic regions raising suspicion about the influence of ethnic factors. MATERIAL & METHODS: We retrospectively evaluated the outcome of 71 South Indian MG patients who were thymectomized between 1987 through 1993 and analyzed the relationship between clinical and histopathological features and postthymectomy outcome. RESULTS: The clinical severity of the disease did not differ between the 29 patients with and 42 patients without a thymoma. Seventynine percent of our patients responded favourably to thymectomy; without additional immunosupression therapy, 52% achieved a near-complete remission. An younger age and milder disease correlated with a good outcome. Patients with thymoma responded as favourably as those without a thymoma. CONCLUSIONS: The postthymectomy response of South Indian MG patients in general did not differ from that of Western and Oriental patients.

Adolescent↗
PubMed1994

Ultrastructure of oral squamous cell carcinoma: a comparative analysis of different histological types.

Twenty-five oral carcinomas and five normal oral epithelial specimens were studied using light and electron microscopy. All histological types (well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma, poorly differentiated squamous cell carcinoma, verrucous carcinoma and spindle cell carcinoma) were seen in the study sample. In addition, 1 case of carcinoma in situ was also present. The normal oral epithelium consisted of three keratinising types (gingiva) and two non-keratinising types (buccal mucosa). The ultrastructural features of oral carcinomas showed good correlation with the features seen in light microscopy. The differentiation status of the lesions showed a relationship with cell and nuclear size, tonofilament and keratin content as well as few other cellular abnormalities. It was also observed that the fine details revealed by electron microscopy were often a means of explaining the characteristic histopathological features of oral carcinoma.

Biopsy↗
PubMed1994

Self-expandable stents for tracheal stenosis: experience in two patients.

Two patients with cervical tracheal stenosis, following prolonged ventilatory support, underwent balloon dilatation and expandable stainless steel stent placement across the stenoses. Following the successful release of the stent, there was gradual widening of the stenosed trachea in one patient, while in the other re-stenosis occurred due to columns of tracheal tissue projecting between the limbs of the stent. In the chronically ill and debilitated, use of expandable stents provides a good alternative to complex reconstructive surgery.

Adult↗
PubMed1994

Expression of proto-oncogenes, genes for muscle specific isoforms and heat shock protein (HSP) -70 gene in hypertrophied cardiac muscles from patients with atrial septal defect or tetralogy of Fallot.

Studies on the expression of proto-oncogenes and muscle specific genes in hypertrophied human hearts have shown that proto-oncogenes such as c-myc, c-fos and c-ras are activated in both atrial and ventricular tissues of patients with atrial septal defect (ASD) and tetralogy of Fallot (TOF). Although the expression of muscle specific genes such as MLC2 and skeletal alpha-actin are induced the expression of tissue specific cardiac actin remained the same in both the control and diseased tissues. Further, an increased synthesis of messengers of heat shock protein gene-HSP70 was observed in the ventricular tissues of TOF patients, with out much of a change in atrial tissues of patients with ASD.

Actins↗
PubMed1993

Ultrastructural variations and assessment of malignant transformation risk in oral leukoplakia.

Oral cancer is the most common malignancy in India, having a well defined precancerous state, leukoplakia. Various follow-up studies have shown that only 4 to 18% of oral leukoplakia lesions subsequently progress into invasive malignancy over a period of time. This study evaluates the potential of electron microscopy in the early detection of malignant changes in leukoplakia. The study revealed that of the 25 leukoplakia lesions examined, 7 showed changes akin to malignancy. Predominant ultrastructural alterations observed were reduplication and discontinuity of the basal lamina, basal cells with pleomorphic and bizarre nuclei containing perichromatin and interchromatin granules, prominent intercellular spaces and poorly formed desmosomes. Since none of these changes were evident under light microscopy the study demonstrates the value of electron microscopy in evaluating oral carcinogenesis. A long term follow-up of such patients is needed to understand the prognostic implications of these ultrastructural variation and how they can be used as a base line for better light microscopic evaluation.

Cell Transformation, Neoplastic↗
PubMed1993

Structural basis for mitral valve dysfunction associated with ostium secundum atrial septal defects.

Mitral valve (MV) specimens obtained at operation from 50 patients with ostium secundum atrial septal defect and associated MV dysfunction were studied macro- and microscopically to evaluate the structural lesions. The functional abnormalities in these patients were isolated mitral stenosis, isolated mitral regurgitation, mitral valve prolapse or mitral stenosis with regurgitation. Post-inflammatory lesions were commonly found in those with mitral stenosis who had a past history of rheumatic fever. Patients with mitral valve prolapse had either post-inflammatory lesions or lesions attributable to haemodynamic stress but different from the extensive lesions seen in floppy MV syndrome.

Adolescent↗
PubMed1991

Discordant atrioventricular connection and concordant ventriculoarterial connection in situs inversus: isolated ventricular noninversion.

A case of discordant atrioventricular (AV) connection and concordant ventriculoarterial (VA) connection (with aortomitral fibrous continuity and tricuspid pulmonary discontinuity) in situs inversus (I, D, I) is reported because of its rarity. This segmental combination with abnormally related great arteries in the absence of anomalies of venous connections and/or splenic anomalies is extremely rare.

Female↗