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Biomedical subjects

R Ravikumar

Publications and source records attributed to R Ravikumar.

At least 19 recordsLinked to original sources

Intimal media thickness, glucose intolerance and metabolic syndrome in Asian Indians--the Chennai Urban Rural Epidemiology Study (CURES -22).

AIMS: The aim of the present study was to assess carotid intimal media thickness (IMT) in different grades of glucose intolerance and the metabolic syndrome (MS) in Asian Indians, a high-risk group for diabetes and coronary artery disease. METHODS: Subjects with normal glucose tolerance (NGT) (n = 1600), impaired glucose tolerance (IGT) (n = 330), newly diagnosed diabetes (NDD) (n = 330) and known diabetes (KD) (n = 1170) were recruited from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing study on a representative population of Chennai (formerly Madras), in southern India. Assessment of carotid IMT was performed using high-resolution B-mode ultrasonography. MS was defined using modified adult treatment parel (ATP) III guidelines. Subjects with self-reported diabetes, hypertension and dyslipidaemia were excluded from the analysis on MS. RESULTS: Subjects with glucose intolerance had significantly higher mean carotid IMT values compared with subjects with normal glucose tolerance (NGT 0.69 +/- 0.12 mm, IGT 0.75 +/- 0.16 mm, NDD 0.79 +/- 0.19 mm and KD 0.87 +/- 0.24 mm, P < 0.001). Regression analysis showed that there was a linear increase in mean IMT values with increasing severity of glucose intolerance, even after adjusting for age and gender. Mean IMT values were higher in those with MS and increased with increase in number of metabolic abnormalities (subjects without any metabolic abnormality 0.66 +/- 0.12 mm, one abnormality 0.67 +/- 0.13 mm, two 0.70 +/- 0.12 mm, three 0.72 +/- 0.12 mm, four 0.77 +/- 0.15 mm, five 0.76 +/- 0.13 mm). Regression models showed MS to be associated with IMT, even after adjusting for age, gender and presence of diabetes (P = 0.021). CONCLUSIONS: In Asian Indians, carotid IMT increases progressively with increasing severity of glucose intolerance and is also associated with the metabolic syndrome, independent of age, gender and presence of diabetes.

Adult↗

Proinflammatory synergism of ethanol and HIV-1 Tat protein in brain tissue.

Human immunodeficiency virus type 1 (HIV-1) Tat protein is a potent transactivator of viral replication. It is actively released from HIV-infected cells and has been shown to induce cell injury effects. Alcohol abuse is a risk factor of HIV infection and we hypothesize that alcohol and Tat may interact in an additive or synergistic fashion to influence molecular processes which can contribute to their toxic effects. To study this possibility, we investigated the effects of two intraperitoneal injections of ethanol (EtOH, 3 g/kg each, 16 h apart) and a single intracerebral injection of Tat (25 microg/microl into the right hippocampus, injected 12 h after the first EtOH injection) on generation of cellular oxidative stress, DNA binding activity of redox-responsive transcription factors, and induction of inflammatory genes in the hippocampus and corpus striatum of mouse brain. As compared to control animals, treatment with EtOH plus Tat resulted in increased production of reactive oxygen species in both brain regions. In addition, DNA binding activities of nuclear factor-kappaB (NF-kappaB) and CREB in both brain regions and SP-1 in the hippocampus were more pronounced in mice injected with Tat plus EtOH as compared to the effects of Tat or EtOH alone. Among studied inflammatory genes, induction of IL-1beta and MCP-1 was potentiated in animals injected with EtOH plus Tat. These results indicate that Tat and EtOH can cross-amplify their cellular effects, leading to alterations of redox-regulated inflammatory pathways in the brain. Such potentiation of proinflammatory stimulation may further contribute to CNS pathology in HIV-infected patients who are alcohol abusers.

Animals↗

Nicotine attenuates morphological deficits in a contusion model of spinal cord injury.

Protection against the progression of secondary injury appears to be an effective therapeutic strategy in spinal cord injury (SCI). Evidence indicates that nicotine can induce potent neuroprotective effects against injury to spinal cord neurons. Therefore, the present study was focused on the effects of nicotine on the behavioral and morphological recovery associated with SCI. Adult male Long-Evans rats were subjected to a moderate contusion model of SCI and received subcutaneous injections of nicotine for 14 days at the dose of 0.35 or 7 mg/kg/day. The rats were examined using the BBB locomotor rating scale for 6 weeks. At the end of the BBB recording, spinal cords were examined for the volumetric tissue sparing of gray and white matters. All SCI rats demonstrated a loss of hindlimb function followed by a recovery phase that peaked at 2-3 weeks after the trauma. Compared to untreated SCI rats, chronic nicotine administration appeared to improve the recovery of the locomotor functions. Indeed, nicotine-treated animals scored consistently higher on the BBB scale indicating that the treatment altered animal behavior. However, when taking under consideration correction factors for multiple comparisons, these data did not reach significance at overall experimental levels of significance 0.05. Nevertheless, nicotine administration was effective in sparing tissue at injury epicenter and a lower dose of nicotine also resulted in significant sparing of white matter of the injured spinal cord. These results suggest that agonists of neuronal nicotinic receptors can be attractive candidates for SCI therapy.

Animals↗

Nicotine attenuates oxidative stress, activation of redox-regulated transcription factors and induction of proinflammatory genes in compressive spinal cord trauma.

Pathophysiology of neurodegeneration following spinal cord injury (SCI) involves alterations of cellular redox status, activation of transcription factors and induction of proinflammatory genes. In addition, recent evidence indicates that nicotine can induce potent neuroprotective effects. To study the influence of nicotine on the redox signaling pathways in relationship to SCI, moderate contusions of spinal cords at the level of T-10 were induced in rats treated or untreated with nicotine. Cellular oxidative stress, DNA binding activity of redox-responsive transcription factors (AP-1, NF-kappaB and CREB) as well as mRNA levels of inflammatory genes (MCP-1 and TNF-alpha) were determined in the thoracic and lumbar regions of the spinal cords. Nicotine was administrated 2 h after the SCI in a single i.p. injection at the dose of 0.35, 3.5 or 7 mg/kg, and rats were sacrificed 3 h following such an injection. Spinal cord trauma was associated with a significant increase in oxidative stress, and activation of NF-kappaB, AP-1 and CREB, as well as overexpression of MCP-1 and TNF-alpha in both the thoracic and lumbar regions. Nicotine administration following the SCI markedly attenuated, especially in the lumbar region, these oxidative and proinflammatory responses. These protective effects of nicotine were fully reversed by inhibition of neuronal nicotinic receptors by mecamylamine. The present results indicate that nicotine administration can attenuate the oxidative injury to spinal cords and suggest that neuronal nicotinic receptors can be attractive targets for neuroprotective therapy.

Animals↗

Redox status and lipid peroxidation in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes.

BACKGROUND: Free radical-mediated oxidative stress has been implicated in the progression of alcoholic hypertension and diabetic hypertension. METHODS: The lipid peroxides and antioxidant status of plasma and erythrocytes were investigated in alcoholic hypertensive patients and alcoholic hypertensive patients with diabetes and compared with normal subjects. RESULTS: A significant increase is observed in the levels of glucose, lipid peroxidation (P<0.05) in the alcoholic hypertensive patients with/without diabetes and the increase was significantly higher in alcoholic hypertensive patients with diabetes. The activities of erythrocyte antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) and plasma concentrations of GSH, vitamin C, vitamin E and beta-carotene decreased significantly and the level of ceruloplasmin increased in alcoholic hypertensive patients with/without diabetes when compared to normal subjects. Plasma GSH and vitamin E levels exhibited a further decrease in alcoholic hypertensive patients with diabetes. CONCLUSIONS: An enhanced lipid peroxidation is observed in alcoholic hypertensive patients with diabetes and a more pronounced decrease in the levels of plasma GSH and vitamin E among antioxidants.

Adult↗

Relationship of lipoprotein(a) with intimal medial thickness of the carotid artery in Type 2 diabetic patients in south India.

OBJECTIVE: The objective of this study was to investigate the association of lipoprotein(a) [Lp(a)] levels with intimal medial thickness (IMT) in Type 2 diabetic patients in south India. STUDY DESIGN: We studied 587 consecutive Type 2 diabetic patients at the M.V. Diabetes Specialities Centre, Chennai. The mean age of the study group was 55 +/- 10 years and 71.2% were males. IMT of the right common carotid artery was determined using high-resolution B mode ultrasonography. Lp(a) levels were measured using ELISA. Since the frequency distribution of Lp(a) was skewed, Lp(a) values were log transformed and the geometric mean was used for statistical analysis. The tertiles of IMT were determined to analyse the association of Lp(a) and other factors with IMT. RESULT: The mean Lp(a) level in the study patients was 18.9 +/- 3.1 mg/dl (geometric mean +/- sd) and the mean IMT of the study subjects was 0.93 +/- 0.19 mm (mean +/- sd). The prevalence of carotid atherosclerosis (defined as IMT > 1.1 mm) among subjects with elevated Lp(a) levels > 20 mg/dl was significantly higher compared with those with Lp(a) levels </= 20 mg/dl (26.9% vs. 16.3%, P = 0.003). Lp(a) levels increased with increase in tertiles of IMT (anova, P < 0.05). Pearson correlation analysis of carotid IMT with other cardiovascular risk factors revealed strong correlation of IMT with age (P < 0.0001), duration of diabetes (P < 0.0001), systolic blood pressure (P < 0.0001), diastolic blood pressure (P = 0.006), LDL-cholesterol (P = 0.023), HbA1c (P = 0.017) and Lp(a) (P < 0.0001). Multiple logistic regression analysis showed age (P = 0.010), LDL-cholesterol (P = 0.032) and Lp(a) (P = 0.021) to be associated with carotid atherosclerosis. CONCLUSION: The results suggest that Lp(a) has a strong association with IMT of carotid arteries in Type 2 diabetic subjects in south India.

Age Factors↗

Prevalence of non-diabetic renal disease in type 2 diabetic patients in a diabetes centre in Southern India.

OBJECTIVE: The Aim of Study is to determine the prevalence of non-diabetic renal disease among South Indian type 2 diabetic subjects based on renal biopsy. METHODS: Three thousand five hundred and ninety subjects with complete records were included for the study. One hundred and forty subjects who had proteinuria but no evidence of retinopathy undertook a 24 hour proteinuric estimation. Of these 140 subjects, 28 subjects had proteinuria > 1,000 mg/day and were subjected to renal imaging. Seven subjects were excluded due to renal calculi, cysts or contracted kidneys. Of the remaining 21 diabetic subjects, one subject was excluded as he had a mild diabetic retinopathy on fundus fluorescein angiography. Of the 20 subjects included 18 participated in the renal biopsy study (response rate--90%). Renal pathology of these subjects were studied. RESULTS: Of the 18 renal biopsies, two were excluded due to different reasons. Out of 16 patients, eight (50%) had pathological changes suggestive of diabetic etiology, five (33.3%) had classical membranous nephropathy, one (6.2%) had tubulo-interstitial disease and two (12.5%) were categorized as others with minimal changes. The subjects with non-diabetic renal disease had significantly higher creatinine clearance (p = 0.024), serum cholesterol (p = 0.036), triglyceride levels (p = 0.045) and LDL cholesterol (p = 0.048) compared to subjects with diabetic nephropathy. CONCLUSION: This study suggests that even in subjects clinically suspected to have non-diabetic renal disease many may turn out to have diabetic nephropathy on renal biopsy.

Adult↗

Comparison of colour duplex ultrasound and ankle-brachial pressure index measurements in peripheral vascular disease in type 2 diabetic patients with foot infections.

BACKGROUND AND OBJECTIVES: Peripheral vascular disease (PVD) is a common cause of morbidity and mortality and is reported to be more common among diabetic subjects compared to non-diabetic subjects. The aim of the study was to compare the specificity and sensitivity of ankle-brachial index (ABI) measured by peripheral doppler with the colour duplex ultrasound (CDU) for diagnosis of PVD. METHODS: One hundred type 2 diabetic patients admitted to our diabetic centre with foot lesions underwent both colour duplex ultrasound and ankle-brachial index measurements. PVD was diagnosed if the individual had haemodynamically significant obstruction on CDU, or if the ABI was < 0.9. The sensitivity and specificity of ABI was determined using the CDU as 'gold standard'. RESULTS: The mean age of the study group was 59.5 +/- 10.1 years and the mean duration of diabetes was 11.7 +/- 8.1 years. Of the total 100 subjects, six subjects had calcification of peripheral vessels and they were not included while calculating for sensitivity and specificity of ABI. Twenty (21.3%) subjects diagnosed as PVD by the CDU were not classified as PVD by the ABI measurements. Conversely, only three subjects (3.2%) classified as PVD by ABI had normal arteries based on CDU scanning. Overall, ABI had low sensitivity (70.6%) but a high specificity (88.5%). The overall agreement between CDU and ABI was poor (k = 0.20). CONCLUSION: ABI is a good initial screening tool but some patients with significant stenosis in lower extremities would be missed, if ABI measurement alone is used for diagnosis of PVD.

Aged↗

Intimal medial thickness of the carotid artery in South Indian diabetic and non-diabetic subjects: the Chennai Urban Population Study (CUPS).

AIM/HYPOTHESIS: Increased intimal medial thickness (IMT) of the carotid arteries is considered a useful marker of atherosclerosis. The aim of this study was to compare the intimal medial thickness values in urban non-diabetic and diabetic South Indian subjects who have a high risk of coronary artery disease. METHODS: The subjects for this study were 140 diabetic and 103 non-diabetic control subjects matched with them for age and sex selected from The Chennai Urban Population Study which is an ongoing epidemiological study. Intimal medial thickness of the right common carotid artery was determined using high resolution B mode ultrasonography. RESULTS: The mean intimal medial thickness values of the diabetic subjects (0.95 +/- 0.31 mm) were significantly higher than those of the non-diabetic (0.74 +/- 0.14 mm) subjects (p < 0.001). Both in the normal and diabetic subjects, these values increased with age. At any given age, the diabetic subjects had higher values than the non-diabetic subjects but the difference reached statistical significance after age 50 years (p < 0.05). Intimal medial thickness showed a correlation with age, total cholesterol, LDL cholesterol, waist:hip ratio and systolic blood pressure in non-diabetic subjects and with age and duration of diabetes in the diabetic subjects. Multivariate linear regression analysis showed that age and diabetes were the major risk factors for intimal medial thickness. CONCLUSION/INTERPRETATION: Diabetic subjects have higher intimal medial thickness values than non-diabetic subjects. Diabetes and age are the most important risk factors associated with increased intimal medial thickness in this South Indian cohort.

Adult↗

Chronic (-) deprenyl administration increases dendritic arborization in CA3 neurons of hippocampus and AChE activity in specific regions of the primate brain.

The mechanism by which (-) deprenyl enhances cognitive function in Alzheimer's disease (AD) is not yet understood. (-) Deprenyl (0.2 mg/kg/day) was administered intramuscularly to adult male monkeys (n = 6) for 25 days. Control monkeys (n = 6) received physiological saline by the same route. The activity of acetylcholinesterase (AChE) in different brain regions and the dendritic arborization in CA3 pyramidal neurons of hippocampus were analysed. (-) Deprenyl-treated monkeys showed a significant increase in the AChE activity by 43% (p < 0.001) in the frontal cortex, by 39% (p < 0.025) in the motor cortex, by 66% (p < 0.001) in the hippocampus and by 26% (p < 0.05) in the striatum compared to controls. The branching points and the intersections of both apical and basal dendrites of CA3 hippocampal pyramidal neurons were also significantly increased in (-) deprenyl-treated monkeys. Enhanced AChE activity may increase dendritic arborization in the hippocampus and it may also play a role in improving cognitive functions observed in AD, following (-) deprenyl treatment.

Acetylcholinesterase↗

(-)-Deprenyl attenuates spinal motor neuron degeneration and associated locomotor deficits in rats subjected to spinal cord ischemia.

We have evaluated potential neuroprotection offered by (-)-deprenyl on degenerating motor neurons of the spinal cord when subjected to transient ischemia. Thirty-six healthy adult male Wistar rats were trained for a motor function test in a staircase maze and randomly but equally (n = 6) grouped into normal control, sham control, ischemia (IS), IS rats treated with vehicle (IV), and rats treated with low (0.1 mg/kg) and high (1.0 mg/kg) doses of (-)-deprenyl. (-)-Deprenyl was given intraperitoneally 30 min after the induction of ischemia and thereafter everyday for 14 days. Spinal cord ischemia was produced at the lumbar level in conscious rats by occluding the abdominal aorta just below the branching point of the left renal artery for 30 min. Analysis of the motor performance in all groups of rats revealed a significant (P < 0.001) increase in the time taken to cross the run way of the maze, in i.s. and i.v. rats compared to all other groups of rats. In addition, qualitative and quantitative examination of spinal motor neurons at the lumbar level showed a significant (P < 0.001) decrease in the number of healthy motor neurons in i.s. and i.v. rats compared to controls. Postischemic administration of (-)-deprenyl, at both doses, significantly prevented motor neuron degeneration and the associated locomotor deficits in IS rats.

Animals↗

Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain.

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.

3,4-Dihydroxyphenylacetic Acid↗

Penile cancer--is lymphadenectomy necessary in all cases?

OBJECTIVES: This retrospective study examines the need for lymphadenectomy in all cases of penile cancer. METHODS: Thirty-six patients were followed up regularly by the same person between 1986 and 1992. RESULTS: Nine (25%) patients presented with positive groin lymph nodes and underwent immediate ilioinguinal node dissection. Of the 27 (75%) patients who presented with negative groin lymph nodes, 10 had a delayed lymph node dissection. Four of these patients are alive at 3.7 years. Three died within 1 year of surgery and 3 are lost to follow-up. Seventeen patients (47%) did not require lymphadenectomy and 14 (82%) of these patients are alive at 3.8 years, the other 3 being lost to follow-up. CONCLUSIONS: A careful, closely monitored, follow-up protocol can eliminate the need for lymphadenectomy in select patients with penile cancer.

Adult↗

Changes in cholinesterase system in different brain areas during the development of behavioral tolerance to monocrotophos toxicity in male albino rats.

During the development of behavioral tolerance to the organophosphate monocrotophos, the activities of AChE and BuChE and the content of ACh were affected in different brain areas of male albino rats. The inhibition of AChE and BuChE activities and the elevation of ACh content were progressive till 7 days and were followed by a recovery trend towards normalcy. The changes correlated with the appearance and disappearance of signs and symptoms of toxicity, which were mainly cholinergic. The results suggest the possibility of de novo synthesis of cholinesterases resulting in the development of behavioral tolerance, as was evident by the recovery trend. The shift of toxicity from greater AChE inhibition during initial periods to greater BuChE inhibition during later periods indicates the possible involvement of pseudocholinesterases in the development of tolerance and in the reduction of toxicity. The brain areas were differentially affected. Cerebral cortex was more affected initially but it was the striatum that was affected more during later dosings. The results show that behavioral tolerance to monocrotophos toxicity develops despite changes in AChE and BuChE activities and ACh content.

Acetylcholine↗

Comparison of techniques for the estimation of the prevalence of poliomyelitis in developing countries.

Although reliable data on the prevalence and trends of paralytic poliomyelitis are necessary for health planning, they are often difficult to obtain in developing countries. Comparisons were made of the cost and the time taken to obtain prevalence rates of residual poliomyelitis paralysis in a single community by (1) a surveillance and reporting system using physicians and other practitioners, (2) a school survey covering grades 1 to 12, (3) annual surveys of grade 1 schoolchildren, and (4) a house-to-house questionnaire survey. These techniques gave poliomyelitis prevalence rates of 3-5 per 1000 school-age children, and poliomyelitis incidence rates of 12-29 per 100 000 population per year. The annual grade 1 school survey was the cheapest and easiest to carry out and appears reliable in areas with a high rate of school enrolment.

Adolescent↗