Sudhakar Pemminati

Effect of ethanolic leaf extract of Ocimum sanctum on haloperidol-induced catalepsy in albino mice

Neuroleptic drugs used in the treatment of schizophrenia and other affective disorders are known to produce extrapyramidal side effects. Catalepsy induced by these drugs in

Effects of Swimming Exercise on Learning and Memory in the Kainate-Lesion Model of Temporal Lobe Epilepsy

INTRODUCTION An aerobic exercise (Ex) augments neurogenesis and may ameliorate learning and memory deficits in the rat Kainic Acid (KA) model of temporal lobe epilepsy in the short-term but whether it reverses learning and memory deficits after a substantial period of delay remains unclear. AIM This study tests the hypothesis that aerobic Ex attenuates the learning and memory deficits associated with kainate seizures in the long-term. MATERIALS AND METHODS A total of 60 rats were subjected to chemical lesioning using KA and to an Ex intervention consisting of a 30 days period of daily swimming for 15 min, immediately after KA lesioning (immediate exposure) or after a 60 days period of normal activity (delayed exposure). We evaluated spatial learning on a T-maze test, expressed as percentage of correct responses. We evaluated memory on a passive-avoidance test, expressed as time spent in a compartment in which the rats were previously exposed to an aversive stimulus. RESULTS Ex increases the percentage of correct responses, percentage bias, and number of alternations, associated with the T-maze testing for the normal control, sham-operated control and kainate-lesioned animals after both immediate and delayed exposures to Ex. Ex decreased the time exposed to the aversive stimulus in the smaller compartment of the two-compartment passive-avoidance test, also for the normal control, sham-operated control and kainate-lesioned animals after both immediate and delayed exposures to Ex. CONCLUSION These findings suggest that, after temporal lobe epileptic seizures in rats, swimming exercise may attenuate the learning and memory deficits, even if the exercise treatment is delayed.

Are the Newer Antidiabetic Agents Worth the Cost

Type 2 Diabetes Mellitus (T2DM) is a multisystem metabolic disease that requires lifelong medical management. While the burden of T2DM to society can be measured in dollars and rupees, the cost of T2DM to the patient may be immeasurable, reflecting the daily challenges of this chronic disease and uncertain quality of life. Citizens of the 21st century are experiencing a pandemic of T2DM which has motivated development of an armamentarium of new antidiabetic drugs. The new antidiabetic medicines, classified by mechanism of action, include: (i) the glucagon like polypeptide (GLP-1) analogues exenatide and liraglutide; (ii) the renal sodium glucose transport-2 (SGLT-2) inhibitors canagliflozin and dafagliflozin; (iii) the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin; (iv) the amylin analogue pramlinitide; and (v) the insulin analogues: aspart, lispro, and glargine. The older, conventional antidiabetic medicines such as glibenclamide, glimepiride, metformin, pioglitazone, and the insulin preparations are, largely, much less expensive and therefore more affordable to the diabetic patient than the newer drugs. Furthermore, it is known that patient compliance with antidiabetic treatments, almost exclusively, depends on the direct cost to the patient [1]. This problem of compliance is magnified by the fact that antidiabetic treatments are lifelong and, hence, present the diabetic patient with substantial financial, behavioral and emotional challenges which must be overcome. Another challenge is that patients may not have health insurance, but even if they do, health insurance policies often do not cover drugs for outpatient use. Zhang et al., analysed the benefits and harms of antihyperglycaemic treatment regimens considering clinical effectiveness, quality of life, and cost. They found that older agents like sulfonylureas were associated with greater benefit in terms of both life-years, quality adjusted life years, and less expensive compared with newer glucose lowering agents like, sitagliptin and exenatide. Monthly medication cost (USD) of metformin 81.75, sulfonylurea 54.85, whereas newer medications like GLP-1 agonist 325.97, DPP-4 inhibitor 232.84 [2]. Limited knowledge of the longterm safety of the newer antidiabetic agents is another important issue. For example, it has been reported that, a 51-year-old woman with longstanding T2DM developed liraglutide induced acute pancreatitis. Her symptoms resolved after withdrawal of this GLP-1 analogue [3]. GLP-1 agonists are contraindicated in patients with histories of pancreatitis, glomerular filtration rate < 30 mL/min, or gastroparesis. Another report demonstrates a significant risk of subclinical pancreatic inflammation, pancreatic cancer, and neuroendocrine tumours in users of exenatide [4]. The DPP-4 inhibitors are commonly associated with nasopharyngitis, headache, and respiratory infections, but pancreatitis, pancreatic cancer, elevation of hepatic enzyme activity; skin reactions and severe joint pain are also reported in users of DPP-4 inhibitors [5]. The SGLT-2 inhibitors are known to cause urinary and genital tract infections, dehydration, and hyperkalaemia. As per a recent report of a 60-year-old man with T2DM treated with glimepiride, metformin, insulin, and canagliflozin developed hypercalcaemia due to intestinal and urinary calcium absorption possibly due to inhibition of SGLT by the canagliflozin [6]. These are but a few examples of why more research is needed to support the safe use of these novel antidiabetic agents. Apart from the financial challenges faced by diabetic patients there is substantial uncertainty about the safety of the newer antidiabetic drugs—newer is not necessarily better.

Unique Application of Cryocone to Diagnose Umbilical Pilonidal Cyst

Patients with umbilical disorders who present with complaints of a mass, pain, tenderness or discharge will typically have a differential diagnosis including umbilical hernias, pyogenic granuloma, endometriosis, Sister Mary Joseph nodule and urachal or epidermoid cysts. We would add the inclusion of pilonidal sinus disease and present the case of a patient with an umbilical pilonidal cyst. The use of a cryocone with lubricating jelly, in this case, proved to be an easy and convenient method that aided in visualization and diagnosis of this fairly uncommon condition.

Differentiation of Overweight from Normal Weight Young Adults by Postprandial Heart Rate Variability and Systolic Blood Pressure

INTRODUCTION Obesity and cardiovascular disease are inextricably linked and the health communitys response to the current epidemic of adolescent obesity may be improved by the ability to target adolescents at highest risk for developing cardiovascular disease in the future. Overweight manifests early as autonomic dysregulation and current methods do not permit differentiation of overweight adolescents or young adults at highest risk for developing cardiovascular disease. AIM This study was designed to test the hypothesis that scaling exponents motivated by nonlinear fractal analyses of Heart Rate Variability (HRV) differentiate overweight, otherwise healthy adolescent/young adult subjects at risk for developing prehypertension, the primary forerunner of cardiovascular disease. MATERIALS AND METHODS The subjects were 18-20year old males with Body Mass Index (BMI) 20.1-42.5kg/m(2). Electrocardiographic inter-beat (RR) intervals were measured during 3h periods of bed rest after overnight fasting and ingestion of 900Cal high-carbohydrate and high-fat test beverages on separate days. Detrended Fluctuation Analysis (DFA), k-means cluster and ANOVA analyses of scaling coefficients α, α(1), and α(2), showed dependencies on hourly measurements of systolic blood pressure and on premeasured BMI. RESULTS It was observed that α value increased during the caloric challenge, appears to represent metabolically-induced changes in HRV across the participants. An ancillary analysis was performed to determine the dependency on BMI without BMI as a parameter. Cluster analysis of the high-carbohydrate test beverage treatment and the high-fat treatment produced grouping with very little overlap. ANOVA on both clusters demonstrated significance at p<0.001. We were able to demonstrate increased sympathetic modulation of our study group during ingestion and metabolism of isocaloric high-carbohydrate and high-fat test beverages. CONCLUSION These findings demonstrate significantly different clustering of α, α1, and α2 and Systolic Blood Pressure (SBP) with respect to normal, overweight and obese BMI.

Prevalence of Hypertension in Boloor Diabetes Study (BDS-II) and its Risk Factors.

INTRODUCTION Hypertension is a major public health problem in India and worldwide. Since hypertension is often asymptomatic, it commonly remains undetected, leading to serious complications if untreated. Hypertension is one of the leading causes of end stage renal disease. It doubles the risk of developing coronary artery disease, increases the risk of congestive heart failure by four folds and that of cerebrovascular disease and stroke by seven folds. Hypertension is directly responsible for 57% of all stroke deaths and 42% of coronary heart disease deaths in India. AIM To identify prevalence and risk factors for hypertension in a semi urban population of Mangalore, who participated in Boloor Diabetes Study (BDS-II). MATERIALS AND METHODS This cross-sectional study was conducted on 551 subjects aged ≥ 20 years who were randomly selected. Hypertension was diagnosed and classified according to Joint National Committee 7 (JNC) criteria. Blood pressure was measured by a doctor using calibrated sphygmomanometer. Anthropometric measurements, lipid and glucose estimations were done for all subjects. Statistical analysis was done using Chi-square test and students t-test (unpaired). Multivariate logistic regression analysis was done using hypertension as dependent variable and the various risk factors as independent variables. RESULTS Overall prevalence of hypertension in the community was 41% (227/551) (40.9% in men, 41.3% in women). Prehypertension was found in 40% (223/551) (45.4% in men, 38.1% in women), and only 18.3% (101/551) had normal blood pressure. Stage I hypertension was seen in 29.7% (164/551) (28.9% in men, 30.1% in women). Stage II hypertension was seen in 11.4% (63/551) (12% in men, 11% in women). Age, obesity, diabetes, serum cholesterol and serum triglycerides were strongly associated with hypertension. Only 46% (254/551) of the hypertensive subjects were aware that they were hypertensive. CONCLUSION Prevalence of hypertension was high in this population. Nearly 54% were unaware of their hypertensive status. Prevalence increased with age, obesity, diabetic status and dyslipidemia. Nearly half of subjects were prehypertensives. This study highlights the need for regular screening coupled with educational programmes to detect, improve awareness and optimally treat hypertension in the community to reduce cardiovascular and renal complications.

Co-administration of haloperidol and drugs affecting the angiotensin pathway: effect on the extrapyramidal system.

The present study investigates the extrapyramidal effects of co-administration of enalapril (angiotensin-converting enzyme inhibitor) or losartan (angiotensin receptor blocker) with haloperidol in mice. Enalapril/losartan (as a suspension in 1% gum acacia) was administered by oral gavage and haloperidol was administered as an intraperitoneal injection to all the animals for seven days. Catalepsy was measured 30 min after the administration of haloperidol (1 mg/kg i.p.) on days 1 and 7. Observations on day 1 constituted the acute study (single dose administration) and observations on day 7, constituted the chronic study (repeated dose administration). Both acute and chronic administration of enalapril/losartan produced an increase in the duration of haloperidol induced catalepsy at the highest dose (20 mg/kg). Enalapril produced a more pronounced increase in the duration of catalepsy as compared to losartan on both acute and chronic administration. Results of our study suggest that co-administration of anti-psychotics and drugs affecting the angiotensin system can lead to an increase in motor side effects and therefore should be used with caution in patients with these co-morbid conditions.

Restricted Blood Flow Exercise in Sedentary, Overweight African-American Females May Increase Muscle Strength and Decrease Endothelial Function and Vascular Autoregulation

Objectives: Exercise with partially restricted blood flow is a low-load, low-intensity resistance training regimen which may have the potential to increase muscle strength in the obese, elderly and frail who are unable to do high-load training. Restricted blood flow exercise has also been shown to affect blood vessel function variably and can, therefore, contribute to blood vessel dysfunction. This pilot study tests the hypothesis that unilateral resistance training of the leg extensors with partially restricted blood flow increases muscle strength and decreases vascular autoregulation. Methods: The subjects were nine normotensive, overweight, young adult African-Americans with low cardiorespiratory fitness who underwent unilateral training of the quadriceps’ femoris muscles with partially restricted blood flow at 30% of the 1-repetition maximum (1-RM) load for 3 weeks. The 1-RM load and post-occlusion blood flow to the lower leg (calf) were measured during reactive hyperemia. Results: The 1-RM load increased in the trained legs from 77 ± 3 to 84 ± 4 kg (P < 0.05) in the absence of a significant effect on the 1-RM load in the contralateral untrained legs (P > 0.1). Post-occlusion blood flow decreased significantly in the trained legs from 19 ± 2 to 13 ± 2 mL· min-1· dL-1 (P < 0.05) and marginally in the contralateral untrained legs from 18 ± 2 to 16 ± 1 mL· min-1· dL-1 (P = 0.09). Changes in post-occlusion blood flow to the skin overlying the trained and the contralateral untrained muscles were not significant. Conclusion: These results demonstrate that restricted blood flow exercise, which results in significant gains in muscle strength, may produce decrements in endothelial dysfunction and vascular autoregulation. Future studies should determine whether pharmacopuncture plays a role in treatments for such blood vessel dysfunction.

Effects of a Dietary Beetroot Juice Treatment on Systemic and Cerebral Haemodynamics- A Pilot Study.

INTRODUCTION Beetroot Juice (BJ) contains dietary nitrates that increase the blood Nitric Oxide (NO) level, decrease Blood Pressure (BP), increase athletic performance and improve cognitive functions but the mechanism remains unclear. Ultrasonographic measurement of middle cerebral artery blood flow velocity with computation of Cerebral Augmentation Index (CAIx) is a measure of the reflected flow signal, modulated by changes in cerebrovascular resistance and compliance. AIM This pilot study tests the hypothesis that ingestion of an amount of BJ sufficient to raise the blood NO level two-to three-fold, decreases Transcranial Doppler (TCD) measured CAIx. MATERIALS AND METHODS Ten healthy young-adult African-American women were studied at two levels of submaximal exercise, 40% and 80% of their predetermined peak oxygen consumptions. The subjects ingested nitrate-free orange juice (OJ, control) and an isocaloric BJ beverage (1.5 mg/mL nitrate, 220 Cal), on different days, 1-2 weeks apart. RESULTS The BJ treatment increased blood NO and decreased systolic BP at rest and at the two levels of exercise. The BJ treatment decreased CAIx only at the two levels of exercise (from 79 ± 2% to 62 ± 2% and from 80 ± 2% to 60 ± 3%, p<0.05). Exercise increased TCD-measured resistance and pulsatility indices (RIx, PIx) without changing AIx. The BJ treatment had no effect on RIx and PIx. CONCLUSION These findings suggest that decreased CAIx associated with aerobic exercise reflects the change in cerebral haemodynamics resulting from dietary nitrate supplementation. Future studies should determine whether the BJ-induced decrement in CAIx is correlated with an improvement in brain function.

Nonlinear Conte-Zbilut-Federici (CZF) Method of Computing LF/HF Ratio: A More Reliable Index of Changes in Heart Rate Variability

Objectives: Acupuncture treatments are safe and effective for a wide variety of diseases involving autonomic dysregulation. Heart rate variability (HRV) is a noninvasive method for assessing sympathovagal balance. The low frequency/high frequency (LF/HF) spectral power ratio is an index of sympathovagal influence on heart rate and of cardiovascular health. This study tests the hypothesis that from rest to 30% to 50% of peak oxygen consumption, the nonlinear Conte-Zbilut-Federici (CZF) method of computing the LF/HF ratio is a more reliable index of changes in the HRV than linear methods are. Methods: The subjects of this study were 10 healthy young adults. Electrocardiogram RR intervals were measured during 6-minute periods of rest and aerobic exercise on a cycle ergometer at 30% and 50% of peak oxygen consumption (VO2peak). Results: The frequency domain CZF computations of the LF/HF ratio and the time domain computations of the standard deviation of normal-to-normal intervals (SDNN) decreased sequentially from rest to 30% VO2peak (P < 0.001) to 50% VO2peak (P < 0.05). The SDNN and the CZF computations of the LF/HF ratio were positively correlated (Pearson’s r = 0.75, P < 0.001). fast Fourier transform (FFT), autoregressive (AR) and Lomb periodogram computations of the LF/HF ratio increased only from rest to 50% VO2peak. Conclusion: Computations of the LF/HF ratio by using the nonlinear CZF method appear to be more sensitive to changes in physical activity than computations of the LF/HF ratio by using linear methods. Future studies should determine whether the CZF computation of the LF/HF ratio improves evaluations of pharmacopuncture and other treatment modalities.