Vasavi Rakesh Gorantla

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.

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.

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.

Cardiovascular Responses to an Isometric Handgrip Exercise in Females with Prehypertension

Background: Hypertensive individuals are known to exhibit greater increases in blood pressure during an isometric handgrip exercise (IHE) than their normotensive counterparts. Aim: This study tests the hypothesis that, compared to normotensive individuals, prehypertensive individuals exhibit an exaggerated response to IHE. Materials and Methods: In this study, the effects of IHE were compared in matched prehypertensive vs. normotensive healthy African-American females. Six healthy young adult African-American female university students were screened in a physician′s office for blood pressure in the range of prehypertension, systolic blood pressure (SBP) 120-139 mmHg and diastolic blood pressure (DBP) 80-89 mmHg. Six young adult African-American women were also recruited to serve as a healthy normotensive control group with SBP ≤119 mmHg and DBP ≤79 mmHg. Cardiovascular fitness was determined by peak oxygen uptake (VO 2 peak) measured during a progressive exercise test. Results: During the handgrip exercise, the prehypertensive group exhibited greater increases in SBP (from 139 ± 6 to 205 ± 11 mmHg, +48%) than the controls (from 132 ± 3 to 145 ± 3 mmHg, +10%); intergroup difference P < 0.001. The prehypertensive group also exhibited greater increases in DBP (from 77 ± 2 to 112 ± 5 mmHg, +46%) compared to the controls (from 72 ± 3 to 78 ± 4 mmHg, +8%); intergroup difference P < 0.001. The increase in systemic vascular resistance was also greater in the prehypertensive group (from 1713 ± 91 to 2807 ± 370 dyne.s.cm -5 , +64%) than in the controls (from 1668 ± 80 to 1812 ± 169 dyne.s.cm -5 , +9%); intergroup difference P < 0.05. Conclusion: These results suggest that blood pressure measurements performed during IHE may be a useful screening tool in evaluating prehypertensive individuals for antihypertensive treatments.

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.

The Current Status of New Antidiabetic Drugs

Dear Editor, Type 2 diabetes mellitus (T2DM) is a world-wide public health problem [1]. As such, the Food and Drug Administration (FDA), pharmaceutical companies and medical researchers/practitioners should be discussing the costs vs. the benefits for economically-disadvantaged populations that are disproportionately affected by T2DM and, therefore, suffering the most [2]. The current debate about new antidiabetic drugs is focused mainly on pharmacological efficacy and does not take into account the multimodal mechanisms and treatments for this complex disease [3]. Whether the statistically-significant positive results demonstrated for these drugs translate into real benefits for patients in real-life clinical settings has yet to be established. The multimodal principle of treatment, although welltaught in most medical schools, is often ignored in real-life, particularly when expensive drugs are readily available. For example, treatment of T2DM should start with the least costly, yet effective, nonpharmacological interventions, such as diet/exercise/lifestyle changes, thereafter progressing to first-line gluconeogenesis suppressors, such as metformin and later sulfonylureas. Only after such interventions have failed should the newer, very expensive GLP-1 agonists and SGLT2 inhibitors be introduced [3, 4]. Research should be carefully designed to determine whether the newer drugs benefit patients after diet/ lifestyle changes and standard treatments have failed. Such studies of multimodal treatment for T2DM should include not one, but several, intensities of diet/lifestyle modifications even before standard drug treatments are employed. Likewise, several intensities of standard drug treatments should be used in the presence and in the absence of different intensities of diet/exercise/ lifestyle modifications. The newer antidiabetics should be similarly added to the experimental regimens. Early introduction of SGLT2 inhibitors without trying the safer treatment options first may result in unnecessary harm [5], as well as increased cost to patients for whom diet/lifestyle and standard drugs may work in the correct combinations. Indeed, this approach is in accordance with the principles of personalized medicine, one of the most promising goals of 21 century medical practice. In the recent past, a rapid rise in the prevalence of metabolic syndrome has been observed globally, especially in developing countries like India. This increased prevalence of metabolic syndrome is thought to be an important predisposing factor for the current epidemic of T2DM [6, 7]. Complex environment-gene interactions give rise to most, if not all, human diseases, and metabolic syndrome is no exception. For example, two single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3), T > C 455 and C > T 482, alone or in combination with the fatty acid binding protein-2 (FABP2), Ala54Thr SNP, appear to be associated with a high risk for developing metabolic syndrome [8]. Even in populations such as those in India with low-fat diets, individuals with these genetic risk factors do not usually escape metabolic syndrome. This knowledge Ltter to he eitor

Effects of Swimming Exercise on Limbic and Motor Cortex Neurogenesis in the Kainate-Lesion Model of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a common neurological disease and antiseizure medication is often inadequate for preventing apoptotic cell death. Aerobic swimming exercise (EX) augments neurogenesis in rats when initiated immediately in the postictal period. This study tests the hypothesis that aerobic exercise also augments neurogenesis over the long term. Male Wistar rats (age of 4 months) were subjected to chemical lesioning using KA and to an EX intervention consisting of a 30 d period of daily swimming for 15 min, in one experiment immediately after KA lesioning (immediate exposure) and in a second experiment after a 60 d period of normal activity (delayed exposure). Morphometric counting of neuron numbers (NN) and dendritic branch points and intersections (DDBPI) was performed in the CA1, CA3, and dentate regions of hippocampus, in basolateral nucleus of amygdala, and in several areas of motor cortex. EX increased NN and DDBPI in the normal control and the KA-lesioned rats in all four limbic and motor cortex areas studied, after both immediate and 60 d delayed exposures to exercise. These findings suggest that, after temporal lobe epileptic seizures in rats, swimming exercise may improve neural plasticity in areas of the brain involved with emotional regulation and motor coordination, even if the exercise treatment is delayed.