TELMISARTAN ALLEVIATES NITROSATIVE STRESS IN TURN DOPAMINERGIC DEGENERATION IN MICE MPTP MODEL OF PARKINSONISM–BIOCHEMICAL AND HISTOPATHOLOGICAL EVIDENCES

Objective: Telmisartan (TEL), an angiotensin type 1 receptor blocker, exerts neuroprotection in MPTP induced Parkinson's disease. The present study was aimed to investigate its effects on oxidative stress markers–inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reduced glutathione (GSH) content in C57BL/6J mice brain.Methods: Young healthy male C57BL/6J mice were injected intraperitoneally with MPTP at 80 mg/kg in two divided doses (2 x 40 mg/kg at 16h interval). TEL was administered one hour prior to first MPTP intoxication and thereafter once in two consecutive days. The animals were sacrificed 48 h after first MPTP injection and brains were collected for further analysis.Results: TEL administration increased GSH content and decreased iNOS expression and NO level in MPTP intoxicated mice brains. Histopathological evaluation revealed that TEL decreased the cytoplasmic vacuolation and nuclear pigmentation in striatal and substantial nigral regions of MPTP intoxicated mice brain. The neuroprotective effect of TEL was further evidenced with increased neuronal nuclei (NeuN) immune fluorescence in MPTP mice brains.Conclusion: The present study showed that TEL exerts neuroprotection by suppressing nitric oxide induced oxidative stress and the dopaminergic degeneration. The above findings suggests that TEL may act as a potential target in the management of PD.Â

Study of urinary uric acid and creatinine ratio as a marker of neonatal asphyxia for babies born in a tertiary care hospital

Background: Perinatal asphyxia is a common neonatal problem and there is significant contribution to neonatal morbidity and mortality. It is regarded as an important and common cause of preventable cerebral injury. The prediction of perinatal asphyxial outcome is important but formidable. There is only a limited role for the Apgar score for predicting the immediate outcome, such as HIE and the long-term neurological sequelae observational error can happen in APGAR. But biochemical parameters can be truly relied upon. This study was to evaluate the utility of urinary uric acid to creatinine ratio (UA/CR ratio) as non-invasive, easy, cheap and at the same time early biochemical means of asphyxia diagnosis.Methods: In this prospective case control study conducted in KAPV Government medical college between Feb 2017 to Sept 2017, 100 asphyxiated and 100 non-asphyxiated newborns were included. Detailed history and assessment were for all the enrolled newborns. Spot urine samples were sent for uric acid and creatinine estimation. Results were recorded, and statistical analysis was done.Results: The mean Uric acid/Creatinine ratio in the cases and controls groups were 2.58±1.09 and 0.86±0.17 respectively. The ratio also correlated well with the stage of HIE.Conclusions: The ratio of UA/Cr enables early and rapid recognition of asphyxial injury and also the assessment of its severity and the potential for short term morbidity or death

Trial of vitamin D supplementation to prevent asthma exacerbation in children

Background: To assess the level of vitamin D in children with bronchial asthma and to study the effects of vitamin D supplementation in asthmatic children who had vitamin D deficiency in terms of asthma control test score and Number of exacerbations.Methods: This interventional study was conducted in Department of Paediatrics, KAPV Government medical college, Trichy, Tamil Nadu, India from September 2016 to February 2017. 96 asthmatic children of age group 5-12 years who attended outpatient department and admitted in ward for asthma exacerbation were selected. After assessing their Vitamin D level, Vitamin D supplementation given along with standard treatment for asthma. Outcomes measured were ACTS (Asthma control test score), number of emergency room visits, number of hospital admissions and reliever medication use.Results: Out of 96 children, 83 (86.4%) children had vitamin D deficiency. There was significant correlation between vitamin D level and absolute eosinophil count (p-value-0.037), asthma severity (p-value<0.001) and asthma control (p-value<0.001). Significant reduction in emergency room visits, (p-value<0.001) reliever medication use (p-value<0.001) and improvement in asthma control test score (p-value-0.008) occurs after vitamin D supplementation.Conclusions: There is a significant correlation between vitamin D level, asthma severity and its control. Asthma exacerbation in terms of emergency room visits and reliever medication use were further reduced by vitamin D supplementation

Evaluation of cord bilirubin and hemoglobin analysis in predicting pathological jaundice in term babies at risk of ABO incompatibility

Background: Cord bilirubin and hemoglobin analysis helps not only in predicting the pathological jaundice in ABO incompatibility but also useful for early referral and intervention for better outcome. Aim of this study is to evaluate the cord blood bilirubin and hemoglobin analysis in predicting pathological hyperbilirubinemia in newborn at risk of ABO incompatibility.Methods: In this descriptive study conducted in Government Stanley medical college between January 2016-June 2016, A positive or B positive babies born to O positive mothers with birth weight >2.5 kgs and gestational age >37 weeks were included. A total of 191 babies were studied. Cord bilirubin, reticulocyte count, hemoglobin and fourth day bilirubin were evaluated and data was analysed using Pearson’s Chi square and ANOVA.Results: Out of 191 babies, 25 (13%) did not develop any jaundice, 122 (64%) developed physiological jaundice and 44 (23%) had pathological jaundice. The mean cord bilirubin and cord hemoglobin values of newborn who did not develop jaundice were 1.35mg/dl and 15.3g/dl while the values among pathological jaundice were 3.15mg/dl and 14.97g/dl. Conclusions: Babies with cord bilirubin >1.8mg/dl and hemoglobin <15.1gm/dl are more prone for pathological hyperbilirubinemia

Intramedullary Fixation of Unstable Peritrochanteric Fractures with Interlocking Proximal Femoral Nail: A Prospective Analysis

INTRODUCTION: In unstable trochanteric fractures where there is loss of posteromedial cortex continuity, when load is applied increased bending force on the DHS lead to implant breakage, screw cutout or separation of plate from shaft. This lead to the introduction of Intramedullary devices which theoretically due to its position provides more efficient load transfer and shorter lever arm can decrease tensile strain thereby decreasing the risk of implant failure. Though Zickel introduced his nail long ago it was not very popular due to higher incidence of complications, so was the case with ender’s nail. Zickel nail was later modified and renewed interest is being given to intra medullary fixation with devices like the IMHS (intra medullary hip screw), Gamma nail, Russell – Taylor reconstruction nail, ATN ( Ante grade trochanteric nail), TFN (Trochanter fixation nail) and the PFN (Proximal femoral nail) due to advantages of reduced operating time, less blood loss, better biomechanical stability and earlier mobilization provided by this devices. In 1997, PFN (Proximal femoral nail) was introduced in Czechoslovakia by Synthes company which has the biomechanical advantage of all IM devices and considered to be as a second generation nail. Several recent studies are going on for comparison with DHS and other IM devices and the results are encouraging but needs time and further evaluation to be accepted. AIM OF THE STUDY: To assess the effectiveness of Intramedullary fixation of unstable peritrochanteric fractures with interlocking proximal femoral nail. MATERIALS AND METHODS: At our institution we selected 21 cases of peritrochanteric fractures for this prospective study. All 21 cases were treated with proximal femoral nail (indigenous) of which 20 patients came for regular follow up and they were included in the study. The age group varied from a minimum of 32 years to a maximum of 72 years and average age was 52.7 years. The duration of the study was from June 2004 to June 2006. The mean follow up was 10.75 months. Of the 20 patients 14 were males and 6 were females. Right side was involved in 7 patients and in 13 patients the left side was involved. 13 patients were sedentary workers and 7 patients were manual laborers. All the fractures were classified according to the Boyd and Griffin classification for peritrochanteric fractures. 11 patients were classified as type II, 4 patients were classified as type III, 5 patients were classified as type IV. All of them are unstable trochanteric fractures. RESULTS: The operating time was calculated from the start of surgical incision to wound closure. In the initial cases our operating time was on the higher range, with experience the operating time reduced. Operating time varied from 58 to 84 minutes. The blood loss was calculated from the number of surgical mops that were used, each corresponding to 50 ml blood. Blood loss varied from 150 to 350 ml. The average blood loss was 230 ml. The duration of image intensifier usage was calculated in seconds. CONCLUSION: Intra medullary nailing with PFN as claimed has distinct advantages over DHS like reduced operating time, less blood loss, rigid fixation and positive effect on the speed of restoration of walking. It also has advantage over Gamma nail in rotational stability of proximal fragment and reduction in the complication rate of femoral shaft fractures. The incidence of per operative and post operative femoral shaft fractures can be reduced by pre-reaming the shaft one size more than the diameter of the nail and by distal locking meticulously without creating additional stress risers. The incidence of cutout of cervical lag screw can be reduced by optimal reduction of the fracture and accurate positioning of cervical lag screws and nail. Finally, we conclude that the PFN is a significant advancement in the treatment of unstable peritrochanteric fractures which has the unique advantages of closed reduction, preservation of fracture hematoma, less tissue damage, early rehabilitation and early return to work

IN VITRO AND IN VIVO PROTECTIVE EFFECTS OF AMBREX, A POLYHERBAL FORMULATION, AGAINST METHOTREXATE INDUCED DAMAGES IN HEPATIC CELLS

Objective: To evaluate the hepatoprotective effect of Ambrex, a poly herbal formulation against methotrexate (MTX) induced hepatotoxicity in Swiss albino mice as well as in Chang liver cell lines.Methods: Ambrex was exposed to MTX intoxicated chang liver cells and cells were harvested for studying the gene expressions of Dihydrofolate reductase (DHFR), B-cell lymphoma 2 (BCL2) and Bcl-2-associated X protein (BAX). In in vivo study, Ambrex was administered orally for a period of 7 days at two dose levels (250 and 500 mg/kg b. wt) and MTX (20 mg/kg b. wt, i. p) was injected one hour after the last test drug administration. Protective effect of Ambrex was evaluated by measuring aspartate transaminase (SGOT), alanine transaminase (SGPT), alkaline phosphatase (ALP), γ–glutamyl transferase (γGT) and total bilirubin. Its effect on superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and lipid peroxide (LPO) was also determined.Results: Data revealed that Ambrex was able to restore the levels of antioxidants such as SOD, Catalase, and Glutathione to near normal and reduced the elevated plasma levels of SGOT, SGPT, ALP, γ–GT and total bilirubin. It also inhibited the formation of hepatic malondialdehyde induced by MTX. In vitro studies revealed that Ambrex protected MTX induced hepatotoxicity at the dose of 50 and 500ng/ml. Further, mRNA expression also illustrated that Ambrex inhibited the over expression of BAX and suppressed BCL2 and DHRF expressions.Conclusion: Results suggest that Ambrex has potent hepatoprotective effect which was evident from both in vivo and in vitro results.Â

3-AMINOBENZAMIDE, A POLY (ADP-RIBOSE) POLYMERASE INHIBITOR, RESTORES BIOENERGETICS BUT FAILS TO ALLEVIATE EXCITOTOXICITY AND MOTOR FUNCTIONS IN 3-NITROPROPIONIC ACID INTOXICATED MICE

Objective: The present study was undertaken to investigate the effects of 3-aminobenzamide (3-AB), a poly (ADP-ribose) polymerase 1 (PARP1) inhibitor, on motor functions along with brain excito toxicity and bioenergetics alterations in 3-nitropropionic acid (3-NPA) intoxicated mice model of Huntington's disease (HD).Methods: Young healthy male C57BL/6J mice were pre-treated with vehicle/3-AB for a period of five days and intoxicated with two doses of 3-NPA (15 mg/kg, i. p) at 24 h interval on day 4 and 5. Animals were observed for motor functions 5 days after 3-NPA injection. They were sacrificed at the end of motor tests and brains were collected for neurochemical, bioenergetics, glial cells and cytokines analysis.Results: 3-AB treatment significantly increased the bioenergetics (ATP and NAD) and succinate dehydrogenase activity in 3-NPA intoxicated mice brains. But, it failed to decrease glutamate content, cytokines-TNFα and IL-1β and glial markers–glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA1) expressions. Further, 3-AB administered produced only a non-significant restoration of motor functions in 3-NPA intoxicated mice.Conclusion: The present study revealed that excito toxicity and inflammatory pathways are major perpetrators in 3-NPA induced neuro degeneration and motor dysfunction. Therapeutic approach with 3-AB alone may not be sufficient to manage the multi-cascade pathogenetic mechanisms in HD neither symptomatic management too.Â

Evidence for altered insulin signaling in the brains of Genetic Absence Epilepsy Rats from Strasbourg

Peer Reviewe

Advances in Batteries, Battery Modeling, Battery Management System, Battery Thermal Management, SOC, SOH, and Charge/Discharge Characteristics in EV Applications

The second-generation hybrid and Electric Vehicles are currently leading the paradigm shift in the automobile industry, replacing conventional diesel and gasoline-powered vehicles. The Battery Management System is crucial in these electric vehicles and also essential for renewable energy storage systems. This review paper focuses on batteries and addresses concerns, difficulties, and solutions associated with them. It explores key technologies of Battery Management System, including battery modeling, state estimation, and battery charging. A thorough analysis of numerous battery models, including electric, thermal, and electro-thermal models, is provided in the article. Additionally, it surveys battery state estimations for a charge and health. Furthermore, the different battery charging approaches and optimization methods are discussed. The Battery Management System performs a wide range of tasks, including as monitoring voltage and current, estimating charge and discharge, equalizing and protecting the battery, managing temperature conditions, and managing battery data. It also looks at various cell balancing circuit types, current and voltage stressors, control reliability, power loss, efficiency, as well as their advantages and disadvantages. The paper also discusses research gaps in battery management systems.publishedVersio

Concussion/Mild Traumatic Brain Injury (TBI) Induces Brain Insulin Resistance: A Positron Emission Tomography (PET) Scanning Study

Brain injury/concussion is a growing epidemic throughout the world. Although evidence supports association between traumatic brain injury (TBI) and disturbance in brain glucose metabolism, the underlying molecular mechanisms are not well established. Previously, we reported the release of cellular prion protein (PrPc) from the brain to circulation following TBI. The PrPc level was also found to be decreased in insulin-resistant rat brains. In the present study, we investigated the molecular link between PrPc and brain insulin resistance in a single and repeated mild TBI-induced mouse model. Mild TBI was induced in mice by dropping a weight (~95 g at 1 m high) on the right side of the head. The procedure was performed once and thrice (once daily) for single (SI) and repeated induction (RI), respectively. Micro PET/CT imaging revealed that RI mice showed significant reduction in cortical, hippocampal and cerebellum glucose uptake compared to SI and control. Mice that received RI also showed significant motor and cognitive deficits. In co-immunoprecipitation, the interaction between PrPc, flotillin and Cbl-associated protein (CAP) observed in the control mice brains was disrupted by RI. Lipid raft isolation showed decreased levels of PrPc, flotillin and CAP in the RI mice brains. Based on observation, it is clear that PrPc has an interaction with CAP and the dislodgment of PrPc from cell membranes may lead to brain insulin resistance in a mild TBI mouse model. The present study generated a new insight into the pathogenesis of brain injury, which may result in the development of novel therapy