Novel spiro[indoline-3,2'thiazolo[5,4-e]pyrimido[1,2-a] pyrimidine] derivatives as possible anti-dermatophytic and anti-candidiasis agent.

A novel series of 5'-benzylidene-3'-phenylspiro[indoline-3,2'-thiazolidine]-2,4'(1H)-diones 6a-d and spiro[indoline-3,2'-thiazolo[5,4-e]pyrimido[1,2-a]pyrimidin]-2(1H)-one 9a-d derivatives have been synthesized. All the newly synthesized compounds were evaluated for antifungal and anti-candidiasis activity by using Disc Diffusion and Modified Microdilution methods. The antimicrobial experiments have shown that the synthesized compounds demonstrated broad-spectrum antifungal activity in vitro. Among them, compounds 9a-9d had stronger antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes, and Candida albicans; compounds 6a-d also showed significant antifungal activity against selected fungal strains as compared to ketoconazole, the reference antifungal drug. The evaluation of antifungal activity against drug-resistant fungal variants showed that the designed compounds had significant antifungal activity against the tested variants. The combination of compounds (6a-d) and (9a-d) exhibited that the synthesized compounds had synergistic effects or additive effects. These results demonstrated that the synthesized compounds were putative chitin synthase inhibitors exhibiting broad spectrum antifungal activities. The present results indicate that novel spiro pyrimidine derivatives can be used as an active pharmaceutical ingredient for novel drug candidate for treatment of dermatophytosis and other fungal agents.

Bone marrow derived mesenchymal stem cells enriched PCL-gelatin nanofiber scaffold for improved wound healing.

Electrospun nanofibers exhibit a significant potential in the synthesis of nanostructured materials, thereby offering a promising avenue for enhancing the efficacy of wound care. The present study aimed to investigate the wound-healing potential of two biomacromolecules, PCL-Gelatin nanofiber adhered with bone marrow-derived mesenchymal stem cells (BMSCs). Characterisation of the nanofiber revealed a mean fiber diameter ranging from 200 to 300 nm, with distinctive elemental peaks corresponding to polycaprolactone (PCL) and gelatin. Additionally, BMSCs derived from bone marrow were integrated into nanofibers, and their wound-regenerative potential was systematically evaluated through both in-vitro and in-vivo methodologies. In-vitro assessments substantiated that BMSC-incorporated nanofibers enhanced cell viability and crucial cellular processes such as adhesion, and proliferation. Subsequently, in-vivo studies were performed to demonstrate the wound-healing efficacy of nanofibers. It was observed that the rate of wound healing of BMSCs incorporated nanofibers surpassed both, nanofiber and BMSCs alone. Furthermore, histomorphological analysis revealed accelerated re-epithelization and improved wound contraction in BMSCs incorporated nanofiber group. The fabricated nanofiber incorporated with BMSCs exhibited superior wound regeneration in animal model and may be utilised as a wound healing patch.

Deciphering the genetic landscape of lumpy skin disease: Unraveling variable virulence through comprehensive genome sequence analysis in India.

Lumpy Skin Disease (LSD), a poxvirus disease affecting cattle, emerged in India in 2019 and intensified in 2022, resulting in significant economic losses for dairy farmers. There was unusual shift in mortality and morbidity patterns during the second wave. A comprehensive genetic study conducted, analyzing samples from 2019 to 2022 revealed circulation of two distinct subclades (subclade 1.2a and 1.2b) in India, with the latter showing a different pattern in morbidity and mortality. Notably, the Ankyrin repeats gene-based analysis could differentiate animals with varying clinical scores. Genetic variations were significant, with unique deletions identified, including a 12-nucleotide deletion in the GPCR gene in virus isolates collected during 2022 outbreaks, not reported earlier in Indian LSDV strains. A crucial finding was a significant 95-nucleotide deletion in the Functional Resolution Sequence (FRS) repeats of LSDV genomes from 2022 outbreaks, absent in 2019 samples. These deletions may have influenced the virus's virulence in India.

A STUDY ON THE INFORMATION TRANSFER AND LONG-TERM PSYCHOLOGICAL IMPACT OF CHILD SEXUAL ABUSE.

Children who experience sexual abuse often face severe challenges in seeking help and disclosing their traumatic experiences. Objectives - to investigate critical aspects of information transfer, help-seeking behavior and the long-term psychological impact of child sexual abuse. This was a pilot study done on 114 victims of child sexual abuse. The study participants filled a semi-structured proforma through social media using Google forms. It was a descriptive cross-sectional study carried out using SPSS (Statistical Package for Social Sciences) version 28. This pilot study on 114 child sexual abuse victims reveals critical insights. Only 15.8% confided in parents, while 37.7% turned to friends. Shockingly, 46.5% kept their ordeal hidden. Disturbingly, only 8.8% sought professional help. The impact on adult life was profound, with 70.2% reporting personal effects. Regrettably, 24.6% resorted to self-harm. Insights on reasons were stark: 63.1% felt defenseless, 23.7% lacked awareness, and 5.3% blamed lax legislation. Encouragingly, 86% actively raised awareness. The study provides a compelling view of child sexual abuse survivors, and emphasizes the need for improved communication within families, accessible support services, and educational initiatives.

Exploring the therapeutic potential of allogeneic amniotic membrane for quality wound healing in rabbit model.

BACKGROUND: The amniotic membrane (AM) has shown immense potential in repairing wounds due to its great regenerative qualities. Although the role of AM as a biological scaffold in repairing wounds has been studied well, the tissue regenerative potential of AM-derived mesenchymal stem cells (MSCs) and conditioned media (CM) derived from it remains to be discovered as of now. Here, we examined the wound healing abilities of fresh and frozen thawed rabbit AM (rAM) along with the MSCs and their lyophilised CM in rabbits challenged with skin wounds. METHODS: To elucidate the role of rAM-MSCs and its CM in repairing the wound, we isolated it from the freshly derived placenta and characterised their differentiation potential by performing an in vitro tri-lineage differentiation assay besides other standard confirmations. We compared the wound repair capacities of rAM-MSCs and lyophilised CM with the fresh and cryopreserved AM at different timelines by applying them to excision wounds created in rabbits. RESULTS: By monitoring wound contractions and tissue histology of wounded skin at different time points after the application, we observed that rAM-MSCs and rAM-MSC-derived CM significantly promoted wound closure compared to the control group. We also observed that the wound closure capacity of rAM-MSCs and rAM-MSC-derived CM is as efficient as fresh and cryopreserved rAM. CONCLUSION: Our findings suggest that rAM-MSCs and rAM-MSC derived CM can be effectively used to treat skin wounds in animals and correctly delivered to the damaged tissue using AM as a bioscaffold, either fresh or frozen.

Comparison of efficacy of ultrasound-guided platelet rich plasma injection versus dry needling in lateral epicondylitis-a randomised controlled trial.

PURPOSE: To assess whether Ultrasound guided dry needling is adequate for both common extensor tendon tears and tendinosis or whether ultrasound guided platelet rich plasma (PRP) has a superior outcome when compared to dry needling when there are tears of the common extensor tendon. MATERIALS AND METHODS: This is a single-centre, single-blinded, randomised controlled trial conducted between November 2018 and April 2020. 40 patients diagnosed with lateral epicondylitis based on clinical and sonographic features and having comparable baseline characteristics were randomly assigned to the two study groups (dry needling and PRP). Inclusion criteria were patients aged 20 years or more who were symptomatic for at least 3 months with sonographic evidence of lateral epicondylitis. Exclusion criteria were complete tear of common extensor tendon confirmed on ultrasound and presence of other associated diseases like osteoarthritis of shoulder and elbow. RESULTS: There was significant improvement in the visual analogue scale pain score in PRP group compared to the dry needling group at 9 months. However, this difference was not evident at 3 and 6 months follow-up. Mean improvement in common extensor tendon thickness in PRP group (5.1 mm at 3 months and 4.3 mm at 6 months) was slightly better than dry needling (4.4 mm at 3 months and 4.0 mm at 6 months). There was no difference in tear (if present) healing between both groups at 3 months. However at 6 months follow up, PRP demonstrated significant (mean-2.5) healing in tear compared to dry needling (mean-3.1). CONCLUSION: Two injections of Ultrasound guided PRP are more beneficial non operative treatment compared to ultrasound guided dry needling, in lateral epicondylitis.

A prospective case-control study on the evaluation of oxidative stress in renal stone formers.

Association of increased oxidative stress (OS) with the pathophysiology of renal stone formation has not been explored greatly in the field of urolithiasis. In this prospective case-control study, we measured 24-h urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with urolithiasis and compared them with matched healthy controls. We also measured 24-h urinary uric acid, calcium, oxalate, and citrate levels in patients with renal stone disease and studied their relation with urinary 8-OHdG levels. Seventy-five cases of renal stone disease and 75 well-matched controls were included. Median 24-h urinary 8-OHdG levels were significantly higher in cases compared to controls (7.6 vs. 3.7 µg/g of creatinine; p < 0.000). Receiver-operating curve (ROC) analysis for 8-OHdG between cases and controls revealed an area under the curve of 0.90. At 8-OHdG (µg/g of creatinine) value of 5 or more, a sensitivity and a specificity of 84% each were obtained. A positive correlation between 8-OHdG (µg/g of creatinine) and 24-h urinary oxalate level was noted (r = 0.461, p = 0.000). No correlation between 8-OHdG (µg/g of creatinine) and other variables was noted. On multivariate linear regression analysis, we noted 24-h urinary oxalate levels to be an independent predictor of urinary 8-OHdG levels. OS is significantly higher in patients with renal stone diseases compared to healthy controls. Urinary oxalate levels were significantly correlated with urinary 8-OHdG levels.

Plummeting toxic contaminates from water through phycoremediation: Mechanism, influencing factors and future outlook to enhance the capacity of living and non-living algae.

Freshwater habitats hold a unique role in the survival of all living organisms and supply water for drinking, irrigation, and life support activities. In recent decades, due to anthropogenic activities, deterioration in the water quality has been a long-lasting problem and challenge to the scientific fraternity. Although, these freshwater bodies have a bearable intrinsic capacity for pollution load however alarming increase in pollution limits the intrinsic capacities and requires additional technological interventions. The release of secondary pollutants from conventional interventions further needs revisiting the existing methodologies and asking for green interventions. Green interventions such as phycoremediation are natural, eco-friendly, economic, and energy-efficient alternatives and provide additional benefits such as nutrient recovery, biofuel production, and valuable secondary metabolites from polluted freshwater bodies. This systemic review in a nut-shell comprises the recent research insights on phycoremediation, technological implications, and influencing factors, and further discusses the associated mechanisms of metal ions biosorption by living and non-living algae, its advantages, and limitations. Besides, the article explores the possibility of future research prospects for applicability at a field scale that will help in the efficient utilization of resources, and improved ecological and health risks.

Liquid chromatography separation and identification of new oxidative degradation impurity in edoxaban tosylate hydrate drug substance by using liquid chromatography with tandem mass spectrometry.

Edoxaban is an anti-coagulant medication and a director factor Xa inhibitor. A novel reverse phase liquid chromatography-mass spectrometry compatible method developed for separation and identification of new oxidative degradation impurities in edoxaban tosylate hydrate drug substance. The separation of three oxidative degradation impurities was achieved by using YMC Triart phenyl (250 × 4.6) mm, 5 µm column with mobile phase containing gradient elution of mobile phase-A as 10 mM ammonium acetate and mobile phase-B as acetonitrile:methanol (1:1)% (v/v). The flow rate of the mobile phase is 0.7 mL/min with a column temperature of 40 °C and detection wavelength of 290 nm. Edoxaban tosylate hydrate shows significant degradation in oxidative stress conditions and forms three oxidative degradation products. The degradation products were identified and characterized by using a high-resolution mass spectrometry quadrupole-time of flight mass detector. The three oxidative degradation impurities of Edoxaban drug substance were well resolved with each other and along with Edoxaban drug substance peak. Among the three oxidative degradation impurities di-N-oxide impurity was the new oxidative degradation impurity identified for the first time and a novel reverse-phase high-performance liquid chromatography method was developed for separation of the three oxidative degradation impurities.

Kiloh-Nevin syndrome: an unusual cause of forearm pain.

The popularity of weight training, bodybuilding and general physical conditioning has led to an increased rate of musculoskeletal injuries, such as nerve compression caused by muscle hypertrophy and, stretching of nerves peripherally. We present a case of anterior interosseous nerve (AIN) entrapment syndrome/neuropathy otherwise known as Kiloh-Nevin syndrome in a 22-year-old weightlifter. Knowledge of this injury is paramount for practitioners to increase awareness among athletes and bodybuilders.

Disease-specific wearable sensor algorithms for profiling activity, gait, and balance in individuals with Charcot-Marie-Tooth disease type 1A.

BACKGROUND/AIMS: Charcot-Marie-Tooth Disease type 1A (CMT1A), the most common inherited peripheral neuropathy, is characterized by progressive sensory loss and weakness, which results in impaired mobility. Increased understanding of the genetics and pathophysiology of CMT1A has led to development of potential therapeutic agents, necessitating clinical trial readiness. Wearable sensors may provide useful outcome measures for future trials. METHODS: Individuals with CMT1A and unaffected controls were recruited for this 12-month study. Participants wore sensors for in-clinic assessments and at-home, from which activity, gait, and balance metrics were derived. Mann-Whitney U tests were used to analyze group differences for activity, gait, and balance parameters. Test-retest reliability of gait and balance parameters and correlations of these parameters with clinical outcome assessments (COAs) were examined. RESULTS: Thirty individuals, 15 CMT1A, and 15 controls, participated. Gait and balance metrics demonstrated moderate to excellent reliability. CMT1A participants had longer step durations (p < .001), shorter step lengths (p = .03), slower gait speeds (p < .001), and greater postural sway (p < .001) than healthy controls. Moderate correlations were found between CMT-Functional Outcome Measure and step length (r = -0.59; p = .02), and gait speed (r = 0.64; p = .01); 11 out of 15 CMT1A participants demonstrated significant increases in stride duration between the first and last quarter of the 6-min walk test, suggesting fatigue. INTERPRETATION: In this initial study, gait and balance metrics derived from wearable sensors were reliable and associated with COAs in individuals with CMT1A. Larger longitudinal studies are needed to confirm our findings and evaluate sensitivity and utility of these disease-specific algorithms for clinical trial use.

Point-of-care detection of Japanese encephalitis virus biomarker in clinical samples using a portable smartphone-enabled electrochemical "Sensit" device.

Japanese encephalitis (JE), a neglected tropical zoonotic disease prevalent in south-east Asian and western pacific countries, caused by the flavivirus JE virus (JEV), has a dearth of electrochemical point-of-care (PoC) diagnostic tools available to manage endemic breakouts. To overcome this, we have developed a screen-printed carbon electrode (SPCE) immunosensor for rapid PoC detection of JEV nonstructural 1 (NS1) antigen (Ag), found circulating in serum of infected individuals using a smartphone based portable "Sensit" device. The modification of SPCE surface with JEV NS1 antibody (Ab) was confirmed via observation of globular protein structures via scanning electron microscopy (SEM), increase in electrode surface hydrophilicity via contact angle measurement and decrease in current via differential pulse voltammetry (DPV). The fabrication and testing parameters were optimized based on highest current output obtained using DPV. The SPCE was tested for detection limit of target JEV NS1 Ag ranging from 1 fM to 1 µM, which was determined as 0.45 fM in spiked serum. The disposable immunosensor was also found to be highly specific in detecting JEV NS1 Ag over other flaviviral NS1 Ag. Finally, the modified SPCE was clinically validated by testing 62 clinical JEV samples using both a portable miniaturized electrochemical "Sensit" device coupled with a smartphone and a laboratory-based potentiostat. The results were corroborated with gold-standard RT-PCR and showed 96.77% accuracy, 96.15% sensitivity, and 97.22% specificity. Hence, this technique may further be developed into a one-step rapid diagnostic tool for JEV, especially in rural areas.

[Pharmacological importance of novel spiro derivatives against human pathogenic fungi]. / Farmakologicheskoe znachenie novykh spiro 1,4-digidropiridinov protiv patogennykh dlia cheloveka gribov.

Human mycoses have become a threat to health world-wide. Unfortunately there are only a limited number of antimycotic drugs in use. In the present study, antifungal activity of earlier synthesized spiro-1,4-dihydropyridines (1,4-DHPs) was investigated. The antifungal activity of spiro-1,4-DHPs compounds were screened against Aspergillus flavus, A. fumigatus, and Candida albicans by using Disc Diffusion and Modified Microdilution method. Among six spiro-1,4-DHPs compounds tested all of them showed stronger antifungal activity possibly through inhibiting the synthesis of chitin in cell wall against A. flavus, A. fumigatus, and C. albicans as compared to fluconazole, a standard antifungal drug. The combination of compounds showed that the synthesized compounds had synergistic, additive effects as compared to currently used drugs as an antifungal agent. These results indicated that these designed compounds were potential chitin synthase inhibitors and had excellent antimycotic activity for the treatment of fungal infections.

Allogenic bone marrow-derived mesenchymal stem cells and its conditioned media for repairing acute and sub-acute peripheral nerve injuries in a rabbit model.

The present study evaluated healing potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and BM-MSCs-conditioned medium (BM-MSCs-CM) for acute and subacute injuries in the rabbit peripheral nerve injury model. The regenerative capacity of MSCs was evaluated in 40 rabbits divided into eight groups, four groups each for acute and subacute injury models. BM-MSCs and BM-MSCS-CM were prepared by isolating allogenic bone marrow from the iliac crest. After inducing sciatic nerve crush injury, different treatments consisting of PBS, Laminin, BM-MSCs + laminin, and BM-MSCS-CM + laminin were used on the day of injury in the acute injury model and after ten days of crush injury in the subacute groups. The parameters studied included: pain, total neurological score, gastrocnemius muscle weight and volume ratio, histopathology of the sciatic nerve and gastrocnemius muscle, and scanning electron microscopy (SEM). Findings indicate that BM-MSCs and BM-MSCS-CM have augmented the regenerative capacity in acute and subacute injury groups with a slightly better improvement in the subacute groups than the animals in acute injury groups. Histopathology data revealed different levels of regenerative process undergoing in the nerve. Neurological observations, gastrocnemius muscle evaluation, muscle histopathology, and the SEM results depicted better healing in animals treated with BM-MSCs and BM-MSCS-CM. With this data, it could be concluded that BM-MSCs support the healing of injured peripheral nerves, and the BM-MSCS-CM does accelerate the healing of acute and subacute peripheral nerve injuries in rabbits. However, stem cell therapy may be indicated during the subacute phase for better results.

Is tranexamic acid associated with decreased need for blood transfusion in percutaneous nephrolithotomy: a systematic review and meta-analysis.

INTRODUCTION: Bleeding is a common complication after percutaneous nephrolithotomy (PNL) for renal stone disease. Tranexamic acid (TXA) has been found to reduce mortality and blood transfusion in surgical and trauma patients. This review aimed to assess the safety and efficacy of TXA in patients undergoing PNL. METHODS: A systematic literature review was performed to recognise all randomised controlled trials (RCTs) comparing the use of TXA in PNL. The primary outcome of the study was to compare the need for blood transfusion with and without TXA. FINDINGS: Six RCTs with 1,323 patients were included in this review. Haemoglobin fall was lower in the TXA group compared with the control group, and the need for blood transfusion was reduced by 67% (odds ratio (OR) 0.33, confidence interval (CI) (0.21, 0.52), p<0.00001). However, blood loss was comparable for the two groups (mean difference -116.9, CI (-244.5,10.7) p=0.07). Length of stay and duration of surgery was significantly shorter with TXA. Furthermore, both minor and major complications were lower in the TXA group. Stone-free rate was higher with the TXA group. No thromboembolic complications were noted in the TXA group. CONCLUSIONS: TXA is safe and efficacious for PNL with a reduction in need for blood transfusion and without an attending increase in complication rates.

Quality of clinical practice guidelines on interventional management of low back pain: A systematic review.

OBJECTIVE: To appraise the quality of low back pain (LBP) clinical practice guidelines (CPG) that include interventional management recommendations and to associate their quality with characteristics including publication year and creating organization. TYPE: Systematic Review. LITERATURE SURVEY: LBP (subacute or chronic) CPGs in English (symptom based, governmental or professional society created, January 1990-May 2020) were found using MEDLINE, EMBASE, CINAHL, Ortho Guidelines, CPG Infobase, ECRI, Guidelines International Network, NICE, and SIGN. METHODOLOGY: In this third order systematic review, search results were deduplicated, title and abstract screened by two independent reviewers, and full texts reviewed by four reviewers. Discrepancies were resolved by a third reviewer. Resulted CPGs were appraised using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Tool by four appraisers each. Association of their quality with creating organization, geographical region, and year of creation was calculated. SYNTHESIS: Seven hundred fourteen screened documents resulted in 21 final CPGs. On appraisal, average overall CPG quality was 5.2 (range 2.5-6.75). Domain 5 (applicability) had the lowest average (44%) and domain 4 (clarity of presentation) had the highest average score (82%). For overall recommendation, 16 received "yes" or "yes with modifications," six received unanimous "yes" and two unanimous "no" votes. The interrater agreement of domain scoring was excellent (0.8-1.0; p < .001). There was no association found between quality of CPG and (1) year of publication (R2  = 0.0006), (2) whether the CPG was updated or new (p = .17), and (3) region of publication (p = .37). CONCLUSIONS: The majority of the 21 CPGs identified in this systematic review were of high quality, but overall quality and recommendation ratings were variable. The quality of appraised CPGs showed no association with their characteristics. Some domains such as "applicability" scored uniformly lower, revealing opportunity for improvement in future CPG development. LBP CPGs should be scrutinized before adopting their recommendations.

Clinical practice guidelines on interventional management of low back pain: A synthesis of recommendations.

OBJECTIVE: To summarize the recommendations on the interventional management of subacute and chronic nonradicular low back pain (LBP) from the 21 quality-appraised clinical practice guidelines (CPGs) identified in a previously published paper: "Quality of Clinical Practice Guidelines on Interventional Management of Low Back Pain: A Systematic Review." By disseminating this information, we aimed to facilitate the implementation of these recommendations into clinical practice. TYPE: Systematic Review LITERATURE SURVEY: Electronic bibliographic databases, guideline databases, and gray literature were searched from January 2016 to January 2020 to identify CPGs that met study criteria. METHODOLOGY: A total of 21 CPGs were quality appraised and interventional management recommendations were extracted and organized into several treatment categories including epidural steroid injections, radiofrequency procedures (RF), facet injections, sacroiliac injections, and prolotherapy. Within each treatment category, the recommendations were organized based on two factors: quality of CPG and strength of recommendation. SYNTHESIS: Overall, there was no consistency in recommendations for or against any interventional procedure, even when accounting for the quality of the CPG. In all of the CPGs reviewed, the most common strength of recommendation was weakly for. The second, third, and fourth most common strength of recommendations were inconclusive, weakly against, and strongly against, respectively, and the least common was strongly for. The treatment categories with the greatest number of recommendations were RF procedures (most common strength of recommendation was weakly for) and facet procedures. Among the high-quality CPGs, the most common strength of recommendation was inconclusive. CONCLUSIONS: Most of the interventional management recommendations for management of nonradicular LBP in the 21 CPGs appraised in this review were either weakly for, weakly against, or inconclusive, with several recommendations within each treatment category contradicting each other. Appraisal of Guidelines for Research & Evaluation Instrument quality appraisals of CPGs on interventional management of LBP were of unclear utility in guiding clinical implementation.

Effects of high glutamate concentrations on mitochondria of human neuroblastoma SH-SY5Y cells.

BACKGROUND: The excess amount of glutamate in neurons is associated with the excitotoxicity and neurodegenerative diseases. Glutamate induces neurotoxicity primarily by immense influx of Ca2+ arising from overstimulation of the NMDA subtype of glutamate receptors. The neuronal death induced by the overstimulation of glutamate receptors depends critically on a sustained increase in mitochondrial Ca2+ influx and impairment in mitochondrial functions. The mitochondrial impairment is an important contributor to the glutamate-induced neuronal toxicity and thus provides an important target for the intervention. The present study investigates the effects of high glutamate concentrations on mitochondrial functions. RESULTS: Here, we have shown that the higher concentration of glutamate treatment caused a significant elevation in the N-methyl-D-aspartate (NMDA) receptors expression and elevated the intra-mitochondrial calcium accumulation in SHSY5Y neuronal cells. As a result of an accumulation of intra-mitochondrial calcium, there is a concentration-dependent elevation in ROS in the mitochondria. Tyrosine nitration of several mitochondrial proteins was increased while the mitochondrial membrane potential was dissipated. Furthermore, glutamate treatments also resulted in mitochondrial membrane permeability transition. CONCLUSIONS: These findings suggest that treatment of high glutamate concentration causes impairment of mitochondrial functions by an increase in intra-mitochondrial calcium, ROS production, dissipation of mitochondrial membrane potential and mitochondrial permeability transition pore opening in human neuroblastoma SHSY5Y cells.

Evaluation of thermo-adaptability between Tharparkar (Bos indicus) and crossbred (Bos indicus X Bos taurus) calves in a controlled environment.

The global warming driven climate change has increased the susceptibility of livestock around the globe to heat stress (HS), which reduces animal productivity and threatens the sustainability of marginal farmers. The objective of this investigation was to evaluate thermo-adaptability between Tharparkar calves (TC), an indigenous milch breed of India and crossbred calves (CC) during induced heat stress in controlled environment. For this purpose, 12 apparently healthy male calves (six in each group) aged 5-6 months, were selected. The experiment was conducted at physiologically comfortable temperature (25 °C), moderate HS (31 °C) and severe HS (37 °C) for 21 days each in a psychrometric chamber. In each experimental day, the calves were exposed to 6 h of heat. There were 7 days of acclimatization period before experiment and 10 days of recovery period at ambient temperature between each 21 day exposure period. During experimental period, the blood was collected at 1st, 6th, 11th, 16th, 21st day and among ten-day recovery period the blood was collected at 5th day. Physiological responses, serum electrolytes, metabolic enzymes profiles, antioxidant capacity, oxidative stress status and general endocrine milieu were studied. Relative mRNA expression study of Heat Shock Protein (HSP) 70, HSP90, induced Nitric Oxide Synthase (iNOS) and endothelial NOS (eNOS) were carried out by qPCR. There was significant (p < 0.05) change in the displacement in rectal temperature, respiration rate, serum alanine aminotransferase level between two breeds at moderate and severe HS. Similar change was observed in total antioxidant capacity, superoxide dismutase, and endocrinological parameters. The comparatively lower mRNA expression of HSP70 and higher expression of HSP90 in TC than CC point the better thermo-adaptability of the same. The results of the experiment indicated that TC are more thermo-adaptable than CC at different modality of stress in controlled temperature conditions.