Insight into the Natural Biomolecules (BMs): Promising Candidates as Zika Virus Inhibitors.

Zika virus (ZIKV) is among the relatively new infectious disease threats that include SARS-CoV2, coronavirus, monkeypox (Mpox) virus, etc. ZIKV has been reported to cause severe health risks to the fetus. To date, satisfactory treatment is still not available for the treatment of ZIKV infection. This review examines the last five years of work using natural biomolecules (BMs) to counteract the ZIKV through virtual screening and in vitro investigations. Virtual screening has identified doramectin, pinocembrin, hesperidins, epigallocatechin gallate, pedalitin, and quercetin as potentially active versus ZIKV infection. In vitro, testing has shown that nordihydroguaiaretic acid, mefloquine, isoquercitrin, glycyrrhetinic acid, patentiflorin-A, rottlerin, and harringtonine can reduce ZIKV infections in cell lines. However, in vivo, testing is limited, fortunately, emetine, rottlerin, patentiflorin-A, and lycorine have shown in vivo anti- ZIKV potential. This review focuses on natural biomolecules that show a particularly high selective index (>10). There is limited in vivo and clinical trial data for natural BMs, which needs to be an active area of investigation. This review aims to compile the known reference data and discuss the barriers associated with discovering and using natural BM agents to control ZIKV infection.

A Review on Comparison of Allopathic Medicines to other Drug Therapies in the Management of Asthma.

Asthma, is a chronic disease of the airways and is characterized by exacerbations of bronchospasm and noticeable airway inflammation. Current asthma therapy has emerged from naturally occurring compounds through rational pharmaceutical advancements, and it is very beneficial. In this review, we have discussed the different drug therapies i.e., Ayurvedic, Homeopathic, Unani, and Allopathic affecting asthma treatment. Allopathic medicines are used as a controller medication for regular maintenance of asthma i.e., long-acting ß-agonists, inhaled corticosteroids, anti-leukotriene medicines, and novel biologic agents. Pharmacological research is more important in generating effective, long-lasting, and safe asthma treatments, but it has been difficult to produce new classes of anti-asthmatic therapies. A combination inhaler that contains a long-acting ß2-agonist and a corticosteroid is currently the "gold standard" for treating asthma. Allopathic treatments for asthma have been proven effective in reducing the probability of asthma attacks and for improving symptoms along with lung functions as compared to other therapies. The level of asthma management and the possible risk of future worsening are used to determine the treatment's strategies. This review article describes the comparison of allopathic therapy of asthma with homeopathy, ayurvedic and Unani system and gives justification supported by a number of case studies for being allopathic, a better therapy when compared with others.

Sheehan's Syndrome in India: Clinical Characteristics and Laboratory Evaluation.

Background: Sheehan's Syndrome (SS) is an important cause of hypopituitarism especially in developing countries though it remains underdiagnosed to a great extent. Torrential bleeding after delivery followed by lactation failure and amenorrhoea gives a clue to the diagnosis which is usually made after several years of delivery. Materials and Methods: It was a retrospective observational study conducted by reviewing the case records of 38 cases of SS. The age, anthropometric measurements, signs and symptoms, biochemical parameters, hormone levels and imaging reports were examined and analyzed. Results: The mean age at presentation was 36.5 years because there was a delay of 8.4 years from last delivery before diagnosis could be made. Ninety percent patients presented with lactation failure. Anaemia, hypotension, hypogonadism, hypothyroidism, and altered lipid profile were the most common findings. The mean systolic blood pressure (BP) was 80.95 mm and diastolic BP was 51.6 mm of Hg at the time of presentation. Hyponatremia was the most common electrolyte abnormality noted and low HDL was the commonest lipid abnormality. Conclusion: A large percentage of patients presented with amenorrhea, lactation failure, and decreased or absent axillary/pubic hair. Shock, anemia, and hyponatremia were also common symptoms among the patients studied. The diagnosis of SS rests upon a thorough history taking of the postpartum events in cases presenting with hypopituitarism irrespective of the age at presentation. Proper antenatal care with exclusive institutional deliveries can reduce the prevalence of SS in developing countries.

Histopathological Changes in Placenta of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Infection and Maternal and Perinatal Outcome in COVID-19.

Background: Whether vertical transmission or placental pathology occurs after maternal infection during pregnancy remains unknown. There is a clear need for studies on the impact of COVID-19 on pregnancy outcome. A systemic inflammatory or hypercoagulable state may be the contributing factor for placental pathology. Methods: The pregnant women with COVID-19 who delivered between May 2020 and May 2021 were followed and data were collected about pregnancy course and placentas were examined for macro- and microscopical changes and were compared to controls with non-infected women. Results: Placenta of COVID-19-infected females had increased prevalence of decidual arteriopathy and placental injury reflecting hypoxia and uteroplacental insufficiency within the intervillous space. Features of maternal vascular malperfusion such as increased syncytial knots were present in 100% cases. Fibrinoid necrosis was seen in 100% cases and increased focal perivillous fibrin depositions were presented in 37.7% cases. About one fourth infected placentas had evidence of villitis. Even after matching for comorbidities like preeclampsia, these changes were present. Conclusion: The most common pathological findings of the placenta of COVID-19 infections are signs of maternal and fetal malperfusion. Future studies should target infections in different stage of gestation, including first and second trimesters.

Assessing the SpO2 in a random population - Looking for the best among fingers.

Context: Pulse oximetry is one of the most revolutionary methods used to monitor the patients in the clinical setting, particularly intensive care and anesthesia. We usually use the index or middle finger to measure SpO2 values, but little is known about the inter-digital differences that exist between the fingers. Aim: We aim to compare the peripheral capillary oxygen saturation among fingers of both hands. A total of 93 healthy volunteers aged between 18 and 50 years participated in the study. Materials and Methods: Their SpO2 values were recorded from each finger with at least 1 minute of resting interval. Their blood pressure, heart rate, and body temperature were recorded as well. Result: A total of 930 measurements were obtained from 93 volunteers. The highest average SpO2 value of right-handed volunteers was measured from the left little finger (98.48 ± 0.62) of right-handed volunteers, and it was statistically significant when compared with the right ring finger, right little finger, left thumb, left index, left middle finger, and left ring finger. The highest average SpO2 from left-handed volunteers was obtained from the right index finger, but it was statistically insignificant. Conclusion: We assume ethnic and climatic differences to play a role in contradictory results noted from previous studies conducted, and this needs to be investigated further. It is recommended that multiple readings may be obtained from other fingers as well before coming to any conclusion as inter-finger variability cannot be ignored.

Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression.

Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression.

Glimpse into the Lifestyle of Doctors.

Background: Lifestyle disorders are on rise world over. Also, the role of doctors as leaders in propagating healthy lifestyles needs to get a reality check. Aims and Objectives: This study aimed to investigate the prevalence of lifestyle disorders, eating habits, nutrition patterns, and lifestyle of doctors by assessing health-related behaviours considering gender and other relevant demographic parameters. The objectives of the present study are to find out the relationship of lifestyle disorders among doctors and to study lifestyle disorders and related behaviour among male and female doctors and other subgroups. Materials and Methods: Online survey was conducted using Googledoc in June to August 2021. Descriptive statistical analysis has been carried out in the present study. The student's t-test (two tailed, independent) has been used. Results: About 50% rated a happiness quotient of 7 and 8. Surgeons had more diabetes and hypertension than physicians. Prevalence of hypertension was more in self-employed males versus males in job. About two-third participants scored ≥ 80% on healthy lifestyle score. Conclusion: Our results call for a well-thought strategy to overcome the financial and technological hindrances to accurately identify health risk factors and plan corrective interventions. A healthy lifestyle both in terms of diet and exercise should be incorporated into the schedules of doctors.

Coronavirus disease 2019 in pregnancy: Maternal and perinatal outcome.

BACKGROUND: Since the advent of coronavirus disease 2019 (COVID-19) infection, there is debate whether pregnancy outcome in COVID-19 is more severe as compared to general population. Pregnant population is particularly susceptible to viral infections due to altered immune response. H1N1 infection and Zika virus infection led to unfavorable maternal and fetal outcomes. SARS during pregnancy has been linked previously with high risk of spontaneous abortions, preterm births and intrauterine growth restriction. The effects of this novel virus need to be studied. MATERIALS AND METHODS: This is a single-center descriptive prospective observational study of 65 pregnant women with reverse transcriptase-polymerase chain reaction confirmed COVID-19 infection, regardless of gestational age at diagnosis, admitted from April 15 to June 30, 2020, at the COVID hospital in SN Medical college a tertiary center of Agra in North India. Maternal and perinatal outcomes were studied. Data were analyzed using the SPSS software for windows. Continuous variables were expressed as mean ± standard deviation. Categorical variables were expressed as numbers and percentages. RESULTS: Majority 88.4% of the women were asymptomatic. Rest had mild illness only. Majority 94.23% were third-trimester pregnancies; preterm birth was not reported in any singleton pregnancy. Majority 85% were delivered by cesarean section done for obstetric indications. Maternal outcome of all patients was favourable, and only two women who had moderate pneumonia recovered. Maternal mortality was reported in only 1 case. All neonates were negative for COVID-19. Neonatal outcome was favorable. CONCLUSION: COVID-19 in pregnancy led to mild symptoms only. Infection in the third trimester did not led to adverse obstetric outcome including preterm labor and premature membrane rupture. SARSCoV2 infection in pregnancy did not increase the risk of maternal mortality. Vertical transmission of COVID-19 was not found in neonates. The maternal, neonatal, and perinatal outcomes of COVID-19 patients infected in late pregnancy were favorable.

COVID-19 Outcomes in Postmenopausal and Perimenopausal Females: Is Estrogen Hormone Attributing to Gender Differences?

BACKGROUND: Globally, case fatality rate is more in males compared to females. Some studies have suggested. It is hypothesized that estrogen hormone may decrease susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS CoV-2.). OBJECTIVE: The objective of the study was to evaluate the gender differences in SARS CoV-2 outcomes and to analyze if there are any differences in outcomes in premenopausal females compared to postmenopausal females. MATERIALS AND METHODS: Patients tested positive for SARS CoV-2 through real-time reverse transcription-polymerase chain reaction by Thermo Fischer Taqpath assay approved by the Indian Council of Medical Research were included in the study. The data obtained was analyzed for the epidemiological, clinical, and laboratory characteristics from their medical records. RESULTS: The mortality rate in females was 12.6%, whereas mortality in males was 19.4%. In between-group analysis, 8.6% (16/185) of females died in premenopausal age group versus 12.8% (27/211) in postmenopausal group. The proportion of females who expired due to COVID significantly differ by age and postmenopausal status X2 (1, n = 293) = 7.2, the P value is 0.007. The difference is statistically significant at P < 0.05. Postmenopausal women were more likely to expire due to COVID-19 infection compared to premenopausal women. CONCLUSION: The mortality rate in postmenopausal age group was greater than mortality in premenopausal females emphasizing the protection provided by estrogens hormone in them. Postmenopausal women are also at higher risk of severe COVID-19 infection than premenopausal women. Mortality is greater in males compared to females, further strengthening the role of estrogens.

Novel p-Functionalized Chromen-4-on-3-yl Chalcones Bearing Astonishing Boronic Acid Moiety as MDM2 Inhibitor: Synthesis, Cytotoxic Evaluation and Simulation Studies.

BACKGROUND: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenylboronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substitutedphenyl) prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. OBJECTIVES: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 protein. METHODS: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). RESULTS: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 µM) overall against tested cancer cell lines. Interestingly, para- Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 µM. Besides the emblematic hydrophobic interactions of MDM2 inhibitors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. CONCLUSION: Novel compounds were obtained with good anticancer activity especially 6- Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.

Consensus Statement Supporting the Recommendation for Single-Fraction Palliative Radiotherapy for Uncomplicated, Painful Bone Metastases.

Single-fraction palliative radiation therapy is a shorter course treatment option for veterans with terminal cancers and offers effective, convenient pain relief.

The Availability of Advanced Radiation Oncology Technology within the Veterans Health Administration Radiation Oncology Centers.

Radiation oncologists were surveyed to determine how accessible advanced radiation delivery modalities are within the VHA.

Variations in the peak expiratory flow rate with various factors in a population of healthy women of the malwa region of punjab, India.

OBJECTIVE: The present study was undertaken to study the variations in the Peak Expiratory Flow Rate (PEFR) with various factors like age, height, weight, body surface area (BSA) and the Body Mass Index (BMI) in healthy women of the Malwa region of Punjab, India. MATERIAL AND METHODS: Three hundred healthy women who were aged 20-50 years were selected from the Malwa region of Punjab and their PEFRs were determined. The influences of age, height, weight, BSA and BMI on the PEFR were studied. The PEFR test was performed by using a mini Wright Peak Expiratory flow meter. RESULTS: The mean PEFR of the women of the Malwa region of Punjab was found to be 395.87 ± 56.81 litres/minute. The PEFR increased with an increase in the age, height, weight and the BSA, but it decreased with an increase in the BMI. CONCLUSION: This study generated the preliminary values of PEFR for the women of the Malwa region of Punjab, India.

Nerve conduction studies in the upper limb in the malwa region-normative data.

OBJECTIVE: To establish the normal electrophysiological data for the median and the ulnar nerves in normal healthy adults in the Malwa region of Punjab, India. METHODS: Nerve conduction studies were performed prospectively in the upper limbs of 100 carefully screened, healthy individuals of either sex, who were between the ages of 20 and 60 years, by using a standardized technique. RESULTS: Motor studies: The median distal latency (DL) in men was 3.4 (0.2) ms, the amplitude (CMAPA) was 10.80 (2.8) mV, the conduction velocity (MNCV) was 55.6 (2.5) m/s and the F-wave (min latency) was 27.57±2.54(21.5-34.2). In the ulnar nerve , the motor DL was 2.34 (0.25) ms, the amplitude (CMAPA) was 9.8(2.6) mV, MNCV was 63.4 (3.0) m/s and the F-Wave(min latency) was 26.29±2.12(21.6-34.7). In the sensory studies, the median nerve DL was 2.0(0.35) ms, SNCV was 53.4±3.0 m/s and the amplitude (SNAPA)was 59.3 (16.4) µV for men and it was 68.7(28.4) µV for women. For the ulnar nerve in men, the DL was 1.85(0.25)ms, SNCV was 55.5 (4.1) m/s and the amplitude(SNAPA) was 55.5 (18.4) µV for men and it was 64.9 (16.8) µV for women. Only the gender showed a statistically significant effect on the sensory nerve action potential for the median (p < 0.04) and the ulnar nerves (p < 0.041). CONCLUSION: The normative conduction parameters of the commonly tested nerves in the upper limb were established in our EMG lab. The mean motor nerve conduction parameters for the median and the ulnar nerves correlated favourably with the existing literature data. However, for the sensory nerves, a higher value for the nerve action potential amplitude was demonstrated in this study.

Fulminant leukemoid reaction due to postpartum Clostridium sordellii infection.

Clostridium sordellii is gram positive anaerobic spore forming rod and it has been demonstrated to cause gas gangrene, refractory shock, leukemoid reaction, and pleuroperitoneal effusion due to capillary leak. We report here a case of postpartum female who presented with leukemoid reaction, ascites, pleural effusion, and shock without fever 7 days after normal vaginal home delivery.

Footdrop in the farmers in punjab: a retrospective electrodiagnostic study.

AIM: This study was performed to find out the occurrence of the common footdrop which was due to peroneal nerve palsy in the farmers in Punjab, India. METHODS: This study consisted of 100 male subjects of which 50 were farmers (who were aged between 20 to 50 years), who were suffering from a unilateral foot drop and 50 were normal, healthy, age matched controls who were not involved in farming activities. The nerve conduction parameters (the nerve conduction velocities, latencies and amplitudes) of the common peroneal nerve and the tibial and the sural nerves were measured distally at the ankle and proximally at the knee on both the lower limbs of the subjects. RESULTS: On comparative evaluation, the data showed a significantly reduced conduction velocity and amplitude on the affected side as well as on the contralateral side in the common peroneal nerve of the farmers as compared to those in the controls. The F wave latency was increased in both the limbs of the farmers in comparison to the controls. CONCLUSIONS: The patients presented with a unilateral footdrop which was due to peroneal palsy, but a decreased peroneal nerve conduction was observed on the contralateral side as well. Thus, it suggested the involvement of the common peroneal nerve bilaterally. The position of sitting during harvesting or weeding was also important in inducing footdrop along with the type of the hand activity, because of occurrence of the footdrop on the side of the dominant hand.

Nitric oxide modulation in protective role of antidepressants against chronic fatigue syndrome in mice.

BACKGROUND AND OBJECTIVE: The present study was designed to elucidate the possible nitric oxide (NO) mechanism in the protective effect of antidepressants using mice model of chronic fatigue syndrome (CFS). MATERIALS AND METHODS: Male albino laca mice were forced to swim for each 6 min session for 7 days and immobility period was measured on every alternate day (1(st), 3(rd), 5(th), 7(th)). After 7 days various behavioral tests (locomotor, mirror chamber, and plus maze tests for anxiety) were performed and biochemical estimations (lipid peroxidation, nitrite levels, GSH (reduced glutathione), and catalase activity) in mice brain were performed. Animals were pretreated with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) daily for 7 days. RESULTS: The present study showed that continued forced swimming for 7 days caused chronic fatigue-induced anxiety-like behavior as assessed in mirror chamber, plus maze tests, and impairment in locomotor activity followed by oxidative damage (as evidenced by increased lipid peroxidation, nitrite levels, depleted reduced glutathione, and catalase activity) in animals. Seven days pretreatment with citalopram (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) significantly improved behavioral and biochemical alterations. Further, L-nitro-arginine methyl ester (L-NAME,5 mg/kg) and methylene blue (MB, 10 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) potentiated their protective effect. However, l-arginine (100 mg/kg) pretreatment with citalopram (5 mg/kg) or imipramine (10 mg/kg) reversed their protective effect as compared with their effect per se (P < 0.05). CONCLUSION: The present study suggests that protective effect of citalopram and imipramine might be due to its NO modulation against chronic fatigue induced behavioral and biochemical alterations.

Possible role of NO modulators in protective effect of trazodone and citalopram (antidepressants) in acute immobilization stress in mice.

Stress is an aversive stimulus which disturbs physiological homeostasis and is reflected on a variety of biological systems. The present study was designed to investigate the nitric oxide mechanism in neuroprotective effect of trazodone and citalopram against acute immobilization-induced behavioral and biochemical alteration in mice. Mice were immobilized for a 6 h. Acute immobilization stress caused anxiety, hyperalgesia, impaired locomotor activity and oxidative damage. Pretreatment with trazodone and citalopram significantly reversed immobilized stress-induced behavioral and biochemical alterations. L-arginine, pretreatment with trazodone or citalopram significantly reversed their protective effects. However, L-NAME or methylene blue pretreatment with trazodone or citalopram significantly potentiated their protective effects alone. Results suggest the involvement of nitric oxide pathways in the protective effect of trazodone and citalopram against immobilization stress induced behavioral and biochemical alterations.

Effect of St. John's Wort (Hypericum perforatum) treatment on restraint stress-induced behavioral and biochemical alteration in mice.

BACKGROUND: A stressful stimulus is a crucial determinant of health and disease. Antidepressants are used to manage stress and their related effects. The present study was designed to investigate the effect of St. John's Wort (Hypericum perforatum) in restraint stress-induced behavioral and biochemical alterations in mice. METHODS: Animals were immobilized for a period of 6 hr. St. John's Wort (50 and 100 mg/kg) was administered 30 minutes before the animals were subjecting to acute immobilized stress. Various behavioral tests parameters for anxiety, locomotor activity and nociceptive threshold were assessed followed by biochemical assessments (malondialdehyde level, glutathione, catalase, nitrite and protein) subsequently. RESULTS: 6-hr acute restraint stress caused severe anxiety like behavior, antinociception and impaired locomotor activity as compared to unstressed animals. Biochemical analyses revealed an increase in malondialdehyde, nitrites concentration, depletion of reduced glutathione and catalase activity as compared to unstressed animal brain. Five days St. John's Wort treatment in a dose of 50 mg/kg and 100 mg/kg significantly attenuated restraint stress-induced behavioral (improved locomotor activity, reduced tail flick latency and antianxiety like effect) and oxidative damage as compared to control (restraint stress). CONCLUSION: Present study highlights the modest activity of St. John's Wort against acute restraint stress induced modification.

Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice.

Present study has been designed to elucidate the nitric oxide modulatory mechanism of venlafaxine in experimental model of chronic behavior despair in mice. Animals (male albino laca mice) were forced to swim daily for 6 min test session for 7 days and immobility period of each animal was measured on every alternate days. Six minutes forced swimming test session for 7 days caused anxiety-like behavior (as assessed by mirror chamber and plus maze tests) and impairment in locomotor activity followed by oxidative damage (increased lipid peroxidation, nitrite concentration, depleted reduced glutathione and catalase activity) as compared to naïve animals. Seven days venlafaxine (5 and 10 mg/kg) treatment significantly caused anti-anxiety-like effect, improved locomotor activity and attenuated oxidative damage (reduced lipid peroxidation, nitrite concentration and caused restoration of reduce glutathione and catalase activity) as compared to control. Caffeine (10 mg/kg) pretreatment with venlfaxine (5 mg/kg) did not produce any significant effect on locomotor activity, immobility period and oxidative damage as compared to their effect per se. Further, L-NAME (5 mg/kg) and methylene blue (10 mg/kg) pretreatment with sub effective dose of venlafaxine (5 mg/kg) potentiated its protective effect which was significant as compared to their effect per se. However, L-arginine (100 mg/kg) pretreatment with venlafaxine (5 mg/kg) significantly reversed the protective effect of venlafaxine (P<0.05). Present study suggests that nitric oxide modulation might be involved in the protective effects of venlafaxine.