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Predictions are made by artificial intelligence, especially through machine learning, which uses algorithms and past knowledge. Notably, there has been an increase in interest in using artificial intelligence, particularly generative AI, in the pharmacovigilance of pharmaceuticals under development, as well as those already in the market. This review was conducted to understand how generative AI can play an important role in pharmacovigilance and improving drug safety monitoring. Data from previously published articles and news items were reviewed in order to obtain information. We used PubMed and Google Scholar as our search engines, and keywords (pharmacovigilance, artificial intelligence, machine learning, drug safety, and patient safety) were used. In toto, we reviewed 109 articles published till 31 January 2024, and the obtained information was interpreted, compiled, evaluated, and conclusions were reached. Generative AI has transformative potential in pharmacovigilance, showcasing benefits, such as enhanced adverse event detection, data-driven risk prediction, and optimized drug development. By making it easier to process and analyze big datasets, generative artificial intelligence has applications across a variety of disease states. Machine learning and automation in this field can streamline pharmacovigilance procedures and provide a more efficient way to assess safety-related data. Nevertheless, more investigation is required to determine how this optimization affects the caliber of safety analyses. In the near future, the increased utilization of artificial intelligence is anticipated, especially in predicting side effects and Adverse Drug Reactions (ADRs)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present investigation has focused on developing an eco-friendly method to extract bioactive compounds from orange peel using natural deep eutectic solvents (NADES). NADES-II composed of choline chloride (ChCl) and ethylene glycol (1:2) and 50% water shows the maximal extraction yield with higher antioxidant activity in terms of DPPH and ABTS scavenging activity with a high total phenolic content (TPC) and total flavonoid content (TFC). The microwave-assisted extraction (MAE) process was optimized using response surface methodology (RSM) and an artificial neural network (ANN). ANN showed a higher value of R 2 and lower values of other statistical parameters when compared to RSM. The ideal extraction conditions were optimized as a 13 min rising time, 52 °C temperature, a 21 min holding time, and a 20 mL/g liquid-to-solid ratio. MAE was compared with the conventional heating-stirring extraction (HSE) method using the NADES-II solvent under optimum conditions. The results show that higher extraction yield and antioxidant capacities (DPPH and ABTS), TPC, and TFC can be obtained from orange peel using the MAE process compared to the HSE process. Overall, this study shows an optimiztic approach for the extraction of bioactive compounds from an orange peel using eco-friendly solvents and microwave technology. It also highlights the potential of this approach for valorizing orange peel waste., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Hydrocephalus is rarely described in Joubert-Boltshauser syndrome (JBTS). The aim of this study was to investigate whether this association is a chance occurrence or potentially signifies a new phenotypic subtype. The databases of Wolfson Medical Center, Sourasky Medical Center, and EB's personal collection were reviewed. Records from an additional family were obtained from RG. The patients' medical records, prenatal ultrasounds, and magnetic resonance imaging were assessed. In addition, we reviewed the medical literature for the association of ventriculomegaly/hydrocephalus (VM/HC) in JBTS. Only seven cases (from five families) were found with prenatal onset of VM/HC, diagnosed during the second trimester; three pregnancies were terminated, one was stillborn and three were born, of which one died within a week, and another died at the age of 6 years. Additional central nervous system findings included dysgenesis of the corpus callosum, delayed sulcation, polymicrogyria, and pachygyria. We found 16 publications describing 54 patients with JBTS and VM/HC: only five were diagnosed at birth and three were diagnosed prenatally. Hydrocephalus is extremely rare in JBTS. The recurrence of this association, reported in several publications in multiple family members, suggests that it might represent a new phenotypic subtype of JBTS possibly associated with specific genes or variants. Further genetic studies are needed to confirm this hypothesis. WHAT THIS PAPER ADDS: The association of fetal hydrocephalus with Joubert-Boltshauser syndrome (JBTS) is very rare but not a chance association. This association represents a new phenotypic subtype of JBTS possibly linked to specific genes or variants., (© 2024 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Central nervous system (CNS) infection is one of the important risk factors for epilepsy. COVID-19 pandemic, which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has primarily been considered to involve respiratory system only, but it can also affect the CNS. A wide range of neurological manifestations have been reported in SARS-CoV-2 infected patients including seizures, status epilepticus, stroke, which are considered as important risk factors for the development of epilepsy. In post-mortem, brain tissue samples of COVID-19 patients have shown neuropathological changes and presence of SARS-CoV-2 RNA and viral proteins. In this review, mechanisms of SARS-CoV-2 neuroinvasion like neuronal retrograde trans-synaptic route and vascular route are described along with important neurological manifestations in COVID-19 patients such as seizures and cerebrovascular diseases, which have been found to be associated with the development of epilepsy. Hence, an increased risk of future burden of epilepsy in susceptible COVID-19 survivors has been proposed and preventive measures are suggested. The present review highlights about the possible association between neurological manifestations and future risk of epilepsy in COVID-19 patients.

Abstract: Aqueous enzyme-assisted solvent extraction (AE-SE) of oil from apricot ( Prunus armeniaca L.) kernel was investigated in this study and the operational parameters were optimized. After preliminary screening, a cocktail of enzymes (Celluclast 1.5 L and Alcalase Pure 2.4 L [60:40, v/v)] of 1% (v/w) was chosen. The extraction process parameters: temperature (40-60 °C), time (1-5 h), and pH (4-9) were optimized using Box-Behnken design to achieve the highest oil yield (%) and antioxidant activity (DPPH, %). Under optimized conditions, i.e., temperature 40 °C, time 2.5 h, and pH 8.28, the highest oil yield and DPPH were 47.93% and 67.31%, respectively. The gas chromatography analysis disclosed that apricot kernel oil extracted by solvent extraction and AE-SE have similar fatty acid compositions, and the oil is rich in unsaturated fatty acids. The physicochemical analysis showed AE-SE method produces high-quality oil and can be substituted as green technology for industrial oil extraction purposes., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: This study evaluated the effect of sertraline with desvenlafaxine and sertraline with mirtazapine on HAM-D score and inflammatory markers (IL-6 and TNF-α levels) in major depressive disorder., Methods: Patients (18-60 years) with MDD diagnosed by DSM-V criteria and HAM-D score 18 or more were included ( n  = 60). Group A patients ( n  = 30) received sertraline 50 mg/day and desvenlafaxine 50 mg/day. Group B patients ( n  = 30) received sertraline 50 mg/day and mirtazapine 30 mg/day. All patients were followed up for 8 weeks for the evaluation of clinical efficacy, safety, serum IL-6, and TNF-α levels., Results: Our study showed a comparatively similar and statistically significant ( p  < 0.05) reduction in HAM-D score in both groups in the 4th and 8th week of the treatment. Both drug combinations significantly ( p  < 0.05) decreased serum IL-6 and TNF-α after 8 weeks of treatment., Conclusion: The present study suggests that the combination therapy (as treatment initiation) with sertraline and desvenlafaxine, and sertraline with mirtazapine is effective and well tolerated in MDD patients with moderate to severe depression, and their therapeutic efficacy is accompanied by decreased inflammatory markers (serum IL-6 and TNF-α).

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to an increase in mental health problems such as depression and anxiety. This study aims to investigate the prescribing pattern of psychotropic drugs in patients with common mental disorders which might be altered during the pandemic and also whether the pandemic could alter their quality of life (QOL) and medication adherence., Materials and Methods: After prior ethical approval, a descriptive cross-sectional drug utilization study (DUS) of 200 prescriptions was undertaken to evaluate the pattern of psychotropic drug usage as per WHO (World Health Organization)/International Network of Rational Use of Drugs (INRUD) guidelines. The correlation of the average number of drugs per prescription with QOL was observed. The correlation of adverse drug reactions (ADRs) with medication adherence was also analyzed., Results: The average number of drugs per prescription during the pre-COVID-19 and COVID-19 period was estimated to be 2.48 and 2.96. The percentage of drugs prescribed by generic name in the two different periods (pre-COVID-19 and COVID-19) was 97.40 and 95.77%. The percentage of drugs prescribed from the list of essential medicines was 89.40 and 85.12%, respectively. The percentage of prescriptions with injections was 0.45% and 0.53%, respectively for the two periods. The QOL during the COVID-19 pandemic was found to be negatively correlated to the average number of drugs per prescription (correlation coefficient = -0.61) and medication adherence was found to be poor in patients who developed ADRs with the drugs prescribed ( p -value of 0.001)., Conclusion: In the tertiary care hospital described, rational drug prescribing was followed. Increase in the number of drugs per prescription was found to be associated with poor QOL and the development of ADRs led to medication nonadherence in the patients. Further studies with larger sample sizes are needed to confirm these results. How to cite this article: Kumar A, Halder S, Srivastava S, et al. Increased Pill Burden and Adverse Effects of Psychotropics Correlated with Poor Quality of Life and Medication Nonadherence: A Cross-sectional Drug Utilization Study at a Tertiary Care Hospital in Delhi during COVID-19 Pandemic. J Assoc Physicians India 2023;71(9):14-18., (© Journal of the Association of Physicians of India 2023.)

The present study was performed to optimize the modified aloe polysaccharide (MAP) foaming process and to determine the effect of drying process parameters on the quality of obtained MAP powder. The studied process parameters were glycerol monostearate (GMS), carboxymethyl cellulose (CMC), and whipping time (WT) which was varied between 1 and 4% w/v, 0.1-0.5% w/v, and 1-5 min, respectively. The optimized values of foaming process parameters were 3.87% GMS, 0.39% CMC, and 4.89 min WT with a desirability of 0.889. The optimized foamed MAP juice was dried at different foam thicknesses (FT) (1, 3, and 5 mm) and drying temperatures (DT) (50, 60, and 70 °C) to develop MAP powder and compared with non-foamed aloe powder developed under the same drying condition. Based on functional properties, the best GMS foamed MAP powder was achieved at 50 °C DT and 1 mm FT, recording powder yield (16%), solubility (20.85%), and polysaccharide content (282 mg/L)., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01354-6., Competing Interests: Conflicts of interestThere is no conflict of interests or competing interests., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

To date, nanomaterials have been widely used for the treatment and diagnosis of rheumatoid arthritis. Amongst various nanomaterials, polymer-based nanomaterials are becoming increasingly popular in nanomedicine due to their functionalised fabrication and easy synthesis, making them biocompatible, cost-effective, biodegradable, and efficient nanocarriers for the delivery of drugs to a specific target cell. They act as photothermal reagents with high absorption in the near-infrared region that can transform near-infrared light into localised heat with fewer side effects, provide easier integration with existing therapies, and offer increased effectiveness. They have been combined with photothermal therapy to understand the chemical and physical activities behind the stimuli-responsiveness of polymer nanomaterials. In this review article, we provide detailed information regarding the recent advances in polymer nanomaterials for the non-invasive photothermal treatment of arthritis. The synergistic effect of polymer nanomaterials and photothermal therapy has enhanced the treatment and diagnosis of arthritis and reduced the side effects of drugs in the joint cavity. In addition, further novel challenges and future perspectives must be resolved to advance polymer nanomaterials for the photothermal therapy of arthritis., Competing Interests: The authors declare no conflict of interest.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin‑noradrenaline reuptake inhibitor) on brain‑derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione‑s‑ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM‑IV criteria, with Hamilton Depression Rating scale (HAM‑D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50‑100 mg once daily. Patients were followed up for 12 weeks. HAM‑D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre‑ and post‑treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.

Purpose: Antenatal detection of limb anomalies is not uncommon, and pregnancies are usually terminated in view of the expected physical handicap. The aim of this retrospective observational study is to delineate the spectrum of fetal limb anomalies and provide evidence in support of complete postnatal evaluation in establishing recurrence risk., Methods: We present 54 cases of limb malformations detected antenatally and discuss the spectrum of abnormalities, the utility of fetal autopsy, and genetic testing to establish recurrence risk in subsequent pregnancies., Results: 16/54 cases were isolated radial ray anomalies. There were five cases of amniotic band syndrome, five limb body wall complex cases, three VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) associations, one case of sirenomelia, two cases of limb pelvis hypoplasia, and one case of OEIS (Omphalocele Exstrophy Imperforate anus and spinal defects). Four fetuses with non-isolated radial ray anomaly had trisomy 18. One case with bilateral radial ray defect had a mutation in the FANC-E gene confirming fanconi anemia. Twelve cases were unclassified., Conclusion: Autopsy is the most important investigation in fetuses with limb anomalies. We suggest chromosomal microarray (CMA) as a first-tier test after autopsy. However, in cases of bilaterally symmetrical limb anomalies, in case of previous similarly affected child, or history of consanguinity, whole exome sequencing (WES) can be offered as the primary investigation, followed by CMA if WES is normal., (© 2022 Wiley Periodicals LLC.)

Background: Long term effects of COVID are not fully understood yet. The geriatric population has been badly affected. The impact of COVID-19 on the health-related quality of life after recovery and patient compliance is a matter of concern especially in the geriatric population where polypharmacy is often prevalent., Aims and Objectives: This study intended to observe the occurrence of polypharmacy (PP) among COVID-19 recovered older patients with multimorbidity and explore its association with health-related quality of life and compliance in these patients., Materials and Methods: Total 90 patients, above 60 years of age having two or more co-morbidities and recovered from COVID-19 infection were included in this cross-sectional study. Number of pills taken daily by each patient was noted, to determine the occurrence of PP. WHO-QOL-BREF was used to assess the effect of PP on health-related quality of life (HRQOL). Medication adherence was measured using a self-reported questionnaire., Results: PP was found in 94.4% while hyper polypharmacy was found in 45.56% of patients. The overall mean score of HRQOL in patients with PP was 187.91 ± 32.98, indicating poor quality of life with PP ( p value 0.0014) whereas the overall mean score of HRQOL in patients with hyper polypharmacy was 177.41 ± 26.11, showing poor quality of life with hyper polypharmacy ( p value 0.0005). Increased number of pills corelated with poor quality of life ( r =0.49). The medication adherence was found to be poor in patients who received mean number of pills 10.44 ± 2.62 whereas the adherence was good if the mean number of pills was 8.20 ± 2.63, ( p value of 0.0001)., Conclusion: Polypharmacy is highly prevalent among COVID-19 recovered patients and is associated with poor quality of life as well as poor medication adherence., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Mid-life Health.)

Objective: We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST)., Method: Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45 mg/day or ST 25-200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL., Result: We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs., Conclusion: Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants., (© 2022 John Wiley & Sons Ltd.)

Objective: To study the correlation between telomere length (TL) and long-acting injectable (LAI) and oral atypical antipsychotic (OAA) efficacy on schizophrenia (SCZ) severity and cognitive impairment., Methods: Sixty Schizophrenia patients of 18-50 years and of either sex were included in a 12-week study. Thirty patients were recruited in each group, LAI and OAA. Positive and Negative Syndrome Scale (PANSS) and National Institute of Mental Health and Neuro-Sciences (NIMHANS) neuropsychological battery tests were evaluated at baseline and 12 weeks. TL was estimated at baseline., Results: Both groups showed a significant improvement in PANSS and NIMHANS battery test scores after treatment ( p  < 0.001) within the group, though not between the groups. Mean TL at baseline was 407.58 ± 143.93 and 443.40 ± 178.46 in LAI and OAA groups respectively. A significant negative correlation ( r = -0.28, p  = 0.03) of TL was seen with the mean change in negative PANSS score after treatment., Conclusions: LAI antipsychotics are similar to OAA in decreasing the disorder severity and improving the cognitive impairment in schizophrenia. Also, patients who have shorter TL show greater improvement in the negative PANSS score. Hence, TL holds the potential of predicting antipsychotic drug response in schizophrenia patients.KEY POINTSLong-acting injectable antipsychotic was comparable to oral atypical antipsychotics in bringing out improvement in disorder severity, cognitive functions over 12 weeks.Shorter telomere length has been found to be associated with a greater response in negative symptoms of schizophrenia.

Background: Contemporary research indicates the role of neuroinflammation/inflammatory markers in epilepsy. In addition, comorbidities such as anxiety and poor health-related quality of life are vital concerns in clinical care of pediatric patients with epilepsy. This open-label, prospective, observational study evaluated the effect of valproate and add-on levetiracetam on serum levels of C-C motif ligand 2 (CCL2) and Interleukin-1 beta (IL-1β) in pediatric patients with epilepsy. We also studied effect of valproate and add-on levetiracetam on anxiety and health-related quality of life (HRQoL) in specified age subgroups., Methods: Children aged 1 to 12 years, diagnosed with epilepsy (generalized or focal seizures), treated with valproate (n = 40) and valproate with add-on levetiracetam (n = 40) were included. All patients were followed up for 16 weeks and assessed for changes in serum CCL2 and IL-1β levels. Spence Children Anxiety Scale short version (SCAS-S) and QOLCE-16 scales were used to measure anxiety and HRQoL, respectively, in specific age groups., Results: The serum CCL2 level decreased significantly (p < .001) from 327.95 ± 59.07 pg/ml to 207.02 ± 41.50 pg/ml in the valproate group and from 420.65 ± 83.72 pg/ml to 250.06 ± 46.05 pg/ml in the add-on levetiracetam group. Serum IL-1β level did not change significantly in both groups. Spence Children Anxiety Scale short version scores were decreased and QOLCE-16 scores were increased significantly (p < .001) in both valproate and add-on levetiracetam groups., Conclusions: The results of our study suggest that valproate and levetiracetam led to decrease serum CCL2 levels without any change in serum IL-1β levels in children with epilepsy. Anti-inflammatory property of valproate and levetiracetam might underlie their antiepileptic effect and CCL2 could be a potential marker of drug efficacy in epilepsy. Also, valproate and levetiracetam reduced anxiety and improved quality of life in children with epilepsy in the age groups evaluated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer., Objective: To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ)., Methods: PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis., Results: Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737)., Conclusion: In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Isolated fetal ascites is an uncommon finding, and it may be difficult to elucidate the underlying pathology. This is more so when there are limited resources to investigate the patient adequately. This study was undertaken to see the etiology of isolated fetal ascites and analyze the outcomes., Materials and Methods: Twenty-three cases of isolated fetal ascites were retrospectively analyzed from December 2007 to June 2018. All cases were investigated with detailed ultrasound with other investigations as required. Postnatal data included gestational age at birth, mode of delivery, weight, and postnatal outcome., Results: The mean age at diagnosis was 26 gestational weeks. Structural abnormalities without any underlying chromosomal or genetic cause were identified in 10/23 (43.4%) cases with the most common structural abnormality related to the gastrointestinal tract where ultrasound proved to the most useful tool. The overall good prognosis was seen in 13/23 (56.5%) cases., Conclusion: Appropriate perinatal care, timely referral and delivery at tertiary care setup, and timely surgical intervention are measures which can improve the outcome and survival in fetuses diagnosed with isolated fetal ascites., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Indian Association of Pediatric Surgeons.)

Background: Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) indicate the role of neurotrophic factors and inflammation. This study assessed the association between therapeutic response of bupropion and serum brain-derived neurotrophic factor (BDNF) and tumour necrosis factor-α (TNF-α) levels in patients with MDD., Methods: Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM-5 criteria, with Hamilton Depression Rating scale (HAM-D) score ≥ 20 were included in the study. Patients were given bupropion sustained release (SR) in the doses of 150 mg once daily. All patients were followed up for 12 weeks., Results: HAM-D score at the start of the treatment was 25.57 ± 1.85 which significantly reduced to 10.8 ± 4.24 at 12 weeks of treatment. The serum BDNF level increased significantly (p < 0.05) from 2.42 ± 0.19 ng/ml to 2.97 ± 0.10 ng/ml and the levels of serum TNF-α reduced significantly (p < 0.05) from 4.45 ± 0.95 pg/ml to 2.11 ± 0.84 pg/ml at 12 weeks of treatment, in responders to treatment., Conclusion: The results of our study suggest that bupropion SR monotherapy is effective and well tolerated in MDD patients with moderate to severe depression, and its therapeutic efficacy is accompanied by an increase in serum BDNF levels and a decrease in serum TNF-α levels., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of people living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to the build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in the fight against HIV. Few long-acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, long-acting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. Long-Acting Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Furthermore, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated., Materials and Methods: A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1 and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels., Results: Zinc 2.5 μg/embryo showed significant (P < 0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 μg/embryo. The combination of zinc 2.5 μg/embryo with sorafenib 2 μg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 μg/embryo with sorafenib 1 μg/embryo produced an antiangiogenic activity which was comparable (P > 0.05) to that of sorafenib 2 μg/embryo., Conclusion: Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor., Competing Interests: None

Background: Cyclic neucleotides are involved in many cellular functions including smooth muscle relaxation, inflammation, and signal transduction. Sildenafil and tadalafil are phosphodiesterase-5 (PDE-5) inhibitors which prevent the degradation of cyclic neucleotide i.e. guanosine 3',5' cyclic monophosphate (cGMP) and increase the levels of cGMP. In this study sildenafil and tadalafil were evaluated for their anti-inflammatory, anti-oxidative and anti-nitrosative stress potential in animal model of bronchial asthma., Methods: Wistar rats were sensitized with 10 mg intraperitoneal (ip) ovalbumin adsorbed to 10 μg of aluminum hydroxide on day 0. Animals were given sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip) from day 1 to day 14. Also, on day 14 animals were challenged with ovalbumin (1 mg ip). After 24 h, samples were collected to analyze interleukin-4 (IL-4) and tumour necrosis factor-α (TNF-α), in serum and bronchoalveolar lavage fluid (BALF). The oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide metabolites (NO x ) were also measured in serum., Results: Pre-treatment with sildenafil (1 and 3 mg/kg ip) and tadalafil (1 and 3 mg/kg ip) significantly reduced the levels of pro-inflammatory cytokines IL-4 and TNF-α in rat serum and BALF. In addition, pre-treatment with both the drugs decreased the levels of MDA and NO x and increased the levels of GSH in serum., Conclusions: Sildenafil and tadalafil decreased pro-inflammatory cytokines in serum and BALF. Both drugs inhibit oxidative and nitrosative stress in animal model of bronchial asthma and could have a therapeutic potential in bronchial asthma., (Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Evidence suggests that neurotrophic factors, inflammatory markers, and circadian rhythm dysfunctions could be involved in pathophysiology of major depressive disorder. This study evaluated the efficacy and tolerability of agomelatine, a melatonergic drug, and fluoxetine (positive comparator) and their effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor (TNF)-α level in patients having major depressive disorder with severe depression. In the present study, we chose TNF-α and BDNF because reduction of TNF-α and rise in BDNF levels are linked with improvement in major depressive disorder. Patients with Hamilton Rating Scale for Depression (HAM-D) score ≥25 were treated with agomelatine or fluoxetine and followed up for 12 weeks. In the agomelatine group, the HAM-D score, BDNF level, and TNF-α level at the start of treatment were 31.1 ± 1.88 ng/mL, 2.44 ± 0.38 ng/mL, and 512.5 ± 86.2 pg/mL, respectively, which significantly changed to 13.67 ± 2.22 ng/mL, 2.87 ± 0.44 ng/mL, and 391.64 ± 104.8 pg/mL, respectively (P < .05 for all 3 measures), at 12 weeks. In the fluoxetine group, the HAM-D score, BDNF level, and TNF-α level at the start of treatment were 30.83 ± 2.60 ng/mL, 2.54 ± 0.37 ng/mL, and 554.14 ± 46.8 pg/mL, respectively, which significantly changed to 13.67 ± 1.79 ng/mL, 3.07 ± 0.33 ng/mL, and 484.15 ± 49.9 pg/mL, respectively (P < .05 for all 3 measures) at 12 weeks. The BDNF level was significantly increased posttreatment with both drugs, and TNF-α level fell significantly more with agomelatine compared to fluoxetine. Thus, chronic neuroinflammatory biomarkers contribute to circuitry dysregulation in depression. Trophic factors repair dysfunctional circuits in depression. Both treatments were found to be safe and well tolerated., (© 2017, The American College of Clinical Pharmacology.)

Introduction: People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

Aims: Angiopoietin-like growth factors (ANGPTLs) regulate glucose, lipid homeostasis, and insulin sensitivity. This study aimed to find whether long-term glycemic control (glycated hemoglobin [HbA 1c ]) has any correlation with serum ANGPTL6 levels in patients of type 2 diabetes mellitus., Materials and Methods: It was an open-label, observational, prospective clinical study. Sixty-five participants (41 diabetic patients receiving daily dose of oral metformin for a minimum of 3 months and 24 matched controls) completed the study. A single venous blood sample was taken from each participant to determine serum HbA 1c and serum ANGPTL6 levels. Comparison of serum ANGPTL6 levels according to the HbA 1c levels, in groups A, B, and C ranging from 6.5%-8%, 8.1%-9.5%, and >9.5%, respectively, was done using Kruskal-Wallis H -test followed by pairwise comparisons., Results: Serum HbA 1c and serum ANGPTL6 levels were raised significantly ( P < 0.05) in diabetic patients when compared with control participants. A positive correlation was observed between serum HbA 1c and serum ANGPTL6 levels ( r = 0.88, 95% confidence interval 0.81, 0.92). Mean ANGPTL6 level for Group A ( n = 20) was 394.3 pg/ml, for Group B ( n = 8) 692.8 pg/ml, and for Group C ( n = 13) 896.2 pg/ml., Conclusions: Serum ANGPTL6 levels were significantly higher in type 2 diabetic patients in comparison with healthy controls. Poor glycemic control in diabetes mellitus as reflected by higher serum HbA 1c levels is associated with raised serum ANGPTL6 levels., Competing Interests: There are no conflicts of interest.

Objective: To evaluate first-trimester screening protocols for detecting trisomy 21 in an Indian population., Methods: The present prospective study collected data from women with singleton pregnancies and a crown-to-rump length of 45-84 mm who presented at the fetal medicine unit of a tertiary care center in North India between June 1, 2006, and December 31, 2015, for combined first-trimester screening. Maternal age, nuchal translucency, nasal bone, and maternal serum levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were assessed for calculating the risk of trisomy 21. Tricuspid regurgitation and qualitative analysis of ductus venosus data were available from June 2010, and were included where available. Trisomy-21 detection rates were calculated for various screening protocols and were compared., Results: There were 4523 women screened and 24 records of trisomy 21. Combined screening with maternal age, nuchal translucency, nasal bone, tricuspid regurgitation, and ductus venosus demonstrated optimal detection and false-positive rates of 93.8% and 1.9%, respectively. Screening using only maternal age yielded a detection rate of 37.5%; using fixed nuchal translucency cut-off values of 2.5 and 3 mm resulted in detection rates of 66.7% and 37.5%, respectively., Conclusion: Combined first-trimester screening performed well in an Indian population; combining maternal age, nuchal translucency, nasal bone, ductus venosus, and tricuspid regurgitation yielded the most accurate screening., (© 2016 International Federation of Gynecology and Obstetrics.)

Objective: Good biomarkers are important to guide decisions in the clinical management of rheumatoid arthritis (RA). RA patients harbor antibodies directed against carbamylated proteins which may predict joint damage. This study investigated whether antibodies against carbamylated proteins (anti-CarP) may serve as surrogate prognostic markers., Material and Methods: Fifty-three patients with a diagnosis of rheumatoid arthritis according to ACR 1987 criteria were included. Blood samples were analyzed for CarP antibody levels using the ELISA method. Quality of life (QoL) was assessed by the WHO SF-36 questionnaire, and disease activity was assessed using the DAS28 calculator. Newly diagnosed patients were assessed at the first visit and at 12 weeks of treatment, while a single assessment was made for patients already on maintenance therapy., Results: Out of 53 patients, 22 had titers of anti-CarP above the cut-off range and considered as positive for anti-CarP antibodies. Anti-CarP antibody serum level was significantly higher in patients with deformity of joints and with erosions in comparison to those without any destructive changes ( p < 0.05). There was a weak positive correlation between anti-CarP and DAS 28 ( p > 0.05). Also there was a weak negative correlation in all domains of quality of life with anti-CarP antibody titers ( p > 0.05). There was no significant correlation between titers of anti-CarP antibodies and presence or absence of rheumatoid factor., Conclusions: Serum levels of anti-CarP antibodies in RA patients with joint erosions/deformities were much higher than in those without any joint damage. Anti-CarP antibodies may have good prognostic value in RA patients with erosions. Disease activity and QoL of RA patients improved during treatment, but no correlation was found between DAS 28/QoL and anti-CarP antibody serum levels., Competing Interests: The authors declare no conflict of interest. This study is registered with Clinical Trials Registry, India, No. CTRI/2015/06/005878.

Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression-like behavior and cognition in rats or mice. Nociception was assessed using tail-flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail-suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine. In tail-flick test sitagliptin (6 mg/kg) produced transient nociceptive effect. Liraglutide (200 µg/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6 mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency. This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression., Methods: Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels., Results: HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p < 0.05) reduced to 13.47 ± 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 ± 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 ± 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-α levels at the start were 5.18 ± 0.67 pg/ml, which significantly decreased to 4.36 ± 0.72 pg/ml (p < 0.05) at 12 weeks of treatment., Conclusion: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels., (© 2016 S. Karger AG, Basel.)

Purpose: The objectives of this study were to assess visual and structural outcomes in mycotic keratitis after conventional treatment (topical and systemic antifungals) and intracameral amphotericin B (ICAMB), and to evaluate any complications., Design: This was a prospective, nonrandomized, nonblinded interventional study., Methods: This study was conducted on 104 eyes of 104 patients with fungal corneal ulcers. Patients were categorized into 2 groups: group A, who received conventional topical and systemic antifungal medications, and group B, who received ICAMB in the dose of 5 to 10 μg in 1 mL of 5% dextrose. Response to treatment was evaluated. Results of the 2 groups were compared with appropriate statistical indices., Results: The mean final visual acuity in patients in group B receiving ICAMB was 1.22 ± 0.31 logMAR units. The improvement in mean visual acuity was 1.40 ± 0.2 logMAR units. In group A, mean visual outcome was 1.25 ± 0.73 logMAR units. There was an improvement by 0.55 ± 0.30 logMAR units. Healing with varying degrees of opacification occurred in a significant number of patients (81.48%) treated with ICAMB as compared with conventional treatment (Z = 2.24, P < 0.05). Complications, such as sloughing, occurred in significantly fewer patients treated with ICAMB as compared with conventional treatment (Z = 2.29, P < 0.05)., Conclusions: In cases of keratomycosis where response to local and systemic antifungal treatment is not evident after 7 days, ICAMB can be safely administered to prevent the progression of ulcers and the development of complications.

For the prevention of postoperative ocular infections prophylactic topical antibiotics are routinely used. Studies evaluating comparative difference between single dose versus multiple dose administration on aqueous humour concentration of moxifloxacin are lacking. This study compared the aqueous humour concentration of moxifloxacin following its topical administration in rabbit eyes with two dose regimens. Twelve albino rabbits were divided into two groups. In group-1, two drops were administered thrice (total six drops) at 2 min intervals, in both the eyes; in group-2, two drops of moxifloxacin were administered three times a day for three days and also two h before aqueous humour collection i.e. on fourth day. Mean aqueous humour concentrations were calculated and compared using Student's 't' test and P<0.05 was considered significant. Moxifloxacin concentration in aqueous humour in group-1 was 23.79 μg/ml and in group-2 was 42.08 μg/ml. Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for most bacteria. Moxifloxacin concentration in aqueous humour with multiple instillations is significantly higher than single instillation (P<0.05), which is adequate to cover ciprofloxacin-resistant gram-negative bacteria. Repeated topical moxifloxacin administration achieved significantly higher aqueous humour concentrations than single administration.

Modafinil [2-((diphenylmethyl) sulfinyl) acetamide] is a central nervous system stimulant. It has received considerable attention as a potential psychotropic agent in several psychiatric disorders. The current study was carried out to investigate the effect of modafinil after acute administration on animal models of pain in mice. Also, this study evaluated the effect of L-NG-nitroarginine methyl ester (L-NAME), 7-nitroindazole (7-NI) and naloxone following chronic administration of modafinil. Modafinil was administered in the doses of 50, 100 or 200 mg/kg once in acute study and it showed significantly increased tail-flick latency (tfl) and paw-licking latency. In formalin test modafinil (100 mg/kg) significantly reduced licking/biting time in both early and late phases in comparison to control. In chronic study, modafinil 100 mg/kg administered for 10 days, produced a progressive decrease in the reaction time (i.e., tfl/paw-licking latency) in comparison to day 1 values which started building up from day 4 and fully established at day 6, indicating hyperalgesic response. Prior administration of 7-NI (on day 7) and L-NAME (on day 10) prevented the hyperalgesic response while naloxone on day 10 did not have a significant effect on modafinil-induced hyperalgesia. These results demonstrate that modafinil has a potential role in pain as it exhibited antinociceptive effect after acute administration in a dose-dependent manner and on chronic administration it caused hyperalgesia. This hyperalgesia is reversed by nitric oxide synthase inhibitors, suggesting the possibility of involvement of nitric oxide pathway. Further studies are required to evaluate the role of modafinil in clinical pain., (Copyright © 2014 Elsevier B.V. All rights reserved.)

As the eyes are in close proximity to the skull, they can get simultaneously affected in head injuries. This close association warrants careful ocular examination in all cases of head injury. This is a prospective non-randomized analytical study to evaluate various ocular manifestations in cases of head injury with special reference to ocular motor nerve involvement, correlation between pupillary changes, and survival. A total of 1,184 patients with head injury were screened for ocular manifestations. This study comprises 594 patients with ocular manifestations of head injury. All the relevant data was compiled and analyzed as per proforma. Ocular manifestations were evaluated in each patient and appropriate investigations were carried out. Patients with ocular morbidity were analyzed for age, sex, mode of injury, Glasgow Coma Score, and associated injuries in addition to ophthalmic and neurosurgical evaluations. Of the 594 patients, 81.6 % were male and 18.4 % were female, with a male-to-female ratio of 4:1. The major cause of head injury was road traffic accidents (70.37 %). The most common age group involved was, 21-40-year-olds (67.40 %). Out of 594 patients, ecchymosis was found in 51.85 %, subconjunctival hemorrhage in 44.44 %, lid edema in 41.48 %, lacerated wound in 22.59 %, pupillary involvement in 21.04 %, ptosis in 6.73 %, cranial nerve palsy in 11.62 %, orbital fractures in 10.44 %, optic nerve trauma in 4.04 %, and exposure keratitis in 4.21 %. Patients with bilaterally dilated or pinpoint fixed pupils had a 10 times higher risk of mortality than patients without pupillary involvement. Third nerve involvement was seen 2.85 times more frequently in frontal and parietal region injuries compared to other sites of injury. The involvement of the sixth nerve occurred 4.6 times more frequently in parietal region injuries compared to other sites of injury.

Introduction: Burn injuries are a serious public health problem. In our study we have identified different epidemiological factors based on 10 years of our experience at a burn unit in central India and recommend some strategies to prevent burn injuries., Materials and Methods: This is a retrospective analysis (2001-2010) of database from burn unit of S.S. Medical College, Rewa, India., Results: 2499 patients with burn injury were analysed. 66.8% and 38.2% patients were females and males respectively, with a median age of 25 years. Flame (80.1%) was most common cause, home (96%) was most common place, traditional Indian stove (28.8%), kerosene lamp (26.7%), hot liquid (12.2%) and kerosene stove (10.4%) were common causes. Median Total Body Surface Area (TBSA) burn was 40.0%; females had significantly greater (P < 0.001) burn than males (median 50% vs 26.0%). High mortality (40.3%) seen; female sex (OR 3.22, 95% CI 2.65-3.92); young age (15-29 year) (OR 3.48, 95% CI 2.45-4.94); flame burn (OR 12.9, 95% CI 1.69-98.32); suicidal burn OR 6.82 95%CI 4.44-10.48) and TBSA > 76% (OR 3099, 95%CI 1302-7380) were significant risk factors for death. Median hospital stays was 8 days; shorter hospital stays seen among TBSA burn > 76% (2 days), suicidal intent (4 days), and those who expired (4 days). Septicemia (45.8%) and burn shock (41%) were the major cause for death., Conclusions: Cooking and lighting equipments are major cause of burn injury among females and young age group. Equipment modification to improve safety features and public awareness programs are necessary to reduce burn incidents.

Background: Fissure-in-ano is a common condition that leads to pain and affects quality of life. Sphincterotomy remains the gold standard, but it may lead to troublesome incontinence in some patients. To overcome this problem, numerous pharmacologic therapies have been tested with varying outcomes. The investigators compared the effect of the addition of oral and topical nifedipine to conservative measures in the treatment of patients with fissure-in-ano., Methods: Ninety patients with fissure-in-ano, randomized into 3 groups of 30 each, were included in the study. Group I received conventional treatment, group II received oral nifedipine and conventional treatment, and group III received topical nifedipine along with conventional treatment. Patients were followed for 8 weeks for pain relief (assessed using a visual analogue scale) and healing to evaluate the effect of treatment., Results: Pain relief was significantly better in the group III at 3 weeks and 2 months compared with group I (P < .05). Groups II and III were comparable in terms of pain relief. Healing rates were significantly better in group II (P = .03) and group III (P = .00) compared with group I, but groups II and III were found to be comparable. Adverse effects were most commonly reported by group II patients, but these were not significantly higher than in other 2 groups., Conclusions: We recommend the addition of either oral or topical nifedipine to conservative measures to significantly improve pain relief and healing rates in patients with fissure-in-ano., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists (thiazolidinediones) are widely prescribed for the treatment of type-II diabetes mellitus. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. The current study was carried out to investigate the effects of chronic administration of pioglitazone, a PPAR-γ agonist, on cognitive impairment in a mouse model of Alzheimer's disease induced by scopolamine. Scopolamine was administered in a dose of 1mg/kg intraperitoneally (i.p.). Cognitive functions were assessed using step-down latency (SDL) on a passive avoidance apparatus and escape latency in Morris water maze test. Pioglitazone was also investigated for its effects on parameters of oxidative stress by measuring malondialdehyde (MDA) and reduced glutathione (GSH) levels in the brain. Scopolamine produced significant reduction in SDL and prolongation of escape latency indicating cognitive impairment in mice. Pioglitazone (20 and 40 mg/kg, i.p.), administered for 21 days, showed significant dose-dependent improvement in scopolamine-induced dysfunctions in long-term and visuo-spatial memory in passive avoidance and Morris water maze tests, respectively. Furthermore, pioglitazone significantly prevented the fall in GSH levels and elevation in brain MDA levels induced by scopolamine. These results demonstrate that pioglitazone offers protection against scopolamine-induced dysfunctions in long-term and visuo-spatial memory, possibly due to its antioxidant action, and therefore, could have a therapeutic potential in Alzheimer's disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: It was the aim of this study to examine the potential value of cervical length at 11-13 weeks' gestation in the prediction of spontaneous preterm delivery., Methods: This was a screening study for spontaneous preterm delivery in singleton pregnancies from cervical length measured by transvaginal ultrasound at 11-13 weeks' gestation. The performance of screening for preterm delivery by cervical length alone and with maternal characteristics was estimated., Results: In the 9,974 pregnancies included in the study, spontaneous delivery before 34 weeks occurred in 104 (1.0%) cases. Multivariate regression analysis in the term delivery group demonstrated that for the log(10) cervical length, significant independent contributions were provided by fetal crown-rump length, maternal height, age, racial origin and parity. The median cervical length multiple of the median (MoM), corrected for maternal characteristics, was significantly lower in the preterm (0.892 MoM, 95% CI 0.829-0.945) than in the term delivery group (0.994 MoM, 95% CI 0.919-1.082; p < 0.0001). In screening by a combination of maternal characteristics and cervical length, the estimated detection rate of preterm delivery was 54.8% (95% CI 44.7-64.6), at a false-positive rate of 10%., Conclusions: Effective first-trimester screening for spontaneous early preterm delivery can be provided by a combination of maternal characteristics and cervical length., (Copyright © 2012 S. Karger AG, Basel.)

Background: Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring compound found in grapes, wine, peanuts and cranberries. Recently, in vitro and cell culture studies have reported beneficial effects of resveratrol in the neurodegenerative process in Alzheimer's disease (AD). However, in vivo effect of resveratrol in models of learning and memory is not yet evaluated. The present study was performed to examine the effect of resveratrol on cognitive impairment induced by scopolamine, a muscarinic antagonist, in mice., Methods: Scopolamine was administered in a dose of 1 mg/kg intraperitoneally (ip). Cognitive functions were assessed using transfer latency (TL) on elevated plus maze, step-down latency (SDL) on a passive avoidance apparatus and escape latency (EL) in Morris water maze test., Results: Scopolamine produced significant prolongation of TL, reduction in SDL as well as EL showing cognitive impairment in mice. Pre-treatment with resveratrol (10 mg/kg and 20 mg/kg, ip) for 21 days showed no difference in TL, SDL and EL., Conclusion: Resveratrol treatment does not reverse scopolamine-induced deficit in cognitive functions in mice.

Combination of disease-modifying antirheumatic drugs (DMARDs) is increasingly used in the treatment of rheumatoid arthritis (RA) patients. Hepatotoxicity has been an important safety concern with DMARDs therapy. Though leflunomide (CAS 75706-12-6) has emerged as an effective oral DMARD, its use is associated with hepatotoxicity. Limited data is available regarding hepatotoxic risk when leflunomide is used in combination therapy in RA patients. An open-label, prospective study was conducted to evaluate the hepatotoxic risk after addition of leflunomide with other DMARDs in RA patients, who did not respond to their ongoing DMARD therapy. A total of 46 patients were enrolled and leflunomide was given as add-on therapy with earlier DMARDs. Biochemical parameters of serum aminotransferase levels (AST and ALT) were estimated at the baseline and then every month after addition of leflunomide. Study results showed that 13.0% patients developed > 1.5 to < 2 times upper limit of normal (ULN) elevation; 6.5% patients developed > 2 to < 3 times the ULN elevation and 2.2% patients developed > 3 times the ULN elevation. In 20% of the patients with hepatic enzyme elevations, enzyme levels returned to normal within 4-6 weeks after discontinuation of leflunomide therapy, whereas in 50% of patients the dose of leflunomide was reduced from 20 mg/day to 10 mg/day for normalization of enzymes levels. 30% of patients were continued with leflunomide without dose reduction. None of the patients showed clinical signs and symptoms of hepatotoxicity. Leflunomide therapy with other DMARDs requires strict monitoring of serum aminotransferases.

This study was undertaken to study efficacy of single dose of intravenous magnesium sulphate to reduce post-operative pain in patients undergoing inguinal surgery. One hundred patients undergoing inguinal surgery were divided randomly in two groups of 50 each. The patients of magnesium sulphate group (Group-I) received magnesium sulphate 50 mg/kg in 250 ml of isotonic sodium chloride solution IV whereas patients in control group (Group-II) received same volume of isotonic sodium chloride over 30 minutes preoperatively. Anaesthesia was induced with propofol (2 mg/kg) and pethidine (1 mg/kg). Atracurium besylate (0.5 mg/kg) was given to facilitate insertion of LMA. Pain at emergence from anaesthesia and 2, 4, 6, 12 and 24 hours after surgery was evaluated. The timing and dosage of rescue analgesic during first 24 hrs after operation was noted. Pain in postop period was significantly lower in magnesium sulphate group in comparison to control group at emergence from anaesthesia and 2, 4, 6, 12 and 24 hrs postop [1.86 vs. 1.96 (P=0.138), 1.22 vs. 1.82 (P=0.001), 1.32 vs. 1.88 (P=0.000), 2.74 vs. 3.84 (P=0.000), 1.36 vs. 2.00 (P=0.000) and 0.78 vs 1.30 (P=0.000), respectively]. Patients in group-I were more sedated as compared to group-II [sedation score 1.86 vs. 1.40 (P=0.000)]. Rescue analgesia requirement postoperatively in first 4, 8 and 16 hrs was significantly lower in patients of group-1 than in group- II [1.9 vs. 3.8 (P<0.05), 25.50 vs. 52.50 (P<0.05) and 0.000 vs. 7.5 (P<0.05)]. Preoperative magnesium sulphate infusion decreases postop pain and requirement of rescue analgesia.

We describe a biopsy proven case of microsporidial infection of the false vocal cords in a 69-yr-old male with a history of chronic lymphocytic leukemia. The patient had hoarseness for several weeks before his admission to the hospital for shortness of breath. He had received chemotherapy with fludarabine 6 wk before this hospital admission. A biopsy of vocal cord nodules demonstrated an organism that was identified as Anncaliia algerae by electron microscopy. Molecular analysis of the small subunit RNA gene amplified by polymerase chain reaction further confirmed the identification of this organism as A. algerae. This case illustrates the ability of this insect pathogen to cause disease in immune-compromised mammalian hosts., (© 2010 The Author(s). Journal of Eukaryotic Microbiology © 2010 International Society of Protistologists.)

The present study was an attempt to formulate and evaluate enteric coated tablets for esomeprazole magnesium trihydrate. Different core tablets were prepared and formulation (F-1) was selected for further enteric coating, based on the disintegration time. Seal coating was applied to achieve 3% weight gain using opadry®. Enteric coating was carried out using different polymers like Eudragit L-30 D-55, hydroxy propyl methylcellulose phthalate, cellulose acetate phthalate and Acryl-EZE® to achieve 5% weight gain. Disintegration studies showed that the formulations failed in 0.1 N HCl media. Hence the quantity of enteric coating was increased to 8% w/w. In vitro analysis of the developed tablets was carried out. Results from disintegration time and dissolution rate studies indicate that all the esomeprazole enteric tablets prepared possess good integrity, desirable for enteric coated tablets. Among the polymers studied, the methacrylic polymers exhibited better dissolution rate than the cellulose polymers. Stability studies indicate that the prepared formulations were stable for a period of three months. This study concluded that enteric coated tablets of esomeprazole can be prepared using any of the enteric coating polymer studied using a minimal weight gain of 8%.

Genital herpes is the main cause of genital ulcers worldwide; the prevalence of herpes simplex virus (HSV) type 2 infections in the general population ranges from 10% to 60%. Most genital herpes is caused by HSV-2, although HSV-1 accounts for about half of new cases in developed countries. The risk of HIV acquisition is three times higher in people with HSV-2. Neonatal herpes is an uncommon but serious complication of genital herpes. Most genital HSV-2 infections are unrecognised and undiagnosed; infected individuals, even with mild symptoms, shed HSV, and can infect sexual partners. Since clinical diagnosis is neither sensitive nor specific, virological and type-specific serological tests should be used routinely. Oral antiviral drugs for HSV infections are safe and effective and can be used both to treat episodes and to prevent recurrences. Antiviral treatment of the infected partners and condom use reduce the risk of sexual transmission of HSV-2.

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.

The episodic and daily suppressive treatment of genital herpes is safe and effective with the currently available antiviral agents: acyclovir, valacyclovir and famciclovir. Clinical strategies for the comprehensive management of genital herpes simplex virus infections are recommended. Data from recent clinical trials demonstrating the efficacy of shorter duration of therapy for recurrences and the use of antivirals for the prevention of transmission are reviewed in this article. The factors influencing the choice of therapy, such as cost, ease of dosing and acyclovir resistance are also discussed.