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Background: Electroconvulsive therapy (ECT) is the most effective treatment available for the acute treatment of depression in patients who do not respond to medications. It is generally used as a second line treatment for many psychological disorders, mainly major depression and schizophrenia where medication is not effective. ECT is often associated with some complications such as hypertension, tachycardia arrhythmia and even myocardial infarction. Various methods have been used for prevention or control of these cardiovascular side effects. Aim: The aim of this study was evaluating the effect of oral clonidine (0.3 mg) with control group to know the effect of oral clonidine on hemodynamic response during ECT. Methods and Material: This prospective randomized crossover clinical trial was performed on 25 patients aged 20-50 years, weight 50-70 kg with ASA I and II who were candidates for ECT. Prior to ECT, each patient received oral doses of clonidine (0.3 mg) or a placebo 90 minutes before ECT. Baseline Heart rate, systolic, diastolic and mean arterial pressures were noted just before securing the intravenous cannula. The same parameters were noted after induction, immediately after seizure cessation following delivery of the electric shock and at 1 minute interval for 10 minutes. Statistical Analysis: Data was analyzed by ANOVA test (analysis of variance). P < 0.05 was considered statistically significant. Results: Attenuation of maximum rise in the heart rate and mean arterial pressure by clonidine (0.3 mg) was evident and statistically significant when compared with control group. Conclusion: Oral clonidine (0.3 mg) decreases the acute hypertensive response after electroconvulsive therapy; however, this antihypertensive effect was achieved by decreasing the blood pressure before the electrical stimulus. [ABSTRACT FROM AUTHOR]

The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant K D obtained for PCA was 2.1×10 −7 M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that possesses cis-proteolytic activity essential for the structural polyprotein processing and plays a key role in the virus life cycle. CHIKV being an emerging arthropod-borne pathogenic virus, is a public health concern worldwide. No vaccines or specific antiviral treatment is currently available for chikungunya disease. Thus, it is important to develop inhibitors against CHIKV enzymes to block key steps in viral reproduction. In view of this, CVCP was produced recombinantly and purified to homogeneity. A fluorescence resonance energy transfer (FRET)-based proteolytic assay was developed for high throughput screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from the cleavage site present in the structural polyprotein of CVCP was used. The assay with a Z' factor of 0.64 and coefficient of variation (CV) is 8.68% can be adapted to high throughput format for automated screening of chemical libraries to identify CVCP specific protease inhibitors. Kinetic parameters Km and kcat/Km estimated using FRET assay were 1.26 ± 0.34 µM and 1.11 x 10³ M-1 sec-1 respectively. The availability of active recombinant CVCP and cost effective fluorogenic peptide based in vitro FRET assay may serve as the basis for therapeutics development against CHIKV. [ABSTRACT FROM AUTHOR]

Abstract: Neural progenitor cells (NPCs) have drawn attention because they offer possible treatment for neurodegenerative disorders in the form of regenerative therapy or transplantation. NPCs adapt and change in response to the cues in the pathological environment. We assessed the effect of pre-exposure to non-cytotoxic levels of oxidative stress, a common pathogenic factor in a number of neurological disorders, on the cell viability and neurosphere morphology of NPCs derived from the periventricular zone of mice brain. Neural progenitor cell viability and neurosphere morphology (neurosphere number, size and chain migration) were assessed in response to cytotoxic levels of oxidative stress in the presence or absence of preconditioning with non-cytotoxic doses of hydrogen peroxide (H2O2). Preconditioning with non-cytotoxic levels of H2O2 provided significant protection against subsequent exposure to lethal doses of H2O2. Preconditioning also modulated alteration in the neurosphere morphology in response to oxidative stress. Oxidative stress increased chain migration and neurosphere size while decreasing neurosphere numbers, specially in the cultures that were preconditioned with higher doses of H2O2. Non-cytotoxic exposure to oxidative stress can evoke endogenous cytoprotection in NPCs. Redox signaling plays a role in other cellular functions of NPCs, namely the chain migration of NPCs from neurospheres, perhaps as a result of its effect on cell differentiation. [Copyright &y& Elsevier]

The article explores the in vitro antioxidant and anti-inflammatory potential of Polyalthia longifolia's ethanolic and aqueous extracts of leaves in rats. Polyalthia longifolia is a genus of shrubs and tress, part of the family Annonaceae, which is used to treat skin diseases, fever, diabetes, and hypertension. It suggests that the presence of flavonoids and phenolic compounds enabled extracts of P. longifolia produced to produce anti-inflammatory activities.

A eight year old girl presented multiple plaques of lupus vulgaris, numerous papules of lichen scrofulosorum and involvement of right ulnar bone. The patient responded to antituberculosis therapy. The multiple foci were probably due to hematogenous dissemination [ABSTRACT FROM AUTHOR]

Nebivolol, a beta-blocker, has been widely used for the treatment of hypertension and cardiovascular diseases; but has drawbacks like poor solubility and bioavailability requiring frequent dosing. The present study attempts to overcome these issues through nanoparticulate delivery system using widely used carrier PLGA Polymer . The solvent evaporation (single emulsion) technique was used for developing nanoparticles. The impact of formulation and process variables on particle size and entrapment efficiency was studied to optimize the formulation. The physico-chemical characterization confirmed the particle size in nano range with smooth and spherical morphology. Further, Fourier transforms infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies confirm compatibility of drug-polymer combination. The in vitro drug release study of the prepared nanoparticles showed prolongation of drug release with reduced burst release in comparison with pure drug powder. [ABSTRACT FROM AUTHOR]

Oncolytic adenoviruses (OAds) are very promising for the treatment of lung cancer. However, OAd-based monotherapeutics have not been effective during clinical trials. Therefore, the effectiveness of virotherapy must be enhanced by combining OAds with other therapies. In this study, the therapeutic potential of OAd in combination with temozolomide (TMZ) was evaluated in lung cancer cells in vitro and in vivo . The combination of OAd and TMZ therapy synergistically enhanced cancer cell death; this enhanced cancer cell death may be explained via three related mechanisms: apoptosis, virus replication, and autophagy. Autophagy inhibition partially protected cancer cells from this combined therapy. This combination significantly suppressed the growth of subcutaneous H441 lung cancer xenograft tumors in athymic nude mice. In this study, we have provided an experimental rationale to test OAds in combination with TMZ in a lung cancer clinical trial. [ABSTRACT FROM AUTHOR]

Vaccines based on tumor-associated antigens (TAA) have limited therapeutic efficacy due to their weak immunogenic nature and the various immune evasion mechanisms active in advanced tumors. In an effort to overcome these limitations, we evaluated a combination of the T-cell costimulatory molecule SA-4-1BBL with the TLR4 agonist monophosphoryl lipid A (MPL) as a novel vaccine adjuvant system. In the TC-1 mouse allograft model of human papilloma virus (HPV)-induced cancer, a single administration of this combination adjuvant with HPV E7 protein caused tumor rejection in all tumor-bearing mice. On its own, SA-4-1BBL outperformed MPL in this setting. Against established tumors, two vaccinations were sufficient to elicit rejection in the majority of mice. In the metastatic model of Lewis lung carcinoma, vaccination of the TAA survivin with SA-4-1BBL/MPL yielded superior efficacy against pulmonary metastases. Therapeutic efficacy of SA-4-1BBL/MPL was achieved in the absence of detectable toxicity, correlating with enhanced dendritic cell activation, CD8+ T-cell function, and an increased intratumoral ratio of CD8+ T effector cells to CD4+FoxP3+ T regulatory cells. Unexpectedly, use of MPL on its own was associated with unfavorable intratumoral ratios of these T-cell populations, resulting in suboptimal efficacy. The efficacy of MPL monotherapy was restored by depletion of T regulatory cells, whereas eliminating CD8+ T cells abolished the efficacy of its combination with SA-4-1BBL. Mechanistic investigations showed that IFNg played a critical role in supporting the therapeutic effect of SA-4-1BBL/MPL. Taken together, our results offer a preclinical proof of concept for the use of a powerful new adjuvant system for TAA-based cancer vaccines. [ABSTRACT FROM AUTHOR]

The article offers information on Endosulfan (ES) (C9H6Cl6O3S) toxicology, including its symptoms and effect on the central nervous system (CNS). It states that ES poisoning induces T-cell apoptosis, oxidative stress and mitochondrial dysfunction, with over-stimulation of CNS as the predominant toxicological impact in the form of seizures. It says that ES poisoning has no specific treatment and that differences in opinion among intensive care unit teams and lack of consensus in treatment guidelines often lead to permanent morbidity or mortality. Moreover, it discusses the role of pyridine aldoxime methyl chloride (PAM) in organochlorine poisoning.

Primary adenoid cystic carcinoma of lungs with vertebral metastases at presentation is a rare entity with very few treatment options. We report a case of 78-year old non-smoker female who was investigated for low backache and found to have adenoid cystic carcinoma of right lung with lumbar vertebral metastasis. She refused palliative radiation therapy to lumbar spine because of her inability to move and severe pain. She received oral gefitinib and reported remarkable relief in symptoms. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 40-year-old woman presented with complaint of mass in her genitalia with dragging pain and difficulty in coitus. The examination revealed that the patient has multiple nodular swellings on the outer surface of each mass. The author notes that the treatment for patients with lymphedema includes combination of limb elevation, compression garment, compression pump therapy and even surgery if needed.

The article discusses the importance of yearly and twice yearly pharmacology in treating postmenopausal osteoporosis. It examines the efficacy of Zoledronic acid and Denosumab in treating this osteoporosis. It notes that 5 milligram of intravenous infusion of Zoledronic acid can lower bone turnover markers and vertebral marker rate, while the Denosumab can improve bone mineral density and reduce bone resorption in postmenopausal women having low bone mass. Moreover, it explores the adverse effects of these drugs.