Development of a rapid and validated stability-indicating UPLC-PDA method for concurrent quantification of impurity profiling and an assay of ipratropium bromide and salbutamol sulfate in inhalation dosage form.

The objective of the proposed work was to develop a rapid and new reverse phase ultra-performance liquid chromatographic (RP-UPLC) method for the simultaneous quantification of related impurities of ipratropium bromide and salbutamol sulfate in the combined inhalation dosage form. Herein, the chromatographic separation was achieved on Acquity BEH C18 (100mm×2.1mm, 1.7µm) column by following gradient elution of solvent A as 2mM potassium dihydrogen phosphate with 0.025% of 1-pentane sulphonic acid sodium salt (pH 3.0 buffer) and solvent B as pH 3.0 buffer, acetonitrile and methanol in the ratio of (32:50:18, v/v/v) at a flow rate of 0.3mL/min. The samples were detected and quantified at 220nm. To prove the stability-indicating potential of the method, forced degradation studies were performed using acidic, basic, oxidative, thermal, and photolytic conditions. After sufficient exposure, the resultant solutions were injected and found that all degradants and impurities formed during stress studies were well separated from each other and from the main peak compounds. The performance of the method was validated according to the present ICH Q2 (R1) guidelines. The method has good linearity (r≥0.999) and consistent recoveries were obtained with a range of 91.3-108.8% for all compounds. The % RSD obtained for the precision experiments was less than 5% and also there is a good sensitivity (LOQ≤0.5µg/mL) for all compounds. The intended method proved its applicability and that it can be beneficial to pharmaceutical industries for quick quantification of related impurities and assay in quality control department for analysis of ipratropium bromide and salbutamol sulfate inhalation dosage form.

Oral metronomic chemotherapy after definitive chemoradiation in esophageal squamous cell carcinoma: a randomized clinical trial.

BACKGROUND: Improving outcomes in locally advanced esophageal/GEJ squamous cell cancer (SCC) is an unmet need. We investigated the addition of oral metronomic chemotherapy (OMC) following definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: This was a randomized open-label integrated phase II/III study in patients with SCC of esophagus/GEJ following definitive CRT who had no radiologic evidence of progression, and no endoscopically detected disease. Randomization was 1:1 to OMC (celecoxib 200 mg twice daily and methotrexate 15 mg/m2 weekly) for 12 months or observation. The primary endpoint for the phase II portion was progression-free survival (PFS); secondary endpoints were overall survival (OS) and toxicity. P ≤ 0.2 for PFS was required to proceed to phase III. RESULTS: Between Jan 2016 and Dec 2019, we enrolled 151 patients for the phase II portion, 75 to OMC and 76 to observation. The tumor originated in the upper thoracic esophagus in 79% patients. Concurrent CRT consisted of median 63 Gy in a median of 35 fractions; concurrent chemotherapy was weekly paclitaxel + carboplatin in 91%. OMC was started at a median of 2.6 months (IQR 2.3-2.8) from CRT completion. Grade 3 or higher toxicities occurred in 18 patients (24%) in the OMC arm and 9 (12%) in the observation arm; P = 0.071. Median PFS was 25 months (95% CI, 17-58) in the OMC arm and was not attained [NA] (95% CI, 25-NA) in the observation arm; HR, 1.51, 95% CI, 1-2; P = 0.073. Median OS was 36 months (95% CI, 23-NA) in the OMC arm, and not attained (95% CI, NA-NA) in the observation arm; HR, 1.77; 95% CI, 1-2.9; P = 0.023. CONCLUSION: Oral metronomic methotrexate and celecoxib in patients who have not progressed radiologically and have no endoscopic evidence of disease following radical CRT for locally advanced esophageal/GEJ SCC does not improve outcomes and may lower survival. [Funded by the TMC-Research Administration Council (TRAC); CHROME study (CHemoRadiotherapy followed by Oral Metronomic therapy in Esophageal cancer); ctri.nic.in number: CTRI/2015/09/006204]. TRIAL REGISTRATION NUMBER: CTRI/2015/09/006204.

Association of personality traits with performance in military training.

BACKGROUND: In today's era of asymmetric and unconventional warfare, psychological fitness is equally important as physical fitness. Personality assessment of soldiers, and more so officers who are leaders of men is essential in deciding what makes a good "War asset" The present study was conducted to explore the correlation between personality traits of cadets undergoing training in an Armed Forces Training Academy and their performance in terms of their military and academic pursuits. METHODS: Personality traits of 607 cadets determined using Revised Neuroticism-Extraversion-Openness Personality Inventory (NEO PI-R) were compared and correlated with their performance in terms of Officer Like Qualities (OLQ), Outdoor activities (ODT), Academics, and Extracurricular Activities (ECA). RESULTS: Cadets with high personality traits scores in Neuroticism and low scores in Conscientiousness (Work ethics) had performed poorly in all the domains/criteria for evaluation of performance viz Officer like qualities, Outdoor activities, Academics, and Extracurricular Activities. Further, a significant negative correlation was observed between facets of Neuroticism and Academics, ODT, and OLQ. In contrast, personality facets of Conscientiousness (Work ethic) were found to be positively correlated with performance in Academics, ODT, and OLQ. Extracurricular activities were found to be positively correlated with Modesty and Intellectual Curiosity. CONCLUSION: The present study represents the first-ever attempt in Indian Armed Forces to correlate and identify personality traits most suited for military training. The findings of the study indicate that cadets with low scores of neuroticism and high scores of conscientiousness perform well in the military academy. However, more such studies are required to reaffirm the findings of the present study and to conclusively recommend personality traits most conducive for military training.

A systematic review on hepatoprotective activity of quercetin against various drugs and toxic agents: Evidence from preclinical studies.

Quercetin is one of the most abundant flavonoids in human diet that has been reported to exhibit a wide range of pharmacological properties. The biochemical and molecular mechanisms involved in the hepatoprotective activity of quercetin were discussed in this review. Quercetin exhibited hepatoprotective activity against 2-butoxyethanol, acrylamide, acrylonitrile, aflatoxin B1, aroclor-1254, arsenic, sodium arsenite, azathioprine, cadmium chloride, carbon tetrachloride, chlorpyrifos, cyclosporine A, diazinon, dimethylnitrosamine, doxorubicin, epirubicin, ethanol, fenvalerate, isoniazide, rifampicin, lead acetate, lindane, D-galactosamine, methotrexate, methylmercury, nickel sulfate, paracetamol, perfluorooctanoic acid, polychlorinated biphenyls, pyrrolizidine alkaloid clivorine, rotenone, sodium fluoride, streptazotocin, tert-butyl hydroperoxide, thioacetamide, titanium dioxide, tumor necrosis factor-α, tripterygium glycoside, triptolide, ultraviolet A light, concavalin A, bisphenol, and ischemia-induced hepatotoxicity in various animal models due to its antioxidant, free radical-scavenging,anti-inflammatory, antiapoptotic, and cytochrome P450 2E1 (CYP2E1) inhibitory activities. In this review, we provide an overview of the possible mechanisms by which quercetin reduced the hepatotoxicity of different hepatotoxicants. This will help the toxicologists, pharmacologists, and chemists to develop new safer pharmaceutical products with quercetin and other hepatotoxicants.

An assessment of perceived social support among naval personnel.

BACKGROUND: Studies from the Indian Navy have found junior sailors to have higher occupational stress than senior sailors. Positive social support can provide protection against detrimental effects of stress and facilitate in development of individual resilience. Therefore, the present study was conducted to explore the level of perceived social support among naval personnel. METHODS: A cross-sectional survey was conducted using "Interpersonal Support Evaluation List" (Cohen and Hoberman, 1983) among personnel posted on a capital ship of the Indian Navy. Five hundred sixty-eight sailors voluntarily participated in the study. RESULTS: Personnel living on board (in-living) were found to have significantly lower overall perceived social support score (76.14 ± 13.72) than personnel living in family accommodation (79.40 ± 14.14). In addition, in-living personnel were also found to have lower subscale scores viz "appraisal support", "self-esteem support", and "belonging support" (p < 0.05) but not "tangible support" score (p > 0.05). CONCLUSION: Our study brings out that young in-living sailors lack perceived social support. These young in-living sailors, being away from their families, often feel isolated and fall prey to social media, which in turn aggravates feeling of isolation and leads to psychological distress. Therefore, it is important for these individuals to have confidence in his mess mates and belief in commanders who form their primary sources of social support. To ensure this, it is the need of the hour to revitalize the age old divisional system by introduction of concepts of "Keep Your Mates Safe", "promotion of psychological resilience", and so on.

Quercetin reduced the formation of N-acetyl-p-benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes.

N-acetyl-p-benzoquinoneimine (NAPQI) is toxic metabolite of paracetamol formed primarily by cytochrome P4502E1 (CYP2E1) metabolic pathway when administered at therapeutic doses or overdose. The influence of quercetin (flavonoid) on the bioactivation of paracetamol to NAPQI was investigated using rat liver microsomes and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known inhibitor of CYP2E1, CYP3A4 and quercetin (10 and 20 mg/kg) to rats for 15 consecutive days. Area under the plasma concentration-time curve (AUC0-∞ ) and the peakplasma concentration (Cmax ) of paracetamol were dose-dependently increased with quercetin (10 and 20 mg/kg) compared to paracetamol control group (p < 0.001). On the other hand, the AUC0-∞ and Cmax of NAPQI were decreased significantly with quercetin. The same results were observed with silymarin also. The elevated liver and kidney functional enzymes/compounds were significantly reduced by quercetin and silymarin compared to paracetamol control group. The formation of NAPQI was reduced in the incubation samples in presence of quercetin in experiment using isolated rat hepatocytes. The presentstudy results revealed that quercetin might be inhibited the CYP2E1-mediated metabolism of paracetamol; thereby decreased the formation of NAPQI and protected the liver and kidney.

Incidence of microcracks in maxillary first premolars after instrumentation with three different mechanized file systems: a comparative ex vivo study.

OBJECTIVES: The objective of this study is to determine the potential for microcracks in the radicular dentin of first maxillary premolars using three different mechanized endodontic instrumentation systems. METHODS: Eighty extracted maxillary first premolars with two root canals and no externally visible microcracks were selected. Root canal instrumentation was performed with either the ProTaper file system, the WaveOne primary file, or the self-adjusting file (SAF). Teeth with intact roots served as controls. The roots were cut into segments and examined with an intensive, small-diameter light source that was applied diagonally to the entire periphery of the root slice under ×20 magnification; the presence of microcracks and fractures was recorded. Pearson's chi-square method was used for statistical analysis, and significance was set at p < 0.05. RESULTS: Microcracks were present in 30 and 20 % of roots treated with the ProTaper and WaveOne systems, respectively, while no microcracks were present in the roots treated with the SAF (p = 0.008 and p = 0.035, respectively). Intact teeth presented with cracks in 5 % of the roots. The intensive, small-diameter light source revealed microcracks that could not be detected when using the microscope's light alone. CONCLUSIONS: Within the limitations of this study, it could be concluded that mechanized root canal instrumentation with the ProTaper and WaveOne systems in maxillary first premolars causes microcracks in the radicular dentin, while the use of the SAF file causes no such microcracks. CLINICAL RELEVANCE: Rotary and reciprocating files with large tapers may cause microcracks in the radicular dentin of maxillary first premolars. Less aggressive methods should be considered for these teeth.

Can size 20, .04 taper rotary files reproducibly create a glide path for the self-adjusting file? An ex vivo study in MB canals of mandibular molars.

AIM: To test and compare the effectiveness and safety of two size 20, .04 taper rotary files that were used to create a glide path for the self-adjusting file (SAF) in curved canals of mandibular molars. METHODOLOGY: Forty mandibular molars with curved mesial roots and narrow MB root canals were selected based on a passage of size 15 K-files to WL; size 20 K-files could not reach WL. Only roots with no visible microcracks were included. Two types of size 20 rotary files were used for glide path preparation, the new Pre-SAF size 20, .04 taper file and the ProFile size 20, .04 taper, which served as the reference and control. Both files were used with 3-4 pecking strokes, which brought them to WL. Two parameters were tested whether the glide path allowed manual insertion of a 1.5-mm SAF file to WL and whether the procedure caused microcracks in the root dentine. Paired t-tests were used to compare the groups. RESULTS: Glide path preparation with both files allowed the manual insertion of the SAF file to WL in all 20 root canals, with no difference between the two groups. No cracks were detected after the procedure in any of the roots in either group. CONCLUSIONS: Both types of size 20, .04 taper rotary files were effective for glide path preparation for the SAF file in curved canals. Neither file type caused microcracks in root dentine.

Push-out bond strength of root fillings made with C-Point and BC sealer versus gutta-percha and AH Plus after the instrumentation of oval canals with the Self-Adjusting File versus WaveOne.

AIM: To compare the push-out bond strength exhibited by root fillings performed with either C-Point and Endosequence® BC sealer™ (BC Sealer) or gutta-percha and AH Plus® after the instrumentation of oval canals with either the Self-Adjusting File (SAF) System or WaveOne (WO) reciprocating file. METHODOLOGY: Eighty extracted premolars were selected and divided randomly into the following four groups (n = 20): group 1, SAF instrumentation and filling using gutta-percha and AH Plus sealer; group 2, SAF instrumentation and C-Point and BC sealer filling; group 3, WO instrumentation and filling using gutta-percha and AH Plus sealer; and group 4, WO instrumentation and filling with C-Point and BC sealer. Sodium hypochlorite (5.25%) and EDTA (17%) were used as irrigants for all groups. After the sealer was set completely, the teeth were prepared for micro push-out assessment using 1.0-mm-thick root slices. Loading was performed with a universal testing machine at a speed of 0.5 mm min(-1) . Two-way anova and Student's t-test for pairwise comparisons were used to compare groups. RESULTS: All specimens filled with C-Point and BC sealer were associated with significantly higher push-out bond strength compared with gutta-percha and AH Plus sealer (P < 0.001). The bond strength was higher for the coronal and apical samples of the C-Point/BC sealer/SAF group (6.6 ± 0.3 and 3.2 ± 0.3 MPa) versus those of the gutta-percha/AH Plus/WO group (4.8 ± 0.3 and 1.8 ± 0.3 MPa), by 38% and by 80% in the coronal and apical parts, respectively (P < 0.001, P < 0.0001). Adhesive bond failure was more common in the WaveOne-instrumented group in general and in the buccal and lingual recesses in this group in particular. CONCLUSIONS: In oval canals, the instrument used and the root filling material significantly affected the push-out values of root fillings. The highest value was recorded in oval root canals instrumented with the SAF System and filled with C-Point and BC sealer, whereas the lowest strength was noted in oval canals instrumented with WaveOne and filled with gutta-percha and AH Plus sealer.

Systemic exposure of Paracetamol (acetaminophen) was enhanced by quercetin and chrysin co-administration in Wistar rats and in vitro model: risk of liver toxicity.

Intestinal P-glycoprotein (P-gp) and drug-metabolizing enzymes (DMEs) play an important role in the first-pass-metabolism (FPM) and pharmacokinetics (PK) of majority of drugs. Paracetamol is primarily metabolized by conjugation reactions and a little amount (∼15%) undergoes cytochrome P450 (CYP2E1)-mediated oxidative metabolism produces a hepatotoxic metabolite, N-acetyl-p-benzoquinonimine (NAPQI). Quercetin and chrysin are naturally occurring flavonoids, reported as modulators of P-gp and DMEs. Therefore, the objective of this study was to evaluate the effects of quercetin and chrysin on the pharmacokinetics of paracetamol using rats and non-everted gut sacs in vitro. Paracetamol was given orally (100 mg/kg) to rats alone and in combination with quercetin (5, 10 and 20 mg/kg) and chrysin (50, 100 and 200 mg/kg) once daily for 21 consecutive days. Blood samples were collected on the 1st day in single dose pharmacokinetic study (SDS) and on the 21st day in multiple pharmacokinetic studies (MDS). The plasma concentrations of paracetamol were determined by HPLC and PK parameters were calculated by using Kinetica (Version 5.1). The maximum plasma concentration (Cmax) and area under the curve (AUC0-12) of paracetamol was significantly increased by quercetin and chrysin co-administration in SDS and MDS. In non-everted rat gut sac method, the absorption of paracetamol was increased by presence of P-gp inhibitors (verapamil, quinidine and ketoconazole), quercetin and chrysin (50 µg/mL). Our findings suggested that the quercetin and chrysin might be inhibited the P-gp and metabolism of paracetamol; thereby increased the systemic exposure of paracetamol. Further studies are needed to evaluate whether the quercetin or chrysin are involved in the formation of NAPQI by CYP2E1 or not on isolated rat hepatocytes or using cell lines.

Stigma of mental illness: A study in the Indian Armed Forces.

BACKGROUND: Stigma against mental illness exists across all countries. Stigma devalues the ill person and their relatives and denies them from attaining their rightful place in society. Stigma also prevents the ill person from seeking help. Stigma in the Armed Forces of UK and USA has been identified as a barrier to help seeking and a cause for concern as it could affect operational efficiency. However, studies conducted in the services of this country are lacking. Hence we decided to measure stigma perceived by patients and caregivers of the mentally ill and to assess stigma regarding the mentally ill patients and their caregivers, in the general population. METHODS: A cross sectional survey of patients (302), their caregivers (98), and members of the general population (102) who had no relatives suffering from mental illness was done. The patients were given the Stigma Scale developed by King et al. The caregivers (98) were given the devaluation of consumers scale and devaluation of consumer families scale developed by Struening et al. RESULTS: 90% of patients admitted to experiencing stigma. 86% of patients had experienced discrimination. Females experienced more discrimination than males. Stigma perceived was irrespective to age, mental status, rank and education of the patient. Caregivers perceived stigma and felt blamed by the community. Members of the general population gave similar responses. CONCLUSIONS: Study has brought out the high levels of stigma faced by the patients and their caregivers. High levels of stigma observed are a barrier to care.

Validation of effect of composite additive on optimized combustion characteristics of CI engine using AHP and GRA method.

The primary focus of this study is the validation of composite additives with the help of additional optimization methods and the analysis of its effect on the combustion characteristics of compression ignition (CI) engines. Previous work on the identification of the correct multi additive combination by Taguchi and the TOPSIS optimization method has shown substantial improvements in the performance and emission characteristics of CI engines. The same work was extended using the GRA Optimization method with the Multi-Criteria Decision-Making (MCDM) optimization technique known as the Analytic Hierarchy Process (AHP) to validate the optimization results from the previous optimization work. Remarkably, all optimization methods yielded consistent results, pointing to the superiority of the composite additive sample 'D8EH6E4 hence supporting the outcome of previous work. Subsequent testing and comparison of this novel composite additive with baseline diesel fuel for combustion characteristics analysis demonstrated notable improvements in combustion parameters, including a 25 % reduction in the rate of pressure rise, an 18 % decrease in net heat release rate, and a 6 % decrease in mean gas temperature.

Short-course Palliative Hypofractionated Radiotherapy in Patients with Poor-prognosis High-grade Glioma: Survival and Quality of Life Outcomes from a Prospective Phase II Study.

AIMS: To report longitudinal quality of life (QoL) outcomes and survival in patients with poor-prognosis high-grade glioma (HGG) treated with palliative hypofractionated radiotherapy. MATERIALS AND METHODS: Patients with poor-prognosis HGG were accrued on a prospective study of short-course palliative hypofractionated radiotherapy (35 Gy/10 fractions/2 weeks). The European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and brain cancer module (BN20) were used in English or validated Indian vernacular languages (Hindi and Marathi) for QoL assessment at baseline (before radiotherapy), the conclusion of radiotherapy, 1 month post-radiotherapy and subsequently at 3-monthly intervals until disease progression/death. Baseline QoL scores were compared with corresponding scores from a historical HGG cohort. Summary QoL scores were compared longitudinally over time by related samples Friedman's two-way test. Progression-free survival and overall survival were calculated using the Kaplan-Meier method and reported as 1-year estimates with 95% confidence intervals. RESULTS: Forty-nine (89%) of 55 patients completed the planned course of hypofractionated radiotherapy. Longitudinal QoL data were available in 42 (86%) of 49 patients completing radiotherapy, comprising the present cohort. The median age of included patients, comprised mainly of glioblastoma patients (81%), was 57 years, with an interquartile range (IQR) of 50-66 years and a median baseline Karnofsky score of 60 (IQR = 50-60). Baseline QoL scores were significantly worse for several domains compared with a historical institutional cohort of HGG patients treated previously with conventionally fractionated radiotherapy, indicating negative selection bias. QoL scores remained stable for most domains after palliative hypofractionated radiotherapy, with statistically significant improvements in fatigue (P = 0.032), dyspnoea (P = 0.042) and motor dysfunction (P = 0.036) over time. At a median follow-up of 8 months, Kaplan-Meier estimates of 1-year progression-free survival and overall survival were 33.3% (95% confidence interval 21.7-51.1%) and 38.1% (95% confidence interval 25.9-56%), respectively. CONCLUSION: Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis HGG is associated with stable and/or improved QoL scores in several domains, making it a viable resource-sparing regimen.

Improved compressibility, flowability, dissolution and bioavailability of pioglitazone hydrochloride by emulsion solvent diffusion with additives.

Spherical agglomerates of pioglitazone hydrochloride were prepared by the emulsion solvent diffusion method with additives (polyethylene glycol 6000, polyvinyl pyrrolidone, beta cyclodextrin, eudragit RS100, low acyl gellan gum and xanthan gum) using methanol, chloroform and water as a good solvent, bridging liquid and poor solvent respectively. Prepared agglomerates were evaluated for compressibility, solubility, dissolution rate and bioavailability, and characterized by SEM, XRPD, DSC and FTIR spectroscopy. Particle size, flowability, compactibility, packability, solubility, dissolution rate and bioavailability of plain agglomerates and agglomerates with additives (except with polyvinyl pyrrolidone) were advantageously improved compared with raw crystalline pioglitazone hydrochloride. These improved properties for direct compression were due to their large-spherical shape and enhanced fragmentation during compaction, together with increased tensile strength and reduced elastic recovery of the compacts. XRPD and DSC studies indicated polymorphic transition of pioglitazone hydrochloride from form II to I during recrystallization but this was not associated with any chemical transition, as indicated by FTIR spectra, well supported by stability studies. Thus spherical crystallization by the emulsion solvent diffusion method with selected additives is a satisfactory method for direct tableting of pioglitazone hydrochloride giving improved bioavailability.

Occupational stress and social support in naval personnel.

BACKGROUND: Data show that naval personnel have a high incidence of stress related disorders. A high prevalence of occupational stress was seen in a previous survey carried out on Indian Naval personnel. However, the role of social support in reducing occupational stress was not studied. To study occupational stress in Indian Naval personnel and to study the effect of social support on occupational stress. METHODS: 5077 naval personnel were surveyed using study questionnaires which included Occupational Stress Inventory, Multidimensional Scale of Perceived Social Support, and the General Health Questionnaire (GHQ)-12 item version as a measure of psychological health. The data was statistically analysed using chi square test and other non-parametric tests. RESULTS: High occupational stress was seen in personnel serving afloat (66.47%) as compared to those serving ashore (51.55%) and on submarines (53.72%). Among personnel serving afloat, occupational stress was highest among Junior Sailors as compared to Senior Sailors and Officers. Occupational stress was linked to poor psychological health as measured by the GHQ and younger age. Perceived social support was effective in reducing occupational stress in Officers and Senior Sailors but not in Junior Sailors where paradoxically it seemed to lead to greater occupational stress. CONCLUSIONS: High occupational stress was seen in more than half the service personnel studied. Occupational stress is mitigated by social support in Officers and Senior Sailors but not in Junior Sailors.

Involvement of opioid, adenosine and 5-HT(3) receptors in antinociceptive effects of an ayurvedic polyherbal formulation.

OBJECTIVE: The present study was undertaken to evaluate the antinociceptive effects of an ayurvedic polyherbal formulation in rats and mice employing the tail immersion test and acetic acid-induced writhing test, respectively. MATERIALS AND METHODS: With the tail immersion method, rats received two different doses (270 and 405 mg/kg BW, p.o.) of a formulation, pethidine (5.4 mg/kg BW, p.o.) as a reference standard and the combination of the higher dose of the formulation with naloxone (2 mg/kg, i.p.), an opioid receptor antagonist, and caffeine (16 mg/kg, i.p.), used as an adenosine receptor antagonist. In the acetic acid-induced writhing test, mice received two different doses (390 and 585 mg/kg, BW, p.o.) of formulation, diclofenac sodium (15 mg/kg, BW, p.o.) as a reference standard and the combination of the higher dose of the polyherbal formulation with ondansetron (0.5 mg/kg, i.p.), a serotonin receptor antagonist. RESULTS: The polyherbal formulation (405 mg/kg) exhibited a significant (p < 0.01) antinociceptive effect using the tail immersion method. In the acetic acid-induced writhing test, the formulation showed significant (p < 0.01) dose-dependent activity. The antinociceptive effect of the polyherbal formulation apparently involved an opiate-like mechanism, since its antinociceptive action was attenuated by naloxone pretreatment. In addition, antinociceptive activity was attenuated by caffeine and reversed by ondansetron pretreatment. CONCLUSION: Our data suggest that the polyherbal formulation possessed centrally and peripherally mediated antinociceptive properties. The activity could be mediated through opioid, adenosine, and serotonin receptors and via inhibition of cyclo-oxygenase- and/or lipoxygenase-dependent pathways.

Biodegradable dendritic Boltorn™ nanoconstructs: A promising avenue for cancer theranostics.

The family of Boltorn™ H40 dendrimers is an imperative subclass of hyperbranched biodegradable polymers (HBPs), which has received mounting attention as a result of its inimitable chemical, physical and biodegradable properties. These properties embrace three-dimensional dendrimeric nanoarchitecture to avert tanglement between polymer branches, adequate spatial cavities for increased encapsulation of guest molecules, good solubility as well as low viscosity to improve processability, and a huge number of surface functional groups for chemical manipulations. Similarly, low toxicity, non-immunogenicity, and natural biodegradation are significant and critical advantages in therapeutic applications as compared to other dendritic polymers. All these characteristics of Boltorn™ H40 are of pronounced importance for planning and developing advanced targeted cargo delivery carriers for cancer therapy. The present review highlights the applications of Boltorn™ H40 HBPs for the transport of chemotherapeutic agents to manage various types of cancers.

Human leucocyte antigen class II DRB1 and DQB1 associations in human immunodeficiency virus-infected patients of Mumbai, India.

The pathogenesis of human immunodeficiency virus (HIV) infection clearly involves immunoregulatory host factors and products of major histocompatibility complex class II genes, which present antigenic peptides to the T-cell receptor on CD4+ cells, which in turn increase the production of specific antibodies and cytotoxic T lymphocytes. The main objective of this study was to determine the associations of human leucocyte antigen (HLA) DRB1 and DQB1 alleles and their haplotypes in 210 HIV-1-infected patients and compare them with 129 healthy normal individuals with same ethnic background. The HLA DRB1 and DQB1 alleles were genotyped using polymerase chain reaction product and sequence-specific probes for reverse line hybridization, analysed with the Invitrogen Dynal PMP software. Our results revealed a highly significant increase of HLA DRB1*0902 [odds ratio (OR) = 17.12; P = 0.004], DQB1*030103 (OR = 53.53; P = 4.61E-07) and DQB1*050201 (OR = 16.26; P = 0.0002) alleles while in contrast highly significant decrease in frequency of HLA DQB1*030101 (OR = 0.36; P = 0.0002), DQB1*050301 (OR = 0.22; P < 0.0001) and DQB1*060101 (OR = 0.43; P < 0.0001) among the HIV-1-infected patients when compared with the controls. The haplotype DRB1*0902-DQB1*030103 (OR = 10.65; P = 0.06) was significantly increased in HIV1 patients, while haplotypes DRB1*150101-DQB1*060101 (OR = 0.386, P < 0.0001), DRB1*030101-DQB1*020101 (OR = 0.197, P = 0.004) and DRB1*070101-DQB1*0202 (OR = 0.167, P = 0.001) were significantly decreased. Our results indicate clearly that there are HLA class II alleles involved in the susceptibility to and protection from HIV-1 infection in our study group and further they vary in different ethnic groups reported in literature.

PEGylated nanocarriers: A promising tool for targeted delivery to the brain.

Targeted drug delivery across the blood-brain barrier is an extremely challenging quest in the fight with fatal brain ailments, with the major hurdles being short circulation time, reticuloendothelial system (RES) uptake, and excretion of nanocarriers. PEGylation has emerged as a boon for targeted drug delivery to the brain. It is well established that PEGylation can increase the circulation time of nanocarriers by avoiding RES uptake, which is indispensable for increasing the brain's uptake of nanocarriers. PEGylation also acts as a linker for ligand molecules to achieve active targeting to the brain. Using PEGylation, novel approaches are being investigated to facilitate ligand-receptor interactions at the brain endothelium to ease the entry of therapeutic drugs into the brain. In addition, PEGylation made it simpler to assess the brain tissue for delivering diagnostic molecules and theranostic nanocarriers. The potential of PEGylated nanocarriers is being investigated vastly to boost the therapeutic effect several fold in the treatment of brain diseases. This review sheds light on the contribution of PEGylated nanocarriers, especially liposomes, polymeric nanoparticles, and dendrimers for brain-specific delivery of bioactives.