Disability in clinically stable patients of schizophrenia.

PURPOSE: Disability associated with schizophrenia affects every aspect of life. In India, persons with schizophrenia are eligible for disability benefits. Only a handful of patients are aware and able to avail the benefits. We intended to assess disability in clinically stable patients of schizophrenia as even though they are stable but are disabled and may benefit from disability benefits and rehabilitation. METHODS: Sixty-two clinically stable patients of schizophrenia were assessed on the Mini-International Neuropsychiatric Interview, Positive and Negative Syndrome Scale (PANSS), and Schizophrenia Cognition Rating Scale. Disability was assessed on the Indian Disability Evaluation and Assessment Scale (IDEAS). RESULTS: Nearly one-fourth of the "stable patients" had moderate-to-severe disability (22.6% - moderate and 1.6% - severe), i.e., certifiable disability as per IDEAS. Disability had a significant correlation with all three domains of PANSS as well as total PANSS score. The correlation was stronger with negative than with positive symptom scores. Disability also strongly correlated with cognitive impairment. "Work," "communication and understanding," and "interpersonal relationship" domains of IDEAS had a strong correlation with cognitive impairment. CONCLUSION: Nearly 25% of the stable patients had certifiable disability. The "work" domain of IDEAS was most affected. It demonstrates that the rehabilitation of this population may contribute to reducing disability.

Correlation of severity of chronic obstructive pulmonary disease with potential biomarkers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha (TNF-a). The present study was designed to assess the serum cytokines [Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)] levels in chronic obstructive pulmonary disease (COPD) patients and they were correlated with severity of disease by spirometric measurements. MATERIALS AND METHODS: A total of 384 COPD patients and 50 healthy controls were enrolled in this study. The COPD patients were divided according to gold stages ie: mild, moderate, severe and very severe. 5 ml of venous blood samples were taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min. Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL-6. Spirometry was performed according to the criteria set by the Gold 2012 RESULTS: Tnf-α (pg/ml), IL-6 (pg/ml), IL-1ß (pg/ml) serum levels in COPD patients and healthy controls subjects were measured. Tnf-α and IL-6 serum levels were significantly (<0.001) higher in COPD patients compared to healthy control subjects. Likewise, IL-1 beta levels were also significantly (p-value = 0.022) higher in COPD patients compared to healthy control subjects. The distribution of Tnf-α, IL-6, IL-1ß (pg/ml) serum levels in COPD patients in relation to GOLD grading. There was a significant (p < 0.001) difference in the level of TNF-α, IL-6 and IL-1ß (pg/ml) among the severity of COPD. The posthoc analysis revealed that the TNF-α was significantly (p < 0.05) higher among the than mild, moderate, severe and very severe COPD patients. A similar observation was also found for IL-6. However, IL-6 was significantly (p < 0.05) higher among mild, moderate, severe and very severe COPD patients. There was significant (p = < 0.0001) difference in the level of IL-1ß in the different severity of COPD. The posthoc comparison test showed that IL-1ß levels were significantly (p < 0.05) higher among the mild, moderate, severe and very severe COPD patients. CONCLUSION: The present study signifies that the levels of TNF-α, IL-1ß, and IL-6 are directly proportional to the post-bronchodilator FEV1 percentage. Results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.

Effects of a standardized Ayurvedic formulation on diabetes control in newly diagnosed Type-2 diabetics; a randomized active controlled clinical study.

OBJECTIVES: The purpose of this study was to investigate the efficacy of a standardized polyherbal formulation consists of aqueous extracts from six herbs, in patients with Type-2 diabetes mellitus. DESIGN: Randomized, active control study. INTERVENTIONS: 93 patients, newly diagnosed with Type-2 diabetes mellitus were randomly allocated to group 1 (received polyherbal capsules 500 mg/day, up titrated weekly to a maximum of 3 g/day) and group 2 (received Metformin 500 mg/day, up titrated weekly to a maximum of 2 g/day). MAIN OUTCOME MEASURES: The primary endpoint was effect on the change from baseline in blood glucose (Fasting blood Glucose and Postprandial blood glucose), and glycosylated hemoglobin (HbA1c). The secondary outcome includes the effect on lipid levels, liver enzymes and renal function test. RESULTS: After 24 weeks, mean laboratory measured fasting and post prandial blood glucose showed a decrease of 25.52% and 24.22% in polyherbal formulation (PHF) treated group, compared to 31.46% and 24% decrease in Metformin treated group (estimated treatment difference -10.8; 95% CI -22.63 to 1.03 and -0.36; -12.1 to 11.38, respectively). Reduction in HbA1c was also similar for PHF and Metformin (estimated treatment difference 0.01; 95% CI -0.51 to 0.53). However, the decrease in the mean total cholesterol level was more pronounced in PHF treated group (estimated mean difference 61.3; 95% CI 55.32 to 67.28) than Metformin treated group (estimated mean difference 41.12; 95% CI 34.92 to 47.32). Also, there was statistical significance between the treatment groups in total cholesterol level at the end of six months treatment (estimated treatment difference 20.18; 95% CI 12.34 to 28.02). CONCLUSION: The study demonstrated that daily intake of this PHF decreased the glycemic level and improved lipid homeostasis, while maintaining the other serum biochemical levels to the normal, and therefore it may be useful for the patients with Type-2 diabetes. This trial is registered in the Clinical Trials Registry - India (CTRI) (CTRI/2014/03/004490).

HDVDB: a data warehouse for hepatitis delta virus.

Hepatitis Delta Virus (HDV) is an RNA virus and causes delta hepatitis in humans. Although a lot of data is available for HDV, but retrieval of information is a complicated task. Current web database 'HDVDB' provides a comprehensive web-resource for HDV. The database is basically concerned with basic information about HDV and disease caused by this virus, genome structure, pathogenesis, epidemiology, symptoms and prevention, etc. Database also supplies sequence data and bibliographic information about HDV. A tool 'siHDV Predict' to design the effective siRNA molecule to control the activity of HDV, is also integrated in database. It is a user friendly information system available at public domain and provides annotated information about HDV for research scholars, scientists, pharma industry people for further study.

An in silico approach for identification of novel inhibitors as a potential therapeutics targeting HIV-1 viral infectivity factor.

Currently available antiviral drugs target the pol-encoded retroviral enzymes or integrases, in addition, inhibitors that target HIV-1 envelope-receptor interactions have also been recently approved. Recent understanding of the interactions between HIV-1 and host restriction factors has provided fresh avenues for development of novel antiviral drugs. For example, viral infectivity factor (Vif) now surfaced as an important therapeutic target in treatment of HIV infection. Vif suppresses A3G antiviral activity by targeting these proteins for polyubiquitination and proteasomal degradation. In the present study we analyzed the inhibitory potential of VEC5 and RN18 to inhibit the Vif-A3G interaction through protein- protein docking studies. Perusal of the study showed that, VEC5 and RN18 though inhibits the interaction however showed sub optimal potential. To overcome this set back, we identified 35 structural analogues of VEC5 and 18 analogues of RN18 through virtual screening approach. Analogue with PubCID 71624757 and 55358204 (AKOS006479723) -structurally akin to VEC5 and RN18 respectively showed much appreciable interaction than their respective parent compound. Evident from Vif-A3G; protein - protein docking studies, analogue PubCID 71624757 demonstrated 1.08 folds better inhibitory potential than its parent compound VEC5 while analogue PubCID 55358204 was 1.15 folds better than RN18. Further these analogues passed drug likeness filters and predicted to be non- toxic. We expect these analogues can be put to pharmacodynamic studies that can pave way the breakthrough in HIV therapeutics.

Molecular docking analysis of RN18 and VEC5 in A3G-Vif inhibition.

The HIV-1 protein Vif is essential for in vivo viral replication that targets the human DNA-editing enzyme, APOBEC3G (A3G), which inhibits replication of retroviruses. The Vif-A3G interactions are believed to be important targets for antiviral drug development. Since the interactions of A3G and Vif evade the ubiquitination pathways in human host, the viral replication precedes which otherwise spreads infection. In this study, two potent Vif inhibitors RN 18 and VEC5 have been evaluated for their inhibitory potential employing ligand receptor and protein-protein interactions studies. VEC 5 showed better interaction with Vif than RN18. Predicted data show that VEC5 bound Vif and RN18 bound Vif showed diminished interaction to A3G compared to inhibitor unbound Vif. However, this should be further validated using in vitro studies.

Computational analysis of the 3-D structure of human GPR87 protein: implications for structure-based drug design.

The G-protein coupled receptor 87 (GPR87) is a recently discovered orphan GPCR which means that the search of their endogenous ligands has been a novel challenge. GPR87 has been shown to be overexpressed in squamous cell carcinomas (SCCs) or adenocarcinomas in lungs and bladder. The 3D structure of GPR87 was here modeled using two templates (2VT4 and 2ZIY) by a threading method. Functional assignment of GPR87 by SVM revealed that along with transporter activity, various novel functions were predicted. The 3D structure was further validated by comparison with structural features of the templates through Verify-3D, ProSA and ERRAT for determining correct stereochemical parameters. The resulting model was evaluated by Ramachandran plot and good 3D structure compatibility was evidenced by DOPE score. Molecular dynamics simulation and solvation of protein were studied through explicit spherical boundaries with a harmonic restraint membrane water system. A DRY-motif (Asp-Arg-Tyr sequence) was found at the end of transmembrane helix3, where GPCR binds and thus activation of signals is transduced. In a search for better inhibitors of GPR87, in silico modification of some substrate ligands was carried out to form polar interactions with Arg115 and Lys296. Thus, this study provides early insights into the structure of a major drug target for SCCs.

Design of potential siRNA molecules for hepatitis delta virus gene silencing.

Hepatitis D is a liable reason of mortality and morbidity worldwide. It is caused by an RNA virus known as Hepatitis Delta Virus (HDV). Genetic studies of HDV have shown that delta antigen protein is responsible for replication of genome and play a foremost role in viral infection. Therefore, delta antigen protein may be used as suitable target for disease diagnosis. Viral activity can be restrained through RNA interference (RNAi) technology, an influential method for post transcriptional gene silencing in a sequence specific manner. However, there is a genetic variability in different viral isolates; it is a great challenge to design potential siRNA molecules which can silence the respective target genes rather than any other viral gene simultaneously. In current study two effective siRNA molecules for silencing of HDV were rationally designed and validated using computational methods, which may lead to knockdown the activity of virus. Thus, this approach may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of hepatitis D, at genome level.

Suicide and antidepressants: what current evidence indicates.

The documented efficacy and long-term benefit of antidepressants in patients with recurrent forms of severe anxiety or depressive disorders support their use in those individuals with these disorders, who experience suicidal thoughts or behavior. In general, it is assumed that antidepressants are beneficial for all symptoms of depression, including suicidality. However, some evidence suggests that Selective Serotonin Reuptake Inhibitors [SSRIs] may cause worsening of suicidal ideas in vulnerable patients. Systematic reviews and pooled analysis of experimental, observational, and epidemiological studies have investigated the use of SSRIs and their association with suicidality. Taking account of the methodological limitations of these studies, the current evidence fails to provide a clear relationship between their use and risk of suicidality in adults. However, in children and adolescents, there appears to be a bit of increased risk of suicidal ideations and attempts, but not of completed suicides. This risk can be anticipated and managed clinically. Clinicians are, therefore, advised to maintain a close follow-up during the initial treatment periods and remain vigilant of this risk. This advisory, however, should not deter clinicians from the use of effective dosages of antidepressants for a sufficient period of time, in every age group of patients, when clinically needed, and if found suitable otherwise.

Identification and characterization of novel small-molecule inhibitors against hepatitis delta virus replication by using docking strategies.

BACKGROUND: The small delta antigen protein of hepatitis delta virus (HDV) has been shown to be important for replication of the virus and essential for the viral life cycle. Therefore, it may be an appropriate target for designing biological experiments for drug development to identify the potential inhibitors of hepatitis D. OBJECTIVES: To identify a novel molecule as possible drug candidate for the treatment of Hepatitis D. MATERIALS AND METHODS: In the present study, a computational approach was used for the identification of novel small-molecule inhibitors against HDV replication using docking studies. An Autodock tool was used for docking and identifying the active binding sites in target proteins. The Lipinski filter and preADMET program were also used for determining the pharmacokinetic properties in order to filter out potential ligand molecules to restrain virus replication. RESULTS: Our results suggest that pyridinone (3-[(4,7-dichloro-1,3-benzoxazol-2-yl) methylamino]-5-ethyl-6-methyl-pyridin-2(1H)-one) is a validated potential inhibitor of HDV replication and could be as a novel antiviral drug for the treatment of hepatitis D. COUNCLUSIONS: We have identified a novel antiviral drug by using innovative computational approaches. The results provide a basis to experimentally develop into drug which can be used for the treatment of delta hepatitis.

PARFLEX--a very useful drug for management of surgical pain.

The aim was to assess and document the efficacy and tolerability of parflex (FDC of aceclofenac with paracetamol and serratiopeptidase) in management of pain and inflammation in adult patients undergoing surgical procedures (or operations). The design was open, prospective, non-comparative and multi-dose study of patients undergoing surgical procedures at a leading, tertiary-care, teaching hospital (setting) in Lucknow, the name being, King George's Medical College, Lucknow 226003. The patients were 50 adult patients of either sex undergoing surgery. They were given 1 tablet twice daily, taken after meals. Treatment duration was for a total of up to 7 days (intervention). Primary efficacy variables were relief from postoperative pain. Secondary efficacy variables were global assessment of efficacy and toleration by patients and treating physicians. Record was made of spontaneously reported adverse events with their nature, intensity and outcome (tolerability). Out of 50 patients, 31% were (ENT), 36% were (Orthopaedic) and 33% were (Gynaecology). They were enroled in this study. The observations made were mean pain score showed significant improvement with study drug - decreasing from 2.66 at baseline to 1.36 after 48 hours, and to 0.8 at the end of study. Composite score for pain, fever and swelling also showed substantial gains visit-on- visit-decreasing from 3.62 at baseline to 2.04 after 48 hours, and to 0.98 at final visit. None of the patients reported any adverse event. Global efficacy assessment was rated as 'excellent or good' by 54% of patients and in 59% of patients by their treating physicians. To conclude, parflex is an effective analgesic, anti-inflammatory drug that has a valuable therapeutic option for controlling pain and inflammation after surgical procedures.