The activities of drug inactive ingredients on biological targets

Excipients, considered "inactive ingredients," are a major component of formulated drugs and play key roles in their pharmacokinetics. Despite their pervasiveness, whether they are active on any targets has not been systematically explored. We computed the likelihood that approved excipients would bind to molecular targets. Testing in vitro revealed 25 excipient activities, ranging from low-nanomolar to high-micromolar concentration. Another 109 activities were identified by testing against clinical safety targets. In cellular models, five excipients had fingerprints predictive of system-level toxicity. Exposures of seven excipients were investigated, and in certain populations, two of these may reach levels of in vitro target potency, including brain and gut exposure of thimerosal and its major metabolite, which had dopamine D3 receptor dissociation constant Kd values of 320 and 210 nM, respectively. Although most excipients deserve their status as inert, many approved excipients may directly modulate physiologically relevant targets

Bipolar disorder

Bipolar disorder is a serious disorder of mood that is associated with considerable psychosocial and economic morbidity. Even though it is more common than previously thought, it has until relatively recently been somewhat neglected in terms of research when compared to disorders such as schizophrenia and major depression. Recent advances in the fields of nosology, epidemiology, and molecular genetics in particular have begun to unravel some of the complexity of this disorder and the next few years are likely to witness substantial changes to the ways in which the broad spectrum of bipolar disorders is diagnosed and managed

Anti-mycobacterial and anti-inflammatory activity of Peganum harmala

The aim of this study was to evaluate the antimycobacterial and anti-inflammatory activity of the methanolic extracts of Peganum harmala (Esphand) collected from Golestan province, north of Iran. Methods: Hydroalcoholic extract of seeds of Peganum harmala were obtained and screened for anti-mycobacterial activity by disc diffusion (DD) method. The anti-inflammatory activity of the extract was evaluated by cytokines measurement using ELISA in a model of phagocytized intracellular Mycobacterium tuberculosis, H37Rv strain, in dU937cells. Free radical-scavenging activity, total phenolic, flavonoids and Harmalin concentrations were assessed to investigate phytochemical properties of the extract. Our data showed the inhibitory effect of the extract on growth of all strains of Mycobacterium tuberculosis even on drug resistant strains. Cytokines production in culture media showed the anti-inflammatory activity of the extract. The antioxidant (IC50 (DPPH assay) was 53.6 ± 0.50 mg/L. The amount of total phenolic and flavonoids components was 61.5 ± 0.80 gGAE/kg and 42.20 ± 0.60 respectively. These findings revealed the potential ability of the Peganum harmala's seed as a complementary medicine to treat tuberculosis. © 2015, Journal of Chemical and Pharmaceutical Research. All rights reserved

The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis

Abstract Background: Although some authors have recently investigated the co-occurrence of anxiety and bipolar disorders, the topic remains insufficiently studied. Defining the prevalence and predictors of BD-OCD comorbidity has important nosological, clinical and therapeutic implications. Methods: A systematic review and meta-analysis was conducted on the prevalence and predictors of comorbid BD-OCD. Relevant papers published through March 30th, 2015 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. Results: 46 articles met inclusion criteria. The pooled prevalence of OCD in BD was 17.0% (95% CI 12.7-22.4%), which was comparable to the results reported by the pooled prevalence of BD in OCD (18.35%, 95% CI 13.2-24.8%). With regard to OCD-BD predictors, a higher mean age predicted a lower prevalence of OCD in BD patients. Sub group meta-analyses reported higher OCD prevalence rates in BD children and adolescents (24.2%, compared to 13.5% in adults), in BD-I patients (24.6%, compared to 13.6% in mixed BD patients), and among population-based studies (22.2%, compared to 13.2% in hospital-based studies). Limitations: Most studies use retrospective assessment scales with low sensitivity in discriminating true ego-dystonic obsessions from depressive ruminations that may bias results towards an overestimation of obsessive symptom prevalence. Conclusions: This first systematic review and meta-analysis of the prevalence and predictors of comorbid BD-OCD confirms that BD-OCD comorbidity is a common condition in psychiatry with children and adolescents and BD-I patients as the most affected subgroups