The presence of pharmaceuticals in the water supply has been reported since the 1970's [1] and yet, there is little monitoring or regulation of the water supply with respect to concentrations of various pharmaceutical agents.

Psychiatric disorders, such as major psychosis and mood disorders, are among the world's ten most disabling illnesses and taken together, mood disorders (major depression and bipolar depression [BPD]) and schizophrenia (SCZ) affects about 10.6% of the adult U.S. population yearly [1,2].

Abstract:
Obesity is associated with increased risk for breast cancer and also correlated with breast cancer recurrence and high mortality. Leptin, an adipocyte-derived cytokine that is closely associated with obesity, has recently been shown to be involved in carcinogenesis and cancer progression. However, the underlying mechanisms remain to be defined. Here we show that leptin promotes cell migration and invasion and up-regulates the expression of HECTD1, an ubiquitin ligase that ubiquitinates Phosphatidylinositol 4 phosphate 5-kinase type I (PIPKI90) to regulate breast cancer cell migration and invasion, in MDA-MB-231 human breast cancer cells. Meanwhile, leptin down-regulates PIP2 and PIP3 production, but has no influence on mRNA of PIPKI90, suggesting that leptin promotes PIPKI90 ubiquitination. Furthermore, leptin stimulates the migration and invasion of PIPKI90-depleted cells that re-express a codon-modified WT PIPKI90, but has little effect on the migration and invasion of the PIPKI90-depleted cells that re-express PIPKI90K97R. Collectively, leptin stimulates breast cancer cell migration and invasion through regulating HECTD1 expression consequently PIPKI90 ubiquitination. This study provides a new mechanism for leptin-stimulated breast cancer cell migration and invasion.

Abstract: Endothelial progenitor cells (EPC) play an important role in maintaining vascular health both by integrating in endothelium and by providing paracrine support to the resident vasculature. EPCs from patients with cardiovascular disorders and diabetes with complications are typically reduced in number and dysfunctional. In an effort to restore EPC numbers and correct their dysfunction, a variety of commonly prescribed pharmacological agents such as statins, angiotensin converting enzyme (ACE) inhibitors, thiazolidinediones (TZDs) and erythropoietin (EPO) have been evaluated and found to be of benefit in both in increasing EPC numbers and improving EPC function. This review will discuss several of these commonly used pharmacological agents and recent work in our laboratory highlighting some novel approaches to correct EPC dysfunction. Mechanism responsible for modulating EPC function by these agents is also briefly discussed.

Abstract: The physiological and pathophysiological actions of the renin-angiotensin system (RAS) extend far beyond its role as a regulator of cardiovascular homeostasis. The “classical” RAS has evolved into a complex system with multiple pathways and counterbalancing axes which are pivotal to the function of most organ systems in the body. The discovery of "local" RAS's which began with the characterization of a brain RAS now includes a diverse array of tissues: liver, kidney, heart, lungs, reproductive organs, adipose tissue, pancreas, spleen, adrenal and the eye. This review describes the classical RAS as a framework upon which the newest discoveries in the RAS are described. These include the discovery of new enzymatic pathways by which novel angiotensinergic signaling molecules are formed, the expanding number of angiotensin receptor subtypes and molecules that transduce their increasing array of cellular responses. This new understanding is leading to the development of new drugs that can mimic or promote the axes of the RAS that counteract the classical axis that causes its pathophysiological actions.

Abstract:
Purpose: The present study was carried out to analyse the profile of suspect adverse drug reactions (ADRs) reported to the Pharmacovigilance unit. The primary objective was to identify the common drugs implicated and the pattern of the reactions, which would ensure a judicious prescription and further prevention.
Methods: An awareness building lecture on voluntary reporting of ADRs was conducted after which ADR forms were distributed to various departments. They were assessed for the type of reaction based on Rawlins and Thomson criteria; severity based on Hartwig's scale; seriousness as per Centre for Drugs Standards Control Organisation; expectedness as defined by International Conference on Harmonisation and causality based on Naranjo's algorhythm. The common group of offending class of drugs was also identified. The results were analysed using descriptive statistics.
Results: Out of 75 reactions 74 (98.67%) were type B and 1 reaction (1.33%) was type A. There were 5 unexpected reactions. Sixty four reactions (85.3%) were mild, 4 (5.33%) moderate and 7 (9.33%) were severe in nature. Seven (9.33%) out of 75 were considered serious as they required hospitalisation. The causality assessment for 154 drugs from 75 forms showed 118 (51%) to be possibly related, 36 (49%) as probably related and none were definitely related. The major group of drugs implicated was Antimicrobials followed by Non-steroidal anti-inflammatory drugs.
Conclusion: ADRs were mostly due to antimicrobials and Non-steroidal antiinflammatory drugs. It is necessary to create more awareness to curb irrational polypharmacy which helps in prevention and an accurate diagnosis of the reactions.

Abstract: Dipeptidyle peptidase (DPP4) is the enzyme which is known to break down two gut hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) known as incretins effect. Beside this DPP4 plays potential role in modulating immune system. It causes proliferation of T cell by binding with adenosine diaminase (ADA) through co-stimulatory mechanism. Within immune system DPP4 exert mainly stimulating effect on T cells, B cells, natural killer cell ,DNA synthesis and release of TGFb. Evidence from experimental studies suggest the potential role of DPP4 in various inflammatory disease and increased risk of cancer .Inhibitor of DPP4 is novel treatment for diabetes mellitus type2 which inhibit DPP4.DPP4 plays crucial role in immune modulation therefore its prolong inhibition results in implication in immune system and increase risk of developing tumor. Therefore these classes of drugs prescribed with a caution. Further studies needed for more clarification.

Abstract: With better understanding of the cellular and molecular pathophysiology underlying cystic fibrosis (CF), novel drugs are being developed that specifically target the molecular defects of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel on the plasma membrane that causes CF. Starting with cell-based high-throughput screening, small molecules have been identified that are able to fix specific molecular defects of various disease-causing CFTR mutants. With the successful development of ivacaftor, a “potentiator” that enhances CFTR chloride channel activity, new types of small-molecule compounds that “correct” the misfolding and misprocessing of the most common CF-causing mutation, F508del, are actively being sought for. Recent studies focused on the potential mechanisms of action of some of the investigational CFTR “correctors” shed new light on how the F508del mutant can be targeted in an attempt to ameliorate the clinical symptoms associated with CF. A multi-layer combinational approach has been proposed to achieve the highpotency correction necessary for significant clinical outcome. The mechanistic insights obtained from such studies will shape the future therapeutics development for the vast majority of CF patients.