Vildagliptin Recruits Regulatory T Cells in Patients Undergoing Primary Percutaneous Coronary Intervention

Regulatory T cells (Treg) has been documented to be protective against myocardial ischemia–reperfusion injury (MIRI). The administration of drugs which recruit Treg cells may participate in the cardioprotection of MIRI. The purpose of the present study was to investigate whether the add-on vildagliptin (vild) to standard treatment of MIRI prior to reperfusion could increase Treg recruitment, anti-inflammatory, and antioxidant effects of the standard treatment or not. Sixty diabetic patients with ST-segment elevation myocardial infarction were randomly divided into two equal groups: control group was given the standard medical treatment and vild group was given the standard medical treatment plus vild. There were no statistical differences between the mean of percentage of changes in nitric oxide, ischemia modified albumin, highly sensitive C reactive protein, and interferon-gamma levels in the studied groups. While, the percentages of changes of myeloperoxidase level, CD4+CD25+ Treg cells count, and transforming growth factor-beta1 level were significantly higher in vild group compared with control group. We concluded that addition of vild to standard medical treatment of MIRI could increase its effectiveness through recruitment of CD4+CD25+ Treg cells.     

Behavior of In Situ Cross‐Linked Hydrogels with Rapid Gelation Kinetics on Contact with Physiological Fluids

The impact of different physiological fluids on the rheological properties of gellan gum is investigated using a commercially available rheometer with a modified lower plate. The power of this method is demonstrated by measuring in real time, the rapid gelation kinetics, and gel strength of gellan gum exposed to simulated gastric fluid, lacrimal fluid, saliva, and wound fluid (all having a different ionic composition), highlighting potential use in the intelligent design of in situ gelling delivery systems. Changes in rheological behavior are examined in situ, gelation kinetics are modeled, and microstructure analyzed in the different simulated physiological environments.     

A review on current status of antiviral siRNA

Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene‐silencing phenomenon in which sequence‐specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.     

Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition

GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2^−/−) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2^−/− mice show cortical PV⁺ interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus. Ccnd2^−/− mice show several neurophysiological and behavioral phenotypes that would be predicted to be produced by hippocampal disinhibition, including increased ventral tegmental area dopamine neuron population activity, behavioral hyperresponsiveness to amphetamine, and impairments in hippocampus-dependent cognition. Remarkably, transplantation of cells from the embryonic medial ganglionic eminence (the major origin of cerebral cortical interneurons) into the adult Ccnd2^−/− caudoventral hippocampus reverses these psychosis-relevant phenotypes. Surviving neurons from these transplants are 97% GABAergic and widely distributed within the hippocampus. Up to 6 mo after the transplants, in vivo hippocampal metabolic activity is lowered, context-dependent learning and memory is improved, and dopamine neuron activity and the behavioral response to amphetamine are normalized. These findings establish functional links between hippocampal GABA interneuron deficits and psychosis-relevant dopaminergic and cognitive phenotypes, and support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.Precursors of most γ-aminobutyric acid (GABA)-releasing interneurons of the cerebral cortex and the hippocampus originate in the embryonic medial ganglionic eminence (MGE) (1–3). A subpopulation of MGE-derived cells differentiates into fast-spiking, parvalbumin-expressing (PV⁺) interneurons that tightly regulate the activity and synchronization of cortical projection neurons (2, 4). Structural and functional deficits in PV⁺ interneurons are hypothesized as a pathophysiological mechanism in schizophrenia and psychotic disorders (4–6).Although psychotic disorders are clearly heterogeneous in etiology, disinhibition within temporolimbic cortical circuits is postulated as a core pathophysiology underlying positive symptoms (e.g., delusions and hallucinations) and a subset of cognitive disturbances that manifest with psychosis (4, 5, 7). Postmortem studies of brains from individuals with psychotic disorders show reduced molecular markers of the number and/or function of PV⁺ interneurons in the hippocampus (6, 8). Consistent with these observations, basal metabolic activity in the hippocampus, as measured with functional magnetic resonance imaging (fMRI), is increased in schizophrenia, a phenotype that predicts psychosis and positive symptom severity (5, 7). This abnormal resting activity is postulated to underlie abnormal recruitment of hippocampal circuits during cognitive performance (5, 9). Striatal dopamine (DA) release capacity is also increased and correlated with positive symptoms in schizophrenia and its risk states (10, 11). Importantly, hippocampal hyperactivity may contribute to DA dysregulation (12), because rodent studies show that caudoventral hippocampal (in the primate, anterior hippocampal) efferents regulate the activity of DA neurons and medial striatal DA release (13, 14).Thus, converging evidence implicates hippocampal disinhibition in the abnormal striatal DA transmission and cognitive impairment in schizophrenia. However, the role of hippocampal inhibitory interneurons in psychosis-relevant circuitry remains to be established. To this end, we used the cyclin D2 (Ccnd2) knockout mouse model (15), which displays a relatively selective deficit in cortical PV⁺ interneurons, and transplantation of interneuron precursors from the MGE to elucidate relationships between reduced hippocampal GABA interneuron function and multiple psychosis-relevant phenotypes, and to explore a novel treatment strategy for psychosis.     

Association between ACE inhibitors and acute pancreatitis in the elderly

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor-induced acute pancreatitis has been described in various case reports and drug surveillance databases. At present, no epidemiologic studies examining the potential association between ACE inhibitors and acute pancreatitis have been identified. OBJECTIVE: To determine whether there is an association between ACE inhibitor use and pancreatic events (acute pancreatitis, pancreatic surgery). METHODS: A retrospective cohort of Ontario residents aged >/=66 years was created using population-based administrative databases from January 1, 1994, through March 31, 2000. We compared the incidence of pancreatic events among new users of ACE inhibitors (study group), warfarin (null baseline group), and dihydropyridine calcium-channel antagonists (DCCAs; disease control group) using multivariate Cox proportional hazard models. OUTCOME MEASURES: The primary outcome measure was hospitalization with acute pancreatitis; the secondary outcome measure was incidence of pancreatic surgery. RESULTS: For acute pancreatitis, the crude incidence rates per 10,000 person-years were 9.0 for the ACE inhibitor group (n = 174,824); 7.1 for the DCCA group (n = 73,719), and 7.6 for the warfarin group (n = 40 057). Relative to warfarin users, neither ACE inhibitor users (adjusted rate ratio [aRR] = 1.35; 95% CI 0.94 to 1.93) nor DCCA users (aRR = 1.09; 95% CI 0.72 to 1.62) were at significantly higher risk of hospitalization for acute pancreatitis. For pancreatic surgery in the same population, the crude incidence rates per 10,000 person-years were 10.5 for the ACE inhibitor group, 10.6 for the DCCA group, and 10.7 for the warfarin group. Relative to subjects taking warfarin, neither ACE inhibitor users (aRR = 1.09; 95% CI 0.80 to 4.49) nor DCCA users (aRR = 1.11; 95% CI 0.79 to 1.56) were at significantly higher risk for pancreatic surgery. CONCLUSIONS: The use of ACE inhibitors does not appear to be associated with significant risk of acute pancreatitis among the elderly.     

Nonopioid analgesics

NSAIDs are useful analgesics for many pain states, especially those involving inflammation. Their use is frequently overlooked in patients with postoperative and chronic pain. Unless there is a contraindication, the use of an NSAID should be routinely considered to manage acute pain, chronic cancer, and noncancer pain.