Structure-Activity Relationship of NMDA Receptor Ligands and Their Activities on the ERK Activation through Metabotropic Signaling Pathway.

The N-methyl-D-aspartate receptor (NMDA-R) subunit GluN2B is abundantly expressed in brain regions critical for synaptic plasticity and cognitive processes. This study investigated the structure-activity relationships (SAR) of NMDA-R ligands using GluN2B as a molecular target. Thirty potential NMDA-R antagonists were categorized into two structural classes: 1-(1-phenylcyclohexyl) amines (series A) and α-amino-2-phenylcyclohexanone derivatives (series B).

Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor.

The type-1 cannabinoid receptor (CBR) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CBR ligands. In this study, CBR ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CBR.

Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor.

Among 14 subtypes of serotonin receptors (5-HTRs), 5-HTR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HTR have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HTR was determined.

Potential Functional Role of Phenethylamine Derivatives in Inhibiting Dopamine Reuptake: Structure-Activity Relationship.

Numerous psychotropic and addictive substances possess structural features similar to those of β-phenethylamine (β-PEA). In this study, we selected 29 β-PEA derivatives and determined their structure-activity relationship (SAR) to their ability to inhibit dopamine (DA) reuptake; conducted docking simulation for two selected compounds; and identified their potential functionals. The compounds were subdivided into arylethylamines, 2-(alkyl amino)-1-arylalkan-1-one derivatives and alkyl 2-phenyl-2-(piperidin-2-yl)acetate derivatives.

Wellens Syndrome Electrocardiogram Pattern in a Patient With Multi-Vessel Coronary Artery Disease.

Wellens syndrome is an electrocardiogram (ECG) pattern associated with critical stenosis of the proximal left anterior descending (LAD) artery. In patients with Wellens syndrome, characteristic biphasic or inverted T waves are seen on ECG. This case report presents a 48-year-old male admitted for chest pain and shortness of breath who was found to have a Wellens syndrome ECG pattern.

Neurosyphilis: A Monkey Among Men.

Neurosyphilis is the progression of the untreated sexually transmitted infection caused by . When the initial infection is not adequately treated, progression of primary syphilis can lead to a wide variety of serious health sequelae. While neurosyphilis can appear up to 10-30 years after the initial infection, syphilis can invade the nervous systemat any stage of infection and can imitate symptoms of many other diseases.

Stroke Secondary to Iron Deficiency Anemia: A Case Report.

Cerebrovascular accident is the fifth leading cause of death in the United States, with about 795,000 cases reported to the Centers for Disease Control and Prevention (CDC) each year. Several risk calculators for the development of stroke have been developed throughout the years, but none included iron deficiency anemia (IDA). We therefore would like to highlight the case of a 34-year-old female with severe iron deficiency anemia secondary to menorrhagia who had an ischemic stroke.

Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors.

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition.

Novel GPR43 Agonists Exert an Anti-Inflammatory Effect in a Colitis Model.

GPR43 (also known as FFAR2), a metabolite-sensing G-protein-coupled receptor stimulated by short-chain fatty acid (SCFA) ligands is involved in innate immunity and metabolism. GPR43 couples with Gα and Gα heterotrimeric proteins and is capable of decreasing cyclic AMP and inducing Ca flux. The GPR43 receptor has additionally been shown to bind β-arrestin 2 and inhibit inflammatory pathways, such as NF-ΚB.

Structural Requirements for Modulating 4-Benzylpiperidine Carboxamides from Serotonin/Norepinephrine Reuptake Inhibitors to Triple Reuptake Inhibitors.

8k: and a serotonin/norepinephrine reuptake inhibitor.

7j: showed that the regions spanning transmembrane domain (TM)1, TM3, and TM6 form the ligand binding pocket. The compound.

Design, synthesis, and systematic evaluation of 4-arylpiperazine- and 4-benzylpiperidine napthyl ethers as inhibitors of monoamine neurotransmitters reuptake.

Two series of 4-arylpiperazine- and 4-benzylpiperidine naphthyl ethers were designed based on structure-activity relationship (SAR) and docking model of reported monoamine neurotransmitters reuptake inhibitors. The compounds were synthesized in 3-simple steps and their biological activities were evaluated. Several compounds were proven to be potent inhibitors of serotonin and norepinephrine reuptake.

Design, synthesis and docking study of 4-arylpiperazine carboxamides as monoamine neurotransmitters reuptake inhibitors.

Rational drug design method has been used to generate 4-arylpiperazine carboxamides in an effort to develop safer, more potent and effective monoamine neurotransmitters reuptake inhibitors. Out of twenty-seven synthesized compounds, compound 9 displayed potent monoamine neurotransmitter reuptake inhibitory activity against HEK cells transfected with hSERT or hNET. A Surflex-Dock docking model of 9 was also studied.

Triple reuptake inhibitors: Design, synthesis and structure-activity relationship of benzylpiperidine-tetrazoles.

Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors.

Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors.

Monoamine transporters regulate the concentration of monoamine neurotransmitters, which are essential for vital physiological processes, and their dysfunction can cause several central nervous system diseases. Monoamine transporters currently appear to be the potential target in the management of these disorders. In this study, homologation and bioisosterism techniques have been used in the designing of new 1,4-disubstituted piperazines and piperidines.

Antidiabetic effect of SN158 through PPARα/γ dual activation in ob/ob mice.

In this study, we aimed to demonstrate the antidiabetic potential of (E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxyphenyl)acryloyl) phenyl)-4-tert-butylbenzamide (SN158) through peroxisome proliferator-activated receptor (PPAR)-α/γ dual activation. SN158 interacted with both PPARα and PPARγ, and increased their transcriptional activities. Simultaneously, SN158 treatment led to an increase in adipogenic differentiation of 3T3-L1 preadipocytes and fatty acid oxidation in hepatocytes.

Exploration of substituted arylpiperazine-tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors.

In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine-tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers.

Systematic Review and Meta-analysis of Clinical and Economic Outcomes from the Implementation of Hospital-Based Antimicrobial Stewardship Programs.

The implementation of antimicrobial stewardship programs (ASPs) is a promising strategy to help address the problem of antimicrobial resistance. We sought to determine the efficacy of ASPs and their effect on clinical and economic parameters. We searched PubMed, EMBASE, and Google Scholar looking for studies on the efficacy of ASPs in hospitals.

Design, synthesis, and biological evaluation of arylpiperazine-benzylpiperidines with dual serotonin and norepinephrine reuptake inhibitory activities.

The limitations of established serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitors necessitate the development of safer and more effective therapeutic agents. Based on the structures of 4-benzylpiperidine carboxamides and trazodone, arylpiperazine-benzylpiperidines with chemical scaffolds different from those of marketed drugs were designed, synthesized, and evaluated for their neurotransmitter reuptake inhibitory activities. The majority of the synthesized compounds showed greater NE than 5-HT reuptake inhibition.

Prevalence and Clinical Outcomes of Clostridium difficile Infection in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

Unlabelled: Background.  Intensive care unit (ICU) patients are at higher risk for Clostridium difficile infection (CDI).

Methods: We performed a systematic review and meta-analysis of published studies from 1983 to 2015 using the PubMed, EMBASE, and Google Scholar databases to study the prevalence and outcomes of CDI in this patient population.

Design and synthesis of 4-benzylpiperidine carboxamides as dual serotonin and norepinephrine reuptake inhibitors.

A series of 4-benzylpiperidine carboxamides were designed and synthesized, and tested for their dual (serotonin and norepinephrine) reuptake inhibition. The synthesis of 4-benzylpiperidine carboxamides involved two main steps: amidation and substitution. Derivatives with 3 carbon linker displayed better activity than with 2 carbon linker.

Synthesis and evaluation of arylpiperazine-reverse amides as biased dopamine D3 receptor ligands.

The dopamine D3 receptor (D3R) preferential ligands have been universally adopted as a strategy for the treatment of drug addiction and other neuropsychiatric disorders due to fewer side effects. However, the high sequence homology between D3R and the D2 receptor (D2R) challenges the development of D3R-biased compounds. Herein, we design and synthesize a novel series of reverse amide-piperazine hybrid ligands and evaluate their biological affinities in vitro.

Prevalence of Clostridium difficile infection among solid organ transplant recipients: a meta-analysis of published studies.

Several factors including antibiotic use, immunosuppression and frequent hospitalizations make solid organ transplant (SOT) recipients vulnerable to Clostridium difficile infection (CDI). We conducted a meta-analysis of published studies from 1991-2014 to estimate the prevalence of CDI in this patient population. We searched PubMed, EMBASE and Google Scholar databases.

Concise synthesis of licochalcone C and its regioisomer, licochalcone H.

Licochalone C (7a) is a retrochalcone isolated from Glycyrrhiza inflata, which shows potent antioxidant properties and inhibition of bacterial growth and cellular respiration. Biological studies have suggested that licochalcone C attenuates the lipopolysaccharide and interferon-gamma induced inflammatory response by decreasing the expression and activity of inducible nitric oxide synthase and modulating the antioxidant network activity of superoxide dismutase, catalase, and glutathione peroxidase activity. Licochalcone C also inhibits NADH-cytochrome C reductase in the membrane fraction of Micrococcus luteus.