Optimization of Se- and Zn-Enriched Mycelium of (Berk.) Pegler as a Dietary Supplement with Immunostimulatory Activity.

Mycelial cultures of , an edible and medicinal mushroom, have been used in our previous research to obtain selenium-containing immunomodulatory preparations. Our current attempts to obtain a new preparation containing both selenium and zinc, two micronutrients necessary for the functioning of the immune system, extended our interest in the simultaneous accumulation of these elements by mycelia growing in media enriched with selenite and zinc(II) ions. Subsequently, we have studied the effects of new mycelium water extracts with different concentrations of selenium and zinc on the activation of T cell fraction in human peripheral blood mononuclear cells (PBMCs).

The Synthesis and Absolute Configuration of Enantiomeric Pure (R)- and (S)-3-(piperidin-3-yl)-1H-Indole Derivatives.

This article describes the synthesis of new chiral 3-(piperidin-3-yl)-1H-indole derivatives and from the corresponding diastereomers: (3R, 2R) and (3S, 2R)-2-[3-(1H-indol-3-yl)-1-piperidyl]-2-phenyl-acetamides and . Diastereomers were obtained by N-alkylation of derivatives of racemic 3-(piperidin-3-yl)-1H-indoles using (S)-2-(4-toluenesulfonyloxy)-phenylacetic amide . The same method was applied to obtain (3R, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate and (3S, 2S)-methyl-2-[3-(1H-indole-3-yl)-1-piperidyl]-2-phenylacetate diastereomers by treating amine with (R)-2-(4-toluenesulfonyloxy)-phenylacetic acid methylester .

5-HT Receptors and the Development of New Antidepressants.

Serotonin modulates several physiological and cognitive pathways throughout the human body that affect emotions, memory, sleep, and thermal regulation. The complex nature of the serotonergic system and interactions with other neurochemical systems indicate that the development of depression may be mediated by various pathomechanisms, the common denominator of which is undoubtedly the disturbed transmission in central 5-HT synapses. Therefore, the deliberate pharmacological modulation of serotonergic transmission in the brain seems to be one of the most appropriate strategies for the search for new antidepressants.

Synthesis of Novel Pyrido[1,2-]pyrimidine Derivatives with 6-Fluoro-3-(4-piperidynyl)-1,2-benzisoxazole Moiety as Potential SSRI and 5-HT Receptor Ligands.

Two series of novel 4-aryl-2H-pyrido[1,2-c]pyrimidine (6a-i) and 4-aryl-5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine () derivatives were synthesized. The chemical structures of the new compounds were confirmed by H and C NMR spectroscopy and ESI-HRMS spectrometry. The affinities of all compounds for the 5-HT receptor and serotonin transporter protein (SERT) were determined by in vitro radioligand binding assays.

Understanding performance of 3D-printed sorbent in study of metabolic stability.

Metabolic stability tests are one of the fundamental steps at the preclinical stages of new drug development. Microsomes, used as a typical enzymatic model of liver biotransformation, can be a challenging matrix for analytical scientists due to a high concentration of cellular proteins and membrane lipids. In the work, we propose a new procedure integrating biotransformation reaction with SPME-like protocol for sample clean-up.

Evaluation of Transcatheter Alcohol-Mediated Perivascular Renal Denervation to Treat Resistant Hypertension.

Catheter-based renal denervation (RDN) has been investigated for hypertension (HTN) treatment with variable success. One of the novel approaches to RDN is the delivery of micro-doses of dehydrated alcohol to the adventitial space of the renal artery to perform perivascular ablation of the sympathetic nerves. We sought to assess the safety and efficiency of transcatheter alcohol-mediated perivascular renal denervation in patients with resistant hypertension.

Structure-activity relationship and cardiac safety of 2-aryl-2-(pyridin-2-yl)acetamides as a new class of broad-spectrum anticonvulsants derived from Disopyramide.

A series of 2-aryl-2-(pyridin-2-yl)acetamides were synthesized and screened for their anticonvulsant activity in animal models of epilepsy. The compounds were broadly active in the 'classical' maximal electroshock seizure (MES) and subcutaneous Metrazol (scMET) tests as well as in the 6 Hz and kindling models of pharmacoresistant seizures. Furthermore, the compounds showed good therapeutic indices between anticonvulsant activity and motor impairment.

Synthesis of new 5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine derivatives with rigidized tryptamine moiety as potential SSRI and 5-HT receptor ligands.

Extended studies in the 4-aryl-pyrido[1,2-c]pyrimidine group resulted in 27 new compounds (10.1-10.27), 5,6,7,8-tetrahydropyrido[1,2-c]pyrimidine derivatives.

Molecular Docking Supplements an In vitro Determination of the Leading CYP Isoform for Arylpiperazine Derivatives.

Background: Molecular docking has often been used before to calculate in silico affinity of drugs towards their molecular target, but not to estimate leading CYP isoform responsible for metabolism of studied compounds.

Objective: The aim of this study is to present molecular docking as a valid alternative for costly in vitro studies resulting in estimation of leading CYP isoform.

Methods: In vitro part was based on incubations of studied compounds with isolated CYP3A4 isoform followed by LC-MS analysis.

Synthesis of novel pyrido[1,2-c]pyrimidine derivatives with rigidized tryptamine moiety as potential SSRI and 5-HT receptor ligands.

The study enabled obtaining a number of new derivatives of 4-aryl-pyrido[1,2-c]pyrimidine 9.1-9.27 having conformationally restricted tryptamine moiety.

Short and long-term results of endoscopic atraumatic coronary artery off-pump bypass grafting in patients with left anterior descending artery stenosis.

Background: To perform a retrospective analysis of patients who underwent endoscopic atraumatic coronary artery off-pump bypass grafting (EACAB) in a single center over a period of 11 years.

Methods: Data was acquired from the hospital registry and patient medical records. In order to determine changes in clinical profile, patients were subdivided into three groups regarding year of surgery: 1998-2002 (group 1), 2003-2005 (group 2), 2006-2009 (group 3).

An optical coherence tomography study of neointimal morphology and strut coverage at different time intervals from implantation of biodegradable polymer-coated sirolimus-eluting stents.

Objectives: The aim of the study was to capture the evolution of neointima after implantation of a biodegradable polymer-coated, sirolimus-eluting, cobalt-chromium coronary stent system (BP-DES).

Background: Optical coherence tomography (OCT) suggests that in-stent neointimal morphology influences clinical outcomes after DES implantation.

Methods: Sixty patients treated with single BP-DES implantation were examined by quantitative coronary angiography (QCA) and OCT at 3, 6, and 12-month follow-up.

Evaluation of safety and efficacy of NexGen - an ultrathin strut and hybrid cell design cobalt-chromium bare metal stent implanted in a real life patient population - the Polish NexGen Registry.

Introduction: Despite the dominance of drug-eluting stents in modern interventional cardiology, there is still a niche for bare metal stents.

Aim: The aim of the Polish NexGen registry was to evaluate the safety and efficacy of a new generation cobalt-chromium NexGen stent in a real life patient population.

Material And Methods: A prospective multi-center registry was conducted in five clinical sites of American Heart of Poland.

Comparison of Chemical Composition in Tuber aestivum Vittad. of Different Geographical Origin.

Truffles are prized and nutrition-rich edible hypogeous fungi. The aim of this study was a comprehensive investigation of chemical composition of Burgundy truffle (Tuber aestivum Vittad.).

Renal Artery Stenting Associated With Improvement in Renal Function and Blood Pressure Control in Long-Term Follow-Up.

Background/aims: Clinical benefits of percutaneous treatment of renal artery stenosis (RAS) remain controversial. The aim of this study was to evaluate the effects of renal artery stenting on kidney function and blood pressure (BP) control in the log-term follow-up. Additionally angiographic follow up was performed in selected subgroup of patients.

Surgical removal of entrapped guidewire fragment following direct circumflex artery angioplasty and stenting.

We present a case of a 64-year-old man with coronary artery disease, who underwent a percutaneous coronary intervention of the circumflex artery. As the guidewire was being withdrawn from the target vessel, it became entrapped by the structure of the previously implanted stent. Attempts to retrieve the foreign body were unsuccessful.

Characterization of Disopyramide derivative ADD424042 as a non-cardiotoxic neuronal sodium channel blocker with broad-spectrum anticonvulsant activity in rodent seizure models.

It was reported that antiarrhythmic drugs (AADs) can be useful in controlling refractory seizures in humans or in enhancing the action of antiepileptic drugs (AEDs) in animal models. Disopyramide phosphate (DISO) is an AAD that blocks sodium channels in cardiac myocytes. We evaluated a DISO derivative, 2-(2-chlorophenyl)-2-(pyridin-2-yl)acetamide (ADD424042) for its anticonvulsant activity in a battery of rodent models of epileptic seizures.

Prediction of overall in vitro microsomal stability of drug candidates based on molecular modeling and support vector machines. Case study of novel arylpiperazines derivatives.

Other than efficacy of interaction with the molecular target, metabolic stability is the primary factor responsible for the failure or success of a compound in the drug development pipeline. The ideal drug candidate should be stable enough to reach its therapeutic site of action. Despite many recent excellent achievements in the field of computational methods supporting drug metabolism studies, a well-recognized procedure to model and predict metabolic stability quantitatively is still lacking.

Safety and biocompatibility of a novel self-expanding nitinol carotid stent with hybrid cell design in a porcine model of neointimal hyperplasia.

Background: Stent design may influence the outcomes, suggesting that adverse event rates vary according to free cell area and cell design. Open cell design technology of self-expandable stents, dedicated for carotid revascularisation has better deliverability, although closed cell technology is expected to cause fewer thromboembolic events.

Aim: To evaluate the feasibility and vascular response of novel, hybrid cell, self-expandable nitinol stents (MER®, Balton, Poland) implanted into porcine carotid arteries.

Recent development of potent analogues of oxazolidinone antibacterial agents.

The oxazolidinones are a new and potent class of antimicrobial agents with activity mainly against Gram-positive strains. The commercial success of linezolid, the only FDA-approved oxazolidinone, has prompted many pharmaceutical companies to devote resources to this area of investigation. Until now, four types of chemical modifications of linezolid and oxazolidinone-type antibacterial agents, including modification on each of the A-(oxazolidinone), B-(phenyl), and C-(morpholine) rings as well as the C-5 side chain of the A-ring substructure, have been described.

Enhancement of tacrolimus productivity in Streptomyces tsukubaensis by the use of novel precursors for biosynthesis.

In this report the optimization of biosynthesis of tacrolimus, the immunosupressant widely used in transplantology and dermatology was described. The enhancement of the productivity of Streptomyces tsukubaensis strain was achieved by development of new precursors of tacrolimus biosynthesis, which should allow to reduce the costs of the process. The enrichment of the fermentation medium in pyridine-2-carboxylic acid (picolinic acid), piperidine-2-carboxylic acid (pipecolic acid), pyridine-3-carboxylic acid (nicotinic acid) or pyridine-3-carboxylic acid amide (nicotinamide) caused significant growth of the productivity of tacrolimus: 7-fold, 6-fold, 3-fold and 5-fold, respectively.

Mobilization of CD34+CXCR4+ stem/progenitor cells and the parameters of left ventricular function and remodeling in 1-year follow-up of patients with acute myocardial infarction.

Mobilization of stem cells in acute MI might signify the reparatory response. Aim of the Study. Prospective evaluation of correlation between CD34+CXCR4+ cell mobilization and improvement of LVEF and remodeling in patients with acute MI in 1-year followup.

Long-term results of cephalad arteries percutanoeus transluminal angioplasty with stent implantation (The CAPTAS registry).

Introduction: Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy. Moreover, percutaneous transluminal angioplasty (PTA) allows other cephalad arteries revascularization. The aim of this study was to evaluate late outcomes of cephalad arteries PTA.

Early and long-term outcomes after surgical and percutaneous myocardial revascularization in patients with non-ST-elevation acute coronary syndromes and unprotected left main disease.

Unlabelled: Surgical myocardial revascularization (CABG) in patients with unprotected left main coronary artery disease (ULMCA) is a Class I recommendation in the AHA/ACC guidelines, however it is associated with increased perioperative risk in non-ST elevation acute coronary syndromes (NSTE-ACS). The aim of this study was to compare early and late results after percutaneous coronary intervention (PCI) and CABG in this cohort of patients.

Methods: A multicenter prospective registry included 138 patients with patent but severely narrowed (> 50%) ULMCA disease and NSTE-ACS diagnosed between January 2005 and April 2007.

Early and long-term results of unprotected left main coronary artery stenting: the LE MANS (Left Main Coronary Artery Stenting) registry.

Objectives: The aim of the study was to evaluate early and late outcomes after percutaneous coronary intervention (PCI) of unprotected left main coronary artery disease (ULMCA) and to compare bare-metal stent (BMS) and drug-eluting stent (DES) subgroups.

Background: PCI is an increasingly utilized method of revascularization in patients with ULMCA.

Methods: This multicenter prospective registry included 252 patients after ULMCA stenting enrolled between March 1997 and February 2008.