Comparative, Single-Dose, 2-Way Cross-Over Bioavailability Study of Two Olanzapine 10 Mg Tablet Formulations in Healthy Volunteers Under Fasting Conditions.

: Olanzapine is an atypical antipsychotic that is approved across Europe, the USA, and in many other countries for oral treatment of schizophrenia and acute manic episodes in patients with bipolar disorder as well as for maintenance therapy to prevent recurrence in responders. The objective of the present study was to compare the pharmacokinetics of two 10 mg tablet formulations of Olanzapine following a single oral dose in healthy volunteers under fasting conditions, as per the European Medicine Agency (EMA) guidelines to grant marketing authorization. : This study was a randomized, open-label, two-treatment, two-period, two-sequences, single-dose, cross-over design with a washout period of 14 days.

AKR1D1*36 C>T (rs1872930) allelic variant is associated with variability of the CYP2C9 genotype predicted pharmacokinetics of ibuprofen enantiomers - a pilot study in healthy volunteers.

The relative contribution of CYP2C9 allelic variants to the pharmacokinetics (PK) of ibuprofen (IBP) enantiomers has been studied extensively, but the potential clinical benefit of pharmacogenetically guided IBP treatment is not evident yet. The role of AKR1D1*36C>T (rs 1872930) allelic variant in interindividual variability of CYP450 mediated drug metabolism was recently elucidated. A total of 27 healthy male subjects, volunteers in IBP single-dose two-way cross-over bioequivalence studies were genotyped for CYP2C9*2, CYP2C9*3 and AKR1D1*36 polymorphisms.

Importance of 6-Thioguanine Nucleotide Metabolite Monitoring in Inflammatory Bowel Disease Patients Treated with Azathioprine.

The active metabolite of azathioprine, 6-thioguanine nucleotide (6-TGN) is the main component responsible for the immunosuppressive effect in treatment of inflammatory bowel disease (IBD). The aim of this study was to assess the correlation between the concentration of 6-thioguanine nucleotide and disease activity, azathioprine-related adverse effects and time duration of treatment in patients with inflammatory bowel disease. Thirty-four patients were included in this study.

Expression of Indoleamine 2,3-Dioxygenase Induced by IFN-γ and TNF-α as Potential Biomarker of Prostate Cancer Progression.

Inflammation has been suggested to play an important role in onset and progression of prostate cancer (PCa). Histological analysis of prostatectomy specimens has revealed focal inflammation in early stage lesions of this malignancy. We addressed the role of inflammatory stimuli in the release of PCa-specific, tumor-derived soluble factors (PCa-TDSFs) already reported to be mediators of PCa morbidity, such as indoleamine 2,3-dioxygenase (IDO) and interleukin (IL)-6.

In vitro and in vivo characterization of the bifunctional μ and δ opioid receptor ligand UFP-505.

Background And Purpose: Targeting more than one opioid receptor type simultaneously may have analgesic advantages in reducing side-effects. We have evaluated the mixed μ opioid receptor agonist/ δ opioid receptor antagonist UFP-505 in vitro and in vivo.

Experimental Approach: We measured receptor density and function in single μ, δ and μ /δ receptor double expression systems.

The Influence of Smoking on the Variations in Carboxyhemoglobin and Methemoglobin During Urologic Surgery.

Introduction: Surgery is supposed to modulate the production of carbon monoxide by the reduction of heme oxygenase activity or transcriptional regulation of inducible heme oxygenase. On the other hand, the inhalation of tobacco smoke can substantially raise the level of carboxyhemoglobin in the blood. Furthermore, methemoglobin is maintained at a constant level.

Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.

Purpose: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes.

Vitamin K2 Improves Anxiety and Depression but not Cognition in Rats with Metabolic Syndrome: a Role of Blood Glucose?

Background: The metabolic syndrome is a socially important disorder of energy utilization and storage, recognized as a factor predisposing to the development of depression, anxiety and cognitive impairment in humans.

Aim: In the present study we examined the effects of vitamin K2 on the behavior of rats with metabolic syndrome and looked for relationships with the effects on blood sugar.

Materials And Methods: Male Wistar rats were divided in four groups: a control group on a regular rat chow, a metabolic syndrome (MS) group fed a high-fat high-fructose diet, a control group treated with vitamin K2 and a MS group treated with vitamin K2.

Transient Receptor Potential Ankyrin 1 Channels Modulate Inflammatory Response in Respiratory Cells from Patients with Cystic Fibrosis.

Pseudomonas aeruginosa colonization, prominent inflammation with massive expression of the neutrophil chemokine IL-8, and luminal infiltrates of neutrophils are hallmarks of chronic lung disease in patients with cystic fibrosis (CF). The nociceptive transient receptor potential ankyrin (TRPA) 1 calcium channels have been recently found to be involved in nonneurogenic inflammation. Here, we investigate the role of TRPA1 in CF respiratory inflammatory models in vitro.

Effects of Aronia melanocarpa Fruit Juice on Isolated Rat Hepatocytes.

Background: Aronia melanocarpa (Michx.) Elliot fruits are very rich in polyphenols - procyanidins, flavonoids, and phenolic acids.

Objective: On rat hepatocytes, isolated by two-stepped collagenase perfusion, we investigated the effect of A.

Novel Approach Targeting the Complex Pathophysiology of Hypertrophic Cardiomyopathy: The Impact of Late Sodium Current Inhibition on Exercise Capacity in Subjects with Symptomatic Hypertrophic Cardiomyopathy (LIBERTY-HCM) Trial.

Unlabelled: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, with an overall prevalence of at least 1:500 in the adult population although only a fraction of affected patients come to clinical recognition. It is also the most common cause of sudden cardiac death in young adults and a major cause of morbidity caused by chronic heart failure symptoms. However, more than half a century since the original description of the disease, there is no currently approved therapy for the treatment of patients with HCM, and to date there have been only 5 randomized studies of medical therapies in HCM.

Urological infections due to multidrug-resistant bacteria: what we need to know?

Purpose: Recent epidemiological data have confirmed the increasing problem of antimicrobial resistance not only for hospitalized, healthcare-associated patients, but also for outpatients. In particular, the progressive increase in resistance to broad-spectrum antibiotics, such as third-generation cephalosporins, fluoroquinolones or carbapenems in Enterobacteriaceae, is an alarming situation for all urologists and general practitioners. Here, we aimed to review the epidemiological data of multidrug-resistant bacteria in the urological setting, in order to summarize all diagnostic and therapeutic recommendations to use in everyday clinical practice.

Distribution of the most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia.

Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response. This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations.

The use of antidepressants and the risk of idiopathic pulmonary arterial hypertension.

Background: Serotonin has been implicated in the development of idiopathic pulmonary arterial hypertension (IPAH). Drugs modulating serotonin pathways, including antidepressants, have been associated with the incidence of IPAH, with conflicting reports as to the direction of the effect. We aimed to determine whether antidepressant exposure is associated with the incidence of IPAH.

Memory effects of Aronia melanocarpa fruit juice in a passive avoidance test in rats.

Aim: To study the effect of Aronia melanocarpa fruit juice on memory in male Wistar rats.

Materials And Methods: The juice was administered orally for 7, 14, 21 and 30 days at doses of 2.5 ml/kg, 5 ml/kg and 10 ml/kg.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

Background: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.

Patients And Methods: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.

Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats.

Background: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols.

Objective: We studied the protective effect of A.

Reliability Assessment of Arthroscopic Findings Versus MRI in ACL Injuries of the Knee.

Introduction: This study was conducted to analyze the reliability of clinical diagnosis in ACL tear injuries.

Material And Methods: All patients attending our clinic with knee pain from 2009 to 2013 underwent systematic and thorough clinical assessment. From one hundred and three patients with knee problems in 73 were arhroscopicaly diagnosed ACL tears.

Six week follow-up of metabolic effects induced by a high-fat diet and streptozotocin in a rodent model of type 2 diabetes mellitus.

This study was initiated to refine and characterize a nongenetic experimental model of type 2 diabetes mellitus and to follow up various metabolic parameters up to six weeks after diabetes induction. Male Wistar rats were divided into 4 groups: CON group--consumed standard rat chow and served as control; HFD group--consumed high-fat diet (45% calories as fat); STZ group-was injected once intraperitoneally with streptozotocin (35 mg/kg) on day 14, and DM-2 group--consumed high-fat diet and was injected with streptozotocin. The metabolic parameters were measured one week after streptozotocin injection (week 3) and at the end of the study (week 9).

Validation study in four health-care databases: upper gastrointestinal bleeding misclassification affects precision but not magnitude of drug-related upper gastrointestinal bleeding risk.

Objective: To evaluate the accuracy of disease codes and free text in identifying upper gastrointestinal bleeding (UGIB) from electronic health-care records (EHRs).

Study Design And Setting: We conducted a validation study in four European electronic health-care record (EHR) databases such as Integrated Primary Care Information (IPCI), Health Search/CSD Patient Database (HSD), ARS, and Aarhus, in which we identified UGIB cases using free text or disease codes: (1) International Classification of Disease (ICD)-9 (HSD, ARS); (2) ICD-10 (Aarhus); and (3) International Classification of Primary Care (ICPC) (IPCI). From each database, we randomly selected and manually reviewed 200 cases to calculate positive predictive values (PPVs).

Potential statin-drug interactions: prevalence and clinical significance.

Background: Statins are cholesterol-lowering drugs widely used for cardiovascular prevention. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. The exposure of the Bulgarian population to coprescriptions leading to potential statin-drug interactions is currently unknown.

Protective effect of Aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in vitro.

Aim: The aim of the present study was to investigate the protective potential of Aronia melanocarpa fruit juice in a model of cisplatin-induced cytotoxicity in the human embryonal kidney cell line HEK293T.

Materials And Methods: The cellular viability was assessed using the MTT-dye reduction assay based on the reduction of the yellow tetrazolium dye MTT to a violet formazan product via the mitochondrial succinate dehydrogenase in viable cells. Cisplatin was applied in various concentrations either alone or after a 24-hour pretreatment of the cells with Aronia melanocarpa fruit juice at 0.

Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer.

Background/aim: Matrix metalloproteinases (MMPs) are perceived to play a key role in tumor invasion and metastasis by their capacity to degrade basement membranes and extracellular matrix proteins. The aim of this study was to investigate the expressions of MMP-2, MMP-7 and MMP-9 in tumor tissue and their relation to clinicopathologic features in patients with colorectal cancer.

Methods: Specimens of resected colorectal cancer and surrounding normal tissue of 82 patients were immunohistochemically stained for MMP-2, MMP-7 and MMP-9.