Complete hematological and major molecular response through treatment with low-dose Interferon alpha 2a in high-risk polycythemia vera patient: a case report.

Low-dose interferon-α 2a treatment may be considered as an alternative to cytoreductive therapy with hydroxyurea or regularly dosed interferon in high-risk polycythemia vera patients.

First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy.

Background: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear.

Pharmacokinetics of Transdermal Etofenamate and Diclofenac in Healthy Volunteers.

Little is known about the course of the plasma concentration and the bioavailability of non-steroidal anti-inflammatory drugs (NSAIDs) contained in dermal patches. We compared an etofenamate prototype patch (patent EP 1833471) and a commercially available diclofenac epolamine patch regarding the bioavailability of the active ingredients relative to respective i.m.

Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity-3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS).

Objective: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS).

Methods: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland.

Anti-inflammatory effects of the petasin phyto drug Ze339 are mediated by inhibition of the STAT pathway.

Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers.

Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects.

With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies.

Time controlled pulsatile transdermal delivery of nicotine: A phase I feasibility trial in male smokers.

Nicotine substitution is a mainstay component in smoking cessation schemes. Current products including patches are poorly effective mainly because they do not give smokers the same pharmacokinetic profile of nicotine as cigarette consumption. This work evaluates a new computer operated delivery system for time controlled pulsatile transdermal administration of nicotine in a phase I clinical trial with twelve heavy smoking male volunteers.

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial.

Background/objectives: The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.

A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients.

The cardinal climacteric symptoms of hot flushes and night sweats affect 24-93% of all women during the physiological transition from reproductive to post-reproductive life. Though efficacious, hormonal therapy and partial oestrogenic compounds are linked to a significant increase in breast cancer. Non-hormonal treatments are thus greatly appreciated.

Data mining for potential adverse drug-drug interactions.

Introduction: Patients, in particular elderly ones, frequently receive more than one drug at a time. With each drug added to a regime, the number of potential drug-drug interactions (DDIs) increases by a power law. Early prediction of relevant interactions by computerized tools greatly aids clinicians and can guide their prescribing choices.

The effect of a Cimicifuga racemosa extracts Ze 450 in the treatment of climacteric complaints--an observational study.

Background: Root extracts of Cimicifuga racemosa (L.) Nutt. have been successfully used in the treatment of climacteric complaints.

Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study.

Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa) have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.

Decision tree models for data mining in hit discovery.

Introduction: Decision tree induction (DTI) is a powerful means of modeling data without much prior preparation. Models are readable by humans, robust and easily applied in real-world applications, features that are mutually exclusive in other commonly used machine learning paradigms. While DTI is widely used in disciplines ranging from economics to medicine, they are an intriguing option in pharmaceutical research, especially when dealing with large data stores.

Heat exposure of Cannabis sativa extracts affects the pharmacokinetic and metabolic profile in healthy male subjects.

The most important psychoactive constituent of CANNABIS SATIVA L. is Δ (9)-tetrahydrocannabinol (THC). Cannabidiol (CBD), another important constituent, is able to modulate the distinct unwanted psychotropic effect of THC.

Pharmacokinetic evaluation of idebenone.

Importance Of The Field: Idebenone is a synthetic short chain benzoquinone that acts as an electron carrier in the mitochondrial electron transport chain, thereby, facilitating the production of ATP. In addition, idebenone is an antioxidant and can inhibit lipid peroxidation and may protect cell membranes and mitochondria from oxidative damage. High dose idebenone (Catena(®)) is approved in Canada for the symptomatic treatment of Friedreich's ataxia and is currently under clinical investigation for use in a number of mitochondrial and neuromuscular diseases.

An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography-tandem mass spectrometry.

A fully automated screening using liquid chromatography-mass spectrometric method applying data-dependent acquisition was developed to identify toxicologically relevant substances in serum and urine. A library including more than 405 spectra of about 365 compounds (main drugs and important metabolites) was established. An easy to use program was created to automate and accelerate library search.

Oral administration of glucagon-like peptide 1 or peptide YY 3-36 affects food intake in healthy male subjects.

Background: Peripheral infusion of glucagon-like peptide 1 (GLP-1) or peptide YY 3-36 (PYY3-36) reduces food intake in healthy, obese, and diabetic subjects. In vivo, both peptides are cosecreted from intestinal L cells; GLP-1 is subject to rapid breakdown by dipeptidyl peptidase IV, and together with PYY3-36 it is likely to be degraded in the liver before entering the systemic circulation. The largest concentrations are observed in the splanchnic blood rather than in the systemic circulation.

A new intestinal cell culture model to discriminate the relative contribution of P-gp and BCRP on transport of substrates such as imatinib.

P-glycoprotein (P-gp/MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) play an important role in transport of a wide variety of endogenous compounds, drugs and toxins. Transport of some drugs, for example the tyrosine kinase inhibitor imatinib, is influenced by both P-gp and BCRP. Establishing an intestinal Caco-2 cell culture model with specific knock-downs of P-gp and BCRP and double knock-down of both proteins, we aimed to elucidate the impact of each transporter on transport of imatinib.

Effects of Curcuma extracts and curcuminoids on expression of P-glycoprotein and cytochrome P450 3A4 in the intestinal cell culture model LS180.

Curcuma longa L. is a widely used spice. Its main ingredients, the curcuminoids, are used in the treatment of inflammatory diseases and cancer.

Role of fat hydrolysis in regulating glucagon-like Peptide-1 secretion.

Context: Glucagon-like peptide-1 (GLP-1) is produced by specialized cells in the gut and secreted in response to carbohydrates and lipids. The mechanisms regulating fat-stimulated GLP-1 release have, however, not been clarified in detail.

Aim: We aimed to investigate the effect of intraduodenal (ID) fat hydrolysis on GLP-1 release and test whether the signal is mediated through cholecystokinin (CCK)-1 receptors.

Classification of cytochrome p(450) activities using machine learning methods.

The cytochrome P(450) (CYP) system plays an integral part in the metabolism of drugs and other xenobiotics. Knowledge of the structural features required for interaction with any of the different isoforms of the CYP system is therefore immensely valuable in early drug discovery. In this paper, we focus on three major isoforms (CYP 1A2, CYP 2D6, and CYP 3A4) and present a data set of 335 structurally diverse drug compounds classified for their interaction (as substrate, inhibitor, or any interaction) with these isoforms.

Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial.

Background: The exclusion of the proximal small intestine is thought to play a major role in the rapid improvement in the metabolic control of diabetes after gastric bypass.

Objective: In this randomized, prospective, parallel group study, we sought to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) with those of laparoscopic sleeve gastrectomy (LSG) on fasting, and meal-stimulated insulin, glucose, and glucagon-like peptide-1 (GLP-1) levels.

Methods: Thirteen patients were randomized to LRYGB and 14 patients to LSG.

Development of decision tree models for substrates, inhibitors, and inducers of p-glycoprotein.

In silico classification of new compounds for certain properties is a useful tool to guide further experiments or compound selection. Interaction of new compounds with the efflux pump P-glycoprotein (P-gp) is an important drug property determining tissue distribution and the potential for drug-drug interactions. We present three datasets on substrate, inhibitor, and inducer activities for P-gp (n = 471) obtained from a literature search which we compared to an existing evaluation of the Prestwick Chemical Library with the calcein-AM assay (retrieved from PubMed).

Effect of food on the pharmacokinetics and pharmacodynamics of an oral ghrelin agonist (ARD-07) in healthy subjects.

ARD-07 (also known as EP01572) is a peptidomimetic growth hormone secretagogue that can be administered orally. The primary objective of this study is to determine the effects of a meal on the oral bioavailability of ARD-07 after a single oral dose (0.5 mg/kg).

In vitro interactions with repeated grapefruit juice administration--to peel or not to peel?

Interactions of acutely administered grapefruit juice (GFJ) with cytochrome P450 isoform 3A4 (CYP3A4) and P-glycoprotein (Pgp) function are well established. In this study, we investigated in vitro the effect of repeated administration of GFJ and its major constituents (the flavonoid naringin, its aglycone naringenin and the furanocoumarin bergamottin) on mRNA expression of MDR1 and CYP3A4 in LS180 cells. Since the bergamottin content is higher in the peel than in the fruit, we compared GFJ containing peel (GFJP+) with juice without any peel extract (GFJP-).