Alteration of the aortic vascular reactivity associated to excessive consumption of Linnaeus: Preliminary findings.

The moderate production of reactive oxidative species (ROS) is important because ROS act as second messengers. However, their depletion through the over-activity of the antioxidant system may lead to reductive stress (RS) which is characterized by an increase in reducing equivalents and an elevation of some components of the antioxidant system disturbing redox homeostasis. Linnaeus (HSL) is a plant with antioxidant properties that provides compounds that favor the antioxidant system.

Kinetic-Pharmacodynamic Model of Platelet Time Course in Patients With Moderate-to-Severe Atopic Dermatitis Treated With Oral Janus Kinase 1 Inhibitor Abrocitinib.

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib reduced signs and symptoms of atopic dermatitis (AD) in a placebo-controlled, randomized, double-blind, phase IIb trial (dose range 10-200 mg). A kinetic-pharmacodynamic (K-PD) model consisting of proliferation, maturation, and blood circulation compartments was developed to characterize platelet count changes during the study. The K-PD model consisted of a drug elimination constant, four system parameters describing platelet dynamics, variance terms, correlation, and residual errors.

Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout.

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality-adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues.

Impact of Non-Adherence and Flare Resolution on the Cost-Effectiveness of Treatments for Gout: Application of a Linked Pharmacometric/Pharmacoeconomic Model.

Background: Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses.

Immunologic Responses in Biological and Mechanical Valve Prostheses: Inflammation and Functionality Are Not Always Related.

Background And Aim Of The Study: The aim of this retrospective study was to evaluate the inflammatory response in patients with aortic and/or mitral prostheses, and to correlate the level of inflammatory markers with prosthesis functionality.

Methods: A total of 48 patients with biological or mechanical prostheses was included in the study, in which levels of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, -4, and -6, interferon-gamma (IFNγ), osteopontin (OPN), intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), endothelin-1 and C-reactive protein were analyzed. Functionality of the prosthesis was evaluated using transthoracic echocardiography at three years after surgery.

Impact of non-adherence on the safety and efficacy of uric acid-lowering therapies in the treatment of gout.

Aims: Dual-urate-lowering therapy (ULT) with xanthine oxidase inhibitor and uricosuric medications is a treatment option for severe gout. Uricosuric agents can cause hyperuricosuria, a risk factor for nephrolithiasis and acute uric acid nephropathy. The aims of the present study were to simulate the relationship between suboptimal drug adherence and efficacy, and to quantify the risk of hyperuricosuria in gout patients receiving mono- and dual-ULTs.

Semimechanistic cell-cycle type-based pharmacokinetic/pharmacodynamic model of chemotherapy-induced neutropenic effects of diflomotecan under different dosing schedules.

The current work integrates cell-cycle dynamics occurring in the bone marrow compartment as a key element in the structure of a semimechanistic pharmacokinetic/pharmacodynamic model for neutropenic effects, aiming to describe, with the same set of system- and drug-related parameters, longitudinal data of neutropenia gathered after the administration of the anticancer drug diflomotecan (9,10-difluoro-homocamptothecin) under different dosing schedules to patients (n = 111) with advanced solid tumors. To achieve such an objective, the general framework of the neutropenia models was expanded, including one additional physiologic process resembling cell cycle dynamics. The main assumptions of the proposed model are as follows: within the stem cell compartment, proliferative and quiescent cells coexist, and only cells in the proliferative condition are sensitive to drug effects and capable of following the maturation chain.

Population pharmacokinetics of ampicillin and sulbactam in patients with community-acquired pneumonia: evaluation of the impact of renal impairment.

Aims: The aims of this study were to develop a population pharmacokinetic (PK) model of ampicillin and sulbactam, to identify patient characteristics influencing the PK, and to explore the relationship between dose regimen and degree of renal impairment with exposure and time above minimum inhibitory concentration (MIC).

Methods: This analysis was performed on PK data for ampicillin and sulbactam and MIC data from a clinical trial in Japanese patients with community acquired pneumonia. Simulations were performed to investigate the effects of different dosing intervals on exposure and time above MIC in various degrees of renal impairment.

Population pharmacokinetic/pharmacodynamic modeling of drug-induced adverse effects of a novel homocamptothecin analog, elomotecan (BN80927), in a Phase I dose finding study in patients with advanced solid tumors.

Purpose: To characterize the pharmacokinetic profile of elomotecan, a novel homocamptothecin analog, evaluate the dose-limiting toxicities, and establish the relationship between exposure and toxicity in the first Phase I study in patients with advanced malignant solid tumors. Preliminary antitumor efficacy results are also provided.

Design: Elomotecan was administered as a 30-min intravenous infusion at doses ranging from 1.

Comparison of different semi-mechanistic models for chemotherapy-related neutropenia: application to BI 2536 a Plk-1 inhibitor.

Purpose: The aim of this investigation was to compare the performance of a commonly used semi-mechanistic model for drug-related neutropenia with other semi-mechanistic models published in the literature.

Methods: After their implementation in NONMEM VI, five semi-mechanistic models were assessed using the pharmacokinetic and absolute neutrophil count data obtained from 95 patients with non-small cell lung cancer receiving either 200 mg on day 1 or 50 or 60 mg on days 1, 2 and 3 of a 21-day treatment course with the new Plk-1 inhibitor BI 2536. The model performance was compared by means of predictive (visual and numerical) checks, precision in the parameter estimates and objective function-based measures.

Predictive ability of a semi-mechanistic model for neutropenia in the development of novel anti-cancer agents: two case studies.

In cancer chemotherapy neutropenia is a common dose-limiting toxicity. An ability to predict the neutropenic effects of cytotoxic agents based on proposed trial designs and models conditioned on previous studies would be valuable. The aim of this study was to evaluate the ability of a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for myelosuppression to predict the neutropenia observed in Phase I clinical studies, based on parameter estimates obtained from prior trials.

Semi-mechanistic population pharmacokinetic/pharmacodynamic model for neutropenia following therapy with the Plk-1 inhibitor BI 2536 and its application in clinical development.

Purpose: (1) To describe the neutropenic response of BI 2536 a polo-like kinase 1 inhibitor in patients with cancer using a semi-mechanistic model. (2) To explore by simulations (a) the neutropenic effects for the maximum tolerated dose (MTD) and the dose at which dose-limiting toxicity occurred, (b) the possibility to reduce the cycle duration without increasing neutropenia substantially, and (c) the impact of the initial absolute neutrophil count (ANC) on the degree of neutropenia for different doses.

Experimental Design: BI 2536 was administered as intravenous infusion over 60 min in the dose range from 25 to 250 mg.

Population in vitro-in vivo correlation model for pramipexole slow-release oral formulations.

Purpose: To establish an in vitro-in vivo level A correlation (IVIVC) for pramipexole slow-release formulations.

Methods: The IVIVC was developed based on data from an immediate-release (IR) and three slow-release (SR) formulations of pramipexole; a fourth SR formulation was used for validation purposes. In vitro dissolution profiles were obtained from all SR formulations.

Fatty acid composition of salami from different countries and their nutritional implications.

'Milano-type' salami from 13 European and American countries were analysed to establish their nutritional value in relation to fat and fatty acid composition. The fat content, fatty acid profile, ratio of n-6/n-3 polyunsaturated fatty acids, ratio of hypocholesterolemic/hypercholesterolemic fatty acids (h/H) and the contribution to the daily intake recommended for the population were studied. Differences (P<0.

[Pure aortic stenosis and magnetic resonance in adult patients].

Objective: To evaluate the utility of the cardiovascular magnetic resonance imaging (cMRI) for quantify the aortic area in adult patients with pure aortic stenosis (AS).

Method: Comparative cross-sectional study, blinded, in patients with AS, without another valvular pathology associated. A transthoracic echocardiogram (TTE) and cMRI were performed, in all of them.

Non-compacted cardiomyopathy: clinical-echocardiographic study.

Unlabelled: The aim of the present study was to describe the clinical and echocardiographic findings of ventricular noncompaction in adult patients. Fifty-three patients underwent complete clinical history, electrocardiogram, Holter and transthoracic echocardiogram. Forty patients (75%) were in class I/II of the New York Heart Association, and 13 (25%) in class III/IV.

Myocardial perfusion defects in patients with autoimmune diseases: a prospective study. Analysis of two diagnostic tests.

A significant correlation between autoimmune diseases and premature or accelerated coronary atherosclerosis has been found. The objectives of the study were: (a) to evaluate myocardial perfusion defects in patients with autoimmune diseases by contrast echocardiography and nuclear imaging; and (b) to evaluate the prevalence of alterations in subclinical myocardial perfusion defects in autoimmune diseases. Myocardial perfusion in 37 patients was evaluated by contrast echocardiography at rest and with dobutamine and with nuclear imaging.