. Serial noninvasive assessment of progressive pulmonary hypertension in a rat model. Am J Physiol Heart Circ Physiol 283: H364-H371, 2002; 10.1152/ajpheart.00979.2001.-Current methods used to investigate pulmonary hypertension in rat models of the disease allow for only one to two measurements of pulmonary artery (PA) pressure in the life of a rat. We investigated whether transthoracic echocardiography can be used to assess the progression of pulmonary hypertension in rats at multiple time points. Serial echocardiographic measurements were performed over a 6-wk period on rats injected with monocrotaline (MCT) or placebo. Development of a midsystolic notch in the PA waveform, a decrease in the PA flow acceleration time (PAAT), an increase in right ventricular (RV) free-wall thickness, and the development of tricuspid regurgitation (TR) were observed as pulmonary hypertension developed. Changes in the PA waveform and PAAT began in week 3 of disease development as the PA systolic pressure (PASP) reached 25-30 mmHg according to right heart catheterization. The RV free-wall thickness increased significantly by week 5 (PASPs 40-50 mmHg). Development of quantifiable TR occurred in week 6 or at PASPs Ͼ 65 mmHg. A linear correlation was found between the PAAT and PASP in the range of 30-65 mmHg and between the RV-right atrial pressure gradient (derived from TR velocity) and PASP at pressures Ͼ65 mmHg, which enabled a noninvasive estimate of the PASP over a wide range of pressures based on these parameters. These data indicate that transthoracic echocardiography can be used for monitoring the progress of pulmonary hypertension in a rat model. echocardiography; monocrotaline; pulmonary artery acceleration time IN ANIMAL STUDIES OF PULMONARY hypertension (9), a rat model has often been used in which a single monocrotaline (MCT) injection induces pulmonary hypertension over a period of 3-5 wk. Performing right heart catheterization to measure right ventricular (RV) systolic pressure has been central to establishing the presence and quantifying the severity of pulmonary hypertension. Furthermore, gross and histological evaluation of heart and lung tissue has been performed to gain information as to the severity of disease development (7,8,10). However, these methods are limited by the number of measurements performed in the rat and in the ability to characterize rigorously the time course of pulmonary hypertension. Rat models are increasingly being utilized to evaluate the effectiveness of various therapeutic interventions for pulmonary hypertension. Because transthoracic echocardiography (TTE) is noninvasive and allows for multiple assessments of progressive pulmonary hypertension, it can be a useful complement to traditional methods of evaluating pulmonary hypertension in rats.In humans, TTE is one modality for observing the progression of pulmonary hypertension. Although not the "gold standard" for identifying prognostic determinants in patients with pulmonary hypertension, qualitative parameters such as RV hypertrophy an...

Innovations in information and communication technology infuse all branches of science, including life sciences. Nevertheless, healthcare is historically slow in adopting technological innovation, compared with other industrial sectors. In recent years, new approaches in modelling and simulation have started to provide important insights in biomedicine, opening the way for their potential use in the reduction, refinement and partial substitution of both animal and human experimentation. In light of this evidence, the European Parliament and the United States Congress made similar recommendations to their respective regulators to allow wider use of modelling and simulation within the regulatory process. In the context of in silico medicine, the term 'in silico clinical trials' refers to the development of patient-specific models to form virtual cohorts for testing the safety and/or efficacy of new drugs and of new medical devices. Moreover, it could be envisaged that a virtual set of patients could complement a clinical trial (reducing the number of enrolled patients and improving statistical significance), and/or advise clinical decisions. This article will review the current state of in silico clinical trials and outline directions for a full-scale adoption of patient-specific modelling and simulation in the regulatory evaluation of biomedical products. In particular, we will focus on the development of vaccine therapies, which represents, in our opinion, an ideal target for this innovative approach.

Identifying latently infected individuals is crucial for the elimination of tuberculosis (TB). We evaluated for the first time the performance of a new type of interferon-γ release assay, QuantiFERON-TB Plus (QFT-Plus), which includes an additional antigen tube (TB2), stimulating both CD4 and CD8 T-cells in contacts of TB patients.Contacts were screened for latent TB infection by tuberculin skin test, QFT-Plus and QuantiFERON-TB Gold in Tube (QFT-GIT).In 119 TB contacts, the overall agreement between QFT-Plus and QFT-GIT was high, with a Cohen's κ of 0.8. Discordant results were found in 12 subjects with negative QFT-GIT and positive QFT-Plus results. In analyses of markers of TB exposure and test results, the average time spent with the index case was the strongest risk factor for positivity in each of these tests. The difference in interferon-γ production between the two antigen tubes (TB2-TB1) was used as an estimate of CD8 stimulation provided by the TB2. TB2-TB1 values >0.6 IU·mL were significantly associated with proximity to the index case and European origin.QFT-Plus has a stronger association with surrogate measures of TB exposure than QFT-GIT in adults screened for latent TB infection. Interferon-γ response in the new antigen tube used an indirect estimate of specific CD8 response correlates with increased Mycobacterium tuberculosis exposure, suggesting a possible role in identifying individuals with recent infection.

No abstract