Search results for "Preclinical"

AB0458 A PHASE II RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY OF ORAL SELETALISIB IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROM…

2019

Background: Seletalisib is a potent, selective oral inhibitor of phosphoinositide-3 kinase delta (PI3Kδ). Preclinical data have shown that the PI3Kδ pathway is upregulated within salivary glands of patients with PSS and contributes to disease pathogenesis.1 Objectives: To assess the efficacy and safety of seletalisib in patients with PSS. Methods: In this Phase II, double-blind, proof of concept study (NCT02610543), patients with PSS having an EULAR Sjogren’s Syndrome Disease Activity Index (ESSDAI) score ≥5 were randomised 1:1 to seletalisib once daily or placebo (PBO) in addition to current PSS therapy for 12 weeks. The primary endpoint was change from baseline in ESSDAI at Week 12. The s…

Resistance to water and abrasion of a broad-spectrum sunscreen: a prospective, open-label study.

2015

Double Flow Bioreactor for In Vitro Test of Drug Delivery.

2015

In this work, double-structured polymeric scaffolds were produced, and a double flow bioreactor was designed and set up in order to create a novel system to carry out advanced in vitro drug delivery tests. The scaffolds, consisting of a cylindrical porous matrix, are able to host cells, thus mimicking a three-dimensional tumor mass: moreover, a “pseudo-vascular” structure was embedded into the matrix, with the aim of allowing a flow circulation. The structure that emulates a blood vessel is a porous tubular-shaped scaffold prepared by Diffusion Induced Phase Separation (DIPS), with an internal lumen of 2 mm and a wall thickness of 200 micrometers. The as-prepared vessel was incorporated…

In vivo confocal laser endomicroscopy of the human liver: a novel method for assessing liver microarchitecture in real time

2008

Background and study aims Confocal endomicroscopy is a unique novel tool for in vivo histology in humans. Due to limitations imposed by the form of the equipment and by sterilization workflows, its use has been limited to the gastrointestinal tract so far. We have developed a rigid miniaturized probe for confocal endomicroscopy of the human liver during laparoscopy. Patients and methods To assess the feasibility and potential clinical value of this new system (diameter 6.3 mm), 25 patients with liver disease were examined during routine minilaparoscopy under conscious sedation. Results Subsurface serial images (from surface to 250 microm) were generated in real time after fluorescein inject…

COMPARISON OF T-1 ESTIMATION TECHNIQUES IN CARDIAC MRI

1994

International audience; Abstract: We have shown that the use of a simple combination of inversion recovery/spin-echo (IR/SE) sequences provides undeniably superior precision in quantitative in vivo myocardium T-1 estimation than the standard multiple spin-echo approach. On a group of 25 healthy subjects, the T-1 dispersion was, respectively, 3.8% for the IR/SE combination and 19.6% for the best SE pair combination. Moreover, repeated measurements were carried out on seven of the volunteers in order to assess T-1 reproducibility. The mean intra-individual T-1 precision was found to be 2.8% for the IR/SE pair and 20.0% for the best SE pair. The in vivo imaging work was supported and corrobora…

Tidal Volume Estimation during Helmet Noninvasive Ventilation: an Experimental Feasibility Study

2019

AbstractWe performed a bench (BS) and human (HS) study to test the hypothesis that estimation of tidal volume (VT) during noninvasive helmet pressure support ventilation (nHPSV) would be possible using a turbine driven ventilator (TDV) coupled with an intentional leak single-limb vented circuit. During the BS a mannequin was connected to a lung simulator (LS) and at different conditions of respiratory mechanics, positive end expiratory pressure (PEEP) levels and leaks (30, 50 and 80 L/min). All differences were within the 95% limits of agreement (LoA) in all conditions in the Bland-Altman plot. The overall bias (difference between VT measured by TDV and LS) was 35 ml (95% LoA 10 to 57 ml), …

Imaging photoplethysmography for clinical assessment of cutaneous microcirculation at two different depths

2016

The feasibility of bispectral imaging photoplethysmography (iPPG) system for clinical assessment of cutaneous microcirculation at two different depths is proposed. The iPPG system has been developed and evaluated for in vivo conditions during various tests: (1) topical application of vasodilatory liniment on the skin, (2) skin local heating, (3) arterial occlusion, and (4) regional anesthesia. The device has been validated by the measurements of a laser Doppler imager (LDI) as a reference. The hardware comprises four bispectral light sources (530 and 810 nm) for uniform illumination of skin, video camera, and the control unit for triggering of the system. The PPG signals were calculated and…

Screening of pharmacologic adulterant classes in herbal formulations using voltammetry of microparticles.

2013

A solid state electrochemical method for screening different families of adulterant chemicals illegally added to commercial phytotherapuetic formulations is described. The proposed method, based on the voltammetry of microparticles approach, permits a fast and sensitive way to distinguish between anorexics (amfepramone, fenproporex, sibutramine), benzozodiazepinic anxiolytics (clonazepam, flurazepam, alprazolam, midazolam, medazepam, chlordiazepoxide, diazepam), antidepressants (bupropione, fluoxetine, sertraline, paroxetine), diuretics (hydrochlorothiazide, furosemide, chlortalidone, amiloride, spironolactone), and hypoglycemics (glimepiride, chlorpropamide, glibenclamide) based on charact…

Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors.

2021

Simple Summary The clinical efficacy of immunotherapies when treating cold tumors is still low, and different treatment combinations are needed when dealing with this challenging scenario. In this work, a middle-out strategy was followed to develop a model describing the antitumor efficacy of different immune-modulator combinations, including an antigen, a toll-like receptor-3 agonist, and an immune checkpoint inhibitor in mice treated with non-inflamed tumor cells. Our results support that clinical response requires antigen-presenting cell activation and also relies on the amount of CD8 T cells and tumor resistance mechanisms present. This mathematical model is a very useful platform to ev…

Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis

2020

Abstract Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimo…