Time filter

Source Type

Lysy P.A.,Institute Of Recherche Experimentale Et Clinique | Weir G.C.,Harvard Stem Cell Institute | Bonner-Weir S.,Harvard Stem Cell Institute
Current Diabetes Reports | Year: 2013

Cell therapy is currently considered as a potential therapeutic alternative to traditional treatments of diabetes. Islet and whole pancreas transplantations provided the proof-of-concept of glucose homeostasis restoration after replenishment of the deficiency of β cells responsible for the disease. Current limitations of these procedures have led to the search for strategies targeting replication of pre-existing β cells or transdifferentiation of progenitors and adult cells. These investigations revealed an unexpected plasticity towards β cells of adult cells residing in pancreatic epithelium (eg, acinar, duct, and α cells). Here we discuss recent developments in β-cell replication and β-cell transdifferentiation of adult epithelial pancreatic cells, with an emphasis on techniques with a potential for clinical translation. © 2013 Springer Science+Business Media New York. Source

Fadl Elmula F.E.M.,University of Oslo | Jin Y.,Catholic University of Leuven | Yang W.-Y.,Catholic University of Leuven | Thijs L.,Catholic University of Leuven | And 21 more authors.
Blood Pressure | Year: 2015

Objective. The blood pressure (BP)-lowering effect of renal sympathetic nervous denervation (RDN) in resistant hypertension (rHT) shows large variation among studies. Methods. We meta-analyzed summary statistics of randomized clinical trials on RDN in rHT. For continuous outcomes, we assessed heterogeneity by Cochran's Q test and used random-effect models weighted for the inverse of the variance. We assessed safety by assessing the risk of major adverse events from stratified contingency tables. Results. Of 5652 patients screened in seven trials, 985 (17.4%) qualified and were randomized to control (n = 397) or RDN with SYMPLICITY™ catheters (n = 588). Follow-up was 6 months. In both control and RDN patients, antihypertensive treatment was continued or optimized. At enrolment, age averaged 58.1 years, systolic/diastolic office and 24 h BP 168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular filtration rate (eGFR) 79.3 ml/min/1.73 m2. For BP outcomes, there was heterogeneity among trials. Pooled effects (control minus RDN) were -4.9/-3.5 mmHg (95% confidence interval, -20.9 to 11.1/-8.9 to 1.9) for office BP, -2.8/-1.5 mmHg (-6.5 to 0.8/-3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m2 (-1.69 to 3.30) for eGFR. Removing one trial at a time produced confirmatory results. Adverse events occurred in 7.4% and 9.9% of control and RDN patients, respectively (p = 0.24). Conclusion. In selected rHT patients maintained on antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly decrease BP but is safe. Future trials with next-generation catheters should aim at identifying responders in patients with evidence of sympathetic nervous overactivity. © 2015 © 2015 Informa UK Ltd. Source

Baert C.,AMETIF | Novack L.,SIST VO | Lison D.,Institute Of Recherche Experimentale Et Clinique
Archives des Maladies Professionnelles et de l'Environnement | Year: 2013

Summary Nanotechnology is a fast-growing innovative sector presenting new risks for workers, and it is necessary to evaluate these. We are faced with questions regarding skin protection against nanomaterials (NM), including the following: do NM penetrate the skin? Are they absorbed through the skin? Do they cause toxic effects? In order to address these questions, we have first conducted a review of the literature. Titanium dioxide and zinc oxide nanoparticles (NP) have been largely investigated because of their uses in cosmetics. Several in vitro studies show that skin is a relatively effective barrier against these NP, but that they can locally cause an increase in markers of inflammation and oxidative stress, both responsible for cytotoxicity. The results of in vivo studies are more divergent and methodologies differ to the extent that comparisons and, hence, an overall assessment, are difficult. Moreover, even if these experimental studies are relatively reassuring, it should be realised that they have been carried out to evaluate consumer exposure and might not contribute significantly to protect workers. Given these difficulties, it appears prudent to limit exposure and, in the absence of official recommendations, the work carried out by the Institut de Recherche en Santé et Sécurité au Travail (IRSST) and the Commissariat à l'Énergie Atomique (CEA) on the Nanosafe project is very useful to develop practical measures of prevention, complementary to the recommendations issued by the Institut National de Recherche et de Sécurité (INRS), and applicable to occupational health practice. Thus, according to the exposure scenario, it can be recommended to wear TYVEK®-type disposable coveralls with hood, adjustable neck, wrists and ankles, without cuffs or folds, with pocket flaps, and to wear two pairs of gloves for handling NP powder, or butyl or neoprene for handling nanoparticles in colloidal solution. © 2013 Publí par Elsevier Masson SAS. Source

Mesia K.,University of Kinshasa | Tona L.,University of Kinshasa | Mampunza M.M.,University of Kinshasa | Ntamabyaliro N.,University of Kinshasa | And 8 more authors.
Planta Medica | Year: 2012

According to the promising results of the Phase I and Phase IIA clinical trials with the herbal medicinal product PR 259 CT1 consisting of an 80 % ethanolic extract of the stem bark of Nauclea pobeguinii containing 5.6 % strictosamide, a Phase IIB study was conducted as a single blind prospective trial in 65 patients with proven Plasmodium falciparum malaria to evaluate the effectiveness and safety of this herbal drug. The study was carried out simultaneously using an artesunate-amodiaquine combination (Coarsucam®) as a positive control. This combination is the standard first-line treatment for uncomplicated malaria recommended by the National Programme of Malaria Control in the Democratic Republic of Congo (DR Congo). With regard to PR 259 CT1, patients were treated with a drug regimen of two 500-mg capsules three times daily for three days in the inpatient clinic, followed by out-patient treatment of one 500-mg capsule three times daily during the next four days; the positive control group received two tablets containing 100 mg artesunate and 270 mg amodiaquine (fixed-dose) once daily during three consecutive days. Antimalarial responses were evaluated according to the WHO 2003 guideline for a 14-day test. The results from the physical and laboratory examinations did not show any significant changes in values of vital signs, ECG, biochemical, and haematological parameters. The study showed a significant decreased parasitaemia in patients treated with PR 29 CT1 and artesunate-amodiaquine with adequate clinical parasitological responses (APCR) at day 14 of 87.9 and 96.9 %, respectively. The former product was better tolerated than the latter since more side effects were observed for the artesunate-amodiaquine combination. These results indicated that PR 259 CT1 can be considered as a promising candidate for the development of a herbal medicine for the treatment of uncomplicated falciparum malaria. © Georg Thieme Verlag KG Stuttgart · New York. Source

Marique L.,Institute Of Recherche Experimentale Et Clinique | Van Regemorter V.,Institute Of Recherche Experimentale Et Clinique | Gerard A.-C.,Institute Of Recherche Experimentale Et Clinique | Craps J.,Institute Of Recherche Experimentale Et Clinique | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. Objectives: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. Results: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T 4 was not detected in the colloid but in the cytoplasm as well asDUOXand TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1α/interferon decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. Conclusion: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis. © 2014 by the Endocrine Society. Source

Discover hidden collaborations