Antifibrotic action of telmisartan in experimental carbon tetrachloride-induced liver fibrosis in Wistar rats.

BACKGROUND AND AIMS: Liver fibrosis is the increasingly accumulation of extracellular matrix (ECM), caused by chronic liver injuries, and represents a difficult clinical challenge in the entire world. Currently, the advanced knowledge of the cellular and molecular mechanisms of liver fibrosis showed that collagen-producing cells, like activated hepatic stellate cells (HSCs), portal fibroblasts and myofibroblasts are activated by fibrogenic cytokines, such as angiotensin II, transforming growth factor-beta 1 (TGF-ß1), and leptin. Because of these, we tested telmisartan, an angiotensin II (AT1) receptor blocker and a peroxisome proliferator-activated receptor-γ (PPARγ) partial agonist, for investigate its antifibrotic action, on experimental model of carbon tetrachloride-induced liver fibrosis. MATERIALS AND METHODS: In this research, we used two groups of Wistar rats, which received intraperitoneal (i.p.) injection of carbon tetrachloride (CCl4) 40% dissolved in olive oil, twice weekly for four consecutive weeks (initial dose of 5 mL÷kg, and other doses 3 mL÷kg). After one week, one group was received by gavage telmisartan (TS) dissolved in saline 0.9%, daily in dose of 8 mg÷kg, for 28 days. One group of Wistar rats was used for control. The antifibrotic action of telmisartan was investigated on the pathological changes of the liver and immunohistochemical analysis for hepatic stellate (Ito) cells (HSCs) reaction using anti-alpha-smooth muscle actin (anti α-SMA) antibody and macrophages cells (Kupffer cells) reaction using anti-CD68 antibody. RESULTS AND CONCLUSIONS: In group treated with telmisartan, hepatic fibrogenesis process was significantly reduced, in comparison with CCl4 group.

Myocardial interstitial fibrosis - histological and immunohistochemical aspects.

BACKGROUND AND AIM: The process of myocardial fibrosis is based on the remodeling of the extracellular matrix (ECM), which leads to increased myocardium stiffness and, in turn, severe alterations of the cardiac function. This phenomenon is consecutive to various types of cardiac disease, primarily infarction, due to inflammatory reactions involving various types of cellular mechanisms. We aimed in this paper to assess both microscopically and immunohistochemically the main aspects of ischemic myocardium found in areas of fibrosis and compare the findings with normal images from unaffected cardiac tissue of the same type. MATERIALS AND METHODS: Our study included infarction fragments of 2/2/2 cm harvested after autopsy from 26 patients who died during 2014 at the Emergency County Hospital of Craiova, Romania, following the diagnostic of ischemic cardiomyopathy. After usual histological preparations, we performed both classical staining with Hematoxylin-Eosin and trichromic Goldner-Szekely, as well as immunohistochemical assessment using anti-alpha-SMA, anti-desmin, anti-CD34 and anti-CD68 antibodies. RESULTS: We have evaluated myocardial fibrosis in all areas of the myocardium and noted that it primarily develops around the arterioles and metarterioles. The area of myocardial fibrosis was more extensive, myocardiocytes being surrounded by collagen fibers. Collagen interstitial fibrosis, gave a "brindle" look to the myocardium. Myocardial fibrosis areas did not reveal myofibroblasts. We found lower numbers of blood vessels with an uneven distribution in areas of myocardial fibrosis. In the areas of normal myocardium, the macrophage numbers were two to three times lower than in areas of fibrosis, also displaying larger volume, with intense reaction to CD68. CONCLUSIONS: Myocardial interstitial fibrosis occurs in outbreaks, mainly perivascular, but it affects larger areas of the myocardium interstitial space. We believe that interstitial fibrosis is a progressive process that can become permanent, thus constituting a promising therapeutic target for a large variety of cardiac conditions.

One year weight loss in the TRAMOMTANA study. A randomized controlled trial.

BACKGROUND: Morbid obesity is a major health problem and bariatric surgery is currently the most effective therapy available to induce weight loss in these patients. This report describes 1-year changes in weight and metabolic parameters, in a trial designed to examine the effects of a nonsurgical approach, Intensive Life style Intervention (ILI) on the therapy of morbid obesity. METHODS: The primary outcome was change in body weight. Patients were randomized to ILI (n = 60) or conventional obesity therapy (COT) (n = 46). The ILI group received behavioural therapy and nutritional/physical activity counselling. The COT group received the standard medical treatment available for these patients. A third group consisted of the patients already included in our bariatric surgery waiting list (n = 37). FINDINGS: We present here 1-year data showing that patients who received ILI with no restrictions in calorie intake had a greater percentage of weight loss than patients receiving COT (-11·58% vs -0·4%; P < 0·001). Importantly, 31·4% of patients included in the ILI group were not morbidly obese after 6 months of intervention. This number increased to 42·8% after 12 months of intervention. INTERPRETATION: ILI was associated with significant weight loss compared with COT in a group of morbidly obese patients. The weight loss effect was already obtained after 6 months of ILI intervention. These results seriously question the efficacy of the COT approach to morbid obesity. Furthermore, they underscore the use of ILI programmes in the hospital setting to effectively treat morbidly obese patients and might help to reduce the number of candidate patients for bariatric surgery.

TRAMOMTANA (Tratamiento Multidisciplinar de la Obesidad Mórbida: Medicamentos, Terapia de comportamiento, Apoyo Nutricional y Actividad física). De la pregunta a la realidad de un ensayo clínico investigador iniciado (II) / TRAMOMTANA (Multidisciplinary treatment of morbid obesity: Medication, behavioral therapy, nutritional support, and physical activity). From question to reality in an investigator-initiated clinical trial (II)

Comunicamos la puesta en marcha de un programa intensivo y multidisciplinar de pérdida de peso en pacientes con obesidad mórbida (OM). Este ensayo clínico se basa en la educación para la salud, el apoyo en el proceso de cambio, los medicamentos y las sesiones de terapia de grupo. Nuestra intención es demostrar que los resultados obtenidos con este programa de pérdida de peso a 2 años son, cuando menos, comparables a los resultados que se obtienen con la cirugía bariátrica en estos pacientes con OM. Es nuestra intención igualmente (..) (AU)

Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system (AU)

[TRAMOMTANA (Multidisciplinary treatment of morbid obesity: medication, behavioral therapy, nutritional support, and physical activity). From question to reality in an investigator-initiated clinical trial (II)]. / TRAMOMTANA (Tratamiento Multidisciplinar de la Obesidad Mórbida: Medicamentos, Terapia de comportamiento, Apoyo Nutricional y Actividad física). De la pregunta a la realidad de un ensayo clínico investigador iniciado (II).

Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system.