Fibrosis, Enzymatic and Non-Enzymatic Cross-Links in Hypertensive Heart Disease.

Myocardial fibrosis is commonly observed in left ventricular (LV) hypertrophied heart during Arterial Hypertension. This pathological change coupled with vascular stiffening with aging and diabetes may reduce the cardiovascular system elasticity contributing to the functional impairment. Both the LV adaptive response to the increasing blood pressure and the oxidative damage contribute to myocardial fibrosis; in particular, reactive oxygen species (ROS) induce the formation of reactive electrophilic carbonyl species by reacting with lipids and sugars which in turn react with proteins forming irreversible adducts (AGEs, ALEs and EAGLEs) and cross-links.

Episodes of Fall Asleep During Day Time in an Elder Woman with Vascular Dementia: Impact on Cerebral Ischeamic Tolerance and Utility of ECG Holter Monitoring.

Here we report the case of an 86-year-old woman with advanced dementia addressed to our service for routinary ECG Holter Monitoring (EHM) for bradycardia in AV block type I. Several day-time episodes of fall-asleep while sitting had been previously reported by the nurse and generally attributed to the dementia itself, without taking into consideration the hypothesis of an AV block. The EHM reading reported several and often subsequent pauses (561), many of them critical, the longest lasting 15,9 s with no changes in clinical condition of the patient.

Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease.

Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model.

Experimental animal models of myocardial damage in regenerative medicine studies involving adult bone marrow derived stem cells: ethical and methodological implications.

Cardiac performance after myocardial infarction is compromised by ventricular remodeling, which represents a major cause of late infarct-related chronic heart failure and death. In recent years, the scientists' interest has focused on the hypothesis that the administration of bone marrow progenitors, following myocardial infarction, could ameliorate left ventricular remodeling by continuing to differentiate along the haematopoietic lineage. This approach has been developed minding to the consolidated use of transfusions to restore lost or depleted blood components and, therefore, as an enriched dose of various progenitors, generally autologous, injected peripherally or directly in the infarcted area.

Isolation and culture of fibroblasts from endoscopic duodenal biopsies of celiac patients.

Background: Fibroblasts are actually considered pivotal in inflammation and tissue remodelling process and for these reasons they are involved in the pathogenesis of autoimmune disorders such as celiac disease. Investigations to define the role of fibroblasts in celiac diseases are obstructed by the absence of specific models. Our objective is to isolate and culture primary fibroblasts from endoscopic duodenal biopsies of celiac and non-celiac subjects, to analyze their growth patterns and the morphometric characteristics.

Effects of antihypertensive treatment on ultrasound measures of myocardial fibrosis in hypertensive patients with left ventricular hypertrophy: results of a randomized trial comparing the angiotensin receptor antagonist, candesartan and the angiotensin-converting enzyme inhibitor, enalapril.

Objective: To compare the effects of the angiotensin II receptor antagonist candesartan with the angiotensin-converting enzyme inhibitor enalapril on myocardial fibrosis evaluated by echoreflectivity analysis.

Methods: Hypertensive patients (n = 196) with echocardigraphically documented left ventricular hypertrophy were randomized to candesartan 8-16 mg/day (n = 91) or enalapril 10-20 mg/day (n = 105) with possible addition of hydrochlorothiazide (12.5-25 mg/day) for 48 weeks.

Potential advantages of cell administration on the inflammatory response compared to standard ACE inhibitor treatment in experimental myocardial infarction.

Background: Bone Marrow (BM) progenitor cells can target the site of myocardial injury, contributing to tissue repair by neovascolarization and/or by a possible direct paracrine effect on the inflammatory cascade. Angiotensin Converting Enzyme inhibitors (ACE-I) are effective in reducing mortality and preventing left ventricular (LV) function deterioration after myocardial infarction.

Methods: We investigated the short term effects of BM mononuclear cells (BMMNCs) therapy on the pro-inflammatory cytokines (pro-CKs) and on LV remodelling and compared these effects over a standard ACE-I therapy in a rat model of myocardial cryodamage.

Effects of surgery on peripheral N-terminal propeptide of type III procollagen in patients with Crohn's disease.

Aim: This study investigates the effects of surgery on collagen turnover in patients affected by Crohn's disease (CD).

Methods: Fifteen patients affected by active CD, assessed according to the Crohn's disease activity index, and confirmed by histology, with different pharmacological treatments, were enrolled in the study. N-Terminal propeptide of type III collagen was assessed on peripheral blood before and 6 months after surgery, as an index of collagen turnover.

Effects of simulated altitude (normobaric hypoxia) on cardiorespiratory parameters and circulating endothelial precursors in healthy subjects.

Background: Circulating Endothelial Precursors (PB-EPCs) are involved in the maintenance of the endothelial compartment being promptly mobilized after injuries of the vascular endothelium, but the effects of a brief normobaric hypoxia on PB-EPCs in healthy subjects are scarcely studied.

Methods: Clinical and molecular parameters were investigated in healthy subjects (n = 8) in basal conditions (T0) and after 1 h of normobaric hypoxia (T1), with Inspiratory Fraction of Oxygen set at 11.2% simulating 4850 mt of altitude.

Endothelial colony forming capacity is related to C-reactive protein levels in healthy subjects.

The majority of clinical studies on endothelial progenitor cells (EPCs) focuses on the role of these cells in cardiovascular diseases and no systematic studies exist regarding their variations in healthy subjects. In order to define the burden of angiogenesis in physiological conditions we assessed the frequency of peripheral blood endothelial colonies (PB-ECs) and their relation with other factors possibly involved in their function such as high-sensitivity C-reactive protein (hs-CRP), endothelial cell-specific mitogen factor (VEGF) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in a highly selected healthy population. A PB sample was obtained from 37/47 healthy subjects (age 40.

Carotid wall composition in hypertensive patients after 4-year treatment with lacidipine or atenolol: an echoreflectivity study.

Objective: In the European Lacidipine Study on Atherosclerosis (ELSA), against a similar antihypertensive effect, a significantly greater effect of lacidipine was found on carotid intima-media thickness (IMT) progression, indicating a specific anti-atherosclerotic effect of lacidipine. However, not only the extent but also the composition of an atherosclerotic plaque is a determinant of subsequent events.

Design And Methods: Among the 2334 patients enrolled in ELSA, 420 with 4-year treatment were chosen, videodensitometric analysis of their ultrasound carotid scan was performed and the maximum wall lesion (Tmax) was classified as lipidic, fibrolipidic and fibrotic by means of software previously validated against histology.

Elevated serum procollagen type III peptide in splanchnic and peripheral circulation of patients with inflammatory bowel disease submitted to surgery.

Background: In the hypothesis that the increased collagen metabolism in the intestinal wall of patients affected by inflammatory bowel disease (IBD) is reflected in the systemic circulation, we aimed the study to evaluate serum level of procollagen III peptide (PIIIP) in peripheral and splanchnic circulation by a commercial radioimmunoassay of patients with different histories of disease.

Methods: Twenty-seven patients, 17 with Crohn and 10 with ulcerative colitis submitted to surgery were studied. Blood samples were obtained before surgery from a peripheral vein and during surgery from the mesenteric vein draining the affected intestinal segment.

Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial.

Background: In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis.

Methods And Results: We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.

The translocation of marrow MNCs after experimental myocardial cryoinjury is proportional to the infarcted area.

Background: The selective homing of peripherally injected marrow MNCs (MMNCs) has recently been demonstrated in a model of cryodamaged heart. However, the mechanism underlying this phenomenon is still unknown. In the hypothesis that this process is related to the necrotic area extension, the infarcted area was correlated with the number of homed MMNCs in a model of experimental cryodamaged heart.

Left ventricular remodeling after experimental myocardial cryoinjury in rats.

The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats.

Homing of peripherally injected bone marrow cells in rat after experimental myocardial injury.

Background And Objectives: Significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts.

Intravascular Doppler technique for monitoring renal venous blood flow in man.

Background: To measure renal blood flow (RBF) from the renal veins in men using the intravascular Doppler technique (IVD).

Methods: In nine hypertensive male patients (age 46-64 years) undergoing diagnostic renal artery angiography and renal vein catheterization to determine plasma renin activity (PRA), a 3F Doppler catheter was positioned in the renal veins using a 7F guide catheter with a "basket" shaped tip. The radiopaque sectors of the catheter, leaning against the vessel wall, serve to measure the internal diameter of renal veins, and therefore to calculate RBF, by multiplying renal vein cross-sectional area by mean blood flow velocity.

Effects of chronic inflammatory bowel diseases on left ventricular structure and function: a study protocol.

Background: Experimental evidences suggest an increased collagen deposition in inflammatory bowel diseases (IBD). In particular, large amounts of collagen type I, III and V have been described and correlated to the development of intestinal fibrotic lesions. No information has been available until now about the possible increased collagen deposition far from the main target organ.

Assessment of carotid plaque composition in hypertensive patients by ultrasonic tissue characterization: a validation study.

Objective: Ultrasonic tissue characterization of epi-aortic vessels may be useful to define the composition of atherosclerotic plaques. Videodensitometry provides a histogram representing the frequency distribution of gray levels corresponding to different compositions of the carotid wall. However, lack of standardization limits the clinical application of this technique.