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Introduction Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and... more
Introduction Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. Patients and methods We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan–Meier analysis was carried out. Results Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59–0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. Conclusion Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.
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We read with interest the recent work of Leithead and coworkers about the use of non-selective β-blockers (NSBBs) in patients in the transplant waiting list. They studied 322 patients, among those 117 had refractory ascites and observed... more
We read with interest the recent work of Leithead and coworkers about the use of non-selective β-blockers (NSBBs) in patients in the transplant waiting list. They studied 322 patients, among those 117 had refractory ascites and observed higher survival rate in those using NSBB, including the ones with refractory ascites (HR mortality=0.35; confidence interval (CI) 95%: 0.14 to 0.86).1 However, the use of NSBB has been a polemic issue since the hypothesis proposed by Krag and coworkers suggesting the existence of a ‘therapeutic window’, according to which NSBB would not be beneficial to patients in early or end-stage cirrhosis with refractory ascites, when it would impair the compensatory cardiac output increase, worsening organ perfusion in decompensated cirrhosis.2 Considering current controversies about the use of propranolol (PPL) in advanced cirrhosis, and its possible deleterious effect on haemodynamic and organ perfusion, we have investigated the endothelial function in patients with …
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Research Interests: Medicine and Bone marrow
The aim of the present study was to evaluate the effects of acute β-alanine supplementation on the rate of perceived exertion, training impulse and heart rate variability during high intensity functional training. Twelve trained men (age:... more
The aim of the present study was to evaluate the effects of acute β-alanine supplementation on the rate of perceived exertion, training impulse and heart rate variability during high intensity functional training. Twelve trained men (age: 22.0 ± 5.0 years old; body mass index: 23.6 ± 4.2 Kg/m2; fat mass: 9.8 ± 2.3; VO2max: 54.0 ± 4.5 mL/kg/min) participated in the present study. At the first visit to the training center, they performed a cardiopulmonary exercise test in the rowing ergometer to determine the maximum oxygen consumption. At the two subsequent visits, participants were randomized as-signed to the following conditions: a) placebo supplementation and b) 6.4g of β-alanine supple-mentation. The training protocol adopted was to execute the maximal number of repetitions of 5 pull-ups, 10 push-ups, and 15 squats per round in 20 minutes. Simultaneously, the following training load parameters were measured and then also compared during the two experimental conditions: session lo...
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Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule... more
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator) and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine by calculating clearance and fractional excretion of solutes. The RNA and protein content of ClC-5, CFTR, megalin and cubilin was determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin and transferri...
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Introduction Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and... more
Introduction Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. Patients and methods We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan–Meier analysis was carried out. Results Fifty-four patients and 18 controls were ...
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Fructose intake is directly related to vascular dysfunction and it is a risk factor for the development of metabolic and cardiovascular diseases, such as obesity, diabetes, and hypertension. Selenium, a component of antioxidant enzymes,... more
Fructose intake is directly related to vascular dysfunction and it is a risk factor for the development of metabolic and cardiovascular diseases, such as obesity, diabetes, and hypertension. Selenium, a component of antioxidant enzymes, improves hyperglycemia and vascular function in diabetic animals. The aim of this study was to evaluate the effects of dietary selenium supplementation on microcirculatory and metabolic parameters of fructose-fed hamsters. Male hamsters (Mesocricetus auratus) had their drinking water substituted or not by 10% fructose solution for 60 days, during which their microcirculatory function was evaluated in the cheek pouch preparation. Blood glucose and serum insulin levels were also tested. Microcirculatory responses to acetylcholine (an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator), and macromolecular permeability increase induced by a 30-min ischemia/reperfusion (I/R) procedure, showed that e...
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Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule... more
Diabetic nephropathy (DN) occurs in around 40% of those with diabetes. Proteinuria is the main characteristic of DN and develops as a result of increased permeability of the glomerulus capillary wall and/or decreased proximal tubule endocytosis. The goal of this work was to evaluate renal function and the expression of megalin, cubilin, CFTR (cystic fibrosis transmembrane conductance regulator), and ClC-5 in the proximal tubule and renal cortex of rats with type 1 diabetes. Male Wistar rats were randomly assigned to control (CTRL) and diabetic (DM) groups for 4 weeks. Renal function was assessed in 24-h urine sample by calculating clearance and fractional excretion of solutes. The RNA and protein contents of ClC-5, CFTR, megalin, and cubilin were determined in the renal proximal tubule and cortex using real-time polymerase chain reaction and western blotting techniques, respectively. The results showed higher creatinine clearance and higher urinary excretion of proteins, albumin, an...
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We read with interest the recent work of Leithead and coworkers about the use of non-selective β-blockers (NSBBs) in patients in the transplant waiting list. They studied 322 patients, among those 117 had refractory ascites and observed... more
We read with interest the recent work of Leithead and coworkers about the use of non-selective β-blockers (NSBBs) in patients in the transplant waiting list. They studied 322 patients, among those 117 had refractory ascites and observed higher survival rate in those using NSBB, including the ones with refractory ascites (HR mortality=0.35; confidence interval (CI) 95%: 0.14 to 0.86).1 However, the use of NSBB has been a polemic issue since the hypothesis proposed by Krag and coworkers suggesting the existence of a ‘therapeutic window’, according to which NSBB would not be beneficial to patients in early or end-stage cirrhosis with refractory ascites, when it would impair the compensatory cardiac output increase, worsening organ perfusion in decompensated cirrhosis.2 Considering current controversies about the use of propranolol (PPL) in advanced cirrhosis, and its possible deleterious effect on haemodynamic and organ perfusion, we have investigated the endothelial function in patients with …
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Research Interests: Endocrinology, Chemistry, Microcirculation, Biometry, Medicine, and 15 moreMultidisciplinary, Insulin Resistance, Internal Medicine, Glucose, Diabetes mellitus, Animals, Male, Heart rate, Cardiovascular system, Myocardium, Heart Ventricles, Incretin, Energy Intake, Incretins, and Mitochondrial swelling
Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction *These authors contributed equally to th...more
Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology Cellular Physiology and Bone Marrow Mononuclear Cells Attenuate Interstitial Fibrosis and Stimulate the Repair of Tubular Epithelial Cells after Unilateral Ureteral Obstruction *These authors contributed equally to th...more
The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic... more
The growing number of patients suffering from chronic renal disease is a challenge for the development of innovative therapies. Benefits of cell therapy in acute renal diseases in animal models have been reported but seldom for chronic lesions. We present evidence for the improvement of renal morphology in a model of tubulointerstitial fibrosis. Wistar rats were submitted to unilateral ureteral obstruction (UUO), treated with bone-marrow mononuclear cells (UUO+BMMC) infused via the cava vein, and killed on day 14. Labeled BMMC were seen in renal tissue after 7 days in the group UUO+BMMC. UUO+BMMC also showed a reduction in ED1 + cells and tubular apoptotic cells together with enhanced tubular proliferation. Myofibroblasts were also reduced after BMMC which is consistent with a decrease in collagen deposition (picro Sirius staining) and RT-PCR data showing lower levels of procollagen-I mRNA. Simultaneously, nestin + cells increased in the interstitium and decreased in the tubules. Do...
Fructose, an everyday component of western diet associated to chronic hyperglycemia and enhanced free radical production, impairs endothelial function and supplementation with antioxidants might improve it. In this study we investigated... more
Fructose, an everyday component of western diet associated to chronic hyperglycemia and enhanced free radical production, impairs endothelial function and supplementation with antioxidants might improve it. In this study we investigated if vitamin E could reverse the microvascular damage elicited by fructose. Male Syrian golden hamsters drank either 10% fructose solution (F) or filtered water (C), combined with three concentrations of vitamin E in their chows [zero, normal (VE) or 5X (5XVE)] during 60 days. Microvascular reactivity in response to topical application of acetylcholine (Ach; endothelium-dependent vasodilator) or sodium nitroprusside (SNP; endothelium-independent vasodilator) and macromolecular permeability increase induced by either 30 min ischemia followed by reperfusion (I/R) or topical application of histamine (5 μM) were assessed using the cheek pouch preparation. Compared to controls (drinking filtered water), fructose-drinking animals showed decreased vasodilatat...
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The time course of lung mechanics, histology, and inflammatory and fibrogenic mediators are analysed after intratracheal instillation (IT) of bone marrow-derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided... more
The time course of lung mechanics, histology, and inflammatory and fibrogenic mediators are analysed after intratracheal instillation (IT) of bone marrow-derived cells (BMDC) in a model of silicosis. C57BL/6 mice were randomly divided into SIL (silica, 20mg IT) and control (CTRL) groups (saline IT). At day 15, mice received saline or BMDC (2 x 10(6)cells) IT. The biodistribution of technetium-99m BMDC was higher in lungs compared with other organs. At days 30 and 60, lung mechanics, the area of granulomatous nodules, and mRNA expression of IL-1beta and TGF-beta were higher in SIL than CTRL animals. BMDC minimized changes in lung mechanics, the area of granulomatous nodules, and total cell infiltration at day 30, but these effects were no longer observed at day 60. Conversely, BMDC avoided the expression of IL-1beta at days 30 and 60 and TGF-beta only at day 30. In conclusion, BMDC therapy improved lung mechanics and histology, but this beneficial effect was not maintained in the course of injury.
Research Interests: Histology, Morphometry, Medicine, Models, Mice, and 15 moreFemale, Animals, Male, Bone marrow, Medical Physiology, Lung, mRna expression levels, Bone Marrow Transplantation, Analysis of Variance, Neurosciences, Bone Marrow Cells, Gene Expression Regulation, Experimental Model, Cardiovascular medicine and haematology, and mRNA expression
Research Interests: Endocrinology, Macrophages, Medicine, Internal Medicine, Kidney, and 15 moreBlood Glucose, Diabetes mellitus, Animals, Male, Medical Physiology, Diabetic Nephropathy, Renal Function, Nephropathy, Rats, Body Weight, Proteinuria, Bone Marrow Cells, Interleukin, Glomerular Filtration Rate, and Diabetic nephropathies
Research Interests: Pathology, Adult Stem Cells, Medicine, Tissue repair, Cell therapy, and 15 moreKidney, Animals, Male, Animal Model, Bone marrow, Fibrosis, Medical Physiology, Bone Marrow Transplantation, Rats, Epithelial cells, Chronic Renal Disease, Renal disease, Adult Stem Cell, Myofibroblast, and mononuclear cell
The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into... more
The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups ( n = 6 each). In the acute lung injur;y (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 μg, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 × 107 cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance ( Est), resistive (Δ P1), and viscoelastic (Δ P2) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelia...