S100A4 expression is increased in stricture fibroblasts from patients with fibrostenosing Crohn's disease and promotes intestinal fibroblast migration.

Fibroblasts represent the key cell type in fibrostenosing Crohn's disease (FCD) pathogenesis. S100A4 is an EF-hand calcium-binding protein family member, implicated in epithelial-mesenchymal transition and as a marker of activated T lymphocytes and fibroblasts in chronic tissue remodeling. The aim of this study was to examine the expression profile of S100A4 in the resected ileum of patients with FCD.

Insulin sensitivity and body composition in cirrhosis: changes after TIPS.

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production.

Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study.

The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk.

Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure.

The incretin hormone glucagon-like peptide-1 (GLP-1) and its analogs are currently emerging as antidiabetic medications. GLP-1 improves left ventricular ejection fraction (LVEF) in dogs with heart failure (HF) and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-h GLP-1 infusions in patients with congestive HF.

Impact of elevation of total bilirubin level and etiology of the liver disease on serum N-glycosylation patterns in mice and humans.

The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose cirrhotic patients, respectively. These tests are based on the altered N-glycosylation of total serum protein. Our aim was to investigate the impact of etiology on the alteration of N-glycosylation and whether other characteristics of liver patients could have an influence on N-glycosylation.

Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein synthesis and hypoxia-inducible factor-1-mediated gene expression.

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia.

Nasal nitric oxide and regulation of human pulmonary blood flow in the upright position.

There are a number of evidences suggesting that lung perfusion distribution is under active regulation and determined by several factors in addition to gravity. In this work, we hypothesised that autoinhalation of nitric oxide (NO), produced in the human nasal airways, may be one important factor regulating human lung perfusion distribution in the upright position. In 15 healthy volunteers, we used single-photon emission computed tomography technique and two tracers (99mTc and 113mIn) labeled with human macroaggregated albumin to assess pulmonary blood flow distribution.

Edelman's equation is valid in acute hyponatremia in a porcine model: plasma sodium concentration is determined by external balances of water and cations.

Acute hyponatremia is a serious condition, which poses major challenges. Of particular importance is what determines plasma sodium concentration ([Na(+)]). Edelman introduced an explicit model to describe plasma [Na(+)] in a population as [Na(+)] = alpha.

Causes of fatigue in slow-twitch rat skeletal muscle during dynamic activity.

Skeletal muscle fatigue is most often studied in vitro at room temperature and is classically defined as a decline in maximum force production or power output, exclusively linked to repeated isometric contractions. However, most muscles shorten during normal use, and we propose that both the functional correlate of fatigue, as well as the fatigue mechanism, will be different during dynamic contractions compared with static contractions. Under isoflurane anesthesia, fatigue was induced in rat soleus muscles in situ by isotonic shortening contractions at 37 degrees C.

Temporary fatigue and altered extracellular matrix in skeletal muscle during progression of heart failure in rats.

Patients with congestive heart failure (CHF) experience increased skeletal muscle fatigue. The mechanism underlying this phenomenon is unknown, but a deranged extracellular matrix (ECM) might be a contributing factor. Hence, we examined ECM components and regulators in a rat postinfarction model of CHF.

Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients.

Background: The co-morbidity of cystic fibrosis (CF) and celiac disease (CD) has been reported sporadically since the 1960s. To our knowledge, this is the first time a systematic screening is performed in a large cohort of CF patients.

Methods: Transglutaminase-IgA (TGA), endomysium-IgA (EMA) and total IgA in serum were measured in 790 CF patients (48% females, 86% with pancreatic insufficiency).

The effect of posture-induced changes in peripheral nitric oxide uptake on exhaled nitric oxide.

Airway and alveolar NO contributions to exhaled NO are being extracted from exhaled NO measurements performed at different flow rates. To test the robustness of this method and the validity of the underlying model, we deliberately induced a change in NO uptake in the peripheral lung compartment by changing body posture between supine and prone. In 10 normal subjects, we measured exhaled NO at target flows ranging from 50 to 350 ml/s in supine and prone postures.

Slowing of cardiomyocyte Ca2+ release and contraction during heart failure progression in postinfarction mice.

Deterioration of cardiac contractility during congestive heart failure (CHF) is believed to involve decreased function of individual cardiomyocytes and may include reductions in contraction magnitude and/or kinetics. We examined the progression of in vivo and in vitro alterations in contractile function in CHF mice and investigated underlying alterations in Ca(2+) homeostasis. Following induction of myocardial infarction (MI), mice with CHF were examined at early (1 wk post-MI) and chronic (10 wk post-MI) stages of disease development.

Food deprivation promotes oxidative imbalance in rat brain.

The present study was aimed to evaluate the effect of food deprivation in brain oxidative status of Wistar and Goto-Kakizaki (GK) rats. For this purpose, we evaluated several oxidative stress parameters: lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) and protein oxidation markers, hydrogen peroxide (H(2)O(2)) levels, nonenzymatic (reduced [GSH] and oxidized glutathione [GSSG] and vitamin E) and enzymatic (glutathione peroxidase [GPx], glutathione reductase [GRed], and manganese superoxide dismutase [MnSOD]) antioxidant defenses. Four-mo-old Wistar and GK rats were divided into 2 groups.

Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters.

Organic anion transporting polypeptides (humans OATPs, rodents Oatps) are expressed in most mammalian tissues and mediate cellular uptake of a wide variety of amphipathic organic compounds such as bile salts, steroid conjugates, oligopeptides, and a large list of drugs, probably by acting as anion exchangers. In the present study we aimed to investigate the role of the extracellular pH on the transport activity of nine human and four rat OATPs/Oatps. Furthermore, we aimed to test the concept that OATP/Oatp transport activity is accompanied by extrusion of bicarbonate.

Tumor necrosis factor-alpha upregulates 11beta-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-beta in HepG2 cells.

The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion of inactive to active glucocorticoids. 11beta-HSD1 plays a crucial role in the pathogenesis of obesity and controls glucocorticoid actions in inflammation. Several studies have demonstrated that TNF-alpha increases 11beta-HSD1 mRNA and activity in various cell models.

Intracerebroventricular infusion of neuropeptide Y modulates VIP secretion in the fasting conscious dog.

Intracerebroventricular (icv) injection of neuropeptide Y (NPY), which is a widely-distributed neurotransmitter, into the paraventricular nuclear area has been shown previously to increase secretion of insulin and glucagon from the pancreatic islets. Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid peptide that is associated with the mobilisation of energy during situations of energy depletion, such as fasting and exercise. VIP has also been reported to alter insulin and glucagon levels in a glucose-dependent manner.

Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation.

Insulin resistance associated with Type 2 diabetes contributes to impaired vasorelaxation. Previously, we showed the phosphorylation of myosin-bound phosphatase substrate MYPT1, a marker of the vascular smooth muscle cell (VSMC) contraction, was negatively regulated by Akt (protein kinase B) phosphorylation in response to insulin stimulation. In this study we examined the role of Akt phosphorylation on impaired insulin-induced vasodilation in the Goto-Kakizaki (GK) rat model of Type 2 diabetes.

Impact of body composition on very-low-density lipoprotein-triglycerides kinetics.

Upper body obese (UBO) subjects have greater cardiovascular disease risk than lower body obese (LBO) or lean subjects. Obesity is also associated with hypertriglyceridemia that may involve greater production and impaired removal of very-low-density lipoprotein (VLDL)-triglycerides (TG). In these studies, we assessed the impact of body composition on basal VLDL-TG production, VLDL-TG oxidation, and VLDL-TG storage.

Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction.

Release of bilateral ureteral obstruction (BUO) is associated with nephrogenic diabetes insipidus (NDI) and a reduced abundance of the vasopressin-regulated aquaporins. To evaluate the role of the vasopressin type 2 receptor (V2R), we determined V2R abundance in kidneys from rats subjected to 24-h BUO or 24-h unilateral ureteral obstruction (UUO) followed by 48-h release. Because angiotensin II type 1 (AT1) receptor blockade attenuates postobstructive polyuria and aquaporin-2 (AQP2) downregulation, we examined the effect of AT1 receptor blockade on AQP2 phosphorylated at serine 256 (pS256-AQP2) and V2 receptor complex abundance in kidney inner medulla (IM).

Increased renal adrenomedullin expression in rats with ureteral obstruction.

Ureteral obstruction is characterized by decreased renal blood flow that is associated with hypoxia within the kidney. Adrenomedullin (AM) is a peptide hormone with tissue-protective capacity that is stimulated through hypoxia. We tested the hypothesis that ureteral obstruction stimulates expression of AM and hypoxia-inducible factor-1 (HIF-1alpha) in kidneys.

Probiotics enhance pancreatic glutathione biosynthesis and reduce oxidative stress in experimental acute pancreatitis.

Factors determining severity of acute pancreatitis (AP) are poorly understood. Oxidative stress causes acinar cell injury and contributes to the severity, whereas prophylactic probiotics ameliorate experimental pancreatitis. Our objective was to study how probiotics affect oxidative stress, inflammation, and acinar cell injury during the early phase of AP.

Regulatory mechanisms underlying agmatine homeostasis in humans.

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged.

Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells.

PC12 cells were used to examine the in vitro antioxidative and anti-inflammatory effects of oleanolic acid (OA) and ursolic acid (UA). PC12 cells were pretreated with OA or UA at 20 and 40 microM and followed by exposure of hydrogen peroxide (H(2)O(2)) or 1-methyl-4-phenylpyridinium ion (MPP(+)) to induce cell injury. Results showed that H(2)O(2)- or MPP(+)-treatment significantly decreased cell viability and increased lactate dehydrogenase (LDH) release (P < 0.