Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis.

The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis.Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls.ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group a…

Treatment of infected pancreatic necrosis: Outcome in a 9-year, single-center, consecutive series (2006-2014)

Contractile effects of arginine analogues on human internal thoracic and radial arteries

Abstract Objectives: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. Results: N G -monomethyl L -arginine (10 –6 to 10 –3 mol/L) and N G ,N G -dimethyl L -arginine (10 –6 to 10 –3 mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contracti…

Basal release of nitric oxide in the mesenteric artery in portal hypertension and cirrhosis: Role of dimethylarginine dimethylaminohydrolase

Background and Aim Increased basal release of nitric oxide (NO) in the splanchnic circulation contributes to elevated plasma levels of NO observed in decompensated cirrhosis. We evaluated in rat mesenteric arteries whether the differences in basal release of NO, revealed by asymmetric dimethylarginine (ADMA)- and NG-nitro-L-arginine methyl ester (L-NAME)-induced contractions, were associated with changes in messenger RNA (mRNA) expression of endothelial NO synthase (eNOS) and dimethylarginine dimethylaminohydrolases (DDAHs). Methods Rat small mesenteric arteries from 14 Sham-control, from 14 with partial portal vein ligation (PPVL), and from 14 with bile duct excision (BDE)-induced cirrhosi…

Clinical evaluation of drug-induced hepatitis

Objective: to ascertain the epidemiological characteristics, clinical symptoms, and evolution of drug-induced hepatitis over the last 22 years. Experimental design and subjects: an observational, retrospective study between 1982 and 1993, and prospective study between 1994 and 2003. All patients in our department diagnosed with having drug-induced hepatitis were studied analyzing epidemiological (age, sex, cases per year, hospitalization) and clinical features (previous liver disease, hepatic symptoms, laboratory results), and follow-up (complete recovery or chronicity). Results: a total of 61 patients were diagnosed as having drug-induced hepatitis, 26 men and 35 women (57%), mean age 52.4…

Oxidative and Nitrosative Pattern in Circulating Leukocytes of Very Early/Early Hepatocellular Carcinoma Patients

Background/aim In chronic liver disease, various immune cell subsets exert pro or anti-tumour effects by releasing reactive oxygen and nitrogen species (ROS, RNS). Here, we evaluated the oxidative and nitrosative pattern in peripheral blood leukocyte subpopulations of early hepatocellular carcinoma (HCC) patients compared with HCC-free cirrhotic patients. Materials and methods Venous blood samples from 18 HCC-free cirrhotic patients and 17 early stage HCC patients were collected to determine ROS, RNS and reduced glutathione levels in isolated leukocytes analyzed by flow cytometry. Results Intracellular levels of ROS and glutathione were higher in lymphocytes, monocytes, and neutrophils from…

Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

INTRODUCTION: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. METHODS: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive da…

Relaxant effects of antidepressants on human isolated mesenteric arteries

Aims The therapeutic action of tricyclic agents may be accompanied by unwanted effects on the cardiovascular system. The evidence for the effects on vascular and nonvascular smooth muscle comes from animal studies. Whether these studies can be extrapolated to human vessels remains to be determined. Therefore, the present study was designed to investigate the influence of amitriptyline, nortriptyline and sertraline on the contractile responses of human isolated mesenteric arteries to electrical field stimulation, noradrenaline and potassium chloride. Methods Arterial segments (lumen diameter 0.8–1.2 mm) were obtained from portions of the human omentum during the course of 41 abdominal operat…

Metabolite identification in human liver needle biopsies by high-resolution magic angle spinning1H NMR spectroscopy

High-resolution magic angle spinning (HR-MAS) 1 H NMR spectroscopy of intact human liver needle biopsies has not been previously reported. HR-MAS NMR spectra collected on 17 specimens with tissue amounts between � 0.5 and 12 mg showed very good spectral resolution and signal-to-noise ratios. One-dimensional 1 H spectra revealed many intense signals corresponding to cellular metabolites. In addition, some high molecular weight metabolites, such as glycogen and mobile fatty acids, could be observed in some spectra. Resonance assignments for 22 metabolites were obtained by combining the analysis of three different types of 1D 1 H spectral editing, such as T2 filtering or the nuclear Overhauser…

Ca2+-activated K+ channels mediate relaxation of forearm veins in chronic renal failure

In arteries, agonists such as acetylcholine release an endothelium-derived hyperpolarizing factor (EDHF) that is neither nitric oxide nor prostacyclin.To examine the responses to acetylcholine in segments of forearm veins from patients with chronic renal failure who either had never received dialysis or had undergone long-term dialysis, and to determine the contribution of nitric oxide and EDHF to endothelium-dependent relaxation in veins from patients with chronic renal failure.Isometric tension was recorded in rings of forearm vein from 34 non-dialysed patients, 27 dialysed patients and 14 multiorgan donors (controls).Relaxation in response to acetylcholine was reduced in veins of non-dia…

Association of elevated serum triglyceride levels with a more severe course of acute pancreatitis: Cohort analysis of 1457 patients.

Previous publications have reported an association between hypertriglyceridemia (HTG) and severity of acute pancreatitis, but this relationship remains somewhat controversial.To evaluate the outcome of acute pancreatitis according to serum triglyceride levels on admission.Retrospective analysis of prospectively collected data, which included all consecutive cases of acute pancreatitis admitted to a tertiary hospital (January 2002-December 2014). Acute pancreatitis patients were classified into 3 groups based on serum triglyceride levels (mg/dl) measured within 48 h from admission: normal triglycerides-mild HTG (200); moderate HTG (200-749); severe HTG (≥750). Primary outcomes were the diffe…

Accumulation of Symmetric Dimethylarginine in Hepatorenal Syndrome

In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and l-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 ± 0.25 vs. 0.38 ± 0.06 and 0.29 ± 0.04 μM, respectively; P < 0.05). ADMA and NOx concentrations were…

Effects of asymmetric dimethylarginine on renal arteries in portal hypertension and cirrhosis

AIM. To evaluate the effects of asymmetric dimethylarginine (ADMA) in renal arteries from portal hypertensive and cirrhotic rats. METHODS. Rat renal arteries from Sham (n = 15), pre-hepatic portal hypertension (PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis (BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA (10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide (NO) synthase. Concentration-response curves to acetylcholine (1 × 10-9-3 × 10-6 mol/L) were determined in precontracted renal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein e…

Contractile hyporesponsiveness to norepinephrine of forearm veins in chronic renal failure.

Background We recently reported that endothelium-dependent relaxation is impaired in forearm veins from patients with chronic renal failure. However, assessment of responses to norepinephrine remains controversial. We examined the contractile response to norepinephrine in forearm veins from patients on chronic hemodialysis and the role of nitric oxide (NO), prostanoids, and Ca 2+ -activated K + channels in this response. Methods Isometric contraction curves were obtained in rings of forearm vein from 21 dialyzed patients and 12 multiorgan donors in response to norepinephrine (1 nmol/L to 10 μmol/L) or KCl (5 to 100 mmol/L). Results Veins from uremic patients were markedly less responsive to…

Unchanged plasma levels of dimethylarginines and nitric oxide in chronic hepatitis C.

Previous studies have shown that asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and nitric oxide (NO) play a prominent role in liver dysfunction. The objective of this study was to determine whether plasma levels of ADMA, SDMA and NO are altered in patients with chronic hepatitis C.Plasma levels of ADMA, SDMA and NO (nitrite plus nitrate) were measured in 22 patients with chronic hepatitis C and 24 patients with sustained virologic response after treatment with peginterferon plus ribavirin. Seven healthy volunteers served as controls.Plasma levels of ADMA, SDMA and NO were not significantly different between groups: chronic hepatitis C, ADMA 0.55+/-0.06, SDMA 0.22+/-0…

Endothelium-dependent responses in human isolated thyroid arteries from donors

The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect w…