Papers by Giulio Mengozzi
Digestive Diseases and Sciences, 2002
The aim of this study was to monitor nitric oxide blood levels at various times intraoperatively ... more The aim of this study was to monitor nitric oxide blood levels at various times intraoperatively and following liver transplantation in humans. Nitric oxide production was assessed directly as circulating nitrosyl-hemoglobin adducts by electron paramagnetic resonance spectroscopy in 22 patients undergoing orthotopic liver transplantation. Two significant peaks in nitrosylhemoglobin levels were detected at 5 and 60 min after reperfusion (5.02 +/- 3.33 arbitrary units and 5.75 +/- 4.19, respectively, vs 3.33 +/- 2.28 under basal state; P < 0.05 for both comparisons). Postoperative nitrosyl-hemoglobin levels remained elevated, up to 5.42 +/- 0.89 arbitrary units (P < 0.05 vs basal values). Neither soluble intercellular adhesion molecule-1 or soluble endothelial-leukocyte adhesion molecule concentrations were altered intraoperatively. Only the former was significantly raised after transplantation. Neutrophil elastase levels showed an early increase and remained high throughout surgery, returning to basal values after transplantation. No correlations were found among studied parameters. These data suggest that nitric oxide may play a role in ischemia-reperfusion phases in human liver transplantation. Mechanisms other than leukocyte-endothelial adhesion and neutrophil activation seem to affect nitric oxide production under these conditions.
Journal of Hepatology, 1998
Clinical Autonomic Research, 1995
Neuropeptide Y, a potent vasoconstrictor peptide with 36 amino acid residues, is co-stored and re... more Neuropeptide Y, a potent vasoconstrictor peptide with 36 amino acid residues, is co-stored and released with catecholamines in sympathetic nerve endings. In this study responses in circulating neuropeptide Y induced by baroreceptor activation during change from the supine to the head-up position was measured in normal subjects and untreated essential hypertensives. Furthermore, the relationships with plasma catecholamines, endothelin-1, renin and serotonin were studied. No significant differences of plasma neuropeptide Y were found between normotensive and hypertensive subjects, before or after postural changes, and there was no correlation with a range of the vasoactive substances studied. Our results suggest that plasma neuropeptide Y does not increase with noradrenaline on sympathetic activation during postural stress both in normals and in hypertensive subjects. In man, measurement of plasma neuropeptide Y during head-up tilt does not provide a useful estimation of sympathetic nervous activity.
International journal of tissue reactions, 1995
The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of var... more The peroxidative breakdown of membrane polyunsaturated fatty acids leads to the production of various carbonylic compounds: among these, 4-hydroxynonenal (HNE) displays many biological properties related to neutrophil functions. It stimulates rat and human polymorphonuclear (PMN) cell migration and has been detected during inflammation. The aim of this study was to elucidate and well characterize the mechanism of action of HNE. We observed that micromolar HNE concentrations that influence migration do not stimulate differently from many other chemoattractants the human PMN chemiluminescence (CL) induced by opsonized zymosan or phorbol 12-myristate 13-acetate (PMA). Higher HNE concentrations inhibit the light emission of stimulated PMN. Addition of 0.5 mM L-arginine (L-arg), the substrate of nitric oxide synthase, into the incubation medium had the effect of modifying human CL. In fact, HNE at 10-6 M, a concentration which is ineffective in absence of L-Arg, at 10-5 M reduces CL emis...
European Urology Supplements, 2006
Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multi... more Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. We analysed the serum levels of pro-matrix metalloproteinase-9 (MMP-9), pro-matrix metalloproteinase-2 (MMP-2) and serum gelatinase activity (sGAct) in patients with prostate carcinoma (PrCa) and benign prostatic hyperplasia (BPH) according to tumour stage and Gleason score to evaluate their clinical diagnostic/prognostic application.
Nephrology Dialysis Transplantation, 2014
Digestive Diseases and Sciences, 2002
The aim of this study was to monitor nitric oxide blood levels at various times intraoperatively ... more The aim of this study was to monitor nitric oxide blood levels at various times intraoperatively and following liver transplantation in humans. Nitric oxide production was assessed directly as circulating nitrosyl-hemoglobin adducts by electron paramagnetic resonance spectroscopy in 22 patients undergoing orthotopic liver transplantation. Two significant peaks in nitrosylhemoglobin levels were detected at 5 and 60 min after reperfusion (5.02 +/- 3.33 arbitrary units and 5.75 +/- 4.19, respectively, vs 3.33 +/- 2.28 under basal state; P < 0.05 for both comparisons). Postoperative nitrosyl-hemoglobin levels remained elevated, up to 5.42 +/- 0.89 arbitrary units (P < 0.05 vs basal values). Neither soluble intercellular adhesion molecule-1 or soluble endothelial-leukocyte adhesion molecule concentrations were altered intraoperatively. Only the former was significantly raised after transplantation. Neutrophil elastase levels showed an early increase and remained high throughout surgery, returning to basal values after transplantation. No correlations were found among studied parameters. These data suggest that nitric oxide may play a role in ischemia-reperfusion phases in human liver transplantation. Mechanisms other than leukocyte-endothelial adhesion and neutrophil activation seem to affect nitric oxide production under these conditions.
Transplantation Proceedings, 2002
Twenty-four adult patients (32 to 65 years old) included: 2 women and 14 men, were from the Trans... more Twenty-four adult patients (32 to 65 years old) included: 2 women and 14 men, were from the Transplantation Unit of "S. Giovanni Battista" Hospital of Torino, Italy; and 3 women and 5 men from
Nephrology Dialysis Transplantation, 2000
The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological... more The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological conditions, are far from being established. The influence of kinins and angiotensin type 2 receptor are largely speculative and based mainly on animal studies. This study was aimed to address these aspects in humans. Eight IgA nephropathy patients with documented clinical and histological indicators of poor prognosis were given 50 mg of losartan, 10 mg of enalapril, and 40 mg of the NO donor isosorbide 5 mononitrate (as a control of NO generation) in randomized order for 7 days each. Treatment periods were separated by washout periods of 7 days each. Laboratory investigations were performed before and after each study period. Seven healthy controls received losartan and enalapril according to the same study design. Glomerular filtration rate remained stable while effective renal plasma flow increased with each treatment (P<0.05). Under losartan and enalapril, filtration fraction fell (P=0.02), plasma renin activity increased (P<0.05) and urinary aldosterone concentration decreased (P=0.02). Angiotensin-converting enzyme activity was reduced to the limit of detection under enalapril (P<0.001). Blood NO, detected as nitrosylhaemoglobin by a recently developed technique of spin-trap electron paramagnetic resonance, increased significantly, as expected, during treatment with isosorbide 5 mononitrate (P=0.01), with enalapril (P<0.05), and also with losartan (P<0.05). Unlike losartan, enalapril significantly reduced albuminuria (P=0.01) in this short-term period. In the seven healthy controls, neither enalapril nor losartan were able to increase blood NO levels significantly. Blood levels of nitrosylhaemoglobin, a surrogate marker of NO, increased under blockade of the renin-angiotensin system in patients with IgA nephropathy, but not in healthy volunteers. This increase could contribute to changes of effective renal plasma flow in renal disease states.
Nephrology Dialysis Transplantation, 2007
Background. Impaired protein anabolism and insulin resistance are characteristic features of main... more Background. Impaired protein anabolism and insulin resistance are characteristic features of maintenance haemodialysis patients. We have used a randomised, matched-paired, double-blind, placebo-controlled experimental design to determine the capability of intravenous L-carnitine supplementation to modify insulin resistance and protein catabolism in non-diabetic patients with end-stage renal disease (ESRD) undergoing chronic haemodialysis treatment. Methods. L-carnitine (20 mg·kg −1 ) (n = 9) or placebo (n = 10) were given intravenously at the end of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism were assessed on interdialytic days by the L[1-13 C]leucine and the [2,2-2 H 2 ]glucose kinetic models in the postabsorptive state and during euglicemic hyperinsulinemic clamp studies at baseline and at the end of the treatment period. Results. L-carnitine supplementation was associated with lower (P < 0.05) rates of leucine oxidation (−11 ± 12%) and appearance from proteolysis (−6 ± 2%) during the clamp studies than after placebo supplementation. The rates of glucose appearance in the postabsorptive state did not change significantly in the patients receiving L-carnitine treatment. Insulin-mediated glucose disappearance was improved by L-carnitine only in those patients (n = 5) (+18 ± 3%, P < 0.05 vs placebo group, n = 5) with greater baseline insulin resistance, selected according to the median value of insulin sensitivity before treatment. Conclusions. L-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia.
Nephrology Dialysis Transplantation, 1997
The objective of this study was to determine Key words: nitric oxide; biocompatibility; dialysis ... more The objective of this study was to determine Key words: nitric oxide; biocompatibility; dialysis membranes; electron paramagnetic resonance intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramag-Introduction netic resonance at 0, 5, 15, 60, 180 and 240 min Vascular endothelial cells [1 ] and several other cell of a 4-h standard bicarbonate dialysis, using the same lines, including phagocytes [2], synthesize and release dose ( 6000 U ) of heparin and different dialysis memnitric oxide (NO). NO counterbalances the vasoconbranes. The study group included 12 patients treated strictor action of endothelin ( ET-1) and inhibits ET-1 with cellulose-derived dialysis membranes (nine with production via a cGMP-dependent pathway [3,4]. cuprophan and three with cellulose triacetate) Evidence of a role for NO in diverse physiologic and and 10 patients treated with synthetic membranes (five pathologic processes is emerging [2 ]. The capability of with polysulfone and five with polymethylmethacrylthis molecule to oxidize critical compounds, i.e. thiols, ate). Control groups included 11 normal subjects haeme groups and iron sulphurs, sustains its involveand six patients with end-stage renal failure who were ment in different biological processes. Besides vasodilreceiving intermittent peritoneal dialysis. Basal blood atation, its functions include inhibition of platelet levels of nitrosylhaemoglobin in haemodialysis patients aggregation and modulation of inflammatory and were significantly higher than normals, but similar immune processes [2,5,6 ]. to peritoneal dialysis patients. A significant increase Plasma concentrations of arginine, the endogenous (P<0.01) in nitrosylhaemoglobin level was detected substrate of NO synthase, have been reported to be at 15 min of haemodialysis irrespective of the memlower [7 ] or higher [8] than normal in uraemia. brane used. A decrease to basal levels at 180 min Moreover, it has been reported that uraemic plasma was observed in all but two cuprophan-treated patients contains an endogenous compound, NG, NG-dimethylwho, in contrast to the others, had a symptomatic arginine, able to inhibit NO synthesis by interfering hypotension at the end of the session and a further with the -arginine/NO pathway [9]. However, expoincrease in blood nitric oxide. Patients undergoing sure of cultured human endothelial cells to uraemic peritoneal dialysis did not show any change in blood plasma results in potent induction of NO formation levels of nitrosylhaemoglobin during the first 180 [8]. Besides an increased availability of substrate, min of the procedure. Thus, a constant increase in which is still a matter of debate [7,8], it has been nitrosylhaemoglobin levels was observed early in proposed that high plasma levels of cytokines, as a haemodialysis, but not in peritoneal dialysis patients. consequence of monocyte activation by dialysis mem-Very preliminary evidence was obtained for a role of brane [10 ], enhance NO formation contributing to nitric oxide in the vascular instability at the end of haemodialysis (HD) hypotension. The involvement of haemodialysis in a few patients who had hypotensive NO production in haemodialysis-induced hypotension episodes.
Journal of Veterinary Pharmacology and Therapeutics, 2001
oxidation of praziquantel and its effects on the P450 system in three-month-old lambs infested by... more oxidation of praziquantel and its effects on the P450 system in three-month-old lambs infested by Fasciola hepatica. J. vet. Pharmacol. Therap. 24, 251±259.
Journal of Pharmaceutical and Biomedical Analysis, 2011
Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase ... more Tepoxalin is a veterinary drug registered for use in the dog as a dual inhibitor (cyclooxygenase -5 lipoxygenase). In the horse, it predominantly triggers a strong cyclooxygenase inhibition; this bias seems to be due to the action of its metabolite(s). Among these, only the RWJ-20142 is well known, while to the best of our knowledge no information is available on the other metabolites produced in vivo. Hence, the identification of its main metabolic pathway is pivotal to better understand its clinical activity.
Journal of Hepatology, 2000
Probiotics decrease intestinal bacterial overgrowth and bacterial translocation (BT) in experimen... more Probiotics decrease intestinal bacterial overgrowth and bacterial translocation (BT) in experimental acute liver failure. Antioxidants could decrease BT by increasing the stability of the intestinal cell
Journal of Hepatology, 2004
Poster Sessions iments were performed in the distal femoral arteries of the same rats to compare ... more Poster Sessions iments were performed in the distal femoral arteries of the same rats to compare CB1-receptor expression in peripheral and splanchnic circulation. PCR-products corresponding to CB1-receptor were more intense in cirrhotic than in control mesenteric arteries. Similarly, CB1-receptor protein was higher in cirrhotic than in control vessels. In contrast, neither CB1-receptor mRNA nor CB1-receptor protein were detected in distal femoral arteries of cirrhotic rats. Finally, immunohistochemistry revealed the presence of CB1-receptor mainly in the adventitia vessels and in a lesser extent in the endothelial monolayer. Moreover, higher CB1-receptor expression was observed in the cirrhotic vessels. These results suggest that the selective effect of anandamide in the splanchnic vascular territory of cirrhotic rats is due to mRNA and protein CB1-receptor overexpression in the perivascular sensory nerves of the mesenteric arteries of these animals.
Journal of Hepatology, 1997
Background/Aims: Peripheral vasodilation represents the main vascular dysfunction associated with... more Background/Aims: Peripheral vasodilation represents the main vascular dysfunction associated with the hyperdynamic circulation of liver cirrhosis. This study was intended to measure directly regional and systemic levels of nitric oxide, a potent vasorelaxing mediator, in order to assess its role in the development of hemodynamic changes of cirrhosis.
Journal of Hepatology, 1998
Journal of Hepatology, 2004
Aim of the study was to verify the role of the HO inhibitor cromomesoporphyrin (CrMP) in the hypo... more Aim of the study was to verify the role of the HO inhibitor cromomesoporphyrin (CrMP) in the hyporesponsiveness to PE of mesenteric artery in rats with CCl4 cirrhosis with and without ascites. Small resistance mesenteric arteries (diameters <350µm) were mounted on micropipettes connected to a pressure servo controller in a video-monitored perfusion system. Dose-response curves to PE (0.01-100µM) were evaluated in basal condition, after inhibition of nitric oxide synthase (NOS) with N-nitro-Larginine methyl ester (L-NAME)(1mM), and then after inhibition of both NOS (with L-NAME) and HO with CrMP (15µM). Curves were compared by ANOVA. Percent decrease in internal arterial diameter and EC50 were calculated. 29 control rats and 17 with cirrhosis (8 with and 9 without ascites) were studied. PE response was lower in non ascitic (EC50 13.3±0.73µM) and ascitic cirrhosis (EC50 18.4±0.86µM) than in controls (EC50 2.24±0.83µM) (p=0.001). L-NAME increased the response to PE in controls (p<0.01) and in non ascitic cirrhosis (p<0.01) (final response was similar in the two groups), but not in ascitic cirrhosis. The addition of CrMP did not further increase arterial response in controls and non ascitic cirrhosis, while it improved the response to PE in ascitic cirrhosis (p=0.04), with final values not different from those of the other two groups. In conclusion, mesenteric hyporesponsiveness to PE worsens with the progression of cirrhosis. HO mediates hyporeactivity to PE in mesenteric vessels of experimental cirrhosis with ascites. NOS plays a role only in the first stage of the disease.
Journal of Hepatology, 2001
Uploads
Papers by Giulio Mengozzi