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E Gelpi

Publications and source records attributed to E Gelpi.

At least 37 records · Page 2Linked to original sources
PubMed1997

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗
PubMed1997

Differential effect of nitric oxide inhibition as a function of preservation period in pancreas transplantation.

The role of nitric oxide, produced during reperfusion as a function of preservation time, in the development of the inflammatory process in pancreas transplantation has been explored. For this purpose, the effect of nitric oxide synthase inhibition, as well as 6-keto-prostaglandin F1alpha, leukotriene B4, and lipoperoxidation levels were evaluated in an experimental model of rat pancreas transplantation after different periods of cold preservation. The results show posttransplantation increases in 6-keto-prostaglandin F1alpha, leukotriene B4, and lipoperoxidation levels in pancreatic tissue and in plasma lipase. When ischemia was induced for 30 min, nitric oxide synthase inhibition prevented these increases, and L-arginine was able to reverse this effect. By contrast, nitric oxide synthase inhibition has no effect when ischemia was prolonged for 12 hr. In summary, this study suggests that, during reperfusion, nitric oxide modulates 6-keto-prostaglandin F1alpha synthesis, lipoperoxidation levels, and the development of pancreatic injury but only when the ischemic period is quite short.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Eicosanoid production, metabolism and contractile activity in the isolated uterus from non-insulin-dependent diabetic rats during late pregnancy.

Eicosanoid production, glucose (Glu), glycogen (Gly) and triglyceride (TG) metabolism, spontaneous contractile activity, PGF2 alpha and oxytocin-induced contractions have been studied in uterine tissue obtained from control (C) and non-insulin-dependent diabetic (D) rats prior to parturition. Parturition occurs on day 22 of gestation in control animals, whereas a 24 hr delay was observed in diabetic rats. Production of PGE2, PGE1, 6-keto-PGF1 alpha, PGF2 alpha, TXB2 and LTB4 was similar in uterine tissue obtained from control and diabetic rats on day 21 of pregnancy. Uterine metabolism, on day 21 of pregnancy, based on the production of 14CO2 from U14C-glucose was lower in tissues obtained from diabetic rats than in controls. Levels of TG were similar at 0 hr and after 60 min incubation in Glu or Glu-free medium in both experimental groups. Initially Gly levels in diabetic and control uteri were similar. After 60 minutes of incubation, levels of Gly in control tissue decreased only in the absence of Glu in the incubation medium. In contrast, in diabetic uterine strips, levels of Gly decreased after 60 minutes of incubation either in Glu or Glu-free medium. "In vitro" isometric-developed tension (IDT) evaluated on day 21 (C and D) and 22 (D) of pregnancy was similar at 0 hr in control and diabetic uterine preparations, but IDT in both diabetic groups was decreased after a 40 minute incubation when compared to controls. Alterations in PGF2 alpha-induced uterine responses were not seen in 21 or 22 days pregnant diabetic uterine tissue when compared to controls. In contrast, impaired oxytocin responses were observed in diabetic uteri on day 21 of gestation, but they were similar to control responses of uterine tissue from day 22 diabetic rats. We conclude that in the non-insulin-dependent late pregnant rat, there are no alterations in uterine tissue eicosanoid production, but metabolic and contractile abnormalities are present. Involvement of these alterations in the delayed initiation of parturition is discussed.

Animals↗
PubMed1996

Calcium channel blockers in experimental acute pancreatitis: effect on tissue prostanoids and oxygen free radicals.

The effect of verapamil administration on the changes of prostanoid synthesis, and on free radical production associated with acute pancreatitis, has been evaluated. A necrohemorrhagic model of pancreatitis was induced in Wistar rats by intraductal administration of sodium taurocholate (3.5%). This model is associated with initial increases in prostanoid synthesis and peroxidative damage. Verapamil, administered before pancreatitis induction, prevented initial increases in 6-keto prostaglandin F1alpha (PGF1alpha) and thromboxane B2 (TXB2) but had no effect on PGF2alpha or PGE2 or on lipoperoxidative damage. These results indicate that verapamil administration prevents the increases in pancreatic vasoactive prostanoids (TXB2 and 6-keto PGF1alpha) without affecting the increased levels of PGE2 and PGF2alpha and has no effect on oxygen free radical production in the initial stages of experimental acute pancreatitis.

Acute Disease↗
PubMed1996

Development and validation of new screening tests for nephrotoxic effects.

Within the framework of an European Commission-funded project, groups of industrial workers exposed to heavy metals (cadmium, mercury and lead) or solvents were studied together with corresponding control groups. Eighty-one measurements were carried out on urine and serum samples and the scientific results together with individual questionnaire information were entered into a central database. Data obtained was assessed centrally and individually in subsidiary studies. The measurable contributions were assessed either singly or in combination, of smoking, gender, metal exposure and site, to nephrotoxicity. The potential value of each test as an indicator of nephrotoxicity was then assessed on the basis of sensitivity and specificity. A number of new tests including prostaglandins and for extracellular matrix components were investigated as well as established tests for renal damage and dysfunction. The data obtained from this comprehensive study emphasises the value of noninvasive biomarkers for the early detection of nephrotoxicity due to environmental toxins. The urinary profile varied with the type of environmental/occupational toxin. By careful selection of a small panel of markers they can be used to indicate the presence of renal damage, the principal region affected, and to monitor the progress of disease and damage. Biomarkers were also used to confirm and tentatively establish safe exposure levels to nephrotoxins.

Biomarkers↗
PubMed1995

Eicosanoid production and phospholipase A2 activity in uterine tissue from castrated rats with non-insulin dependent diabetes mellitus.

In uterine tissue obtained from castrated control and non-insulin dependent diabetic (NIDDM) rats, eicosanoid production and its regulation by glucose levels and by the activity of phospholipase A2 (PLA2) was assessed. Basal outputs of prostaglandins (PGs) PGE2, PGE1, PGF2 alpha, 6-keto-PGF1 alpha (indicating the production of prostacyclin), thromboxane B2 (TXB2) (indicating the generation of TXA2) and leukotriene B4 (LTB4) were similar in control and NIDDM uterine preparations as assessed by RIA. When uterine conversion of labelled arachidonate into different prostanoids was evaluated, generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was similar in control and NIDDM uterine tissue, while TXB2 production was higher in the diabetic group. Moreover, when control tissue was incubated in the presence of elevated concentrations of glucose (22 mM) and compared to control tissue incubated in concentrations of glucose 11 mM, similar generation of 6-keto-PGF1 alpha, PGE2 and PGF2 alpha was observed, and higher concentrations of TXB2 were found, similar to those observed in diabetic uterine tissue. When NIDDM uterine tissue was incubated in the presence of glucose 22 mM, no difference in any prostanoid evaluated was observed when compared to values obtained in the presence of glucose 11 mM. In this work we have observed in NIDDM uterine tissue a normal TXA2 production when evaluated by RIA from endogenous arachidonic acid (AA) and a higher TXA2 generation from exogenous labelled AA. In addition PLA2 activity was found diminished in the NIDDM uteri in comparison to control uteri. A role of the diminished PLA2 as a protective mechanism that avoids TXA2 overproduction in uterine tissue from NIDDM rats is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

The impact of arterialization on prostanoid generation after liver transplantation in the rat.

Arterial reconstruction is not applied in most studies of hepatic transplantation. Differences in some parameters related to the microcirculatory status, depending on whether the graft has been subjected to both arterial and venous or only venous reconstruction have been demonstrated. We have evaluated whether arterialization has an effect on the production of inflammatory event-related mediators such as eicosanoids and oxygen free radicals. For this purpose, we have measured tissue eicosanoid levels, lipid peroxidation, and superoxide dismutase activity in livers subjected to arterial and venous or only venous reconstruction. No changes were observed in lipid peroxidation or superoxide dismutase activity when single and double revascularization were compared. Prostacyclin and thromboxane metabolites showed increased levels after 24-hr preservation when only venous reconstruction was carried out. In contrast, these metabolites remained unaltered when double revascularization was performed. This result suggests that eicosanoid metabolism is altered only when venous reconstruction was employed, and this fact can help explain microcirculatory changes reported in this experimental model of liver transplantation.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Prostanoids and oxygen free radicals in early stages of experimental acute pancreatitis.

The aim of this work is to establish a relationship between prostanoids and oxygen free radicals in the early stages of acute pancreatitis induced by sodium taurocholate and to study the possible cytoprotective effects of exogenous prostaglandin administration. Tissue prostanoid production (6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2) was studied after induction of an acute pancreatitis by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg). The effect of previous administrations of 16,16-dimethyl prostaglandin E2 (0.5 microgram/kg), indomethacin (20 mg/kg), or superoxide dismutase (13 mg/kg) was evaluated. Early pancreatitis induced significant increases of the three prostanoid levels as soon as 5 min after taurocholate administration. The administration of 16,16-dimethyl prostaglandin E2 was able to maintain the tissue prostanoid production at basal levels while superoxide dismutase treatment only partially prevented the increase of 6-keto-prostaglandin F1 alpha. On the other hand, indomethacin pretreatment, as expected, prevented the taurocholate-induced early prostanoid biosynthesis but increased the mortality, suggesting that endogenous prostanoids play a role in cellular defense mechanisms. The effect of superoxide dismutase suggests that oxygen free radicals are responsible, in part, for prostanoid enhanced biosynthesis in the earlier stages of necrohemorrhagic pancreatitis.

16,16-Dimethylprostaglandin E2↗
PubMed1994

Glucose metabolism, triglyceride and glycogen levels, as well as eicosanoid production in isolated uterine strips and in embryos in a rat model of non-insulin-dependent diabetes mellitus during pregnancy.

Spontaneous contractile activity, glucose (Glu), glycogen (GLY), triglyceride (TG) metabolism and eicosanoid production, was evaluated in isolated uterine strips from control and non-insulin-dependent diabetic rats on day 10 of pregnancy. Metabolism of Glu, levels of GLY and TG and eicosanoid production were also studied in day 10 embryos obtained from both experimental groups. "In vitro" isometric developed tension (IDT), was similar at 0 hr in control and diabetic uterine preparations, but IDT was decreased after a 60 min incubation in the diabetic group. The frequency of contractions (FC) was similar at 0 hr and after 60 min incubation in both experimental groups. On the other hand, the production of 14CO2 from U14C-glucose was lower in isolated uteri and embryos obtained from diabetic rats than in controls. Initial TG levels were similar in uteri isolated from control and diabetic rats, and higher in embryos obtained from diabetic mothers than in controls. Levels of TG in uterine strips suspended in Glu or Glu-free medium did not differ at 0 hr or at 60 min either in controls or in diabetic rats. On the contrary GLY levels in uterine strips from diabetic animals were higher than in controls, whereas in embryos from diabetic mothers GLY levels were similar to controls. Levels of GLY in uterine strips from controls and diabetic animals decreased after 60 min incubation only in the absence of Glu in the incubation medium. Production of PGE2, PGE1, 6-keto-PGF1 alpha, PGF2 alpha, TXB2 and LTB4 was studied in uterine strips and embryos obtained from control and diabetic rats. No differences were found between control and diabetic uterine prostanoid production, but lower production of LTB4 was observed in diabetic uteri. However production of PGE2 and PGF2 alpha was greater in embryos obtained from diabetic mothers than in controls. In this study, we observed lower uterine metabolic alterations than in the pancreatectomized diabetic rat model studied previously, but important anomalies in the embryos obtained from non-insulin-dependent diabetic mother were found.

Animals↗
PubMed1994

Effect of a platelet-activating factor antagonist and desferrioxamine administration on eicosanoid production in rat pancreas transplantation.

Eicosanoid metabolism and its relationship with platelet-activating factor and oxygen free radical production in rat pancreas transplantation has been studied herein. Male Sprague-Dawley rats were classified in 4 experimental groups (n = 8 each) as follows: group 1, control; group 2, pancreas transplantation, after 12 hr of organ preservation in University of Wisconsin solution; group 3, same as group 2 with desferrioxamine administration before revascularization of the organ in the recipient rat; and group 4, same as group 3 with administration of a platelet-activating factor antagonist (BN-52021). The results show post-transplantation increases in eicosanoid production in pancreatic tissue. The fact that desferrioxamine and BN-52021 administration could reverse increases in thromboxane B2, leukotriene B4, and 12-hydroxyeicosatetraenoic acid but only BN-52021 affected 6-keto-PGF1 alpha levels suggests the existence of a close relationship between platelet-activating factor and oxygen free radical in eicosanoid production in pancreas transplantation and it points to a differential role of metabolites produced by circulatory cells and endothelial cells.

Animals↗
PubMed1994

Nephron target sites in chronic exposure to lead.

With established urinary markers of kidney integrity the early renal effects of lead have previously been considered to be mainly tubular or tubulointerstitial. In a cross-sectional study on 81 male lead-exposed workers and 45 age-matched controls (median blood lead concentrations 2.03 and 0.34 mumol/l respectively) not only well-established but also new urinary markers of renal integrity preferentially or exclusively located along the different nephron segments were analysed. Markers related to the glomerulus were 6-keto-prostaglandin 1 alpha, thromboxane B2, mainly produced in the glomerulus, and the extracellular matrix protein fibronectin. Markers of the proximal tubule were the brush-border antigens BBA, BB50, and HF5 and the intestinal alkaline phosphatase. Prostaglandin E2 and F2 alpha, preferentially synthesized in the collecting duct and medullary interstitial cells, served as markers of these more distal nephron segments. In contrast to previous studies on the early phase of lead nephrotoxicity, not only tubular but also glomerular involvement could be shown in the study presented here by increases in the median values of 6-keto-prostaglandin 1 alpha and decreases in fibronectin. The proximal tubular markers intestinal alkaline phosphatase and BBA confirmed that this particular segment of the nephron is affected by lead. Effects on the collecting tubule or medullary interstitial cells could also be observed. It is concluded that lead affects both the glomerulus and the tubular apparatus and that combinations of new and established markers could be valuable for a better definition and early detection of lead nephropathy.

Adult↗
PubMed1993

Effect of prostaglandins and superoxide dismutase administration on oxygen free radical production in experimental acute pancreatitis.

Oxygen free radicals and prostaglandins are implicated in the pathophysiology of acute pancreatitis, although their mechanisms of action remain unclear. We have studied the effect of administration of exogenous 16,16-dimethyl prostaglandin E2 and superoxide dismutase on oxygen free radical production in acute pancreatitis. For this purpose, five experimental rat groups were studied: group I, control; group II, sodium taurocholate-induced acute pancreatitis; group III, same as group II but with previous administration of 16,16-dimethyl prostaglandin E2; group IV, same as group II but with previous administration of indomethacin; and group V, same as group II but with previous administration of superoxide dismutase. In sodium taurocholate-treated rats, xanthine dehydrogenase is completely converted to xanthine oxidase within the first 5 min with subsequent oxygen free radical production while in 16,16-dimethyl prostaglandin E2-treated rats this enzyme transformation does not occur. In the superoxide dismutase-treated group xanthine oxidase activation is partially prevented. These data suggest that xanthine oxidase is the main source of oxygen free radicals, which contribute to extending the cellular damage in sodium taurocholate-induced acute pancreatitis.

16,16-Dimethylprostaglandin E2↗
PubMed1993

Changes of systemic prostacyclin and thromboxane A2 in sodium taurocholate- and cerulein-induced acute pancreatitis in rats.

Systemic prostacyclin and thromboxane A2 production in rat experimental acute pancreatitis has been evaluated by measuring the urinary excretion of the 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2, respectively. Acute pancreatitis was induced by intraductal administration of 4.5% sodium taurocholate (0.1 ml/100 mg body weight) and intravenous cerulein perfusion (5 micrograms/kg/hr) for 6 hr, respectively. Urinary excretion of 2,3-dinor 6-keto prostaglandin F1 alpha and 2,3-dinor thromboxane B2 were much more important in sodium taurocholate- than in cerulein-induced acute pancreatitis. These data confirm an altered prostacyclin and thromboxane metabolism occurring in experimental acute pancreatitis. Phospholipase A2 activity and the effect of gabexate mesilate on the arachidonate metabolism were also evaluated.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Cyclooxygenase and lipoxygenase metabolism in sodium taurocholate induced acute hemorrhagic pancreatitis in rats.

Several studies have reported that prostanoids are involved in many of the physiopathological mechanisms underlying acute pancreatitis but their precise role in this disease remains to be established. The objective of this work is to evaluate the variation of local tissue production of prostanoids and lipoxygenase metabolites of arachidonic acid in acute pancreas inflammation induced by intraductal administration of 3.5% sodium taurocholate (0.1 ml/100 mg body weight) in rats. Pancreatic tissue levels of leukotriene B4 (LTB4), 15 hydroxyeicosatetraenoic acid (15-HETE), 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were determined by HPLC-RIA techniques at 5 and 60 minutes after induction of acute pancreatitis (AP). Prostanoids increased significantly at 5 minutes and LTB4 and 15-HETE at 60 minutes. These data confirm that the prostanoid imbalance could be considered as an early specific response of the pancreas to the inflammatory events characteristic of induced AP while the altered levels of the lipoxygenase products (LTB4 and 15-HETE) would be more of a nonspecific organ response associated to the high cellular infiltration rate and necrosis observed in the late phases of acute pancreatitis.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Eicosanoid production by uterine strips and by embryos obtained from diabetic pregnant rats.

Eicosanoid production by uterine strips and by embryos obtained from normal and diabetic rats at day 10 of pregnancy was studied. It was found that the release of 6-keto-PGF1 alpha (representing PGI2 synthesis) and of LTB4 was less in preparations from diabetic animals than in controls. The production of TXB2 (indicating the formation of TXA2) by uterine tissue obtained from diabetic rats was almost double that of controls. The synthesis and release of eicosanoids when tissues were incubated in glucose-containing solution or in glucose-free medium were similar, with the exception of LTB4, which was diminished with uterine strips from diabetic rats. The mean number of embryos in control pregnant rats (12.4 +/- 0.5) and in diabetic mothers (10.1 +/- 1.3) was not significantly different, but in 4 of the 14 diabetic rats studied, all of their embryos were resorbed. Although embryos released large amounts of PGF2 and PGE2, and small amounts of 6-keto-PGF1 alpha, TXB2 and LTB4, the amounts of each eicosanoid in control and diabetic groups were similar. The present results indicate that the diabetic state, which induces alterations in uterine eicosanoid production, do not influence arachidonic metabolism in their corresponding embryos.

Animals↗
PubMed1993

Analysis of polychlorinated dioxins and furans in samples of the toxic oil syndrome.

1 Polychlorinated dioxins (PCDDs) and furans (PCDFs) are known to produce a wide range of toxic effects. 2 PCDDs and PCDFs are typical contaminants of chlorinated phenols, and pentachlorophenol and related compounds have been shown to be widely distributed among selected oil samples taken from the 1981 Spanish toxic oil epidemic. 3 Six control and eight case oil samples were analysed using GC/MS for PCDDs and PCDFs. Only small concentrations, normally below 1 ng g-1, of the higher chlorinated PCDDs and PCDFs were detected. There were no statistical differences between the case and control oils. 4 These levels seem to be too low to elicit toxic effects, although they could be enough to potentiate the toxicity of other xenobiotics present in the oils. However, it is uncertain whether the levels of these compounds measured in 1990 reflect the levels present when the oils were consumed in 1981, or whether or not the levels measured in crude oils are representative of fried oils.

Brassica↗
PubMed1992

Solid-phase extraction of prostanoids using an automatic sample preparation system.

A commercial automated solid-phase extraction system for cyclooxygenase arachidonic acid metabolites in urine samples has been evaluated. Comparison of manual and automatic batch (36 samples) extraction procedures for tritium labelled prostanoids added as tracers to urine samples has shown equivalent results with recoveries greater than 90% for prostaglandins E2, F2alpha and 6-keto prostaglandin F1alpha as well as thromboxane B2. Analyte stability is not affected by the automated procedure, which uses less solvents and has a faster overall processing time than the manual method. The automated system has been applied to the extraction of prostanoids in urine samples from workers exposed to dichloroethane.

Arachidonic Acids↗