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Biomedical subjects

E Gelpi

Publications and source records attributed to E Gelpi.

At least 19 recordsLinked to original sources
PubMed2001

Determination of aniline derivatives in oils related to the toxic oil syndrome by atmospheric pressure ionization-tandem mass spectrometry.

In 1981, an unknown disease appeared in Spain, the Spanish Toxic Oil Syndrome. Nowadays and despite all efforts, the etiological agent is still unknown. Early studies showed a link between this illness and the consumption of denatured rapeseed oil fraudulently processed and marketed as edible oil. Two families of aniline derivatives present in these oils (fatty acid anilides and acylated phenyl amino propanediol derivatives or PAPs) were found to be good chemical markers of toxic oils. In this work, a new method has been developed to analyze these aniline derivatives in oil samples by HPLC-MS and HPLC-MS/MS with an API source. For their quantification, three different internal standards were used, one for anilides and two for PAPs. Quantification limits were 8 ppm for anilides and 0.2 ppm for PAPs. Anilides and PAPs were found in marker-positive samples at levels up to 50,000 and 330 ppm, respectively. The relative abundance of the different fatty acid anilides and PAPs correlates with the fatty acid composition of the oils. More than 2,600 different samples were analyzed by this method in the most exhaustive screening of suspected toxic oils carried out to date.

Aniline Compounds↗
PubMed2001

International Mass Spectrometry Society (IMSS).

This paper gives a brief description of the recently formalized International Mass Spectrometry Society (IMSS). It is presented here in order to increase awareness of the opportunities for collaboration in mass spectrometry in an international context. It also describes the recent 15th International Mass Spectrometry Conference, held August/September 2000, in Barcelona. Each of the authors is associated with the IMSS. The 15th Conference, which covers all of mass spectrometry on a triennial basis, was chaired by Professor Emilio Gelpi of the Instituto de Investigaciones Biomedicas, Barcelona. The outgoing and founding President of the IMSS is Professor Graham Cooks, Purdue University, and the incoming President is Professor Nico Nibbering, University of Amsterdam. Similar material has been provided to the Editors of other journals that cover mass spectrometry.

International Cooperation↗
PubMed2000

Modification of oxidative stress in response to intestinal preconditioning.

Previous studies have demonstrated that intestinal preconditioning protects the organ from ischemia reperfusion damage. Xanthine oxidase mediating free radical generation contributes to the development of injury associated to ischemia reperfusion. Thus, any process able to modulate the oxygen free radical generation system could attenuate the injury. Also, it is known that nitric oxide is implicated in the preconditioning response. The aim of this work is to determine: (1) the effect of intestinal preconditioning on the xanthine oxidase system, (2) the relevance of this system in the development of injury, and (3) its relationship with nitric oxide. For this purpose, we have determined the activity of the xanthine dehydrogenase/xanthine oxidase system, the levels of its substrate (xanthine), and end-product (uric acid) and oxidant stress status in rat small intestine subjected to ischemic pre-conditioning. The effects of nitric oxide inhibition have also been evaluated. Results show that the percentage of xanthine dehydrogenase to xanthine oxidase conversion, xanthine, uric acid concentration, lipoperoxides, and reduced glutathione were significantly reduced in preconditioned rats irrespectively of nitric oxide inhibition. In summary, this work shows that oxidative stress in intestinal preconditioning is reduced as consequence of the diminished conversion of xanthine dehydrogenase to xanthine oxidase, and also as a consequence of the reduced availability of xanthine.

Animals↗
PubMed2000

P-selectin expression and Kupffer cell activation in rat acute pancreatitis.

This work studied the activation of hepatic macrophages during acute pancreatitis and the involvement of these cells in the lung inflammatory response. Pancreatitis was induced in Wistar rats by intraductal administration of 5% sodium taurocholate. Three hours after pancreatitis induction, the degree of pulmonary inflammation, TNF-alpha levels, and P-selectin expression were evaluated. The generation of TNF-alpha by Kupffer cells was also measured. Pancreatitis increases the serum concentration of TNF-alpha, neutrophil infiltration, and P-selectin expression in pancreas and lung. In addition, Kupffer cells generate increased levels of TNF-alpha. When Kupffer cells were inhibited, the increase in serum TNF-alpha levels and the infiltration of neutrophils in the lung were prevented, but P-selectin expression remained unmodified. We conclude that pulmonary inflammation induced by acute pancreatitis is mediated by Kupffer cell activation and that pancreatitis induces the expression of P-selectin on pulmonary endothelial cells but this effect is not mediated by Kupffer cells.

Acute Disease↗
PubMed2000

Effect of ozone treatment on reactive oxygen species and adenosine production during hepatic ischemia-reperfusion.

This study investigates whether ozone could confer protection from hepatic ischemia reperfusion by modifying the accumulation of adenosine and xanthine during ischemia. A significant increase in both adenosine and xanthine accumulation was observed as a consequence of ATP degradation during hepatic ischemia. Adenosine exerts a protective effect on hepatic ischemia reperfusion injury since the elimination of endogenous adenosine accumulation with adenosine deaminase increased the hepatic injury associated with this process. On the other hand, the high xanthine levels observed after ischemia could exert deleterious effects during reperfusion due to reactive oxygen species generation from xanthine oxidase. The administration of allopurinol, an inhibitor of xanthine oxidase, attenuated the increase in reactive oxygen species and transaminase levels observed after hepatic reperfusion. Ozone treatment in liver maintained adenosine levels similar to those found after ischemia but led to a marked reduction in xanthine accumulation. In order to evaluate the role of both adenosine and xanthine, we tried to modify the protection confered by ozone, by modifying the concentrations of adenosine and xanthine. The metabolization of endogenous adenosine after ischemia abolished the protective effect conferred by ozone. When xanthine was administered previous to ozone treatment, the protection conferred by adenosine disappeared, showing both postischemic reactive oxygen species and transaminase levels similar to those found after hepatic ischemia reperfusion. Ozone would confer protection against the hepatic ischemia reperfusion injury by the accumulation of adenosine that in turns benefits the liver and by blocking the xanthine/xanthine oxidase pathway for reactive oxygen species generation.

Adenosine↗
PubMed1999

Evolution of streptozotocin-pancreatic damage in the rat: modulatory effect of endothelins on the nitridergic and prostanoid pathway.

Many lines of evidence indicate that an increased pancreatic production of nitric oxide (NO) and prostaglandins (PGs) is found in the pancreas of streptozotocin-diabetic rats and that endothelins (ETs) are closely related to the nitridergic and prostanoid pathway in several tissues. In the present study the relationship between NO, ETs, and PGs has been explored in isolated pancreatic tissue from streptozotocin-diabetic rats. Pancreatic ET levels are higher in pancreatic tissues from diabetic (D) rats compared to control (C) animals. The addition of nitric oxide synthase (NOS) inhibitors (1 mM N(G)-nitro-l-arginine methyl ester, 600 microM N(G)-monomethyl-l-arginine) in the incubating medium reduces and NO donors (SIN-1, 300 microM spermine suppress, NONOate 100 microM) increases ET levels in pancreatic slices from C and D animals. PGE(2) (10(-7) M) increases and indomethacin (10(-6) M) decreases ET pancreatic production only in D but not in C tissues when added into the incubating bath. When tissues are incubated in the presence of endothelin 1 (ET-1) (10(-7) M), NOS activity is higher in C pancreas, while the ET-receptor antagonist bosentan (B) decreases NOS levels in D but not in C tissues. When pancreatic arachidonic acid (AA) conversion to prostaglandins was explored, ET-1 increased PGF(2alpha), PGE(2), and TXB(2) levels in C but not in D tissues. B abolishes TXB(2) increment due to the diabetic state, but failed in modulating AA conversion to 6-keto PGF(1alpha), PGF2(alpha) and PGE(2) in D pancreas. Our results show an alteration in AA metabolism, ET production, and NO increment associated with pancreatic damage due to streptozotocin.

Animals↗
PubMed1998

Endothelin mediated nitric oxide effects in ischemia--reperfusion associated with pancreas transplantation.

Formation of nitric oxide (NO) in ischemia-reperfusion (I-R) associated with pancreas transplantation could modulate the inflammatory response. In this sense, previous studies have demonstrated the action of NO on vasoactive substances like prostacyclin or endothelin. The present study was designed to evaluate the contribution of endothelin to the inflammatory events induced by NO in the I-R process associated with pancreas transplantation. For this purpose, pancreatic levels of endothelin, neutrophil infiltration, and prostacyclin were evaluated in an experimental model of pancreas transplantation after inhibition of NO synthesis or after NO inhibition plus addition of endothelin. Results show significant posttransplantation increases in endothelin, neutrophil infiltration, and prostacyclin production. These increases were prevented by NO inhibition. Endothelin administration plus nitric oxide inhibition reversed this effect, resulting in an increase in myeloperoxidase and 6-keto-prostaglandin F1alpha. These results suggest that the proinflammatory effects of NO in I-R associated with pancreas transplantation are mediated by the induction of endothelin generation.

Animals↗
PubMed1998

Adverse effects of chronic low level lead exposure on kidney function--a risk group study in children.

BACKGROUND: Children have been considered a risk group for lead (Pb) toxicity, mainly because of neurophysiological or neuro-cognitive deficits following Pb exposure. Blood Pb levels (b-Pb) of 100 microg/l currently have been defined as the lowest adverse effect level. The aim of this study was to compare, with the help of urinary markers, the kidney function of children with b-Pb just above this threshold with that of unexposed children, to assess from a nephrological point of view whether the current threshold is justified and whether children really are a particularly vulnerable risk group in terms of Pb-induced kidney damage. METHODS: In a cross-sectional study, 112 children, either from unexposed areas (controls, n=50) or Pb-contaminated areas (n=62), the latter partly with a known history of elevated b-Pb, were examined. Twenty nine urinary or serum markers mostly related to the function or integrity of specific nephron segments were determined (e.g. filtered plasma proteins, tubular enzymes, tubular antigens, eicosanoids). RESULTS: b-Pb were 39+/-13 microg/l in controls and 133+/-62 microg/l in exposed children. The main findings were increased excretion rates of prostaglandins and thromboxane B2, epidermal growth factor, beta2-microglobulin and Clara cell protein in the exposed children. A relationship between b-Pb and the prevalence of values above the upper reference limits was observed. CONCLUSIONS: With the help of urinary markers, nephron segment-specific effects of chronic low-level Pb exposure could be detected in children. The pattern of effects on glomerular, proximal and distal tubular and interstitial markers was similar to that previously observed in adults. The changes, however, occur at lower b-Pb levels than in adults. The current threshold appears to be justified also from a nephrological point of view, and children can indeed be considered a special risk group.

Biomarkers↗
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↗