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Biomedical subjects

E Gelpi

Publications and source records attributed to E Gelpi.

At least 55 records · Page 3Linked to original sources

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗

Oxidative metabolism of N-phenyllinoleamide by human nasal polyps.

N-phenyllinoleamide (NPLA), the anilide of linoleic acid, has been associated with the epidemiology of Toxic Oil Syndrome, but no data are available on its metabolism. On account of the similarity in chemical structure between the linoleic acid and NPLA, the aim of this study has been to investigate the oxidative metabolism of this xenobiotic by the human nasal polyp, a tissue with elevated 15-lipoxygenase activity. For this purpose, tissue homogenates have been incubated for 2 h with NPLA (0.1 mM) spiked with either N-(ring G-3H)PLA (0.2 microCi/ml) or N-P(1-14C)LA (0.05 microCi/ml). Gas chromatographic/mass spectrometric analysis of the high performance liquid radiochromatographic fractions shows that the 9,12,13-trihydroxy, 12,13-epoxy-11-hydroxy and 13-hydroxy NPLA derivatives are the major metabolites. These results revealed that NPLA metabolites are chemical structures related to the linoleic acid derivatives, some of which may show biological activity.

Anilides↗

Pancreas prostanoid production in ischemia and reperfusion.

This study was carried out to investigate the proportion of the 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TXB2) alteration that is due to ischemia in pancreas transplantation against the proportion due to reperfusion. For this purpose, Lewis rats were divided in three experimental groups: Group I = Control, Group II = Donor pancreas subjected to 15 minutes of cold ischemia, Group III = Same as group II but pancreas were transplanted to the recipient individual and then subjected to reperfusion. The results indicate that increases in pancreas 6-keto PGF1 alpha occur as a consequence of cold ischemia while TXB2 remains unchanged. When blood flow was restored, 6-keto PGF1 alpha remained unchanged compared to the ischemic group while pancreatic levels of TXB2 were significantly increased. These results suggest a different induction of prostanoid metabolism during ischemia and reperfusion in pancreatic tissue.

6-Ketoprostaglandin F1 alpha↗

Systemic prostacyclin in cirrhotic patients. Relationship with portal hypertension and changes after intestinal decontamination.

The total body production of prostacyclin was shown to be increased in cirrhotic patients, suggesting that its synthesis by blood vessels of the systemic circulation is enhanced. However, the mechanism by which the synthesis of systemic prostacyclin is stimulated is not known. The present study investigated the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha, an index of total body prostacyclin synthesis, first, in cirrhotics with portal hypertension (n = 19) as compared with cirrhotics with reduced portal pressure after portacaval shunt surgery (n = 18) and with control noncirrhotic subjects (n = 11), and; second, in cirrhotics before and after intestinal decontamination by oral nonabsorbable antibiotics (n = 9 antibiotic treated patients, n = 10 control nontreated cirrhotics). Control noncirrhotic subjects showed lower urinary excretion of 2,3-dinor-6-keto-PGF1 alpha than both groups of cirrhotics (P less than 0.001). Interestingly, urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was significantly higher in cirrhotics with portacaval shunt than in those with portal hypertension (P less than 0.01). The urinary excretion of 2,3-dinor-6-keto-PGF1 alpha decreased significantly after intestinal decontamination in the antibiotic-treated group (580.1 +/- 232.4 vs. 431.2 +/- 219.2 pg/mg creatinine; P less than 0.05) but not in nontreated patients (543.9 +/- 214.4 vs. 581.2 +/- 281.4 pg/mg creatinine; P = NS). These data suggest that the increased urinary excretion of 2,3-dinor-6-keto-PGF1 alpha observed in cirrhotics is not directly related to portal hypertension itself but to portal blood factors that bypass the liver. Some such factors may be of intestinal bacterial origin.

6-Ketoprostaglandin F1 alpha↗

In vivo release of 15-HETE and other arachidonic acid metabolites in nasal secretions during early allergic reactions.

The purpose of this study is to examine the "in vivo" release of 15-HETE and other arachidonic acid metabolites in nasal secretions following a challenge with "Dermatophagoides Pteronyssinus" in patients with allergic rhinitis and non-allergic controls. In addition, we examine the effects of a membrane stabilizer, such as sodium cromoglycate, on these metabolites. Thirteen allergic subjects and seven healthy controls are studied. 15-HETE, peptide leukotrienes, LTB4, PGD2, PGE2 and PGF2 alpha levels are evaluated before and after nasal challenge in sodium cromoglycate treated and untreated subjects. This study provides "in vivo" evidence that the pathophysiological responses to nasal antigen challenge could be related to the release of 15-HETE as well as other arachidonic acid metabolites, mainly arising from the lipoxygenase pathway.

Adolescent↗

Altered levels of tissue and urinary prostacyclin in rats subjected to pancreas transplantation.

Significant increases of TXB2 and PGE2 are reported to occur in pancreas transplantation. These increases are prevented with scavengers of oxygen-free radicals. In this communication, we report on changes of prostacyclin metabolites such as tissue 6-keto prostaglandin F1 alpha and urinary 2,3-dinor 6-keto prostaglandin F1 alpha in rats subjected to pancreas transplantation after different periods of organ cold preservation ischemia as well as the effect of superoxide dismutase (SOD) on these changes. For this purpose, male Lewis rats were classified as follows: Group I, Control; Group II, syngenic pancreas transplantation after 15 min of organ preservation in Collins solution at 4 degrees C; Group III, same as II but with 12 hours of organ preservation; Group IV, same as III, but with SOD pretreatment. Results have shown significant posttransplantation increases of both tissue 6-keto PGF1 alpha and urinary 2, 3 dinor 6-keto PGF1 alpha, the latter being a useful marker to evaluate systemic prostacyclin (PGI2) production by rat pancreas. This effect was prevented when the organ had been exposed to SOD during the period of cold preservation ischemia. These results confirm the implication of oxygen-free radicals (OFR) in the ischemia-reperfusion process associated to rat pancreas transplantation leading to enhanced arachidonic acid metabolism.

6-Ketoprostaglandin F1 alpha↗

Increased synthesis and production of prostaglandin E2 by monocytes from drug addicts with AIDS.

We analysed the production of prostaglandin E2 (PGE2) by monocytes in 11 drug addicts with AIDS and opportunistic infections and in 13 controls. In three patients and six controls we isolated the PGE2 fraction from culture supernatants of purified monocytes (greater than 95%) incubated in medium containing (3H) arachidonic acid, using silicic acid columns. In two of three patients PGE2-fraction values (21.9 and 21.6 pmol/g protein) were significantly higher than controls (10 +/- 4). In eight AIDS patients and seven controls, PGE2 levels were determined by high-performance liquid chromatography and radioimmunoassay (HPLC and RIA). In three out of eight patients PGE2 levels were markedly higher (736, 419 and 208 pg/ml) than the mean + 2 s.d. values from controls (73 +/- 51). We tested the effect of PGE2 on the production of interleukin-2 by normal phytohemagglutinin-stimulated peripheral blood lymphocytes (PBL). There was a significant suppression of interleukin-2 production by PGE2 released from AIDS monocytes. PGE2 may be one of the factors involved in the severe immune dysfunction associated with AIDS.

Acquired Immunodeficiency Syndrome↗

Time course of changes in serotonin and noradrenaline in rat brain after predictable or unpredictable shock.

The effects of predictable and unpredictable shock on concentrations of serotonin (5-hydroxytryptamine, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan (TP) and noradrenaline (NA) have been studied in 7 regions of rat brain. Two separate experiments have been carried out determining these substances both at 30 min and 2 h after the stress session. Unpredictable shock depleted NA levels in all brain regions except the striatum. However, at 2 h poststress NA in these regions increased significantly in comparison with both controls and predictably shocked rats. Predictable shock also decreased NA in locus coeruleus, brainstem and hypothalamus, which was not observed 2 h later. Both predictable and unpredictable shock decreased 5-HT in brainstem and hypothalamus. At 2 h poststress, 5-HT levels in these regions were still decreased in predictably shocked rats, but had attained control values in unpredictably shocked rats. 5-HT metabolism expressed as the 5-HIAA/5-HT ratio, was significantly increased 30 min after predictable shock in all regions except the locus coeruleus and hippocampus. Unpredictable shock produced a much more marked increase in 5-HIAA/5-HT ratio. At 2 h poststress 5-HT metabolism returned to control values in most of the brain regions of predictably shocked animals, but it remained high after unpredictable shock. The activation of serotonergic metabolism following each type of shock is different according to the nucleus in which the 5-HT nerve endings originate. Only slight increases in tryptophan were observed after both types of shock. Our results suggest that unpredictable shock is perceived as a more anxiogenic situation and that under this condition both 5-HT and NA levels are more effectively normalized with time.

Animals↗

Determination of oxidation products of N-phenyllinoleamide: Spanish toxic oil syndrome studies.

The early identification of fatty acid anilides in suspect oils directed attention to their possible role in the Spanish toxic oil syndrome. These anilides or their oxidized derivatives could have been spontaneously formed during the handling and/or storage of the oil. The exact cause of the intoxication is still unknown but free radical and peroxidative mechanisms have been implicated in its etiology. Epoxy-hydroxylated derivatives from linoleic acid anilide were obtained using a model of accelerated oxidation. Their mass spectral patterns agree with the trimethylsilyl ethers of N-phenyl-9,10-epoxy-11-hydroxy-12-octadecenamide and N-phenyl-12,13-epoxy-11-hydroxy-9-octadecenamide, respectively. These compounds were also identified is rapeseed oil samples supplemented with N-phenyl-linoleamide and submitted to the reported accelerated oxidation method.

Anilides↗

PGE2 and PGF2 alpha in the nasal lavage fluid from healthy subjects: methodological aspects.

Prostaglandins E2 and F2 alpha were estimated in nasal secretions from ten healthy volunteers by high performance liquid chromatography and radioimmunological assay. Prostaglandin concentrations determined in five consecutive nasal washes with saline at room temperature showed that the nasal mucosa was stimulated after instillation. A substantial increase of basal levels was associated with the second nasal lavage. In all volunteers aspirin treatment inhibited prostaglandin release.

Adult↗

Prostaglandin levels in infertile patients affected by asthenozoospermia and prostatitis.

19-hydroxy-prostaglandins and prostaglandins of the E series (19-OH PGEs) were estimated in the seminal plasma of asthenozoospermic patients (n = 15) and individuals affected by prostatitis (n = 10) and compared to controls (n = 13) and secretory azoospermic patients (n = 8). All of them were free from infections (except individuals affected by prostatitis), biochemical and ultrastructural problems. The results indicate that endogenous prostaglandin levels (19-OH PGEs and PGEs) bear no correlation either to motility or absence of spermatozoa. Significant increases of PGEs were observed in patients affected with prostatitis. Surprisingly PGE levels showed no correlation with the levels of 19-OH PGEs.

Adult↗

Chronic stress increases serotonin and noradrenaline in rat brain and sensitizes their responses to a further acute stress.

The effects of 1 h/day restraint in plastic tubes for 24 days on the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan (TP), and noradrenaline (NA) in six regions of rat brain 20 h after the last restraint period were investigated. The levels of 5-HT, 5-HIAA, and NA but not TP increased in several regions. The effects of 1 h of immobilization on both control and chronically restrained rats were also studied. Immobilization per se did not alter brain 5-HT, 5-HIAA, and TP levels, but decreased NA in the pons plus medulla oblongata and hypothalamus. However, immobilization after chronic restraint decreased 5-HT, increased 5-HIAA, and decreased NA in most brain regions in comparison with values for the chronically restrained rats. We suggest that chronic restraint leads to compensatory increases of brain 5-HT and NA synthesis and sensitizes both monoaminergic systems to an additional acute stress. These changes may affect coping with stress demands.

Animals↗