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O Bulbena

Publications and source records attributed to O Bulbena.

At least 37 records · Page 2Linked to original sources
PubMed1995

Transmucosal potential difference in experimental colitis in rats.

Colon transmucosal potential difference (TPD), macro- and microscopic lesions, myeloperoxidase activity, and leukotriene levels were studied after the induction of experimental colitis in the rat. Forty-three male Wistar rats were subjected to the instillation of 200 mg/ml 2,4,6-trinitrobenzenesulfonic acid (TNB) solution through a rectal cannula. TPD measurements were made at different distances from the anus before and 24 h and one, two, three, and four weeks after lesion induction. Leukotriene B4 levels were assayed by intracolonic dialysis 24 h and one, two, three and four weeks after lesion induction. Macro- and microscopic evaluations were made of the bowel lesions, and myeloperoxidase activity was assayed. The mean basal TPD was -46.06 mV at 1 cm from the anus, and +10.86 mV in the proximal colon. Twenty-four hours after lesion induction the values proved markedly positive. This was correlated with an abrupt increase in LTB4 levels and myeloperoxidase activity. After one week the TPD values exhibited a greater electronegativity, returning to basal values by the fourth week after lesion induction. This coincided with an improved macroscopic lesion index, LTB4 levels, and myeloperoxidase activity. In conclusion, TPD is a useful indicator of acute colonic lesions and correlates well with LTB4 and myeloperoxidase assays. Moreover, the parameter is able to delimit lesion evolution, reflecting possible ad integrum restoration of the bowel mucosa.

Animals↗
PubMed1995

Cytoprotective and antisecretory activity of a ranitidine-zinc complex.

The effects of a ranitidine-zinc complex and ranitidine alone were compared in three different experimental models (pyloric ligation, ethanol and indomethacin) of gastric ulceration in the rat. In the pyloric ligation model, the ranitidine-zinc complex (50, 100 and 150 mg/kg p.o.) showed antiulcerogenic activity similar to that observed with equimolar doses of ranitidine (35, 70 and 105 mg/kg p.o.). Both the ranitidine-zinc complex and ranitidine significantly reduced (p < 0.05) gastric acid secretion in a dose-dependent manner. The protective effect of the ranitidine-zinc complex (100 and 150 mg/kg p.o.) against gastric damage developing after p.o. administration of absolute ethanol or indomethacin was enhanced (p < 0.05) with respect to that obtained with equimolar doses of ranitidine (70 and 105 mg/kg p.o.). The presence of zinc in the ranitidine-zinc complex does not interfere with the antisecretory effects of ranitidine on the gastric mucosa, while it confers an additional cytoprotective action to the final compound.

Animals↗
PubMed1994

Permeation by zinc of bovine chromaffin cell calcium channels: relevance to secretion.

Zn2+ increased the rate of spontaneous release of catecholamines from bovine adrenal glands. This effect was Ca2+ independent; in fact, in the absence of extracellular Ca2+, the secretory effects of Zn2+ were enhanced. At low concentrations (3-10 microM), Zn2+ enhanced the secretory responses to 10-s pulses of 100 microM 1,1-dimethyl-4-phenylpiperazinium (DMPP, a nicotinic receptor agonist) or 100 mM K+. In the presence of DMPP, secretion was increased 47% above controls and in high-K+ solutions, secretion increased 54% above control. These low concentrations of Zn2+ did not facilitate the whole-cell Ca2+ (ICa) or Ba2+ (IBa) currents in patch-clamped chromaffin cells. Higher Zn2+ concentrations inhibited the currents (IC50 values, 346 microM for ICa and 91 microM for IBa) and blocked DMPP- and K(+)-evoked secretion (IC50 values, 141 and 250 microM, respectively). Zn2+ permeated the Ca2+ channels of bovine chromaffin cells, although at a much slower rate than other divalent cations. Peak currents at 10 mM Ba2+, Ca2+, Sr2+ and Zn2+ were 991, 734, 330 and 7.4 pA, respectively. Zn2+ entry was also evidenced using the fluorescent Ca2+ probe fura-2. This was possible because Zn2+ causes an increase in fura-2 fluorescence at the isosbestic wave-length for Ca2+, i.e. 360 nm. There was a slow resting entry of Zn2+ which was accelerated by stimulation with DMPP or high-K+ solution. The entry of Zn2+ was concentration dependent, slightly antagonized by 1 mM Ca2+ and completely blocked by 5 mM Ni2+. The entry of Ca2+ evoked by depolarization with high-K+ solution was antagonized by Zn2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Prostanoid generation in early stages of acute pancreatitis: a role for nitric oxide.

The role of nitric oxide in eicosanoid and oxygen-free radical production in the early stages of sodium taurocholate-induced acute necrotizing pancreatitis has been studied. Male Wistar rats were divided into three groups: group I: control group, a volume of 0.1 ml/100 g body wt saline solution was injected at low pressure in the pancreatic duct; group II: acute pancreatitis was induced by administration of 3.5% sodium taurocholate; and group III: intravenous administration of NG-nitro-L-arginine methyl esther (a nitric oxide synthase inhibitor) 5 min before induction of acute pancreatitis as stated for group II. At 5 and 60 min after induction of pancreatitis, blood and pancreas tissue samples were taken for assays. Increases in 6-keto PGF1 alpha, TXB2, PGE2, PGF2 alpha, and 12-HETE were observed in the pancreatic tissue. Lipoperoxidation was also enhanced and remained unaltered after nitric oxide inhibition. The fact that nitric oxide synthase inhibition could only reverse the increases in 6-keto PGF1 alpha and TXB2 levels indicates that in acute pancreatitis endothelial and platelet eicosanoid generation is mediated through an nitric oxide-dependent mechanism. In contrast, nitric oxide appears to be not related with oxygen free radical damage associated with acute pancreatitis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
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

Gastrotoxic activity and inhibitory effects on gastric mucosal PGE2 production with different non-steroidal anti-inflammatory drugs: modifications induced by pretreatment with zinc acexamate.

Gastrotoxic activities of different non-steroidal anti-inflammatory drugs (NSAIDs) (diclofenac, indomethacin, ketoprofen, naproxen and piroxicam) administered per os were compared with their ability to inhibit gastric prostaglandin E2 (PGE2) synthesis in the rat. In a parallel study, effects of pretreatment with zinc acexamate (ZAC) were also assessed. NSAIDs invariably caused gastric mucosal damage and a decrease of PGE2 levels. A good correlation between the decrease of PGE2 levels and the index of gastric lesion (r = 0.41; p < 0.021) was observed when results obtained with the different NSAIDs were pooled. ZAC pretreatment significantly decreased the overall severity of lesions induced by NSAIDs. However, no correlation between gastric lesion index and depletion of PGE2 gastric levels was observed after treatment with ZAC (r = 0.012; p < 0.948). These data corroborate the hypothesis that preservation of the capability to synthesize endogenous PGs is of critical importance in the maintenance of gastric mucosal integrity. The gastroprotective action observed with ZAC involves alternative mechanisms other than modification of PGE2 levels.

Aminocaproates↗
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

N-phenyllinoleamide metabolism by human polymorphonuclear leukocytes.

1. N-phenyllinoleamide (NPLA), the anilide of linoleic acid, has been associated with the epidemiology of Toxic Oil Syndrome, but so far data available on its metabolism are scarce. On account of the similarities in chemical structure between linoleic acid and NPLA, the objective here has been to investigate the oxidative metabolism of this xenobiotic by human polymorphonuclear leukocytes. 2. Human polymorphonuclear leukocytes were incubated with 0.1 mM NPLA spiked with NPLA labelled either on the aniline or the fatty acid moieties. The metabolites were separated by high-performance liquid chromatography and individually collected prior to gas chromatography-mass spectrometry analysis. 3. Identification of the metabolites as N-phenyl-9-hydroxy- and N-phenyl-13-hydroxy-10,12-octadecenamide (9-HNPLA and 13-HNPLA) and their corresponding non-amidated metabolites, the 9-hydroxy- and 13-hydroxyoctadecenoic acids (9-HODE and 13-HODE), suggests that NPLA can be metabolized via the same hydroperoxidative processes acting upon linoleic acid. 4. Identification of free aniline as a NPLA metabolite suggests an amidase-like activity with liberation of aniline and the free fatty acid moieties.

Anilides↗
PubMed1994

Arachidonate metabolism in ischemia-reperfusion associated with pancreas transplantation.

The implication of eicosanoid metabolism and its relationship with oxygen free radical production in the process of ischemia-reperfusion associated with rat pancreas transplantation has been explored in this study. For this purpose male Sprague-Dawley rats were classified as follows: group I, control animals not surgically manipulated; group II, pancreas transplantation, after 30 min preservation in UW solution; group III, pancreas transplantation after 12 h preservation under the same conditions; group IV, same as group III but with administration of SOD 5 min prior to organ revascularization. The results show post-transplantation increases in 6-keto-PGF1 alpha, TXB2, LTB4 and 12-HETE in pancreatic tissue independent of preservation time. The fact that SOD administration could reverse these increases even though an efficient xanthine oxidase irreversible inhibitor such as allopurinol was present in the preservation solution suggests that eicosanoid generation in the recipient rat would be mediated by an oxygen free radical dependent mechanism not exclusively dependent on endothelial xanthine oxidase activity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Metabolism of N-phenyllinoleamide by rat liver.

N-Phenyllinoleamide (NPLA), the anilide of linoleic acid, has been associated with the epidemiology of toxic oil syndrome, but its contribution to the illness is still undetermined. Because it has been suggested that fatty acid anilides were absorbed via the hepatic portal vein, this study has been aimed at determining the hepatic metabolism of NPLA by rat liver. For this purpose, isolated liver was perfused with NPLA (0.1 mM) spiked with either aniline- or fatty acid-labelled NPLA. Gas chromatographic-mass spectrometric analysis of the peaks appearing in the radiochromatographic metabolic profiles shows that metabolism of NPLA in the liver results in formation of aniline and linoleic acid, both biologically active metabolites whose expected direct effects were not observed in patients suffering toxic oil syndrome.

Anilides↗
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

Gastroprotective effect of zinc acexamate against damage induced by nonsteroidal antiinflammatory drugs. A morphological study.

The gastroprotective effect of zinc acexamate against gastric damage induced by different nonsteroidal antiinflammatory drugs (indomethacin, diclofenac, and piroxicam) was morphologically assessed in the rat glandular stomach by light and scanning electron microscopy. In addition, the capability of these antiinflammatory drugs to inhibit gastric prostaglandin E2 production was compared with their ability to induce gastric lesions. Microscopically, disappearance of mucus glycoprotein and exfoliation of the mucosal surface were the most common findings. Surface ultrastructural lesions varied from minimal lesions of the surface epithelial cells to deep erosions of the gastric mucosa with release of associated cellular elements and sloughing of the denuded lamina propria. Diclofenac elicited the most powerful inhibitory activity on mucosal prostaglandin E2 (98% inhibition vs control), closely followed by piroxicam (97.8%) and indomethacin (91.05%). Pretreatment of animals with zinc acexamate significantly increased the presence of mucus glycoprotein, maintained the continuity of the surface epithelial cells, and decreased the depth of the mucosal erosions. The degree of protection exerted by zinc acexamate varied with the antiinflammatory, but was always evident.

Aminocaproates↗
PubMed1993

Cyclooxygenase and lipoxygenase arachidonate metabolites synthesized by mouse peritoneal macrophages: in vitro effect of N-phenyllinoleamide from toxic oil samples.

N-phenyllinoleamide (NPLA) has been detected as extraneous compound in adulterated cooking oils associated with a unique epidemic disease known as the Toxic Oil Syndrome (TOS). In this communication we report on the action of NPLA on the endogenous cyclooxygenase and lipoxygenase arachidonate metabolism. Results show that mouse peritoneal macrophages (MPM) exposed to 1 mM NPLA for 2 h undergo significant increases of 6-keto prostaglandin F1a, prostaglandin E2, leukotriene B4, 12- and 15-hydroxyeicosatetraenoic acids. MPM prelabelled with 3H-AA showed an enhanced release when exposed to NPLA. Thus, it is concluded that NPLA potentiates AA release from cell membrane phospholipids and the subsequent cyclooxygenase and lipoxygenase oxidative metabolism of this precursor to various eicosanoids. This is in agreement with the implication of peroxidative process mediated by fatty acids anilides in TOS.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
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

Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia.

Nitric oxide derived from vascular endothelium is a potent vasodilator that plays a key role in the homeostasis of blood pressure. Because cirrhotic patients tend to have low arterial pressure, we measured in 51 patients and 10 control subjects serum nitrite and nitrate levels as an index of in vivo nitric oxide generation. We also measured plasma endotoxin, a substance frequently increased in cirrhotic patients and known to induce nitric oxide synthesis. Cirrhotic patients showed significant increases in serum nitrite/nitrate and plasma endotoxin compared with controls. Values were particularly increased in patients with decompensated cirrhosis, as manifested by ascites with or without functional kidney failure. High serum nitrite/nitrate levels were associated with high plasma renin activity, high aldosterone and antidiuretic hormone levels and low urinary excretion of sodium. In addition, serum nitrite/nitrate levels significantly correlated with endotoxemia. Oral administration of colistin to 15 cirrhotic patients reduced significantly plasma endotoxin levels (p < 0.01) and serum nitrite/nitrate levels (p < 0.05). Because endotoxin enhances the expression of inducible nitric oxide synthase, our results suggest that circulating endotoxin in cirrhosis is responsible for excessive synthesis and release of nitric oxide by the vasculature. These findings might explain the hemodynamic dysfunction seen in cirrhotic patients.

Adult↗