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Y Haskel

Publications and source records attributed to Y Haskel.

At least 37 records · Page 2Linked to original sources

Salicylate as an in vivo free radical trap: studies on ischemic insult to the rat intestine.

Ischemia of rat intestine was induced in vivo by occlusion of the superior mesenteric artery (SMA) for 15 min. Sodium salicylate, 100 mg/kg, given IP, 30 min prior to the ischemic event served as a specific trap for hydroxyl radicals. Portions of the bowel were sequentially isolated and removed--2 min prior to ischemia, 2 min prior to declamping of the SMA, and 10 min following reperfusion. The bowel segments were homogenized in 3% TCA. The homogenate was centrifuged and filtrated through a 0.22 mu filter. The hydroxylation products of salicylate, dihydroxybenzoic acid (DHBA) derivatives, were isolated, identified, and quantified by HPLC coupled with electrochemical detection (ECD). The level of 2,5-DHBA (M +/- SE, ng/g tissue) in the preischemic bowel (N = 21) was 241.8 +/- 10.0. In the ischemic specimen the level of 2,5-DHBA increased significantly to 313.3 +/- 15.5 (p = 0.0129), and remained unchanged in the reperfusion period (322.8 +/- 15.5). The histological examination correlated well with these levels: mild villi damage in the ischemic period with no further exacerbation during the reperfusion period. This study in an in vivo animal model of intestinal ischemia-reperfusion provides direct evidence for the involvement of free radicals during the ischemic insult.

Animals↗

Direct evidence for the involvement of free radicals in ischemic insult to the intestine.

Ischemia of rat intestine was induced in vivo by occlusion of the superior mesenteric artery (SMA) for 15 min. Sodium salicylate, 100 mg/kg, given IP, 30 min prior to the ischemic event served as a specific trap for hydroxyl radicals and provided direct evidence for the involvement of free radicals during the ischemic insult. Portions of the bowel were sequentially isolated and removed. The hydroxylation products, dihydroxybenzoic acid (DHBA) derivatives were isolated, identified and quantified by HPLC coupled with electrochemical detection (ECD). The level of 2,5-DHBA (Mean +/- SE, ng/g tissue) in the preischemic bowel (N = 21) was 241.8 +/- 10.0. It rose significantly to 313.3 +/- 15.5 in the ischemic specimen (p = 0.0129) and remained unchanged in the reperfusion period (322.8 +/- 15.5). The histological examination correlated well with these levels: mild villi damage in the ischemic period with no further damage in the reperfusion period.

Animals↗

Mechanistic aspects of 1-methyl-4-phenyl pyridinium iodide toxicity in Escherichia coli: the role of oxygen and hydrogen peroxide.

1-Methyl-4-phenyl pyridinium iodide (MPP+) and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies in a variety of systems have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the Escherichia coli model and demonstrated that MPP+ is toxic to bacterial cells in dose- and time-dependent modes. Additionally, it is shown that only in the presence of molecular oxygen did bacterial inactivation occur. This requirement for oxygen can be circumvented by adventitious H2O2. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

MPP+ toxicity in E. coli under aerobic and anaerobic conditions.

MPP+ and paraquat (PQ+2) are two structurally analogous and highly toxic pyridinium compounds. The mechanism of PQ+2 toxicity is best understood in the bacterial model system. While numerous studies, in a variety of systems, have indicated the causative role of free radicals and other oxygen-derived active species in PQ+2 toxicity, this question is yet unresolved in the case of MPP+. In this study we have used the E. coli model and have demonstrated that MPP+ is toxic to bacterial cells in a dose and time dependent modes. Additionally, it is shown that only in the presence of molecular oxygen, bacterial inactivation occurred. The protective effects of the chemical scavenger--mannitol--and of histidine are presented. These results are in complete accord with a free radical mechanism for MPP+ toxicity.

1-Methyl-4-phenylpyridinium↗

The effect of meperidine on the guinea pig extrahepatic biliary tract.

The effect of meperidine on the mechanical activity of isolated guinea pig common bile duct (CBD) and gallbladder was studied in vitro. The effect was found to consist of inhibitory and excitatory phases. The inhibitory phase, characterized by a decrease in the response of the CBD and gallbladder to carbachol and electrical stimulation, was seen with concentrations of 10(-6) M or higher. The excitatory phase, seen at high concentrations of meperidine (5 X 10(-5)-10(-4) M), involved an increase in spontaneous contractions of CBD and in the tone of the gallbladder. Neither effect of meperidine was affected by 0.5 X 10(-5) M naloxone. These data indicate that meperidine acts on the biliary tract by a mechanism different from that associated with the effect of morphine.

Animals↗

Effect of morphine on the mechanical activity of common bile duct isolated from the guinea pig.

The contractile response of isolated guinea pigs common bile ducts (CBD) to transmural electrical stimulation and the effects of morphine and naloxone was studied. Contractile responses increased as a function of stimulus frequency. In the absence of naloxone morphine inhibited the contractile response to electrical stimulation in a dose-dependent manner. Naloxone prevented the inhibitory effect of morphine on the contractile response to electrical stimulation. We conclude that smooth muscle of the CBD in guinea pig is functional and can contribute to biliary motility, and that opiate receptors exist in nerve elements in the CBD.

Animals↗

Effect of nalbuphine on intrabiliary pressure in the early postoperative period.

The effect of nalbuphine on common bile duct (CBD) pressure was studied by measurements through T-tubes on the first and second postoperative days after cholecystectomy and choledochotomy. Nalbuphine in a dose of 0.25 mg X kg-1 was injected intramuscularly in 11 patients, and changes in biliary pressure, heart and respiratory rate, blood pressure, and arterial blood gases were recorded during the subsequent four hours. The patients were free of pain, had stable common bile duct pressures and did not have any statistically significant changes in their vital signs. These results are similar to our previous observations during perioperative intravenous injection of nalbuphine. It is suggested that nalbuphine does not significantly change, or even may relax, the sphincter of Oddi, and can therefore be recommended as a safe analgesic in the postoperative period after extrahepatic biliary surgery.

Adult↗

Persistent müllerian structures in infertile male.

Müllerian duct derivatives were identified in an infertile adult male patient who had long-standing azoospermia and was operated on for inguinal hernia. Persistent müllerian duct syndrome is reviewed, with special emphasis on the pathophysiologic and surgical considerations involved in the treatment of this abnormality.

Adult↗

A knot of the subclavian venous catheter in a premature neonate.

The percutaneous subclavian venous catheter is used in administration of total parenteral nutrition in premature neonates. Most of the complications observed include catheter-related sepsis, cracking or obstruction of the line, and accidental removal. We encountered an unusual complication when an intravascular knot in the catheter was formed upon removal of the line. If care is taken when advancing the catheter, this complication can be avoided.

Catheterization↗

Common bile duct pressure in dogs after opiate injection--epidural versus intravenous route.

The effect on the common bile duct pressure of epidurally injected morphine and fentanyl, was compared with that of intravenous injections of the same drugs in 12 mongrel dogs. Intravenous injection of morphine (0.1 mg X kg-1) or fentanyl (0.01 mg X kg-1) significantly elevated the common bile duct pressure from 10.48 +/- 0.37 to 21.68 +/- 0.33 cm H2O and from 9.66 +/- 0.33 to 14.14 +/- 0.21 cm H2O respectively. These increases occurred within 4-15 minutes after injection and lasted for about 2-3 hours. When the narcotics in identical dosages were injected epidurally, the common bile duct pressures were unchanged during the four hours of investigation. Further studies are planned to determine whether this beneficial effect of epidural narcotics applies also in the human clinical situation.

Animals↗

Ammonia uptake by skeletal muscle in the hyperammonaemic rat.

A two-stage surgical occlusion of the portal vein was employed to produce hyperammonaemia in the rat. The procedure resulted in a significant rise of arterial blood ammonia level from 70 . 5 +/- 6 . 5 mumol/l (mean +/- SEM, n = 10) to 214 . 0 +/- 37 . 7 mumol/l and in a rise of venous blood ammonia from 65 . 0 +/- 9 . 4 mumol/l to 122 . 2 +/- 7 . 4 mumol/l during the first day following the complete vein occlusion. A marked increase of the arteriovenous difference of ammonia concentration from virtually zero in sham-operated controls to 72 +/- 9 (n = 8) mumol/l in rats 1 day after the surgical manipulation suggested uptake of ammonia by skeletal muscle. Rat muscle glutamine synthetase activity increased from 0 . 46 +/- 0 . 06 u/mg (n = 7) in controls to 2 . 7 +/- 0 . 3 u/mg (n = 7) on the fourth day following portal vein ligation, and muscle branched chain amino acids aminotransferase increased from 0 . 2 +/- 0 . 05 u/mg in controls to 0 . 96 +/- 0 . 1 u/mg (n = 7) during the first day of ligation. Glutamine dehydrogenase and aspartate aminotransferase activities were not affected by the surgical procedure. These observations suggest that ammonia trapping in skeletal muscle is coupled to glutamine formation via amination of glutamic acid. This conclusion was further supported by the finding that ammonia uptake correlated (r = 0 . 92) with enhanced release of glutamine from muscle and that treatment with methionine sulfoximine, a potent inhibitor of glutamine synthetase, changed the arteriovenous difference of glutamine from -0 . 92 +/- 0 . 01 mmol/l in ligated animals (net release) to +0 . 12 +/- 0 . 01 mmol/l (net uptake) in ligated and inhibitor-treated animals. Similarly, the inhibitor also abolished the arterio-venous difference of ammonia. Thus, the animal model of hyperammonaemia and the muscle enzyme assays reveal that skeletal muscle is involved in the regulation of blood ammonia level by conversion of ammonia, via glutamic acid, to glutamine.

Ammonia↗

Direct inhibitory effect of erythromycin on the gallbladder muscle.

Erythromycin, a macrolide antibiotic, stimulates motor activity in various parts of the gastrointestinal tract in humans and animals. This effect of erythromycin resembles that of motilin, a gastrointestinal hormone, in evoking contractions similar to phase 3 activity of the migrating motor complex. Motilin induces contractions in the canine gallbladder but fails to evoke any response, either in vivo or in vitro, in the human gallbladder. Surprisingly, erythromycin stimulates human gallbladder emptying in healthy volunteers and in persons with diabetic autonomic neuropathy. In the present study we examined the effect of erythromycin on chemically and electrically evoked contractions of isolated gallbladders from guinea pigs and humans by use of isometric force measurements. Carbachol, a muscarinic cholinergic agonist, evoked gallbladder contractions that were diminished by erythromycin in a concentration-dependent manner: at 200 micromol/L the contractions were 86% +/- 20% of the control response, at 500 micromol/L they were 63% +/- 21% of control, and at 1000 micromol/L they were 41% +/- 20% of control (P <0.05, N = 10, mean +/- standard deviation). Electrically evoked gallbladder contractions were reduced to 68% +/- 18% of the control response with the addition of 500 micromol/L of erythromycin and to 56% +/- 19% of control after the addition of 1000 micromol/L (P <0.05, N = 8). Guinea pig but not human gallbladders contracted after stimulation with the alpha-adrenergic agonist phenylephrine. Erythromycin reduced these contractions in a concentration-dependent manner but had no effect on gallbladder contractions induced by bradykinin. In human gallbladder strips, erythromycin at 500 micromol/L reduced the contractile response to electrical stimulation to 71% +/- 16% of the control value (N = 10 [5 patients], P <0.01) and the carbachol-evoked contractions to 53% +/- 24% (P <0.01, N = 32). The inhibitory effect of erythromycin persisted in the presence of the nerve blocker tetrodotoxin at 1 micromol/L. It is concluded that erythromycin has a direct inhibitory effect on guinea pig and human gallbladder contractions.

Adrenergic alpha-Agonists↗

Liquid enteral diets induce bacterial translocation by increasing cecal flora without changing intestinal motility.

The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested.

Animals↗