Biomedical subjects

H Kurtel

Publications and source records attributed to H Kurtel.

25 records · Page 2Linked to original sources

PubMed1995

Cyclosporin A reduces the severity of cold-restraint-induced gastric lesions: role of leukocytes.

The objective of this study was to determine the role of cyclosporin A (CsA) on cold-restraint-induced gastric lesions. Animals were subjected to 3 h immobilization at 4 degrees C in plastic restraining devices following a starvation period of 48 h. Gastric samples were obtained for the measurement of myeloperoxidase (MPO) activity, an index of number of peroxidase positive cells and thiobarbituric acid-reactive substances (TBARS; lipid peroxidation). Animals were pretreated with CsA which is a potent immunosuppressant and inhibits ischemia/reperfusion-induced polymorphonuclear leukocyte (PMN) infiltration. Cold-restraint administration significantly elevated the tissue MPO activity and TBARS formation. CsA pretreatment significantly reduced the severity of cold-restraint-induced gastric lesions while attenuating the elevated MPO measurements observed during cold-restraint administration. Animals rendered neutropenic with antineutrophil serum (ANS) exhibited significantly less gastric mucosal injury normally observed after cold-restraint stress. Neither CsA nor ANS treatment effected the elevated TBAR levels, indicating that PMNs are not involved in the lipid peroxidation process observed after cold-restraint stress. In conclusion, the results of this study indicate that CsA is capable of inhibiting cold-restraint-induced gastric mucosal injury and can attenuate the cold-restraint-induced increases in gastric MPO measurements. Our results also indicate that PMNs may be the important mediators of cold-restraint-induced gastric lesions.

Animals↗

PubMed1992

Granulocyte accumulation in postischemic intestine: role of leukocyte adhesion glycoprotein CD11/CD18.

Neutrophils play an important role in ischemia-reperfusion (I/R)-induced vascular injury in the small intestine. Monoclonal antibodies against the leukocyte adhesion glycoprotein CD11/CD18 afford protection against I/R-induced microvascular injury. It has been suggested that the response to I/R differs between the various layers of the bowel wall, with relatively few granulocytes accumulating in the mucosa compared with the serosa or mesentery. The objectives of this study were to determine whether I/R-induced neutrophil accumulation is 1) homogenous in the different layers of intestine (mucosa, submucosa, muscle, and mesentery) and 2) dependent on the expression and/or activation of the leukocyte adhesion glycoprotein CD11/CD18. Neutrophil infiltration was monitored by measuring myeloperoxidase activity in mucosa, submucosa, muscle, and mesentery of cat small intestine subjected to 3 h ischemia (blood flow reduced to 20% of control) and reperfusion. I/R elicited a comparable degree of polymorphonuclear (PMN) infiltration in mucosa, submucosa, and mesentery, with the muscularis exhibiting a greater response. Pretreatment with the CD18-specific monoclonal antibody (IB4) significantly attenuated the I/R-induced PMN accumulation in all layers of the bowel wall and mesentery, indicating that the granulocyte accumulation elicited by I/R is dependent on the expression and/or activation of the leukocyte adhesion molecule CD11/CD18.

Animals↗

PubMed1992

Vulnerability of intestinal interstitial fluid to oxidant stress.

The objective of this study was to quantify free radical-mediated lipid, protein, and sulfhydryl oxidation in intestinal interstitial fluid (lymph) and plasma of fasted rats. Free radicals and oxidants were generated either by thermal decomposition of 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH), which yields peroxyl radicals, or by activated polymorphonuclear neutrophils (PMNs). Incubation of intestinal lymph with AAPH resulted in a time-dependent increase in the formation of thiobarbituric acid-reactive substances (TBARS; lipid peroxidation) and carbonyl content (protein oxidation). TBARS formation was completely inhibited by removal of the apo B-containing lipoproteins in lymph suggesting that very low-density lipoprotein is the major substrate for lipid peroxidation in fasted interstitial fluid. The sulfhydryl content of lymph was reduced significantly on exposure to the peroxyl radical generator. Incubation with activated PMNs revealed qualitatively similar changes in protein and sulfhydryl oxidation; however, there was no detectable TBARS formation. Exposure of plasma to AAPH produced similar increases in protein and sulfhydryl oxidation when plasma protein concentration was adjusted to that of lymph; however, TBARS formation was significantly lower compared with lymph. Incubation of dialyzed plasma with AAPH produced significantly greater amounts of TBARS. Taken together, our data suggest that plasma is more resistant to AAPH-induced lipid peroxidation than interstitial fluid and the substrate for TBARS formation in intestinal interstitial fluid is different from that of plasma.

Amidines↗

PubMed1991

Ischemia-reperfusion-induced mucosal dysfunction: role of neutrophils.

The ability of the small intestine to absorb and transport lipid into lymph is markedly reduced 24 h after a 10-min total occlusion of the superior mesenteric artery (SMA). The aim of this study was to define the role of neutrophils in the ischemia-reperfusion (I/R)-induced decrement in lipid absorption. A lipid test meal containing 40 mumol of radioactive triolein was infused intraduodenally at 3 ml/h for 8 h, and radioactive lipid output in lymph was monitored during lipid infusion in intestinal lymph fistula rats. Animals rendered neutropenic with antineutrophil serum (ANS) did not exhibit the reduction in lipid absorption and transport in lymph normally observed 24 h after I/R. This protective effect of ANS was specifically related to the reduction in the number of neutrophils in the intestinal mucosa. The amount of radioactive lipid detected in the liver of untreated rats was significantly higher than in control rats, suggesting an increased portal transport of infused radioactive lipid. Neutropenia reduced the liver lipid level toward the control value. The intestinal blood flow response to SMA occlusion was not altered by neutropenia. Our results suggest that neutrophils play an important role in the mucosal dysfunction associated with ischemia-reperfusion.

Animals↗

PubMedDate not supplied

Ischemia-reperfusion-induced delay in intestinal transit. Role of endothelins.

BACKGROUND/AIMS: To evaluate the involvement of ET-1 in ischemia-reperfusion (I/R) injury. METHODS: Superior artery occlusion was performed in Wistar albino rats for 30 min followed by 2-hour (early reperfusion; ER) or 24-hour (late reperfusion; LR) reperfusion periods. RESULTS: Intestinal transit was found to be reduced in the ER and LR groups (19.0 +/- 2.5%; p < 0.001 and 72.7 +/- 6.0%; p < 0.05, respectively) compared to the control group (85. 8 +/- 2.5%), while treatment with the ET receptor antagonist bosentan (BOS; 10 mg/kg i.v.) abolished this delay in LR. Myeloperoxidase activity showed a significant increase in ER (7.07 +/- 85.70 U/g; p < 0.001) compared to control (281.16 +/- 43.23 U/g), but BOS had no effect on this increase. The protein oxidation level was found to be higher in LR (5.92 +/- 0.77 nmol/mg protein; p < 0. 05) compared to the control (3.77 +/- 0.45 nmol/mg protein), and was reversed by BOS treatment. CONCLUSION: The results of the present study imply that I/R delays intestinal transit involving an endothelin-dependent mechanism.

Animals↗

PubMedDate not supplied

Role of endothelins in trinitrobenzene sulfonic acid-induced colitis in rats.

To determine the role of endothelins (ET) on experimental colitis, following intracolonic trinitrobenzene sulfonic acid administration, rats were given orally either bosentan (BS), a nonselective ET receptor antagonist (100 mg/kg in 5% arabic gum), or arabic gum by gavage for 2 or 14 days. Macroscopic damage scores obtained in the vehicle (1.4+/-0.4), acute (4.8+/-0.6) and chronic (3.8+/-0.3) colitis groups were significantly higher than in the control group (0). BS treatment reduced the scores in both acute (3+/- 0.5) and chronic (2.3+/-0.5) colitis groups. Myeloperoxidase (MPO) activities of colonic tissues were elevated in acute and chronic colitis groups (325.1+/-44.9 and 431.8+/-54.6 U/g wet weight) as compared with the control group (73.6+/-11 U/g wet weight). Plasma protein oxidation levels were found to be significantly increased in the chronic colitis group (1,158.1+/-63.4 nmol/ml) compared with the control, ethanol and acute colitis groups (274.3+/-23.1, 490+/-52.2 and 422.2+/-50.5 nmol/ml). BS treatment significantly reduced both the protein oxidation level (375.5+/-46.9 nmol/ml) and MPO activity (167.5+/-35.8 U/g wet weight). The results of the present study suggest the involvement of ETs in the pathogenesis of colonic injury in this animal model of colitis.

Analysis of Variance↗

PubMedDate not supplied

Muscarinic receptor subtypes of guinea-pig gallbladder smooth muscle.

The antagonism of acetylcholine-induced contractions of guinea-pig gallbladder and ileum smooth muscle strips via various antagonists has been investigated in order to find out the muscarinic receptor subtype(s) of gallbladder smooth muscle. Atropine, pirenzepine, 4-DAMP and AF-DX 116 were used as nonselective, M1-selective, M1- and smooth muscle M3-selective and cardiac M2-selective muscarinic antagonists, respectively. All the muscarinic antagonists examined displaced the concentration-response curves to the right parallelly in a concentration-dependent manner without affecting the maximum response in both tissues. Schild analysis of data was consistent with competitive antagonism. pA2 values of the antagonists were as follows: a) gallbladder: atropine: 8.43; pirenzepine: 7.81; 4-DAMP: 8.10; AF-DX 116: 6.71; b) ileum: atropine: 9.62; pirenzepine: 6.94; 4-DAMP: 9.41; AF-DX 116: 6.55. It may be concluded that the muscarinic receptors of the guinea-pig gallbladder, which mediate acetylcholine-induced contractions, are not of the cardiac M2-subtype and may be distinguished from ileal smooth muscle M3-receptors because 4-DAMP has a 20.4 times greater affinity for ileal smooth muscle muscarinic receptors.

Acetylcholine↗