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.

Bombesin ameliorates colonic damage in experimental colitis.

In the present study we investigated the possible therapeutic effects of bombesin on an experimentally induced colitis model in rats. Inflammation of the colon was induced by a single intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) at 8 cm from the anus. Immediately after the induction of colitis, some rats were given bombesin (10 microg/kg; subcutaneously) three times a day for 14 days, while another group received vehicle treatment. On day 14, the rats were decapitated and plasma carbonyl content and tissue myeloperoxidase level, as an index of granulocyte infiltration into intestinal tissue, were determined in order to obtain an objective evaluation of colonic injury. In the colitis group, increased macroscopic damage score, elevated MPO level and high plasma carbonyl content, together with the microscopic appearance revealed severe inflammatory changes resembling IBD. Bombesin treatment attenuated the TNBS-induced colonic damage and stimulated histopathologically apparent mucosal proliferation, suggesting that bombesin may play a role in protecting gut integrity.

Primary torsion of the omentum mimicking acute appendicitis: report of a case.

A case of primary omental torsion seen in a 26-year-old man is discussed. All signs and symptoms mimicked acute appendicitis. The patient underwent emergency laparotomy in which a normal appendix and serohemorrhagic fluid in the pelvis were observed. The pathological diagnosis was a primary torsioned omentum which was thus excised. This case helps to emphasize the importance of a routine exploration of the abdomen when serohemorrhagic fluid is found at the time of laparotomy in the absence of any pathological condition in the pelvis.

Captopril prevents the oxidative damage to proteins after renal ischemia reperfusion injury: role of endothelin-1.

Ischemia reperfusion (I/R) injury is one of the leading cause of the transplanted organ loss. In this experimental study, we investigated the effect of captopril on endothelin and eicosanoid release in I/R injury of the kidney. Rats were subjected to 60 min ischemia and 60 min of reperfusion of the left kidney in control and captopril groups. Tissue protein oxidation products, PGE2 and LTB4 levels and plasma endothelin-1 (ET-1) like activity were determined in sham operated, control and captopril groups. There were no differences in the LTB4 levels among the groups. ET-1 and PGE2 levels and protein oxidation products increased in the control group when compared with the sham. Captopril further increased both PGE2 and ET-1 concentrations and prevented protein oxidation. The increased ET-1 concentrations in the captopril treated group may imply the protective role of endothelin as the significant increase in protein oxidation products was reversed by captopril infusion. This has led us to believe that captopril might be useful in preventing I/R injury of the kidney. Also the release of endothelin from the vascular endothelium is increased by captopril and may be mediated by PGE2.

The effect and timing of local anesthesia in laparoscopic cholecystectomy.

Although postoperative pain following laparoscopic cholecystectomy (LC) is less intense than that after open surgery, postoperative morbidity nonetheless increases with LC. The aim of this study was to investigate whether local anesthetic infiltration of trocar sites during LC decreased postoperative pain and, if so, to find the optimum timing for local anesthesia (LA). Seventy patients undergoing LC were randomized into three groups. In the first (control group, n = 25) 3 ml of 0.9% NaCl was subcutaneously infiltrated around each 5-mm trocar site, 4 ml around each 10-mm site. In the second group (n = 20), the same volume of local anesthetic was administered in the same manner prior to surgery, and in the third group (n = 25) an identical dose of local anesthetic was infiltrated at the end of surgery. A visual analog scale was given to all patients, who were asked to record their pain intensity at 1, 3, 5, 7, and 12 h postoperatively. Pethidine HCl 1 mg/kg i.m. was given to those whose pain intensities were greater than 5. The mean pain intensities were 7.6, 5.9, and 5.1 in the control, preoperative, and postoperative LA groups, respectively. In the preoperative LA group, 50% of patients and in the postoperative LA group 28% of patients required analgesics compared with 76% in the control group. The main pain intensities and analgesic requirements were significantly lower in the postoperative LA group compared with other groups. We conclude that local anesthesia during LC reduces postoperative pain and that infiltration of trocar sites following surgery offers better pain relief than local anesthetic given just before the incision.

Preoperative albendazole treatment for liver hydatid disease decreases the viability of the cyst.

OBJECTIVE: Although in experimental models the efficacy of albendazole has been demonstrated, more clinical data are required. In this study, the effect of preoperative albendazole treatment was investigated in patients with liver hydatid cysts. DESIGN: This is a prospective non-randomized study. METHODS: In this study, the viability was assessed by the gross appearance of the cyst and intracystic pressure (ICP). The study consisted of 70 patients with 89 liver hydatid cysts in two groups. The patients in the first group (n = 29) received 10 mg/kg albendazole orally for 3 weeks before surgery. Thirty-five cysts were evaluated in this group. The second group (n = 41) with 54 liver hydatid cysts received no preoperative treatment. RESULTS: In the first group receiving preoperative albendazole, 20 cysts were viable and 15 non-viable. The median ICP was 21 (range 8-56) cm H2O in viable and 0 (range 0-8) cm H2O in non-viable cysts. In the second group, 43 cysts were viable and 11 non-viable. The median ICP was 35 (range 8-75) cm H2O in viable and 0 (range 0-2) cm H2O in non-viable cysts. The ICP values of viable cysts in the first group receiving preoperative albendazole were significantly lower (P < 0.05). The number of non-viable cysts was also significantly higher in the group treated with preoperative albendazole (P < 0.05). CONCLUSION: Albendazole in this study has proved to be effective in decreasing the viability of liver hydatid cysts when given for 3 weeks preoperatively.

Gastric functions in portal hypertension. Role of endothelin.

This study investigated the effects of portal hypertension on gastric motor and secretory functions and the role of endothelin in rats. Control; sham-operated; endothelin-A receptor blocker, BQ 485 (1 microgram/kg)-treated; portal hypertensive; and portal hypertension +, endothelin-A receptor blocker-treated rats were subjected to tests of gastric secretory, motor, and mucosal function studies as well as gastric wall polymorphonuclear infiltration. Portal hypertension was induced by partial portal vein ligation. Portal hypertension suppressed gastric acid and total fluid secretion and delayed gastric emptying. An increase in mucosal permeability and no alteration in gastric wall myeloperoxidase activity were observed. The effects of portal hypertension on gastric secretory, motor, and mucosal functions were reversed by treatment with endothelin-A receptor blocker, BQ-485. It is concluded that portal hypertension suppresses the gastric motor and secretory functions and endothelin plays an important role in the pathophysiology of gastric alterations associated with portal hypertension.

BQ-123, a specific endothelin (ETA) receptor antagonist, prevents ischemia-reperfusion injury in kidney transplantation.

We studied the effects of the specific endothelin (ETA) receptor antagonist, BQ-123, on reperfusion injury in a rat model of kidney transplantation. First, Sprague-Dawley rats were divided into three groups: a sham nephrectomy (SNEPH), an autotransplantation (AUTO-Tx), and an allotransplantation (ALLO-Tx) group. In a fourth group, ALLO-Tx + BQ, allografts were flushed with 20 micrograms BQ-123 containing cold Ringer's lactate before transplantation. For the allograft groups, kidneys from white Wistar albino rats were transplanted into allogeneic Sprague Dawley recipients. Grafts were allowed 120 min of reperfusion after 40 min of cold ischemia. ET-1,2 plasma concentrations in the renal venous blood, and kidney tissue prostaglandin (PG) E2 and leukotriene (LT) B4 levels were studied. Diene conjugates (DC), hydroxyalkanals (HAA), hydroxyalkenals (HAE) and malondialdehyde (MDA) levels, as the products of lipid peroxidation, and protein carbonyls (PC) and protein sulphydryls (PS), as the parameters of protein oxidation, were also analyzed in the kidney tissue. Plasma ET concentrations increased significantly in the AUTO-Tx and ALLO-Tx groups (P < 0.05 and P < 0.01, respectively) but this increase was reversed in the ALLO-Tx + BQ group. None of the lipid peroxidation products except DCs (P < 0.05) increased in the AUTO-Tx group, whereas they all increased in the ALLO-Tx group (P < 0.01). Protein oxidation parameters also changed significantly (P < 0.01) in the ALLO-Tx group but did not in the AUTO-Tx group (P < 0.05). The differences in PGE2 and LTB4 levels were not significant. Histopathologic examination revealed prominent glomerular and tubular injury in the AUTO-Tx and ALLO-Tx groups but less in the ALLO-Tx + BQ group. In the last group, all parameters of lipid peroxidation (P < 0.001 for all) and PCs decreased, and PSs were preserved (P < 0.001 for both) when compared with the AUTO-Tx and ALLO-Tx groups. We conclude that BQ-123, in addition to inhibiting the binding of ET-1,2 to the ETA receptor, may also inhibit the release and/or synthesis of ET-1,2 and prevent reperfusion injury in kidney transplantation.

Endothelin release is augmented with captopril in rat ischemia-reperfusion injury of the liver.

The reactive oxygen metabolites (ROMs) and the vascular endothelial factors such as endothelins (ETs) and thromboxane A2 (TxA2) were found to be mediators of the reperfusion component of ischemia-reperfusion (I/R) injury. Captopril (CPT), a sulfydryl (-SH) group containing angiotensin-converting enzyme inhibitor, has been shown to reverse I/R injury by its ROM scavenging effect. In this experimental study, the effects of CPT and BM 13.177 (a TxA2 receptor antagonist) were assessed on liver I/R injury in rats. Four groups of Wistar albino rats were either sham-operated, control, CPT or BM 13.177-treated. The middle and left lateral hepatic arteries and portal veins were occluded in each group but the sham and the corresponding agents were given to the animals prior to I/R injury. After I/R injury, blood was drawn from the suprahepatic inferior vena cava for ET-1-like activity assay and liver tissue samples were obtained for the determination of prostaglandin E2 (PGE2), leukotriene C4 (LTC4) and histopathologic examination. PGE2 and ET-1 levels were increased significantly in the control group compared with the sham-operated group. In the CPT group, LTC4, PGE2 and ET-1 levels were significantly increased compared with the control group, while only ET-1 levels were not different from those of the control group in the BM 13.177-treated group. It is concluded that ET-1 release increases in response to I/R injury in rat liver and CPT further increases this release. It also appears that CPT has a stimulatory effect on arachidonic acid metabolism in addition to its free radical scavenging effect.

The effect of thermal injury on gastric emptying in rats.

Gastric distension and gastrointestinal discomfort are common complications of burn injuries. This study was designed to examine the effect of thermal injury on the emptying rate of liquids in conscious rats fitted with stainless steel cannulae in the body of the stomach. In rats with partial-thickness burns emptying of the hyperosmolal saline was found to be delayed (P < 0.5) with respect to control only during the chronic phase of injury. However, full-thickness burns delayed hyperosmolal saline emptying in both acute and chronic phases, together with delayed saline emptying in the acute state. Thermal injury did not influence the gastric emptying of peptone and acid solutions, which activate different pathways to delay gastric emptying. Delayed gastric emptying of hyperosmolal solutions may be explained by increased sympathetic and opiatergic nervous activities, resulting in reflex relaxation of gastric smooth muscle.

The effect of Iloprost (ZK 36374) on isolated and transplanted pancreatic islet cells.

Several methods have been described for the prolongation of survival of isolated and transplanted islet cells. To investigate the effect of a stable prostacyclin analogue, ZK 36374 (Iloprost) on isolated and allotransplanted islet cell function, we studied 6 groups of rats: Group 1 (n = 7) animals underwent pancreatectomy and their islets were isolated and cultured by standard techniques. Group 2 (n = 8) animals were treated the same, except for the addition of Iloprost to the culture solutions. Group 3 (n = 7) animals were treated as group 1, but the isolated islets were transplanted to the subcapsular space of the left kidney of group 5 (n = 7) animals. Group 4 (n = 8) animals were treated as group 2, and the isolated islets were transplanted to group 6 (n = 8) animals. The insulin levels in the culture media obtained in group 1 and 2 were measured. In groups 5 and 6 blood glucose levels were measured and intraperitoneal glucose loading tests were performed. Histological examination was performed for both isolated and transplanted islets. The results showed that both insulin levels and histologic evaluation were better for group 2 than group 1. Animals in group 6 reached normoglycemia on the fifth day following transplantation while it was the ninth day for group 5. The intraperitoneal glucose loading test was tolerated better by group 6 animals. We conclude that Iloprost may be responsible for the improved results which seem to be due to its cytoprotective effect.

How minimally invasive is laparoscopic cholecystectomy?

To determine the extent of surgical stress induced by open (n = 20) and laparoscopic (n = 20) cholecystectomy, postoperative serum cortisol, growth hormone, and insulin responses were determined for each group. The groups were similar regarding age, sex distribution, and duration of the surgical procedures. The open cholecystectomy group had significant elevations of serum cortisol, growth hormone, and insulin levels 8 h after surgery (p < 0.05). The increased cortisol and growth hormone levels returned to preoperative control values 48 h after surgery. In the laparoscopically operated group, although all hormones increased after surgery, only the increase in growth hormone was statistically significant (p < 0.05). Serum cortisol and growth hormone levels gradually returned to control values 48 h after surgery, but the increased serum insulin levels remained significantly high in both groups 24 and 48 h after surgery (p < 0.05). It is concluded that acute surgical stress induced by open cholecystectomy is more severe than that induced by laparoscopic surgery as reflected by serum hormone determinations. However, the hormonal convalescence rate was similar for both groups. It appears that laparoscopic cholecystectomy is "minimally invasive" concerning the hormonal responses.

Does PGE2 act as a mediator for endothelin release?

To investigate the effect of iloprost (ZK 36374) and thromboxane synthetase inhibitor UK 38485 on endothelin release by the intestinal vascular endothelium after ischemia/reperfusion (IR) injury, five experimental groups were formed. The groups consisted of sham, control, iloprost treated (ILO), UK 38485 treated (TSI), and iloprost + UK 38485 treated (ILO + TSI) groups. The last three groups received the corresponding agents and then the superior mesenteric artery was clamped for 30 min followed by 90 min reperfusion. Endothelin levels in the portal blood and malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) levels in the intestinal tissue were determined. The MDA levels increased significantly in the control group and this increase was reversed in ILO, TSI, and ILO + TSI groups, the two drugs together showing a synergistic effect in preventing lipid peroxidation. The changes in the LTC4 levels were not significant among the groups. The increased endothelin levels in the control group were reversed in ILO and TSI groups but these two agents did not have a synergistic effect. Increased PGE2 levels were reversed with iloprost but neither UK 38485 nor the combination of the two agents was effective in decreasing PGE2 levels. It is concluded that endothelin release after mesenteric IR injury is relatively unrelated to lipid peroxidation and the lipoxygenase pathway. The cylooxygenase pathway has a direct effect on endothelin release and PGE2 may act as a mediator.

Effect of verapamil and iloprost (ZK 36374) on endothelin release after mesenteric ischemia-reperfusion injury.

In this experimental study we studied the effect of verapamil and iloprost on endothelin release in ischemia/reperfusion (IR) injury of the rat intestine. Endothelin levels in the portal blood and malondialdehyde (MDA), PGE2, and LTC4 levels in the intestinal tissue were determined. The MDA levels increased in the control group and this increase was reversed with iloprost, verapamil and both. The change in the LTC4 levels was insignificant between the groups. Iloprost reduced PGE2 and endothelin release, but verapamil was not as effective and no synergistic effect was encountered. The increased PGE2/LTC4 ratio was also reversed in the experimental groups, verapamil being less effective. Endothelin release seems to be related to both PGE2 levels and the PGE2/LTC4 ratio after mesenteric IR injury.

Captopril increases endothelin serum concentrations and preserves intestinal mucosa after mesenteric ischemia-reperfusion injury.

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Captopril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibitors, contains a sulfhydryl (-SH) group and can act as a free radical scavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and mimics the effects of this compound. This study was designed to investigate the effect of ILO and CPT on the mechanism of endothelin (ET) release after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sprague-Dawley rats were divided into five groups: sham-operated, control, ILO (25 micrograms/kg), CPT (10 micrograms/kg), and ILO + CPT. The superior mesenteric artery was occluded for 30 min and then allowed 90 min of reperfusion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to I/R injury. After I/R injury, portal venous blood was obtained for ET assay, and ileal tissue samples were also obtained for the determination of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) and for histopathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO + CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased in the control group, and this increase was reversed with ILO. In the CPT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latter being more prominent histopathologically. CPT exerts a significant protective effect on the intestinal mucosa after I/R injury. This protection is accomplished by increased ET levels and seems to be unrelated to its inhibitory effect on lipid peroxidation and also unrelated to the arachidonic acid cascade.

Surgical treatment of hepatic hydatid cysts.

Ninety-two surgical procedures were carried out in 82 patients with 92 hepatic hydatid cysts. The most common complication of the hydatid cyst was biliary rupture (17.3%) followed by infection of the cyst cavity (5.4%). Omentoplasty was carried out for uncomplicated cysts (38.0%) with a low morbidity (14.2%) and short hospital stay (mean 12.8 days). External tube drainage was carried out in 30.5% of patients. The morbidity rate was 67.8% and the mean hospital stay was 19.8 days. No single method can be recommended for the treatment of hepatic hydatid cysts but the choice of the surgical method must be made according to the complications of the cyst. Omentoplasty is the procedure of choice for uncomplicated cysts with a low complication rate and relatively short hospital stay. External tube drainage is recommended for infected cysts and a biliary drainage procedure must be added to external tube drainage for cysts with intrabiliary rupture.

Sacrococcygeal hydatid cyst: another entity in the differential diagnosis of sacrococcygeal chordoma. Case report.

A case of hydatid disease of the sacrum with severe neurological symptoms, which was misdiagnosed preoperatively as a chordoma, is presented. The patient had significant improvement of the neurological symptoms after evacuation of the cyst. Sacral hydatid cysts must be considered in the differential diagnosis of sacrococcygeal chordoma.