Development and validation of glycoprotein-based native-subunit vaccine for fish against Aeromonas hydrophila.

Aeromonas hydrophila is known to be causative agent of an infection named as Bacterial haemorrhagic septicaemia or red pest in freshwater fish. The aim of this study was to develop and validate the glycoprotein-based fish vaccine against Aeromonas hydrophila. For this aim, after identification and characterization of A. hydrophila isolates from fish farms, one A. hydrophila isolate was selected as vaccine strain. Antigenic glycoproteins of this vaccine strain were determined by Western blotting and glycan detection kit. The connection types of these glycoproteins were examined by glycoprotein differentiation kit. Two glycoproteins, molecular weights of 19 and 38 kDa, with SNA connection type were selected for use in vaccination trials. After their purification by SNA-specific lectin and size-exclusion chromatography, protection studies with purified proteins were performed. For challenge trials, four experimental fish groups were designated: Group I (with montanide), Group II (with montanide and ginseng), Group III [with Al(OH)3 ] and Group IV [with Al(OH)3 and ginseng]. The survival ratings of fish were determined, and protection was calculated as 21.56%, 29.41%, 69.83% and 78.88% in groups I, II, III and IV, respectively. In conclusion, A. hydrophila glycoproteins with Al(OH)3 and ginseng could be used as a safe and effective vaccine for fish.

Immunohistochemical evaluation of experimental Vagococcus salmoninarum infection in rainbow trout (Oncorhynchus mykiss, Walbaum 1792).

The aim of this study was to investigate the pathogenesis and histopathological and immunohistochemical findings in rainbow trout (Oncorhynchus mykiss) following experimental vagococcosis. For this purpose, 60 rainbow trout were used. The experimental study used the pathogen Vagococcus salmoninarum. The fish were intraperitoneally (IP) administered with an inoculate containing 0.1 mL of the bacteria, resulting in a dose of 1.2 × 10(9) cfu mL(-1) per fish. For histopathological observations, tissue samples were taken from fish that died during the experiment and fish that survived until the end of the trial (60th day). All the tissue samples were immunohistochemically stained by the avidin-biotin-peroxidase complex and immunofluorescence methods using polyclonal antibody to detect V. salmoninarum antigens. In immunoperoxidase staining, positive reactions to bacterial antigens were most commonly seen in the kidney, heart and liver. In the immunofluorescence analysis, the distribution of antigens in the tissue and organs was similar to that observed with the immunoperoxidase staining. The results reveal an important correlation between histochemical and immunohistochemical staining in demonstrating the distribution of V. salmoninarum antigens in the affected tissues.

Molecular typing of Staphylococcus aureus strains from ovine mastitis by pulsed-field gel electrophoresis and polymerase chain reaction based on coagulase and protein A gene polymorphisms.

Staphylococcus aureus is one of the most important etiologic agents of ovine mastitis. To develop effective control measures for mastitis, it is important to type S. aureus strains that have considerable genetic heterogeneity. In the current study, 47 S. aureus strains isolated from ovine mastitis were typed by polymerase chain reaction (PCR) based on coagulase (coa) and protein A (spa) polymorphisms and by pulsed-field gel electrophoresis (PFGE). Eight different coa types and 4 spa types were identified by PCR. While the most prevalent coa type was CG2 (42.56%), the spa types S4 and S1 were the most commonly observed (44.68% and 38.29%, respectively). Nineteen different pulsotypes were identified, and 12 of these were represented by a single isolate. Pulsotypes J and K were predominant and each represented 9 isolates (19.14%). All isolates belonging to J and K pulsotypes were CG2. Although all 9 isolates belonging to the J pulsotype were S4, all isolates in the K pulsotype were S1. While PFGE was found to be the best discriminatory technique for distinguishing strains, coa and spa types were found to be in correlation with PFGE types and can be used for quick, preliminary epidemiologic studies for detecting strains that may cause mastitis.

Comparison of the effects of sodium nitroprusside and L-carnitine in experimental ischemia-reperfusion injury in rats.

AIM: The aim of this study was to evaluate the protective effect of sodium nitroprusside (SNP) as a nitric oxide (NO) donor and L-carnitine intraperitoneal administration to treat experimental ischemia-reperfusion (I/R) in rats. MATERIALS AND METHODS: Rats were divided into four groups, each one consisting of 10 animals. Group 1 was subjected to a sham operation. In group 2, an I/R process was applied to the rats. In group 3, SNP (5 mg/kg) and in group 4, L-carnitine (500 mg/kg) was administered in addition to the I/R process. Ileal tissue samples were obtained for analysis of tissue malonyl dialdehyde (MDA) and for histopathologic examination. RESULTS: By histopathologic examination, the I/R group showed a significant difference from the SNP and L-carnitine groups (P<.05). There was no difference between the sham, the SNP, and the L-carnitine groups (P>.05). SNP used as an NO donor produced a significant decrease in MDA levels. There was a significant difference between the MDA levels of the SNP and the I/R groups (P<.05). Also, the difference between this group and the I/R group was significant (P<.05). CONCLUSION: SNP helped to both prevent and reduce mucosal damage in terms of histological and tissue MDA levels. Since the results of the L-carnitine group and the SNP group were similar, L-carnitine was as effective as exogenous NO.

Effect of tamoxifen on serum IL-18, vascular endothelial growth factor and nitric oxide activities in breast carcinoma patients.

Vascular endothelial growth factor (VEGF) is a multi-functional cytokine that has been suggested to be a major angiogenic factor in breast cancer. Nitric oxide (NO) is a potent biological molecule that participates in the multi-step process of carcinogenesis. Interleukin (IL)-18 has been shown to have potent anti-tumour effects. In this study, we investigated the effect of tamoxifen therapy on serum VEGF, NO and IL-18 activity in breast cancer patients. Serum levels of VEGF, nitrate + nitrite and IL-18 were measured in 34 postmenopausal breast cancer patients before and 3 months after the tamoxifen therapy. Both serum VEGF and IL-18 levels decreased after tamoxifen therapy (P = 0.051, P < 0.05, respectively). Serum VEGF levels increased in patients with endometrial thickness, while patients without endometrial thickness had a significant reduction in serum VEGF levels after therapy (P < 0.05). Serum nitrate + nitrite levels increased after the therapy, but this was not statistically significant (P > 0.05). A decrease in serum VEGF levels with tamoxifen therapy may be a reflection of reduced angiogenic activity in patients without endometrial thickness. The negative effect of tamoxifen therapy on IL-18, which is known to have a potent antitumour activity, may be related to the decreased tumour growth by induction of NO and reduction of VEGF activity as a feedback mechanism.

No association between serum levels of insulin-like growth factor-I, vascular endothelial growth factor, prolactin and clinicopathological characteristics of breast carcinoma after surgery.

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis. Vascular endothelial growth factor (VEGF) has been suggested as the major angio-genic factor in breast carcinoma. Both insulin-like growth factor-I (IGF-I) and prolactin are involved in the progression of breast cancer at least partly by stimulating angiogenesis. AIM: The aim of the present study was to investigate the association between serum IGF-I, VEGF and prolactin levels and clinicopathological characteristics of breast carcinoma. METHODS: Serum IGF-I, VEGF and prolactin levels were measured in breast cancer patients and controls and these levels were compared with well-known clinicopathological characteristics of breast carcinoma, including tumour size, axillary lymph node and oestrogen/progesterone receptor status, tumour grade and disease stage. RESULTS: Serum prolactin, VEGF and IGF-I levels were found to be similar in breast cancer patients and control subjects (P > 0.05). When the patients were divided into groups according to their tumour size, axillary lymph node status, tumour grade, oestrogen/progesterone receptor status and disease stage, no significant differences in serum prolactin, VEGF and IGF-I levels were found among the groups (P > 0.05). CONCLUSIONS: The present study failed to demonstrate an association between serum levels of VEGF, IGF-I and prolactin and well-known clinicopathological characteristics of breast carcinoma.

Effect of different neoadjuvant chemotherapy regimens on locally advanced breast cancer.

In this retrospective study, we evaluated the results of 91 locally advanced breast cancer (LABC) patients (30 patients in stage IIIA - 33.0%, 61 patients in stage IIIB - 67.0%) who had been treated with different neoadjuvant chemotherapy regimens. Forty-three (47.3%) patients treated with FAC (5-Fluorouracil, doxorubicin, cyclophosphamide) or CA (cyclophosphamide, doxorubicin), 33 (36.3%) with FEC (5-Fluorouracil, epirubicin, cyclophosphamide) or CE (cyclophosphamide, epirubicin) and 15 (16.5%) with CMF (cyclophosphamide, methotrexate, 5-Fluorouracil) combination as neoadjuvant setting. Median follow-up duration was 33 (6-116) months in 91 patients. There was no significant difference in the pretreatment characteristics of patients receiving FAC/CA, FEC/CE and CMF including age, disease stage, menopausal and estrogen/progesteron receptor (ER/PR) status (p>0.05). In CMF group, no patient was treated with taxan as adjuvant setting. However, ten patients (30.3%) in FEC/CE group and 21 patients (48.8%) in FAC/CA group were treated with taxans. Overall response rate was lower in CMF group (60.0%), when compared to FEC/CE (81.9%) and FAC/CA (91.0%) groups (p<0.05). Median overall survival (OS) and diseases free survival (DFS) were similar in three groups; 28.0 months (range: 14.8-41.1) and 12.0 months (range: 5.3-18.6) in CMF, 45.0 months (range: 16.8-73.1) and 23.0 months (range: 0.0-48.6) in FEC/CE, 46.0 months (range: 41.1-50.8) and 22.0 months (range: 11.1-32.8) months in FAC/CA groups, respectively (p>0.05). In conclusion, overall response rates were found to be higher in anthracycline-based combinations than CMF, but these regimens had no additional survival advantage over CMF regimen. Long-term effects of these regimens should be investigated in further randomized trials.

Serum leptin, prolactin and vascular endothelial growth factor (VEGF) levels in patients with breast cancer.

Angiogenesis plays an important role in tumor growth and metastasis in solid tumors. VEGF is an important regulator of tumor angiogenesis. Both leptin and prolactin have also been suggested to have roles in the regulation of angiogenic process. In our study, we measured serum leptin, prolactin and VEGF levels in 30 metastatic, 55 non-metastatic breast cancer patients and 25 control subjects. Serum leptin levels were found to be similar in non-metastatic (38.1+/-19.5 ng/ml), metastatic patients (39.6+/-16.3 ng/ml) and control subjects (35.6+/-13.9 ng/ml) (p>0.05). There was no statistically significant difference between patients with visceral metastasis (44.0+/-16.8 ng/ml) and patients with bone metastasis (35.2+/-15.0 ng/ml) (p>0.05). Serum prolactin levels were found to be similar in non-metastatic (12.2+/-10.7 ng/ml), metastatic patients (11.6+/-8.2 ng/ml) and control subjects (12.3+/-8.1 ng/ml), (p>0.05). Moreover, serum prolactin levels were not different in patients with visceral (11.4+/-8.8 ng/ml) and bone metastasis (11.8+/-8.0 ng/ml), (p>0.05). Metastatic patients had higher serum VEGF levels (249.8+/-154.9 pg/ml), when compared to the non-metastatic patients (138.7+/-59.3 pg/ml) and control subjects (108.4+/-47.7 pg/ml), (p<0.05). There was no difference in serum VEGF levels in non-metastatic patients and control subjects (p>0.05). Patients with visceral metastasis (337.0+/-168.0 pg/ml) had higher serum VEGF levels, when compared to patients with bone metastasis (162.6+71.8 pg/ml), (p<0.05). Serum VEGF activity may be used to evaluate angiogenic and metastatic activity in breast cancer patients. However, serum leptin and prolactin levels does not seem to be related with angiogenic activity and metastasis in breast cancer patients.

Using imprint and frozen sections in determining the surgical strategies for thyroid pathologies.

OBJECTIVE: To compare the diagnosis of thyroid pathological findings by using frozen section and preoperative imprint. METHODS: From January 1998 to December 1999, one hundred and three consecutive patients admitted to Department of Surgery, Gazi University Medical Faculty for thyroid operation, were prospectively included into the study. In all patients, imprint and frozen section were carried out from their suspected nodules and the results were compared with the permanent biopsy. Those findings used to find out sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of frozen section and imprint. Because of the definitive differentiation of malignant or benign lesions could not be done, three patient were excluded from the study. RESULTS: In our study; sensitivity, specificity, PPV, NPV and accuracy for imprints was found as 83.3%, 97.7%, 83.3%, 97.7% and 96% (respectively), while respective corresponding data for frozen section were 81.8%, 96.6%, 75%, 97.7% and 95%. In one patient, the pathological finding of follicular carcinoma as found by permanent section was accurately diagnosed by imprint, but missed by frozen section. Both the imprint and frozen section failed to diagnose two papillary carcinoma. Overall cancer rate among 103 patients was 12 % (nine papillary carcinoma, one Hürthle cell carcinoma and two follicular carcinoma). CONCLUSION: Both the frozen sections and imprints showed high sensitivity rate and similar accuracy rates. So, if there is no opportunity for frozen section, the imprints could be used. Furthermore, the use of imprints is less time consuming and less expensive than that of frozen sections.

Protective effect of a lipoxygenase inhibitor, nordihydroguaretic acid, on the ileal motor disturbances induced by Serratia marcescens endotoxin in rats.

This study was conducted to examine the effects of peptidoleukotrienes on the ileal contractility disturbances induced by Serratia marcescens endotoxin in rats. Thirty-two male Wistar rats were divided into four groups (n = 8 each). The first group was given only an anesthetic agent (control group); the second group was given the endotoxin (endotoxin group); the third group was given a lipoxygenase inhibitor, nordihydroguaretic acid (NDGA); and the fourth group was given NDGA 10 min before administration of the endotoxin (NDGA+endotoxin group). The isolated ileum response was recorded in each group. Normal contractile activity was seen in the control group. After the endotoxin was given. the isolated ileum did not respond to 497acetylcholine (ACh) in the endotoxin group, but the contractile results of isolated ileum to ACh were similar to the control group results in both the NDGA and endotoxin+NDGA groups. The results of this study demostrate that leukotrienes may play a role in endotoxin-induced ileal contractility disturbances, and that the lipoxygenase inhibitor, NDGA, could be useful for the treatment of ileal motility disturbances induced by endotoxin.

The effect of pentoxifylline on the healing of intestinal anastomosis in rats with experimental obstructive jaundice.

The aims of this study were (1) to investigate the effect of experimental obstructive jaundice on the healing of intestinal anastomosis, and (2) to investigate the effect of pentoxifylline on the healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after this operation, either pentoxifylline or isotonic saline solution was administered intraperitoneally to these jaundiced rats and controls, and then intestinal anastomosis was performed. The concentrations of serum tumor necrosis factor alpha (TNF-alpha) and serum triglyceride of jaundiced and nonjaundiced rats were measured, and the quality of healing was evaluated by measuring the bursting pressure and hydroxyproline content of the anastomoses on the fifth and tenth days of anastomotic healing. Obstructive jaundice resulted in an impaired wound healing of the intestinal anastomosis in the rats. The administration of pentoxifylline to the jaundiced rats resulted in better anastomotic wound healing. The beneficial effects of pentoxifylline on anastomotic healing in rats with obstructive jaundice was attributed to its inhibitor effect on the endotoxin-induced TNF-alpha release from macrophages and monocytes, and the stabilizing effect on the neutrophils.

Cisplatin plus vinorelbine as a salvage regimen in refractory breast cancer.

AIMS AND BACKGROUND: Breast cancer refractory to known effective agents is one of the major clinical problems frequently encountered in practice. Cisplatin and vinorelbine are known to be active drugs in anthracycline-refractory cases. In this phase II study, the effectiveness and tolerability of cisplatin and vinorelbine was investigated when used in combination as a salvage regimen in the treatment of metastatic refractory breast cancer. STUDY DESIGN: Twenty-four patients with advanced refractory breast cancer who had been previously treated with a regimen containing doxorubicin were included in the study. Six of the 24 patients also received taxanes after failure of doxorubicin. Cisplatin at 80 mg/m2 on day 1 and vinorelbine at 25 mg/m2 on days 1 and 8 were given every 3 weeks. RESULTS: A total of 98 cycles of chemotherapy was given, with a median of 4/patient. The response rate was 25% (2 [8.3%] complete and 4 [16.7%] partial responses). The median survival rates were 14 months in responders and 5.5 months in nonresponders (P = 0.0282). One complete and one partial response were observed in patients previously treated with paclitaxel (overall response rate, 33%). The median response duration was 12.5 mo (range, 4-21) in complete and 4.5 mo (range, 1.5-13) in the partial response group. Grade 3 and 4 neutropenia occurred in 9 patients, with no toxic deaths. Grade 2-3 nausea and vomiting in 6 patients and grade 1 neuropathy in 1 patient were noted. CONCLUSIONS: Although the number of cases is insufficient to indicate that the combination will be effective, it is noteworthy in consideration of anthracycline and taxane refractory cases. A combination of cisplatin and vinorelbine seems to be a reasonable and acceptable choice as an alternative salvage regimen in such cases.

Huerthle cell neoplasms of the thyroid: predicting malignant potential.

OBJECTIVE: Assessment of malignancy criteria in Huerthle cell neoplasm. METHODS: This study intends to review retrospectively the patients who were operated for Huerthle cell neoplasia at Gazi University, Department of General Surgery between January 1986 and October 1999. Pathological specimens from 63 patients (20 males and 43 females) were investigated in this study, 48 of which revealed Huerthle cell adenoma and 15 revealed Huerthle cell carcinoma. The mean age of the patients with Huerthle cell adenoma was 40.7+/-1.59 yr while it was 51.3+/-1.83 yr in patients with Huerthle cell carcinoma. Mann-Whitney U and Chi-square tests were used for statistical analysis. RESULTS: . Fifty-two of the 63 patients had fine needle aspiration (FNA) biopsy prior to operation, 49 of those were reported to have suspected Huerthle cell neoplasia (HCN) and three had suspected Huerthle cell carcinoma (HCC). The sensitivity of FNA for HCN was 20 %, specificity was 100 %, positive predictive value was 100 % and negative predictive value was 76 %. For all patients, peroperative frozen section (FS) biopsy was examined. Fifty-nine of the FS specimens revealed HCN and four revealed HCC. The sensitivity, specificity, positive predictive value and negative predictive value of FS biopsy were 27 %, 79 %, 28.5 % and 77.5 %, respectively. In this retrospective study, there was a statistically significant correlation between malignancy and the size of the tumor (P<0.05) according to Chi-square test, and also a statistically significant correlation between malignancy and the age of the patient (P<0.05) according to Mann-Whitney U test. CONCLUSIONS: In cases where FS and FNA biopsies cannot adequately define the benign or malignant behaviour of the tumor, the age of the patient and the diameter of the tumor must be taken into consideration for accurate surgical strategy. Particularly for 50 year-old and elderly, incidence of malignancy is statistically significant without considering sex of the patient.

Preoperative fine-needle aspiration cytology versus frozen section in thyroid surgery.

OBJECTIVE: In a double blind prospective clinical study to evaluate the diagnostic potential of peroperative fine needle aspiration cytology as compared to peroperative frozen section in thyroid surgery. METHODS: The diagnostic value of one hundred consecutive preoperative (FNA) and peroperative fine needle aspiration (p-FNA), frozen section (FS) and permanent section (PS) examination for thyroid nodules were studied prospectively in order to assess and compare the accuracy, sensitivity and specificity. RESULTS: Out of 100 patients PS showed 11 % of malignancies, while p-FNA showed 5 % and FS showed 6% of malignant cases with no false positive, but with 6 and 5 false negative results, respectively. Thus, as compared with FS, one false negative finding was obtained by p-FNA in a case of malignant tumor which could be definitely ascertained by frozen section technique. However, concerning the benign nodules no differences were found between p-FNA and FS. CONCLUSIONS: Peroperative fine needle aspiration seems to be a useful method which can be properly performed because the nodule can be easily seen during the surgical procedure. However, further clinical observations of large numbers of patients are needed.

The cytoprotective effect of iloprost against carbon tetrachloride induced necrosis in rat liver.

The aim of this study was to investigate the cytoprotective effect of Iloprost on the liver against carbon tetrachloride induced necrosis. The serum histamine-like activity was found to be increased when compared with that of controls after treatment with carbon tetrachloride for 18 weeks while prostaglandin E2- and leukotriene C4-like activities were unchanged. After pretreatment with Iloprost for 18 weeks the increased activity of histamine was found to be unchanged while prostaglandin E2-like activity was increased. It is concluded that Iloprost protects the liver against carbon tetrachloride-induced damage and reduces the level of histamine that has a role in the pathogenesis of portal hypertension.

The effects of indomethacin, NDGA, allopurinol and superoxide dismutase on prostaglandin E2 and leukotriene C4 levels after mesenteric ischemia-reperfusion injury.

In this study, the changes of arachidonic acid metabolites after an ischemia-reperfusion (I/R) period are investigated. The cyclooxygenase and lipoxygenase metabolites were found to be significantly increased after a 45 min period of ischemia followed by 5 min of reperfusion. Prostaglandin E2 (PGE2)- and leukotriene C4 (LTC4)-like activities did not change in the ischemic period, but they both increased after reperfusion. A cyclooxygenase inhibitor indomethacin and lipoxygenase inhibitor nordehydroguaretic acid (NDGA) decreased PGE2- and LTC4-like activities, respectively, while allopurinol and superoxide dismutase (SOD) decreased both activities. According to our results, it can be assumed that free oxygen radicals are responsible for the elevation of PGE2- and LTC4-like activities and both of these arachidonic acid metabolites and free oxygen radicals are the main necrotizing agents in ischemia-reperfusion induced damage.

The comparison of vascular reactivities of arterial and venous grafts to vasodilators: management of graft spasm.

Graft spasm in the perioperative or postoperative period increases the risk of morbidity and mortality after coronary revascularization and hence necessitates urgent treatment. We have studied the effects of various vasodilators against noradrenaline- and endothelin-1-induced spasms in saphenous vein, internal mammary artery and gastroepiploic artery. In internal mammary and gastroepiploic arteries, the nitrovasodilators, sodium nitroprusside and glyceryl trinitrate, effectively reversed the spasms induced either with noradrenaline (for sodium nitroprusside; internal mammary artery: 101.07% +/- 1.63%; gastroepiploic artery: 94.10% +/- 2.07%) or endothelin-1 (for sodium nitroprusside; internal mammary artery: 97.67% +/- 4.94%; gastroepiploic artery: 90.69% +/- 2.61%). However, in saphenous vein contracted with endothelin-1, the responsiveness to nitrovasodilators was significantly blunted (for sodium nitroprusside: 52.33% +/- 5.19%) than that of rings contracted with noradrenaline (for sodium nitroprusside: 95.04% +/- 1.94%). Both arterial and venous grafts exhibited moderate beta-receptor function in response to isoproterenol. Isoproterenol was less effective in inhibiting the contractions of endothelin-1 in saphenous vein and gastroepiploic artery but not in internal mammary artery. On the other hand, nifedipine and papaverine were fully effective in reversing all the spasms in three of the graft materials. From these results, it can be deduced that saphenous vein is refractory against cyclic guanidine monophosphate (cGMP)-dependent and beta-receptor mediated relaxations when endothelin-1 was used as the spasmogenic agent. Internal mammary artery is the most responsive graft material to the vasodilators regardless of the nature of spasmogenic stimulus. Gastroepiploic artery exhibits functional similarity with internal mammary artery, with the exception of beta-receptor responsiveness.

The effects of prostacyclin analogue ZK 36374 and thromboxane synthetase inhibitor UK 38485 on mesenteric ischemia in guinea pigs.

The effects of ZK 36374, a prostacyclin analogue and UK 38485, a thromboxane synthetase inhibitor were studied in guinea pigs after performing mesenteric arterial occlusion. In this study, while ZK 36374 significantly lowered the alkaline phosphatase and creatine phosphokinase values two hours after mesenteric arterial occlusion when compared with the control group (p less than 0.005), UK 38485 did not induce any change. In guinea pigs, when given together, ZK 36374 and UK 38485 lowered the enzyme levels to preligation values and the difference was nonsignificant (p greater than 0.1). The histopathologic investigation of the small intestine after giving ZK 36374 and UK 38345 together revealed minimal changes. These findings stress the importance of preserving the PGI2 levels in the PGI2/TXA2 ratio in preventing the increase of lysosomal enzyme levels and histopathologic changes after mesenteric arterial occlusion in guinea pigs.

The effects of nocloprost, nileprost, iloprost and (15 S)-15-methyl-PGE2 on gastric mucosal damage induced by stress, indomethacin and ethanol.

The preventive effects of nocloprost, nileprost, iloprost and (15S)-15-Methyl-prostaglandin E2 were studied in the rat gastric mucosal damage induced by restraint-cold stress, indomethacin and ethanol. Nocloprost was found to be the most potent orally active compound against rat mucosal damage induced by all noxious stimuli used in this study. Both nocloprost and iloprost were more effective on stress-induced ulcers than on those induced by indomethacin and ethanol. Nocloprost and 15-methyl prostaglandin E2 were also more active on ethanol-induced mucosal damage than on induced by indomethacin. No significant differences were obtained with iloprost and nileprost on indomethacin and ethanol-induced mucosal injury. These results indicate a more potent oral antiulcer activity of nocloprost.

Protective effect of iloprost and UK 38 485 against gastric mucosal damage induced by various stimuli.

This study was undertaken to evaluate the efficacy of iloprost and UK 38485 in the prevention of gastric lesions due to restraint-cold stress, ethanol or indomethacin. Prior injection of iloprost to the rats significantly prevented the increase in ulcer index by restraint- cold stress or indomethacin but nonsignificantly reduced the ulcer index induced by ethanol. UK 38 485 at lower doses caused a highly significant decrease in the ulcer index induced by all noxious stimuli used in this study. UK 38 485 also reduced the increased 3H back diffusion due to restraint-cold stress. Higher doses of the compound, however, failed to decrease the mucosal damage due to restraint-cold stress. Combination of iloprost and UK 38 485 produced a further significant decrease in the ulcer index induced by all noxious stimuli and increased 3H back diffusion induced by restraint-cold stress. In relation to these results the importance of PGI2/TXA2 ratio in the production of gastric mucosal lesions is discussed.