The effects of sirolimus on target organs during mesenteric ischemia and reperfusion damage in an experimental rat model.

BACKGROUND: Mesenteric ischemia and reperfusion (I/R) syndrome (MIRS) has been considered a clinicopathologic entity associated with a variety of clinically severe conditions with decreased intestinal blood flow and has been known to induce I/R damage in various organs. Sirolimus (SRL), a macrolide antibiotic isolated from a strain of Streptomyces hygroscopicus, is a potent and nonnephrotoxic immunosuppressant. OBJECTIVE: This study was designed to investigate the potential impact of sirolimus on MIRS-induced I/R damage in renal, intestinal, pulmonary, and hepatic tissues in an experimental rat model. METHODS: Twenty-four male Sprague-Dawley rats, aged 6 to 8 weeks and weighing 280 (±20 g), were studied. Using computer-generated random numbers, rats were assigned to 1 of the following 3 groups: group 1 (I/R group, n = 8), group 2 (I/R + sirolimus group, n = 8), and group 3 (control group, n = 8). Sirolimus, in a 1 mg/mL (60 mL) solution, was administered intraperitoneally in a dose of 1.5 mg/kg/d to the rats assigned to group 2 starting from 3 days before the surgical procedure. In surgery, a laparotomy was performed to clamp the superior mesenteric artery and, thus, induce bowel ischemia in groups 1 and 2. After 60 minutes of ischemia, the microvascular clamp on the superior mesenteric artery was removed for 3 hours of reperfusion. Soon after experimental induction of MIRS, bowel, lung, kidney, and liver specimens from each animal were harvested for both biochemical and histopathologic analysis. RESULTS: There were statistically significant differences between groups 1 and 3 with regard to degrees of intestinal (P < 0.001), hepatic (P = 0.001), renal (P < 0.001), and pulmonary (P = 0.01) I/R damage. The lung specimens from group 2 had less inflammation and perivascular edema formation compared with specimens from group 1, but no statistical significance was observed between the groups (P < 0.33). There were statistically significant differences between groups 1 and 2 with regard to degrees of intestinal, hepatic, and renal I/R damage (P = 0.001 for all). CONCLUSION: The findings of the present study demonstrate the attenuating effects of sirolimus on I/R damage in the intestine and remote organs, including the liver and kidney in the setting of MIRS in an experimental rat model. As a therapeutic implication, the utility of sirolimus may be of clinical value in procedures associated with a high likelihood of I/R damage, including major abdominal operations and renal transplantation. However, whether these results apply to humans is unclear. Additional experimental and clinical studies are warranted to confirm the clinical utility of sirolimus in conditions potentially associated with I/R damage.

Mucins, trefoil factors and pancreatic duodenal homeobox 1 expression in spasmolytic polypeptide expressing metaplasia and intestinal metaplasia adjacent to gastric carcinomas.

INTRODUCTION: Gastric cancers are the second cause of cancer related deaths all around the world but gastric carcinogenesis remains a mystery. Intestinal metaplasia (IM) and spasmolytic polypeptide expressing metaplasia (SPEM) are the two types of preneoplastic metaplasias. In this study, we aimed to investigate expression of Pancreatic duodenal homeobox 1 (PDX1), mucins (MUCs), trefoil factors (TFFs) in SPEM and IM surrounding gastric carcinomas. MATERIAL AND METHODS: Tissue samples of tumor adjacent gastric mucosa including IM (n = 61) and SPEM (n = 36) from 70 gastrectomy specimens were used for immunohistochemical analysis of PDX1, mucins (MUC5AC, MUC6) and trefoil factors (TFF2, TFF3). RESULTS: Nuclear expression of PDX1 was present in both SPEM (32/36) and IM (60/61) and there was no significant difference in expression of PDX1 between the two types of metaplasias. While TFF3 and MUC5AC were abundant in IM, SPEM showed 100% expression of TFF2 and MUC6 and also lower positivity with TFF3 and MUC5AC. PDX1 positivity was related to expression of MUC5AC (60/61, p < 0.001) and TFF3 (60/61, p < 0.001) in IM and also associated with expression of MUC5AC (14/32, p < 0.05), MUC6 (32/32, p < 0.001), TFF2 (32/32, p < 0.001) and TFF3 (9/32, p < 0.05) in SPEM. Coexpression of TFF3 and TFF2 was present in 10 of 36 (27.7%) samples of SPEM and also 29 of 61 (47.5%) samples of IM exhibited dual expression of trefoil peptides. CONCLUSIONS: PDX1 may affect the development of SPEM and IM. Expression patterns of TFFs and MUCs may indicate that IM evolves from SPEM.

Value of dynamic contrast-enhanced MRI and correlation with tumor angiogenesis in bladder cancer.

OBJECTIVE: The aim of this study was to investigate dynamic contrast-enhanced MRI (DCE-MRI) for the noninvasive measurement of bladder cancer angiogenesis by correlation with microvessel density, histologic grade, and tumor staging, and to predict the outcome of local recurrence. MATERIALS AND METHODS: Twenty-four patients with bladder cancer were examined using DCE-MRI. Hemodynamic parameters obtained by DCE-MRI included peak time enhancement in the first minute (E(max/1)) after contrast administration, second minute (E(max/2)), third minute (E(max/3)), fourth minute (E(max/4)), and fifth minute (E(max/5)), and the steepest slope. Microvessel density was identified by immunostaining of endothelial cells using FVIII-related antigen. The Mann-Whitney U test, multivariate discriminant analysis, Spearman's correlation coefficient, and analysis of variance were used for statistical analysis. RESULTS: Correlation was seen between DCE-MRI parameters (E(max/1) and steepest slope) and microvessel density (p < 0.05). E(max/1) and steepest slope were found to have a statistically significant correlation with histologic grade (p < 0.05 and p < 0.01, respectively). A significant difference was seen between groups of patients with and without local recurrence with regard to two of the DCE-MRI parameters (p < 0.05 for E(max/1) and E(max/2)). CONCLUSION: The contrast enhancement patterns on DCE-MRI are influenced by tumor angiogenesis, as reflected by elevated microvessel density expression. Therefore, they are valuable indicators for assessing tumor angiogenic activity and tumor neovascularization in bladder cancers.

The effects of long-term low-dose cyclosporin A treatment on muscles and tendons: an experimental study.

BACKGROUND: Limited studies report that patients receiving immunosuppressive therapy, including cyclosporin A (CsA), face muscle and/or tendon pathologies. The current study aimed (i) to investigate if CsA cause changes in the microscopic structure of striated muscle tissues and tendons after long-term low-dose therapy and (ii) to examine if the vehicle of CsA, Cremophor EL, or steroid administration might cause additional effects. METHODS: Twenty-four adult female Sprague-Dawley rats weighing 230-300 g were divided at random into four groups. Group 1 served as the control. Groups 2-4 received CsA intraperitoneally for 2.5 months: Group 2 received the oral form of CsA, Group 3 received the intravenous form of CsA, which contains Cremophor EL, and Group 4 received the intravenous form of CsA and prednisolone. Samples from the Achilles tendons and triceps surae muscles were examined at light microscope level. RESULTS: Focal necrotic areas, enlargement of connective tissue and increase in mononuclear cells were clear on muscles in the experimental groups. No morphologic effects were observed on tendons. CONCLUSION: Long-term low-dose CsA therapy causes focal microscopic changes in muscles but not in tendons. No additional effects were demonstrated with Cremophor EL or steroids. It should be noted that muscle tissue damage after trauma or surgeries in patients receiving CsA might be more dramatic due to the pathologic changes already caused by CsA, as supported by several case reports.

Protective effects of L-arginine on rat terminal ileum subjected to ischemia/reperfusion.

OBJECTIVES: Studies have shown that nitric oxide (NO) may play a major role in sustaining mucosal integrity; however, NO has been also implicated in the pathogenesis of ischemia/reperfusion (I/R)-related tissue injury. We investigated the effects of L-arginine and NG-nitro L-arginine methyl ester (L-NAME) on the acetylcholine-induced contractile response of ileum and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). Histopathological changes were also evaluated in ileal preparations. MATERIALS AND METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 hours). Four groups were designed: sham-operated control; I/R; I/R and L-arginine pretreatment; and I/R and L-NAME pretreatment. After reperfusion, ileum specimens were collected to determine the parameters mentioned above. RESULTS: Following reperfusion, a significant decrease in acetylcholine-induced contractile response, an increase in lipid peroxidation, a decrease in GSH content, and mucosal damage of the ileal preparations were observed. We showed that decreased contractility, increased lipid peroxidation, and reduced GSH content have been reversed by L-arginine but not by L-NAME. Mucosal injury was significantly lowered in the L-arginine group. CONCLUSIONS: Treatment with L-arginine exerted a protective effect in intestinal I/R injury, which was mediated in part by regulating MDA and GSH levels, consequently ameliorating impaired contractile response and mucosal injury.

Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat.

OBJECTIVE: Curcumin has antioxidant, antitumor, and anti-inflammatory properties. However, it remains unknown whether curcumin has any protective effects on sepsis. The purpose of this study was to demonstrate whether curcumin prevents organ dysfunction in animals with sepsis. METHODS: Rats were randomized into four groups. The control group (group I, n = 7) did not receive any treatment. The curcumin group (group II, n = 10) only received 1.2 g/kg of curcumin. Escherichia coli were injected into the remaining groups intraperitoneally after general anesthesia. Five hours after injection, 12 rats received placebo (group III), and 10 rats received 1.2 g/kg of curcumin (group IV) for 7 d. All rats were sacrificed on postsepsis day 8 and a midline laparotomy was performed. Livers, kidneys, and small bowels were excised for evaluation of the degree of inflammation and tissue alterations histopathologically. RESULTS: In the liver, widespread hydropic degeneration of hepatocytes were seen in the sepsis group. There was no hydropic degeneration of hepatocytes and no portal inflammation in the sepsis/curcumin group. With respect to the small bowel, the sepsis group showed edema and prominent intraepithelial infiltration of neutrophil leucocytes and plasma cells. Inflammation and hyperemia in the lamina propria in the sepsis/curcumin group were less than those in the sepsis group. With respect to the kidneys, the sepsis group showed severe acute tubular necrosis that was more restricted in the sepsis/curcumin group than in the sepsis group. CONCLUSION: Curcumin reduced organ dysfunction in rats with experimentally formed sepsis. We propose that curcumin may be useful in the therapy of organ dysfunction due to sepsis, shock, and other diseases associated with local or systemic inflammation.

[Papillary carcinoma arising from a thyroglossal duct cyst]. / Tiroglossal duktus kistinden kaynaklanan papiller karsinom.

Thyroglossal duct cyst is the most common midline congenital neck anomaly. Carcinoma arising from a thyroglossal duct cyst is a rare entity, the most common histological type being papillary carcinoma. A 23-year-old male patient presented with a painless mass at the level of the hyoid bone in the midline of the neck. It was mobile on swallowing. With an initial diagnosis of thyroglossal duct cyst, the lesion was removed with the Sistrunk procedure. Histopathological examination of the surgical specimen showed papillary carcinoma arising from the thyroglossal duct cyst. Thyroid suppression therapy was initiated postoperatively. The patient has been under follow-up for 30 months with no recurrence.

Effect of Topical Dexamethasone for Preventing Experimentally Induced Myringosclerosis.

OBJECTIVE: We aimed to examine the effect of topical dexamethasone by otomicroscopic and histologic examinations for preventing myringosclerosis induced by myringotomy in rat tympanic membranes. METHODS: Twenty-one Sprague Dawley rats (42 ears) were randomly divided into the following three groups after otomicroscopic examinations: experimental surgical group (5 rats), control group (8 rats), and study group (8 rats). The rats of all the groups underwent myringotomy in both tympanic membranes. Other than myringotomy, no additional procedure was performed for the rats in the experimental surgical group. In the control group, 0.9% NaCl was applied to the ears, whereas in the study groups, topical dexamethasone was applied to the ears. These applications in the control and study groups were repeated for nine days. On the 10th day of the study, the rat ears of all groups underwent otomicroscopic and histologic examinations. The prevalence and process of myringosclerosis were evaluated by otomicroscopic examination, whereas inflammation, membrane thickness, and myringosclerosis intensity were evaluated by histologic examination. RESULTS: The growth of myringosclerosis with otomicroscopic examination was lesser in the study group in which topical dexamethasone was applied than the control and the experimental surgical groups. Moreover, it was observed that myringosclerosis effected fewer quadrants in the study group.Histologic examinations revealed that inflammation was significantly lesser in the study group than in the experimental surgical and control groups. The average membrane thickness values were significantly lesser in the study group than in the experimental surgical group. With respect to myringosclerosis growth, no statistically significant difference was observed among all groups, whereas with respect to myringosclerosis intensity, the rat ears in the study group were less severely affected. CONCLUSION: Thus, our study results suggest that applying topical dexamethasone after myringotomy has positive effects on limiting the intensity and prevalence of myringosclerosis.

Antioxidants vitamin E and C attenuate hepatic fibrosis in biliary-obstructed rats.

AIM: To investigate whether antioxidants vitamin E and C can retard development of hepatic fibrosis in the biliary-obstructed rats. METHODS: Fifty Wistar albino rats were randomly assigned to 5 groups (10 rats in each). Bile duct was ligated in 40 rats and they were treated as follows: group vitC, vitamin C 10 mg/kg sc daily; group vitE, vitamin E 15 mg/kg sc daily; group vitEC, both of the vitamins; bile duct-ligated (BDL, control) group, physiological saline sc. The fifth group was assigned to sham operation. At the end of fourth week, the rats were decapitated, and hepatic tissue biochemical collagen content and collagen surface area were measured. Hepatic tissue specimens were histopathologically evaluated according to Scheuer system. Serum hyaluronate levels were measured by ELISA method. RESULTS: Despite being higher than sham group, hepatic collagen level was significantly decreased in each of the vitC, vitE and vitEC groups (32.7 +/- 1.2, 33.8 +/- 2.9, 36.7 +/- 0.5 mug collagen/mg protein, respectively) compared to BDL (48.3 +/- 0.6 mg collagen/g protein) (P < 0.001 for each vitamin group). Each isolated vitamin C, isolated vitamin E and combined vitamin E/C supplementation prevented the increase in hepatic collagen surface density (7.0% +/- 1.1%, 6.2% +/- 1.7%, 12.3% +/- 2.0%, respectively) compared to BDL (17.4% +/- 5.6%) (P < 0.05 for each). The same beneficial effect of vitamin C, vitamin E and combined vitamin E/C treatment was also observed on the decrease of serum hyaluronate levels compared to BDL group (P < 0.001). The relative liver and spleen weights, serum transaminases, cholestatic enzymes, bilirubins and histopathological inflammation scores were not different between the antioxidant treatment groups and the control. However, fibrosis staging scores were obviously reduced only in the vitamin E/C combination group (vit EC: 2.4 +/- 0.8 vs BDL: 3.1 +/- 0.7; P < 0.05). CONCLUSION: Each antioxidant vitamin E, vitamin C and their combination retard hepatic fibrosis in biliary-obstructed rats. Oxidative stress may play a role in the pathogenesis of hepatic fibrosis in secondary biliary cirrhosis.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

Nasopharyngeal carcinoma with extensive nodular skin metastases: a case report.

Skin metastasis from nasopharyngeal carcinoma is a rare clinical finding. The most common form of appearance is a few solitary skin nodules. However, massive and extensive nodular dissemination or diffuse dermal lymphatic infiltration is extremely rare. We here present a case of a 40-year-old man with widespread nodular skin metastases from undifferentiated nasopharyngeal carcinoma.

The correlation between TTF-1 immunoreactivity and the occurrence of lymph node metastases in patients with lung cancer.

AIMS AND BACKGROUND: Thyroid transcription factor (TTF-1) is a tissue-specific transcription factor expressed in the epithelial cells of thyroid and lung. The aim of this study was to evaluate the relationship between the expression of TTF-1 and clinico-pathological parameters in pulmonary adenocarcinoma and adenosquamous carcinoma. METHODS: Resection material of pneumonectomies and lobectomies of 39 patients was retrospectively examined. Twenty-eight patients were diagnosed with adenocarcinoma and 11 with adenosquamous carcinoma. Tumors were classified into 3 groups: a strongly positive group (++) with double dagger 50% tumor cells positive for TTF-1; a weakly positive group (+) with 1-49% positive tumor cells; and a negative group (-) with less than 1% or no positive tumor cells. Analysis was performed with Kaplan-Meier estimates and log-rank tests. RESULTS: Staining for TTF-1 was negative in 10 cases. There was focal staining in 9 cases, while there was diffuse staining in 20 (51%) cases out of 39, and 15 (75%) of these were adenocarcinomas. There was a statistically significant association between TTF-1 and lymph node metastases (P = 0.029). No relationship was found between TTF-1 positivity and disease-free and overall survival. CONCLUSIONS: TTF-1 expression may be a predictor of lymph node metastases. Additional work in a larger group of patients is needed to better assess the utility of this marker.

Effects of vitamins E and C supplementation on hepatic glutathione peroxidase activity and tissue injury associated with ethanol ingestion in malnourished rats.

BACKGROUND: Oxidative stress has been associated with tissue injury in alcoholic liver disease. Although this close association is well known, whether prevention of oxidative stress retards tissue injury has not been thoroughly investigated. OBJECTIVE: The aim of this study was to determine the effects of supplementation with vitamins E and C on antioxidant enzyme status and histologic changes in hepatic tissue in a rat model of alcoholic liver disease. METHODS: This 8-week, blinded, controlled study was conducted at the Department of Internal Medicine, Trakya University, Edirne, Turkey. Weanling albino female protein-deficient Wistar rats weighing ∼200 g were randomly assigned to 1 of 6 groups: (1) liquid diet+ethanol+vitamin E 15 mg/kg PO (LDetvitE); (2) liquid diet+ethanol+vitamin C 10 mg/kg PO (LDetvitC); (3) liquid diet+ethanol+vitamin E 15 mg/kg+vitamin C 10 mg/kg PO (LDetvitEC); (4) liquid diet+ethanol (LDet); (5) liquid diet+isocaloric sucrose (LDS); and (6) normal diet (control). The primary end point of the study was to determine whether antioxidant vitamin E/C combination therapy prevents development of hepatic fibrosis (ie, cirrhosis in a period of 1 year). After being euthanized at week 8, the rats were weighed, and their livers and spleens were weighed. Hepatic tissue specimens were histopathologically assessed according to the Brunt system. Hepatic tissue glutathione peroxidase, superoxide dismutase, and catalase activities were determined. Biochemical tissue collagen concentrations were measured to determine the presence of hepatic fibrosis. RESULTS: Seventy-two rats were included in the study (mean [SE] weight, 205 [21] g) (12 rats per group). Initially planned to last 48 weeks, the study was terminated at 8 weeks due to the death of 3 rats in each group (except the LDS group and control group). The relative liver weight was significantly lower in the LDetvitEC group compared with that in the LDet group (mean [SE], 3.7% [0.5%] vs 4.8% [0.9%]; P<0.01). Mean (SE) hepatic tissue glutathione peroxidase activity was significantly reduced in the LDet-treated rats compared with controls (1.2 [0.2] vs 2.6 [0.3] U/mg protein; P<0.001). The groups that received supplementation with vitamin E, vitamin C, and vitamins E and C combined had significantly more hepatic glutathione peroxidase activity (mean [SE], 2.1 [0.5], 2.5 [0.2], and 2.6 [0.7] U/mg protein, respectively) compared with the LDet group (1.2 [0.2] U/mg protein) (all, P<0.001). No significant between-group differences in hepatic superoxide dismutase or catalase activities were found. Compared with controls (14.5 [1.9] µg collagen/mg protein), the mean (SE) histologic hepatic collagen concentration was significantly higher in all groups (19.2 [1.2], 19.5 [3.3], 18.5 [3.0], 25.9 [3.3], and 21.6 [1.5] µg collagen/mg protein in the LDetvitE, LDetvitC, LDetvitEC, LDet, and LDS groups, respectively; P<0.01, P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Compared with the LDet group, the mean hepatic collagen concentration was significantly lower in the LDetvitE, LDetvitC, and LDetvitEC groups (P<0.01, P<0.05, and P<0.01, respectively). The LDetvitEC group had a significantly lower mean (SE) hepatic inflammatory score compared with the LDet group (0.8 [0.1] vs 1.3 [0.2]; P<0.05). The LDetvitEC group had a significantly lower mean (SE) hepatic necrosis score compared with that in the LDet group (1.5 [0.2] vs 2.4 [0.3]; P<0.05). CONCLUSIONS: The results of this study in protein-deficient rats fed with a high-fat liquid diet suggest that supplementation with vitamin E, vitamin C, and a combination of vitamins E and C was associated with decreased ethanol-induced hepatic glutathione peroxidase activity and hepatic fibrosis, and that supplementation with vitamins E and C might have attenuated the development of hepatomegaly and hepatic necroinflammation, whereas this result was not found in the group given a liquid diet and ethanol in this 8-week study. (Curr Ther Res Clin Exp. 2006;67:118-137) Copyright © 2006 Excerpta Medica, Inc.

Gastroprotective effect of L-carnitine on indomethacin-induced gastric mucosal injury in rats: a preliminary study.

BACKGROUND: Numerous studies have shown that use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various gastric mucosal lesions, collectively referred to as NSAID gastropathy, but the detailed mechanism is still not properly understood. L-carnitine, a vitamin-like substance, is a naturally occurring enzymatic antioxidant with a potent free oxygen radical quencher and scavenger capacity; it protects the biological membranes against lipid peroxidation. It has recently been shown that L-carnitine has a gastroprotective effect on gastric mucosa. To our knowledge, the role of L-carnitine on NSAIDs-induced gastric mucosal injury is undefined. AIM: The aim of the present study was to determine the gastroprotective effect of L-carnitine on indomethacin-induced gastric mucosal lesions in the rat stomachs. MATERIAL AND METHODS: In our study, gastric mucosal injury was induced by the intragastric administration of indomethacin (30 mg/kg). L-carnitine (10, 50, 100 mg/kg) was given to rats by gavage 30 min before the indomethacin administration. The animals were killed 3 h after administration of indomethacin. The stomach of each animal was removed. Mucosal damage was evaluated with macroscopic study and histopathologically. RESULTS: The intragastric administration of indomethacin induced hyperemia and hemorrhagic erosions in the rat stomachs. L-carnitine significantly prevented gastric ulcerogenesis induced by indomethacin and decreased the ulcer index macroscopically and histopathologically. CONCLUSION: L-carnitine decreases indomethacin-induced gastric mucosal injury and this gastroprotective effect may be attributed to its well-known antioxidant effect.

[An analysis of genetic transmission in a father and son with osteosarcoma]. / Osteosarkomlu baba ve ogulda genetik geçisin irdelenmesi.

Familial osteosarcoma is a rare hereditary disease. We present a 37-year-old father and a 17-year-old son who developed osteosarcoma in the left and right distal femurs, respectively, at a three-year interval. They were treated with chemotherapy followed by surgery. Both had positive immunostaining for p53 tumor suppressor gene and HER-2/neu oncogene. The son also exhibited deletion of the retinoblastoma 1 gene. Pulmonary metastasis was detected in the father at the time of diagnosis and 13 months after primary treatment, whereas no distant metastasis was present in the child. The father died 39 months after the diagnosis from primary symptoms, but the son led a disease-free survival a year after completion of treatment. Genetic abnormalities documented in the father and son corroborate the presence of specific genetic alterations in the pathogenesis of osteosarcoma.

Protective effect of melatonin on contractile activity and oxidative injury induced by ischemia and reperfusion of rat ileum.

Free radicals derived from molecular oxygen have been reported to be responsible for changes in motility and mucosal damage observed in intestinal ischemia-reperfusion injury. Melatonin has been considered as an antioxidant that prevents injuries resulted from I/R in various tissues. The present study was designed to determine the effect of melatonin on the contractile responses of acetylcholine (Ach) and KCl, on malondialdehyde (MDA), a product of lipid peroxidation, and reduced glutathione (GSH) levels and to assess histopathological changes in the smooth muscle of terminal ileum subjected to ischemia-reperfusion. The intestinal ischemia-reperfusion was induced by occlusion of superior mesenteric artery of rat for 30 min, followed by a period of reperfusion for 3 h. Melatonin at doses of 10 or 50 mg/kg was administered via the tail vein in 5 min prior to reperfusion. Following reperfusion, segments of terminal ileum were rapidly taken and transferred into isolated organ bath and responses to Ach and KCl were recorded. Samples of terminal ileum were also taken for measuring the MDA and GSH levels. EC50 values of these contracting substances were seriously reduced in the ischemia-reperfusion group compared to that of the sham-operated control group. The decreased contraction response to Ach and KCl was significantly ameliorated by a dosage of 50 mg/kg of melatonin, while not by a dosage of 10 mg/kg. Similar pattern of the effect was observed in the tissue levels of MDA and GSH as well as in histological improvement. Melatonin appeared to be restoring the amounts of tissue MDA and GSH back to about control levels. These results suggest that the high dose of melatonin not only physiologically but also biochemically and morphologically could be useful to normalize contractility injured by oxidative stress in intestinal ischemia-reperfusion.

Inhibition of iNOS with S-methylisothiourea was impaired in wound healing in caustic esophageal burn.

OBJECTIVE: Stricture formation is a late complication of caustic esophageal burn, which is a common problem in childhood. For this reason, this experimental study was designed to observe the possible effect of nitric oxide on healing and fibrosis formation in caustic esophageal burns. MATERIALS AND METHODS: The rats were divided into five groups. Group A (n=12) received sham burn and treatment with saline injection. Group B (n=34) received caustic burn. Rats in group C (n=31), were given water supplement with 10 g/L L-arginine that was started 24 h preoperatively and continued until postoperative day 4. In group D (n=21), S-methylisothiourea (SMT, specific inducible nitric oxide synthase (iNOS) inhibitor), was injected at a dose of 3 mg/kg i.p. at 30 min before caustic burn, and similar dose was reinjected immediately after caustic burn. SMT 6 mg/kg/day injections continued for 4 days long. In group E (n=22), Nomega-nitro-L-arginine (L-NNA, nonspecific nitric oxide synthase (NOS) inhibitor) was injected at a dose of 15 mg/kg i.p. at 30 min before caustic burn, and similar dose was reinjected immediately after caustic burn. L-NNA 30 mg/kg/day continues for 4 days. RESULTS: Dead rates were significantly higher in group E than in groups A-D. The mean hydroxyproline levels in esophageal tissue were significantly lower in groups A and B than in group D. Histopathologically, tissue damage scores in the esophageal tissue were higher in group D than in groups A-C. CONCLUSIONS: Inhibition of iNOS with SMT was impaired in wound healing due to caustic esophageal burn and provoked collagen accumulation at a later period. Those effects may due to inhibition of antioxidant, immunomodulatory and antifibrotic effects of NO.

Lymphoepithelioma-like carcinoma of the urinary bladder: a case report and discussion of differential diagnosis.

Lymphoepithelioma-like carcinoma (LELC) of the urinary bladder is very rare. It is mandatory to make differential diagnosis among lymphoma, chronic cystitis and LELC because of different therapeutic approach. A bladder tumor was found in a 90-year-old patient suffering from hematuria. After transurethral resection, undifferentiated tumor with prominent lymphoid infiltration was seen on light microscopy. Immunohistochemical examination demonstrated positive staining of tumor cells with cytokeratin (CK), epithelial membrane antigen and CK-20. We presented the case because of its rarity and related literature was reviewed.

The protective effect of amifostine on radiation-induced acute pulmonary toxicity: detection by (99m)Tc-DTPA transalveolar clearances.

PURPOSE: The purpose of this study was to determine by using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) lung scintigraphy whether amifostine given before irradiation protects alveolocapillary integrity in a rabbit model. METHODS AND MATERIALS: Twenty white New Zealand rabbits were randomly divided into 4 groups: (1) control (CONT), (2) amifostine alone (AMF), (3) radiation (RAD), and (4) radiation plus amifostine (RAD+AMF). The AMF and RAD+AMF groups received amifostine. The RAD and RAD+AMF groups were irradiated to the right hemithorax with a single dose of 20 Gy using a (60)Co treatment unit. Amifostine (200 mg/kg) was given i.p. 30 min before irradiation. The (99m)Tc-DTPA radioaerosol study was performed 14 day after irradiation. RESULTS: The mean clearance rate of (99m)Tc-DTPA in control subjects was 140 +/- 21 min. The highest t((1/2)) value was noted in the RAD group (603 +/- 105 min, p = 0.001). There were no significant differences between the (99m)Tc-DTPA lung clearance rates of the CONT, RAD+AMF (238 +/- 24 min), and AMF groups (227 +/- 54 min). The mean penetration index values of CONT, RAD, AMF, and RAD+AMF are 63% +/- 1.6%, 63% +/- 2.5%, 60% +/- 2.9%, and 63% +/- 2%, respectively. CONCLUSIONS: We concluded that amifostine treatment before the lung irradiation protects the lung alveolocapillary integrity. This study confirms the protective effect of amifostine in an acute phase of radiation lung injury.

Pulmonary alveolar proteinosis in a patient with acute lymphoid leukemia regression after G-CSF therapy.

Pulmonary alveolar proteinosis (PAP) is the intra-alveolar accumulation of periodic-acid schiff (PAS) positive material. PAP is one of the underrecognized causes of pulmonary infiltrates in patients with hematologic malignancies. Here, we present a patient with acute lymphoid leukemia (ALL) in first remission that developed fever and diffuse pulmonary infiltrates during the neutropenic stage of consolidation chemotherapy. The histopathologic examination of bronchoalveolar lavage (BAL) fluid and transbronchial biopsy specimen demonstrated the presence of PAS-positive eosinophilic material. Empirical antibiotherapy and granulocyte-colony stimulating factor (G-CSF) were given. After the correction of neutropenia with G-CSF, the patient's fever disappeared, acute phase reactants decreased, pulmonary infiltrates resolved. We present this case because it was the first patient in whom the correction of neutropenia with G-CSF was followed by resolution of PAP.