Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer.

Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 107 cells from exponentially growing cultures of HCT-15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty NOD.CB17-Prkdcscid/J (NOD/SCID) female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3. Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by CO2 inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC.

Role of Notch, IL-1 and leptin expression in colorectal cancer.

An increasing number of studies have shown that angiogenesis has an important role in the progression of cancer. The growth of a new network of blood vessels is crucial for tumor growth and metastasis, which is promoted by several proangiogenic factors. Leptin, an essential adipokine that is secreted from fat tissue, is one of these pro-angiogenic factors. It has been shown that the inhibition of leptin-induced angiogenesis resulted in decreased levels of vascular endothelial growth factor (VEGF)/VEGFR2, hypoxia inducible factor (HIF) 1α, NF-κB, IL-1 and Notch and reduced the tumor growth in breast cancer. Leptin induces angiogenesis in breast cancer either by upregulating VEGFR2 in endothelial cells or by increasing VEGF/VEGFR2 expression through the Notch, IL-1 and leptin crosstalk outcome (NILCO) pathway. NILCO is a novel mechanism that interacts with proinflammatory and proangiogenic signals, which are critical for cell proliferation and angiogenesis in cancer. Several studies have shown that components of NILCO may affect human cancer incidence and progression. However, to the best of our knowledge, the interactions between Notch, IL-1 and leptin in human colorectal cancer have not been yet studied at the molecular level. The aim of the present study was to investigate the expression levels of genes related to the NILCO pathway in human colorectal cancer specimens. The current results demonstrated that leptin, leptin receptor (ObR) b, Notch-1, Notch-4, IL-1α, IL-1ß, IL-1R, IL-6, JAK-2, STAT-1, STAT-3, VEGFA, VEGFR1, VEGFR2, TNF-α and NF-κB mRNA expression levels in the cancer tissue were increased compared with the normal tissue. No significant changes in the mRNA expression levels of Jagged-1, HIF-1α and TNF receptor 1 were observed. Western blotting revealed that the protein expression levels of IκB were increased in the cancer tissue compared with normal tissue, whereas HIF-1α and phosphorylated STAT-1 levels were decreased. IL-6 and VEGFA plasma concentrations were statistically raised and the leptin plasma concentration was also raised, although significantly, patients with cancer compared with control individuals. Together, the present findings indicated that Notch, IL-1 and leptin may serve a crucial role in the development of colorectal cancer.

Fall of another myth for colon cancer: Duration of symptoms does not differ between right- or left-sided colon cancers.

BACKGROUND/AIMS: Patients with colorectal cancer continue to present with relatively advanced tumors that are associated with poor oncological outcomes. The aim of the present study was to assess the association between localization, symptom duration, and tumor stage. MATERIALS AND METHODS: A prospective, multicenter cohort study was conducted on patients newly diagnosed with a histologically proven colorectal adenocarcinoma. Standardized questionnaire-interviews were performed. Data were collected on principal presenting symptoms, duration of symptoms (time to first presentation to a doctor and time to diagnosis) and treatment, diagnostic procedures, tumor site, and stage of the tumor (tumor, node, and metastasis (TNM)). RESULTS: A total of 1795 patients with colorectal cancer were interviewed (mean age: 60.76±13.50 years, male patients: 1057, patients aged >50 years: 1444, colon/rectal cancer: 899/850, right side/left side: 383/1250, stage 0-1-2/stage 3-4: 746/923). No statistically significant correlations were found between duration of symptoms and either tumor site or stage. Principal presenting symptoms were significantly associated with left colon cancer. Patients who had "anemia," "change in bowel habits," "anal pruritus or discharge," "weight loss," and "tumor in right colon" had a significantly longer symptom time. CONCLUSION: Symptom duration is not associated with localization, nor is the tumor stage. Diagnosis of colorectal cancer at an earlier stage may be best achieved by screening of the population.

Which of the fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography parameters are better associated with prognostic factors in breast cancer?

The aim of the present study is to evaluate the relationship between the immunohistochemical and histopathological prognostic factors and the metabolic fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT) parameters in breast cancer.A total of 94 female patients diagnosed with primary breast cancer (median age: 54.5 years, 94 lesions with size >15 mm) who underwent PET/CT imaging before any treatment were enrolled to this retrospective study. Maximum and average standardized uptake values (SUVmax and SUVavg), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor/liver uptake ratio (TLR) of the primary tumors were calculated and compared between various histopathological and immunohistochemical prognostic factor groups.All metabolic parameters were associated with clinical T stage, metabolic M stage, and nuclear grade. The MTV, TLG, and TLR were significantly higher in patients with suspected lymph node metastasis. There were significant differences according to estrogen receptor and human epidermal growth factor-2 status in the metabolic values other than MTV. In case of progesterone receptor, there were significant differences in the metabolic characteristics except for the MTV and TLG values. The Ki-67 labeling index was moderately correlated with SUVmax, SUVavg, and TLR. All metabolic characteristics except MTV were significantly higher in triple negative breast cancer compared with the other molecular subtypes.The results of the present study suggest that the TLG and TLR values have stronger associations with several prognostic factors in breast cancer (BC) compared with other metabolic parameters.

Evaluating the Use of Hematological Parameters in Staging Hidradenitis Suppurativa.

INTRODUCTION: Recently, it has been shown that hematological parameters may be used as markers of inflammatory response. In this study, the authors aimed to identify the potential roles of the neutrophil-lymphocyte ratio (NLR) and other hematological markers in the evaluation of hidradenitis suppurativa (HS), a chronic, recurrent inflammatory disease. MATERIALS AND METHODS: A total of 35 patients, diagnosed with HS between January 1, 2012 and December 31, 2014, were categorized into 3 groups according to the Hurley staging system. The basic patient demographics, the anatomic regions involved, and the hematological parameters including NLRs were evaluated in the present retrospective chart review. RESULTS: Hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin levels were greater in stage I than stage III, while hematocrit, red cell distribution width (RDW), mean platelet volume, mean corpuscular hemoglobin concentration levels, and platelet counts did not differ between the stages. White blood cell and neu- trophil counts were higher in stage III than stage II, while lympho- cyte counts were lower in stage III than stage II. The NLR of stage I was detected as being significantly higher than stage II and lower than stage III. CONCLUSION: The present study shows hematological markers, and NLR in particular may be related to the severity of HS. Further studies are required to demonstrate the significance of NLR in the evaluation of HS.

Tumor deposits: Prognostic significance in gastric cancer patients.

PURPOSE: Tumor deposits (TDs) are defined as satellite peritumoral nodules in the peritumoral adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule. We aimed to investigate the relation between TDs and clinicopathological characteristics of gastric cancer and to evaluate the effect of TDs on prognosis. METHODS: One hundred and seven non-metastatic gastric cancer patients were enrolled. The relationships between positive and negative TDs with respect to clinicopathological characteristics, as well as disease free survival (DFS) and overall survival (OS), were analyzed. RESULTS: TDs were detected in 28 patients (26.2%). Advanced pT stage and pN stage were significantly higher in TDs-positive compared to TDs-negative patients (p=0.015 and p=0.037, respectively). No significant differences were identified between the groups in other clinicopathological variables such as gender, lymphovascular and perineural invasion. Recurrence and mortality rates were higher in the TDs-positive patients during follow-up of both groups (22/78.6% vs 38/48.1%, p=0.010 for relapse; 20/71.4% vs 3/38%, p=0.005 for mortality). The univariate analysis demonstrated shorter DFS and OS for TDs-positive compared to TDs-negative patients. In multivariate analysis, TDs-positive patients had 1.75-fold higher likelihood to develop recurrence, while the likelihood of death increased 1.99-fold (p=0.041 and p=0.020, respectively). CONCLUSION: TDs-positive gastric cancers demonstrate a more aggressive clinical course compared to TDs-negative. More effective treatment methods should be necessary for management of this subgroup of gastric cancer.

An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

Detection of kinase amplifications in gastric adenocarcinomas.

AIM: To determine the incidences of copy number aberrations of receptor kinases and their relations in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: The prevalence of genomic copy number aberrations of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2)/topoisomerase IIa (TOP2A), centrosome-associated kinase aurora A (AURK A), centrosome-associated kinase aurora B (AURK B), and mesenchymal-epithelial transition factor (MET) genes and polysomies of related chromosomes were analyzed by fluorescent in situ hybridization (FISH) in tumor samples from 35 patients with gastric cancer. RESULTS: There were 28.6%, 65.7%, 20.0%, 17.1%, 60.0%, and 45.7% cases considered FISH-positive for EGFR, MET, HER2, TOP2A, AURK A, and AURK B genes, respectively. Statistically significant associations were determined in detection of amplifications of 1) EGFR gene with chromosome 7 polysomy, 2) MET gene in nonpolysomic chromosome 7 nuclei, 3) HER2/TOP2A genes in nonpolysomic chromosome 17 nuclei, 4) coamplification of HER2/TOP2A in poorly differentiated carcinomas, and 5) AURK A gene in nonpolysomic chromosome 20 nuclei. Most of the aberrations were predominantly seen in poorly differentiated tumors, but a high rate of the amplified MET gene was also detected in moderately differentiated carcinomas. CONCLUSION: Chromosome 7 polysomy may be responsible for EGFR gene amplifications, and we concluded that MET and AURK A genes amplifications were commonly seen aberrations in gastric adenocarcinomas and may offer information about disease progression and administration of individualized treatment for gastric cancer patients.

Anti-apoptotic and antioxidant effect of leptin on CCl4-induced acute liver injury in rats.

The aim of this study is to investigate the effect of leptin in rats on carbon tetrachloride (CCl(4)) induced acute liver damage using immunohistochemical methods for apoptosis and biochemical parameters. In this experimental study, 18 Spraque-Dawley rats were divided into three groups viz; control, CCl(4) and CCl(4)+leptin treatment. 0.8 ml/kg olive oil was administered intraperitoneally (i.p.) to the control group and 0.8 ml/kg CCl(4) (1:1 dissolved in olive oil) was administered i.p. to the CCl(4) and CCl(4)+leptin treatment groups, respectively. After 6 h of administrating CCl(4), CCl(4)+leptin treatment group was given i.p. leptin (10 µg/kg). Twenty-four hours after administrating CCl(4) all of the groups were euthanized. Biochemical assessments were performed using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), plasma tumor necrosis factor alpha (TNF-α) levels and tissue malondialdehyde (MDA), and TNF-α levels. Histological assessments were then performed using Hematoxylin&Eosin (H&E) staining in light microscope and apoptosis assessment using Terminal Transferase dUTP Nick End Labeling (TUNEL)-staining. Serum AST, ALT, ALP and plasma TNF-α levels, tissue MDA and TNF-α levels had all increased in CCl(4) group, but were found to be significantly decreased in CCl(4)+leptin treatment group. Moreover, TUNEL-positive cell counts in liver had significantly increased in CCl(4) group, but decreased in CCl(4)+leptin treatment group (P < 0.05). The results of our study the biochemical, histological and TUNEL-staining showed that leptin has treatment effects on liver CCl(4) induced injury. It plays a role as a potent free radical scavenger, a powerful antioxidant and it also has anti-apoptotic effects.

Effects of doxycycline on renal ischemia reperfusion injury induced by abdominal compartment syndrome.

BACKGROUND: The aim of this study was to determine the effects of doxycycline on renal ischemia reperfusion (I/R) injury in a rat model of abdominal compartment syndrome (ACS). MATERIALS AND METHODS: Forty-two Sprague-Dawley rats were divided into six groups. In the control group (group 1), kidney samples were collected with no manipulation; in the sham group (group 2) induction of ACS was followed by decompression. In groups 3 and 4, 1 cc of saline was administered intraperitoneally (i.p.) during the induction of ACS, and the kidneys were removed 1 and 24h after decompression, respectively. In groups 5 and 6, doxycycline (10mg/kg i.p.) was injected during the induction of ACS, and similarly all tissue samples were removed 1 and 24h after decompression, respectively. MDA, IL-1ß, IL-6, TNF-α, MMP-2, and TIMP-1 were studied, and the apoptotic cells were enumerated histopathologically, and apoptosis and bcl-2 expression were assessed immunohistochemically. RESULTS: Creatinine, MDA, IL-1ß, and IL-6 levels were significantly higher in group 3, 1h after the reperfusion period compared with the control group, and the same parameters were significantly lower in the groups in which doxycycline was administered, 1 hour after decompression. However, there remained no difference between groups at 24h, except IL-1ß, which was decreased to even lower values. TNF-α and TIMP-1 levels were not statistically different in all groups. The MMP-2 level was significantly higher in group 4 by 24h, and there remained no difference between groups 1, 2, and 6. In group 6, there were not any apoptotic cells as were observed in the other groups. The number of apoptotic cells and the expression of bcl-2 was significantly less in the groups in which doxycycline was administered. CONCLUSION: Doxycycline had protective effects on I/R injury by decreasing apoptosis via reducing the level of pro-inflammatory cytokines, increasing the level of TIMP-1, and inhibiting the activity of MMP-2.

Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report.

Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

Effects of doxycycline on intestinal ischemia reperfusion injury induced by abdominal compartment syndrome in a rat model.

BACKGROUND: Abdominal compartment syndrome (ACS) refers to organ dysfunction and ischemia resulting from intra-abdominal hypertension (IAH). Ischemia of the gut results in the triggering of a systemic inflammatory response by releasing cytokines which, in turn, causes capillary leakage leading to bowel edema, further increasing intra-abdominal pressure and resulting in a morbid cycle of ischemia and edema. OBJECTIVE: The aim of this study was to determine the effects of doxycycline on intestinal ischemia reperfusion (I/R) injury in a rat model of ACS. METHODS: Sprague-Dawley rats were divided into 5 equal groups. In groups 1 and 2, saline (1 cc IP) was administered during induction of ACS and intestinal samples were removed at 1 and 24 hours, respectively, after decompression. In groups 3 and 4, doxycycline (10 mg/kg IP) was injected during induction of ACS and, similarly, intestinal samples were removed at 1 and 24 hours after decompression. In the control group (group 5), intestinal samples were collected without induction of ACS. Malon-dialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 were studied and the apoptotic cells were enumerated histopathologically. Apoptosis and ß-cell lymphoma 2 (ßcl-2) expression were assessed immunohistochemically. RESULTS: Thirty-five rats were evenly divided into 5 groups of 7 rats each. MDA, IL-1ß, IL-6, TNF-α, and MMP-2 levels were significantly higher in group 1 one hour after the reperfusion period compared with the control group (P < 0.001, P < 0.001, P < 0.05, P < 0.001, and P < 0.01, respectively). The same parameters were significantly lower in group 3, in which doxycycline was administered, than in group 1 (P < 0.001, P < 0.05, P < 0.05, P < 0.001, and P < 0.01, respectively). However, there was no significant difference between groups 2 and 4 in the 24th hour (all, P > 0.05). The mean (SD) number of apoptotic cells and the expression of ßcl-2 was highest in group 2 at 24 hours after the reperfusion period (92.5 [11.4] and 35.9 [5.0], respectively) and significantly greater than that in group 4 (P < 0.001 and P < 0.05, respectively). CONCLUSION: Doxycycline was associated with protective effects against I/R injury through decreasing apoptosis via attenuating the response of proinflammatory cytokines and inhibiting the activity of MMP-2 in this rat model.

Mast cell stabilizator and antioxidant effects of epidermal growth factor (EGF) on gastric mucosal injury induced by ethanol in rats.

The role of epidermal growth factor (EGF), a polypeptide containing 53 amino acids, on protection and repair of ethanol-induced gastric mucosal injury was investigated in rats. In addition, the effects of EGF on the gastric damage were evaluated histopathologically. We used 48 Spraque-Dawley rats which were divided into [corrected] three groups as control rats, ethanol treated rats and ethanol+EGF treated rats. The ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. EGF (100 microg/kg) was given by intragastric gavage 30 min before the administration of ethanol. We studied histopathological evaluation and the histochemical heterogeneity of mast cells and its degree of degranulation. Besides, gastric tissue malondialdehyde (MDA), protein sulfhydryl groups (SH), and protein carbonyl levels were measured. EGF treatment stabilized mast cells degranulation and had lower polymorphonuclear leukocytes (PMNL) infiltration, ulcer index, histamine, and MDA; protein carbonyl levels were also lower, compared to the non-treated animals. EGF exerts a protective effect on gastric mucosa to ethanol-induced gastric injury probably through antioxidant and mast cell stabilizing mechanism.

The protective effect of erythropoietin on ischaemia/reperfusion injury of liver.

BACKGROUND: Besides its haematopoietic effect, erythropoietin (EPO) has multiple protective effects, i.e. antiapoptotic, antioxidant and angiogenic properties. The neuroprotective effects of EPO against ischaemia have all been demonstrated in cell culture and animal models. The aim of the study was to evaluate the effect of erythropoietin on ischaemia-reperfusion injury (I/R injury) of the liver. METHODS: Forty-eight adult male Sprague-Dawley rats weighing 250-300 g were divided into three groups: group I, hepatic ischaemia-reperfusion (Hepatic I/R); group II, hepatic ischaemia-reperfusion + EPO (Hepatic I/R+ EPO); group III, sham. Hepatic ischaemia was created by placing a microvascular clamp on the hepatic pedicle for 45 minutes. EPO was given to group II at a dose of 1000 U/kg 120 minutes before the onset of the ischaemia. Blood samples and liver tissues were obtained after 45 minutes of reperfusion from half of the rats in each group. The remaining rats were killed after a 24-hour observation period and blood and tissue samples were obtained. Blood alanine aminotransferase, tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and liver tissue malondialdehyde (MDA) levels were determined. Liver tissue histopathology was also evaluated by light microscopy. RESULTS: In rats with hepatic ischaemia, serum levels of ALT, TNF-alpha, IL-2 and liver tissue levels of MDA were reduced by the administration of erythropoietin and the histopathological score was also less severe. CONCLUSION: This study demonstrates that pre-ischaemic administration of EPO has protective effects on hepatic I/R injury.

Ectopic thyroid in the gallbladder: report of a case.

Ectopic thyroid is a rare developmental anomaly. We describe an unusual case of ectopic thyroid tissue found in the gallbladder wall of a 68-year-old man who underwent cholecystectomy for acute cholecystitis. Pathological findings were compatible with ectopic thyroid tissue in the gallbladder wall. This very rare pathology is discussed with a review of the relevant literature.

The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions.

The role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effects of quercetin were evaluated in an experimental model. In addition, the effects of quercetin on gastric damage were evaluated histopathologically. Rats were divided into three groups as control rats, ethanol treated rats and ethanol+quercetin treated rats. Ethanol group was given a gastric gavage containing 1 ml of 80% ethanol (v/v) prepared in distilled water. Quercetin (200 mg/kg body wt.) was given by intragastric gavage 120 min before the administration of ethanol. Gastric tissue thiobarbituric acid reactive substance levels, carbonyl compounds, histamine levels and myeloperoxidase activities were found to be increased in ethanol treated rats and quercetin treatment reversed these increases. No statistically significant changes were found between all groups in catalase activity. The superoxide dismutase activity dropped significantly after ethanol treatment and quercetin treatment increased this enzyme activity. Gastric damage was confirmed histomorphometrically by significant increases in the number of mast cells and gastric erosions in ethanol treated rats. It was also confirmed that quercetin treatment significantly decreased the number of mast cells and reduced the area of gastric erosions. The results suggest that the gastroprotective effect of quercetin in this experimental model could be due to its antiperoxidative, antioxidant and antihistaminic effects.

Renal protection by brief liver ischemia in rats.

BACKGROUND: In this study, we evaluated the beneficial effect of brief ischemia and reperfusion, which was shown to have local effects on liver previously, on kidney as a remote organ in rats. METHODS: Male Wistar rats were divided into three groups: group I, sham; group II, renal ischemia for 45 min; and group III, 10 min of brief hepatic ischemia and 10 min of reperfusion after 45 min of renal ischemia. Biochemical determination, tumor necrosis factor (TNF)-alpha and tissue thiobarbituric acid-reactive substances (TBARS) levels, and histopathologic findings were evaluated at 45 min and 24 hr of reperfusion. RESULTS: Although blood urea nitrogen and creatinine levels were similar at 45 min in groups II and III, these levels were lower in group III at 24 hr. Creatine clearance values were higher and fraction excretion of sodium values were lower in group II than in group III at 24 hr. Lactate dehydrogenase levels of groups III and II were similarly elevated at 45 min, whereas group III values decreased more rapidly than those of group II at 24 hr. At 45 min of reperfusion, TNF-alpha and tissue TBARS levels were found lower in group III than in group II. Histopathologic parameters including congestion and tubular vacuolization, tubular cell detachment, and necrosis were significantly reduced in group III as compared with results of group II 45 min after ischemia. All histopathologic parameters were defined as statistically better in group II at 24 hr. CONCLUSIONS: The beneficial effect of brief ischemia of liver on renal ischemia as a remote organ was confirmed by biochemical, histopathologic, and ultrastructural findings.