Gul Yuce

Ege University, İzmir, Izmir, Turkey

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Publications (25)39.37 Total impact

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    ABSTRACT: Pancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type 1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis. Rats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20microg/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct. Captopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed. Captopril decreased serum amylase (10,809+/-1867 vs. 4085+/-1028U/L, p<0.01), myeloperoxidase activity (3.5+/-0.5 vs. 1.5+/-0.1, p<0.05) and histopathological score (5.0+/-0.4 vs. 1.1+/-0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1+/-1.2 vs. 3.4+/-0.5, p<0.01), pancreatic parenchymal necrosis (4.5+/-0.6 vs. 0.0+/-0.0, p<0.001), fatty necrosis (2.8+/-0.9 vs. 0.1+/-0.1, p<0.01) and edema (2.1+/-0.3 vs. 1.4+/-0.3, p<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration. This study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.
    Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie 07/2009; 62(4):353-60. · 1.43 Impact Factor
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    ABSTRACT: Both C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD. Fifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system. Serum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 +/- 0.01, 0.04 +/- 0.01 versus 0.06 +/- 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 +/- 1.6 and 5.2 +/- 2.5 versus 2.9 +/- 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels. Serum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.
    BMC Gastroenterology 02/2009; 9:16. · 2.11 Impact Factor
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    ABSTRACT: Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.
    HPB 02/2008; 10(6):459-63. · 1.94 Impact Factor
  • Pancreas 04/2007; 34(2):275-7. · 2.95 Impact Factor
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    ABSTRACT: The aim was to reveal the mechanism of hemolysis-induced acute pancreatitis and to evaluate the role of heme and heme oxygenase activity in inducing pancreatic inflammation in an experimental hemolysis model. Hemolytic anemia was induced in rats by intraperitoneal injection of 60 mg/kg acetylphenylhydrazine (APH). To evaluate the toxic effect of free heme after hemolysis, heme oxygenase inhibitor (HOI) was used to inhibit the enzyme which decreases the free heme concentration after hemolysis. One hundred and fifty rats were divided into two treatment and three control groups. Rats in the hemolysis group were given APH intraperitoneally. Rats in the HOI+hemolysis group were given Cr(III)mesoporphyrin IX chloride as HOI and then APH intraperitoneally. Serum amylase and lipase levels as well as pancreatic tissue cytokine content were determined and histological examination performed. No hemolysis or pancreatitis was seen in the control groups. Massive hemolysis was seen in 22 of the 30 rats of the hemolysis group and 20 of the 30 rats of the HOI+hemolysis group. The total pancreatitis rates were 60% and 76.6% in the hemolysis and HOI+hemolysis groups, respectively (p<0.05). Pancreatic cytokine levels were significantly higher in the HOI+hemolysis and hemolysis groups than in all control groups. The highest ICAM-1 and MCP-1 levels were in the HOI+hemolysis group. Histological signs of acute pancreatitis were also more severe in this group. Acute massive hemolysis can induce acute pancreatitis. Excess of free vascular heme seems to be an inducer of inflammation by modulating ICAM-1 and MCP-1.
    Medical science monitor: international medical journal of experimental and clinical research 03/2007; 13(3):BR67-72. · 1.36 Impact Factor
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    ABSTRACT: Living donor liver transplantation (LDLT) is a good alternative to cadaveric liver transplantation for end-stage liver disease. Herein we report the outcome of 132 LDLTs performed between 1999 and 2005, with special emphasis on the incidence and management of acute and chronic rejection. Among the LDLT population a first acute rejection episode (ARE) was clinically suspected in 24% and proven by liver biopsy in 11%. According to the Banff classification, 50% of AREs were grade 1, and 50%, grade 2. There was no grade 3 AREs. The first ARE occurred between 7 days and 23 months posttransplantation (mean 97 days, median 70 days). Ninety-seven percent (31/32) of the AREs occurred within the first year after transplantation and 3% (1/32) in the second year. Among the patients with ARE, 23% developed a second ARE between 4 and 11 months. A third ARE was detected in 8% of patients after month 18. All AREs responded to adjustment of immunosuppressive doses or steroid boluses. Chronic rejection (CR) was detected in 2%. In conclusion, the incidences of ARE and CR are consistent with the previously reported data. Acute and chronic rejections seem to be mild and easily manageable clinical conditions. Our results also showed a significant difference between clinically suspected and biopsy-proven ARE emphasizing the importance of indicated liver biopsies in the management of the LDLT population.
    Transplantation Proceedings 07/2006; 38(5):1435-7. · 0.95 Impact Factor
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    ABSTRACT: Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model.
    European Surgical Research 02/2006; 38(1):4-10. · 0.75 Impact Factor
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    ABSTRACT: The only beneficial agent for the treatment of chronic delta hepatitis (CDH) is interferon (IFN). However, there is no consensus on the best dosage or duration of IFN therapy. As ribavirin (RBV) increases the sustained response when added to IFN in chronic hepatitis C, probably because of its immunomodulatory effect, we aimed to investigate the efficacy of 2-year IFN treatment and whether RBV had any additive effect to IFN in CDH. Patients (n = 31) with CDH were randomized with a 1:2 ratio as 10 patients (3 females/7 males, age 39 +/- 9) receiving IFN monotherapy (9 MU IFN-alpha2a three times weekly) and 21 patients (8 females/13 males, age 38 +/- 11) receiving IFN plus RBV for 2 years (IFN at the same dosage and RBV at 1000-1200 mg/day). Alanine transferase normalization and hepatitis delta virus (HDV) RNA negativity at the end of treatment and at the end of the follow-up period (at least 6 months following 2-year treatment) were primary endpoints of the study. In addition, virological response and biochemical response were determined separately. Eight of 31 patients (25%) had cirrhosis in liver biopsies. Six patients from the IFN monotherapy group and 12 patients from the combination group had biochemical response. Five patients from the IFN monotherapy group and 11 patients from the combination group had virological response at the end of therapy. Two patients from the IFN group and five patients from the combination group had sustained biochemical response at the end of the follow-up period. Hepatitis B virus (HBV) activations with HBV DNA positivity were observed in two patients (one from the IFN monotherapy group, one from the combination group). Two patients (20%) in the IFN group and five patients (23.5%) in IFN plus RBV group remained as virological responders at the end of the follow-up period (P > 0.05). None of the patients with liver cirrhosis were responsive at the end of the follow-up period. Almost 20% of the patients with CDH were responsive to 2-year IFN treatment at the end of the follow-up period and no additional effect of RBV was observed. Patients with advanced liver disease failed to respond to treatment.
    Antiviral therapy 01/2005; 10(6):721-6. · 3.07 Impact Factor
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    ABSTRACT: The presence of microchimerism in transplanted tissues is well defined; however, the timeframe of appearance and disappearance of engraftment in liver allograft is unknown. The aims of this study were to analyze for the presence of "recipient-derived cells" in sex-mismatched individuals after liver transplantation, comparing the frequency of "recipient-derived cell repopulation" in early versus late transplant biopsies and to evaluate the relationship between "recipient-derived cell repopulation" and the severity of graft injury. Paraffin-embedded liver biopsy samples of 18 recipients were reviewed. Sixteen of them were obtained from recipients with sex-mismatched donors. The remaining two were obtained from recipients with sex-matched donors and were used as controls. Immunohistochemistry and fluorescence in situ hybridization double-labeling method were performed on pretreated slides using anti-human hepatocyte antibody to identify hepatocytes, a mouse anti-human cytokeratin-7 to identify ductal epithelial cells, and using CEPX/Y DNA probes for visualizing X and Y chromosomes. The double-labeled slides were examined systematically using an image analyzer system. The mean time from transplantation to biopsy was 8.1 months. Eleven of the 16 samples obtained from recipients with sex-mismatched grafts demonstrated "recipient-derived hepatocyte repopulation," comprising a mean of 2.1% of the hepatocytes. In the control biopsies, none of the cells demonstrated different nuclear signals from the donor's sex origin. The presence and proportion of "recipient-derived hepatocyte repopulation" rate were significantly higher in early transplant biopsies than in late transplant biopsies (P < 0.05). Some hepatocytes of sex-mismatched liver grafts were replaced by "recipient-derived cells" during injury. Such repopulation is more common in the early liver-graft biopsies. The severity of acute cellular rejection appears to have no effect on the rate of recipient-derived repopulation.
    Transplantation 12/2004; 78(11):1647-52. · 3.78 Impact Factor
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    ABSTRACT: Results of studies using lamivudine and interferon combination in the treatment of chronic hepatitis B are not consistent or conclusive. This study aimed to evaluate the efficacy of interferon plus lamivudine use versus single lamivudine in anti-HBe-positive chronic hepatitis B. Eighty patients were treated with either lamivudine or lamivudine plus simultaneously started interferon. Patients were assigned in groups according to random allocation rule. Lamivudine was given 150 mg/day for 96 weeks in each group; interferon was administered 10 MU three times a week for 24 weeks in the combination therapy group. Alanine aminotransferase (ALT) normalization was achieved earlier in patients treated with lamivudine alone. At the end of treatment, there was no difference between the groups with respect to HBV DNA negativity, ALT normalization and breakthrough rate. Histological improvement was remarkable in each group, but fibrosis score and necro-inflammatory activity were much lower in lamivudine-treated patients. Addition of interferon to the lamivudine regimen does not increase the effectiveness of the treatment. Considering the side effects of interferon treatment, this combination seems not to be convenient for anti-HBe-positive chronic hepatitis B.
    Antiviral therapy 07/2004; 9(3):325-34. · 3.07 Impact Factor
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    ABSTRACT: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-alpha, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis.
    ANZ Journal of Surgery 07/2004; 74(7):591-5. · 1.50 Impact Factor
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    ABSTRACT: We present an uncommon case of hyaline vascular type Castleman's disease mimicking a pancreatic tumour. A 56-year-old woman with constitutional symptoms was investigated. Pre-operative interventions failed to produce a definitive diagnosis. Surgical excision was performed and the tumour was diagnosed to be the hyaline vascular type of Castleman's disease histopathologically. Pancreatic Castleman's disease should remain a consideration in the differential diagnosis of a pancreatic mass.
    Acta chirurgica Belgica 07/2004; 104(3):354-6. · 0.36 Impact Factor
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    ABSTRACT: Acute pancreatitis is a multifactorial disease caused by activation of several inflammatory mediators. Leukotrienes, beside other mediators, may be involved in acute pancreatitis. The aim of this study was to investigate the effects of 'zafirlukast', a leukotriene receptor antagonist, in acute pancreatitis and its relation with prostaglandin synthesis. Eighty rats were randomly divided into eight groups. Acute pancreatitis was induced by subcutaneous injection of cerulein (20 microg/kg), four times at 1-h intervals. Zafirlukast (20 mg/kg) was applied intraperitoneally as a pretreatment. Prostaglandin synthesis was inhibited by low-dose indomethacin (5 mg/kg subcutaneously). Pancreatic histopathology, serum amylase activity and pancreatic myeloperoxidase activity were determined to assess the severity of pancreatitis. Zafirlukast pretreatment alone did not induce any inflammation and fatty necrosis in pancreatic tissue. However, it increased the histopathological score from 3.70 +/- 0.57 to 6.62 +/- 0.53 in rats with acute pancreatitis (P < 0.001). Fatty necrosis was especially prominent in the zafirlukast-treated acute pancreatitis group compared with the untreated group (2.62 +/- 0.26 versus 0.40 +/- 0.22, respectively; P < 0.001). Inhibition of prostaglandin synthesis by indomethacin partially suppressed the harmful effects of zafirlukast in acute pancreatitis. It decreased the pathological score (4.62 +/- 0.73) and fatty necrosis (1.50 +/- 0.32) in that group. Interestingly, leukotriene receptor antagonism by zafirlukast increased the pancreatic histopathological score and fatty necrosis in rats with acute pancreatitis. Blocking of cysteinyl leukotriene receptors might cause an induction of mediator synthesis via other pathways. Effects of leukotriene receptor antagonism on the pancreas must be evaluated extensively in further studies.
    European Journal of Gastroenterology & Hepatology 04/2004; 16(4):383-8. · 1.92 Impact Factor
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    ABSTRACT: We report a case of leiomyosarcoma of the inferior vena cava, which was successfully treated by surgical en bloc resection and reconstruction of the inferior vena cava, followed by adjuvant radiation therapy. A 39-year-old man presented with nausea, vomiting, epigastric pain, and weight loss. Radiologic examinations showed a mass originating from the inferior vena cava and surgical resection was performed. Histopathological examination of the specimen revealed a moderately differentiated (grade II) leiomyosarcoma arising from the inferior vena cava. We believe that radical resection with clear surgical margins followed by adjuvant radiation therapy is a good curative strategy for achieving any chance of long-term survival.
    Surgery Today 02/2004; 34(4):370-3. · 0.96 Impact Factor
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    ABSTRACT: Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats. One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 microg/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed. Infliximab treatment significantly decreased serum amylase activity (11939 +/- 1914 U/L versus 3458 +/- 915 U/L, P < 0.001) and histopathologic score (4.1 +/- 0.5 versus 1.5 +/- 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 +/- 1.2 versus 3.6 +/- 0.8, P < 0.001) and serum amylase activity (20442 +/- 2375 versus 8990 +/- 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant. Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.
    Pancreas 02/2004; 28(1):e1-8. · 2.95 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and the prognosis is usually poor. Today, liver transplantation (LT) is a radical but frequently curative treatment modality for HCC. In selected patients, it cures HCC and the underlying cirrhosis at the same time. The present clinicopathological study examined the importance of tumor characteristics for their effects on recurrence and survival rates after LT for HCC. Forty-two native hepatectomy specimens among 250 consecutive orthotopic liver transplantations contained HCC. Patients were predominantly men (30 men, 12 women), ranging in age from 1 to 61 years (median 51). While 20 patients received cadaveric organs, 22 were transplanted from living donors. In 14 patients (33%) HCC presented as a solitary nodule, 5 (12%) as two nodules; 2 (5%) as three nodules; and 21 patients (50%) as more than three nodules. The maximal diameter of the largest tumor not larger than 3 cm in 28 patients (66%), exceeding this size in 14 patients (34%). There was a significant correlation between nodule number and tumor size (r = 0.36, P = 0.05). While 23 patients had no sign of vascular involvement, 17 tumors showed microscopic invasion and two large vessel involvement. There was a positive correlation between vascular invasion and nodule number (r = 0.41, P = 0.05). The histopathological grade of differentiation of the tumors was assessed as "well" in seven patients (14%), moderate in 28 (72%), and poor in 7 (14%). The differentiation was significantly poorer when vascular invasion was observed (r = 0.43, P =.01). According to the TNM classification, 11 patients (26%) were stage I, 6 (14%) stage II, 13 (31%) stage III, and 12 (29%) stage IV. After a median follow-up of 10 months (1-50 months), the overall mortality was 18% (n = 8). Patient survival at 6 month, 1, and 4 years was 88%, 80%, and 60%, respectively. The outcome was significantly poorer for TNM stage IV versus stage I,II, and III tumors to (P =.02). Tumor recurred in three patients at 4,6, and 50 months after liver transplantation. The sites of recurrence were bone, lung, and adrenal glands. In conclusion, liver transplantation represents a safe and feasible treatment for hepatocellular carcinoma with excellent outcomes compared with other treatment modalities. Liver transplantation offers excellent survival rates and chance for cure in stages I, II, and III hepatocellular carcinoma in cirrhotic patients.
    Transplantation Proceedings 01/2004; 35(8):2986-90. · 0.95 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2004; 40:104-104.
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    ABSTRACT: The literature indicates that acute pancreatitis is a complication of massive hemolysis with a prevalence of about 20%. We describe an experimental model of hemolysis-induced acute pancreatitis. Hemolytic anemia was induced in rats by a single ip injection of 60 mg/kg of 20 mg/ml acetylphenylhydrazine (APH) in 20% (v/v) ethanol on the first experimental day (day 0). One hundred and fifty Wistar albino rats weighing 180-200 g were divided into three groups of 50 animals each: groups 1, 2 and 3 were injected ip with APH, 20% ethanol, and physiological saline, respectively. Ten rats from each group were sacrificed on study days 1, 2, 3, 4 and 5. Serum amylase, lipase levels and pancreatic tissue tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) contents were determined and a histological examination of the pancreas was performed. No hemolysis or pancreatitis was observed in any of the rats in groups 2 and 3. In group 1, massive hemolysis was observed in 35 (70%) of 50 rats, moderate hemolysis in seven (14%), and no hemolysis in eight (16%). Thirty-three of 35 (94.2%) rats with massive hemolysis had hyperamylasemia, and 29 of these rats (82.8%) had histologically proven pancreatitis. The most severe pancreatitis occurred on day 3, as demonstrated by histology. Tissue TNF-alpha and PAF levels were statistically higher in group 1 than in groups 2 and 3. Acute massive hemolysis induced acute pancreatitis, as indicated by histology, in almost 80% of cases. Hemolysis may induce acute pancreatitis by triggering the release of proinflammatory and immunoregulatory cytokines.
    Brazilian Journal of Medical and Biological Research 08/2003; 36(7):879-86. · 1.14 Impact Factor
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    ABSTRACT: The samples of hepatocellular carcinoma from Turkey, a country with a high prevalence of hepatitis B virus and hepatitis C virus, but low dietary exposure to aflatoxin B1, were examined in order to detect the frequency of mutant p53 and its association with clinical and pathological data. Fifty-two samples of hepatocellular cancer from the patients who were diagnosed in our clinic were included in this study. The mutant p53 protein was searched for by specific enzyme-linked immunosorbent assay. Of 52 patients with hepatocellular carcinoma, 26 (50%) had the mutant p53. The incidence of p53 mutation in hepatocellular cancer patients with chronic liver disease due to hepatitis B virus infection was significantly higher than in those with chronic liver disease due to alcohol, indicating that not alcohol but hepatitis B virus, in fact induces the mutations in p53 gene. In addition, it has been shown that the p53 mutation was significantly associated with the diameter of tumor nodule and the degree of cellular differentiation in hepatocellular cancer. The p53 mutation rate found in our study is concordant for a geography where hepatitis B virus and hepatitis C virus are common. Hepatitis B virus and possibly hepatitis C virus, but not alcohol, should be responsible, to a degree, for the mutational change in p53 protein in hepatocellular cancer patients with chronic liver disease. The p53 mutation is a late event in hepatocarcinogenesis because it is related with cellular differentiation and tumor diameter. The specific ELISA can be a useful screening test in future studies to select the patients for gene therapy using wild-type p53.
    Digestive Diseases and Sciences 06/2003; 48(5):865-9. · 2.26 Impact Factor
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    ABSTRACT: Extensive and severe hepatic centrilobular hemorrhagic necrosis is a common finding in hepatic vein obstruction and Budd-Chiari syndrome. Some drugs, including allopurinol, can also cause this histopathologic appearance but to our knowledge in this setting the lesions are not so massive. Here we report a case of a 41-year-old female who developed fever, pruritic skin rash, jaundice, eosinophilia, abnormal liver function tests, and acute renal failure 3 weeks after the beginning of allopurinol treatment, complicated with severe hepatocyte necrosis around most terminal hepatic venules suggesting Budd-Chiari syndrome.
    Journal of investigational allergology & clinical immunology: official organ of the International Association of Asthmology (INTERASMA) and Sociedad Latinoamericana de Alergia e Inmunología 02/2003; 13(4):281-3. · 1.89 Impact Factor