Protective effect of ursodeoxycholic acid and resveratrol against tacrolimus induced hepatotoxicity.

Tacrolimus (TAC) is a potent and well-tolerated immunosuppressive drug, but serious side effects including nephrotoxicity and hepatotoxicity have been reported. Ursodeoxycholic acid (UDCA) and resveratrol (RSV) exhibit hepatoprotective effects in liver diseases. We investigated the hepatoprotective effect of UDCA and RSV against TAC induced hepatotoxicity. We divided 40 male rats into five equal groups: A) control group, B) TAC group, C) TAC + UDCA group, D) TAC + RSV group, E) TAC + UDCA + RSV group. We administered 0.5 mg/kg TAC once daily, 25 mg/kg UDCA twice daily and 10 mg/kg RSV once daily. The drugs in the experimental groups were given by gavage from the first day of the study and continued for 21 days. Histopathologic and biochemical analyses were performed on day 22. In group B, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6), total oxidative status (TOS) and malondialdehyde (MDA) levels were higher compared to group A, and catalase (CAT), superoxide dismutase (SOD) levels and total antioxidant status (TAS) were lower compared to group A. Severe cellular swelling, degeneration and focal necrosis were more evident in group B than in groups C-E. Histopathological improvement was observed in groups C-E, where UDCA and RSV were combined, compared to group B. We found that UDCA and RSV, together or separately, protected the liver against oxidative stress damage caused by TAC.

Mitochondrial Homeostasis and Mast Cells in Experimental Hepatic Ischemia-Reperfusion Injury of Rats.

BACKGROUND: Ischemia-reperfusion injury is a histopathological event and is an important cause of morbidity and mortality after hepatobiliary surgery. We aimed to investigate the protective effect of uridine on hepatic ischemia-reperfusion injury in rats. METHODS: The animals were divided into 4 groups (n = 8): group I (control), group II: ischemia-reperfusion (30 minutes ischemia and 120 minutes reperfusion), group III: ischemia-reperfusion+uridine (at the beginning of reperfusion), and group IV: ischemia-reperfusion+uridine (5 minutes before ischemia-reperfusion). Uridine was administered a single dose of 30 mg/kg IV. The 3 elements of the hepatoduodenal ligament (hepatic artery, portal vein, and biliary tract) were obliterated for 30 minutes. Then hepatic reperfusion was achieved for 120 minutes. RESULTS: In the ischemia-reperfusion group, both liver tissues and serum chymase activity and high-temperature requirement A2 levels were higher. Severe central vein dilatation and congestion, widening sinusoidal range, diffuse necrotic hepatocytes and dense erythrocyte accumulation in sinusoids, and strongly inducible nitric oxide synthase expression were seen in the ischemia-reperfusion group. A clear improvement was seen in both uridine co-administration and pretreatment groups. CONCLUSION: Our results revealed that uridine limits the development of liver damage under conditions of ischemia-reperfusion, thus contributing to an increase in hepatocyte viability.

Use of the Right Lobe Graft With Double Hepatic Arteries in Living-Donor Liver Transplant.

OBJECTIVES: We aimed to examine management of double hepatic artery reconstruction in patients under going living-donor liver transplant. MATERIALS AND METHODS: Between January 2002 and June 2014, one thousand thirty-six living-donor liver transplants were performed at the Liver Transplant Institute of Malatya Inonu University. Living liver grafts with a single hepatic artery were used in 983 living-donor liver transplants, while grafts with double hepatic artery branches were used in 53 living-donor liver transplants. All of the liver grafts with double hepatic artery branches were right lobe grafts. Hepatic artery anastomosis technique and the other medical data of recipients who used grafts with double hepatic arteries were analyzed retrospectively. RESULTS: A double hepatic artery anastomosis was created in 43 recipients, while a single anastomosis was created in the remaining 10 because of ligation of the nondominant hepatic artery branch. In 40 recipients, double hepatic artery branches in the graft were anastomosed with the recipient's right and left hepatic artery. In the remaining 3 recipients, double hepatic artery branches in the graft were anastomosed with the recipient's right hepatic artery and large segment 4 hepatic arteries. Postoperative complications related with hepatic artery anas-tomoses developed in 3 recipients: hepatic artery thrombosis (n = 1), hepatic artery aneurysm (n = 1), and hepatic artery stenosis (n = 1). A recipient with hepatic artery aneurysm immediately underwent a retransplant. A recipient with a hepatic artery thrombosis relapsed and required retransplant, which was treated with thrombectomy on postoperative day 10. A recipient with hepatic artery stenosis was followed conservatively. In our series, the incidence of complications related with double hepatic artery anastomosis was found to be 6.9%. CONCLUSIONS: According to our experiences, a double hepatic artery anastomosis does not increase the risk of hepatic artery thrombosis and can be performed safely by surgeons who are experienced with hepatic vascular reconstructions in a living-donor liver transplant recipient.

The effects of FDI and government expenditures on environmental pollution in Korea: the pollution haven hypothesis revisited.

This paper uses the pollution haven hypothesis (PHH) to examine the effects of foreign direct investment (FDI) and government expenditures on environmental quality in Korea. For this purpose, we conducted autoregressive distributed lag (ARDL) bounds testing for the period 1970-2018. Empirical results indicate that in Korea, increased FDI, per capita gross domestic product (GDP), energy use, and imports have led to increased per capita carbon dioxide (CO2) emissions, while government expenditures, renewable energy, and exports have led to decreased per capita CO2 emissions. Empirical results also reveal an N-shaped relationship between per capita GDP and per capita CO2 emissions. Moreover, the PHH is valid in Korea to a moderate degree, and the detrimental effect of FDI on environmental quality is relatively limited. Furthermore, government expenditures improve environmental quality. These empirical findings support Korea's leading role in implementing comprehensive green growth initiatives.

Hepatic Venous Outflow Obstruction After Living-Donor Liver Transplant: Single Center Experience.

OBJECTIVES: In this study, we share our approach for care of patients with hepatic venous outlet obstruction after living-donor liver transplant. MATERIALS AND METHODS: We retrospectively examined the demographic, clinical, and radiologic data of 35 patients who developed hepatic venous outlet obstruction after living-donor liver transplant. Patients were subgrouped on the basis of onset (8 patients with early onset [< 30 days posttransplant] and 27 patients with late onset [≥ 30 days posttransplant]) and postoperative survival (24 survivors, 11 nonsurvivors). RESULTS: Patients ranged in age from 1 to 61 years (24 adults and 11 children). All adult patients had undergone right lobe living-donor liver transplant. In the pediatric group, 8 had undergone left lateral segment and 3 had undergone left lobe living-donor liver transplant. Nineteen adult patients and all 11 pediatric patients underwent hepatic venous reconstruction, with all procedures based on common large-opening drainage models using various vascular graft materials. Development of hepatic venous outlet obstruction occurred at mean posttransplant day 233 ± 298.5 in the adult patients and mean posttransplant day 139 ± 97.8 in the pediatric patients. After development of obstruction, the patients underwent 1-6 sessions (1.5 ± 1.1 sessions) of balloon angioplasty. After the first balloon angioplasty procedure, 25% of the adults and 36.3% of the pediatric patients developed recurrence. The early-onset and late-onset subgroups showed statistically significant differences in serum albumin (P = .01), underlying causes (P < .001), time from transplant to obstruction (P = .02), and time from transplant to last visit (P = .02). The survivor and nonsurvivor subgroups showed statistically significant differences in total bilirubin (P = .03) and time from transplant to last visit (P = .03). CONCLUSIONS: Common large-opening reconstruction minimizes hepatic venous outlet obstruction development after living-donor liver transplant. Balloon angioplasty and/or stenting is almost always the first option in the care of this complication.

Comparison of Two Pancreatic Anastomosis Techniques in terms of Postoperative Complications After Pancreaticoduodenectomy.

OBJECTIVE: In this retrospective study, we compared the postoperative complications by using both the Clavien-Dindo classification and the Revised 2016 International Study Group on Pancreatic Surgery (ISGPS) classification methods after pancreaticoduodenectomy. MATERIALS AND METHODS: The data of patients were retrospectively reviewed. Pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) were performed on 41 and 40 patients, respectively. The patients were assigned into two groups for anastomosis types and compared with each other according to postoperative complications. The postoperative follow-up period of the patients was limited to 90 days. RESULTS: No significant difference was detected between the two groups in terms of gender (P = .581) and age (P = .809). According to the Clavien-Dindo classification system, grade 1 complication rates were 29.3% and 35.0% in PJ and PG groups, respectively. Also, grade 2 complication rates were 34.1% and 32.5% in PJ and PG groups, respectively. Besides, grade 3B complication rates were 9.8% and 17.5% in PJ and PG groups, respectively. No grade 3A, grade 4A, and grade 4B complications were detected in both groups. But, grade 5 complications rates were 2.4% and 5.0% in PJ and PG groups, respectively. Based on the ISGPS classification system, the pancreatic fistulas were classified. The biochemical leak rates were calculated as 26.8% and 37.5% in PJ and PG groups, respectively. The rates were 14.6% and 10% in PJ and PG groups, respectively, for grade B complications. Also, grade C complication rates were 9.75% and 12.5% in PJ and PG groups, respectively. No statistically significant differences were detected between the two groups for postoperative complications. CONCLUSION: The evidence from this retrospective study suggests that there is no difference between the two types of pancreatic anastomosis techniques (PJ or PG) in terms of the rate of postoperative complications.

Testing validity of the EKC hypothesis in South Korea: role of renewable energy and trade openness.

This paper investigates the dynamic short-term and long-term relationships among per capita GDP, per capita energy consumption, per capita renewable energy consumption, trade openness, and per capita carbon dioxide (CO2) emissions within the framework of the environmental Kuznets curve (EKC) hypothesis for Korea from 1971 to 2017. According to the empirical findings of the autoregressive distributed lag (ARDL) bounds testing procedure, although increases in per capita GDP and per capita energy consumption increase per capita CO2 emissions, per capita renewable energy consumption and trade openness decrease per capita CO2 emissions. Furthermore, according to the empirical results, an N-shaped relationship has been identified between per capita CO2 emissions and per capita GDP. This indicates that our empirical findings do not support the EKC hypothesis in Korea. Thus, economic growth alone is not sufficient to address environmental pollution; in response, active environmentally friendly policies should be implemented, and the energy matrix should be transformed in favor of renewable energy in Korea.

Medical ozone treatment ameliorates the acute distal colitis in rat.

PURPOSE: To investigate the effect of medical ozone treatment on the experimental acute distal colitis in rats. METHODS: Eighteen rats were randomly distributed into three equal groups; control, acute distal colitis (ADC) without and with medical ozone treatment. Rats in the control group were taken saline. ADC was performed by rectal way with 4% acetic acid in groups 2 and 3, and the group 3 was treated with medical ozone for three weeks both rectally and intraperitoneally. At the twenty second day the distal colons samples were obtained for malondialdehyde and myeloperoxidase, blood samples were obtained to measure the levels of TNF-α and IL-1ß levels. Histolopatological examination was evaluated with Ki-67, IL-1ß and VEGF immunostaining densities. RESULTS: There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1ß after ozone administration. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSIONS: Medical ozone treatment ameliorated the experimental acute distal colitis induced by acetic acid in rats. Its possible effect is by means of decreasing inflammation, edema, and affecting the proliferation and the vascularization.

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury.

PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

Medical ozone treatment ameliorates the acute distal colitis in rat

PURPOSE: To investigate the effect of medical ozone treatment on the experimental acute distal colitis in rats. METHODS: Eighteen rats were randomly distributed into three equal groups; control, acute distal colitis (ADC) without and with medical ozone treatment. Rats in the control group were taken saline. ADC was performed by rectal way with 4% acetic acid in groups 2 and 3, and the group 3 was treated with medical ozone for three weeks both rectally and intraperitoneally. At the twenty second day the distal colons samples were obtained for malondialdehyde and myeloperoxidase, blood samples were obtained to measure the levels of TNF-α and IL-1β levels. Histolopatological examination was evaluated with Ki-67, IL-1β and VEGF immunostaining densities. RESULTS: There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β after ozone administration. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSIONS: Medical ozone treatment ameliorated the experimental acute distal colitis induced by acetic acid in rats. Its possible effect is by means of decreasing inflammation, edema, and affecting the proliferation and the vascularization.

Effect of ozone on colon anastomoses in rat peritonitis model.

PURPOSE: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. METHODS: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1ß, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1ß and the VEGF immunostaining densities were also compared. RESULTS: Intraperitoneal ozone administration reversed TNF-α, IL-1ß, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSION: Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.

Grape seed protects cholestatic rats liver from ischemia/reperfusion injury

ABSTRACT PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.

Effect of ozone on colon anastomoses in rat peritonitis model

PURPOSE: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. METHODS: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1β, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1β and the VEGF immunostaining densities were also compared. RESULTS: Intraperitoneal ozone administration reversed TNF-α, IL-1β, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination. CONCLUSION: Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.

Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1ß, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1ß (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.

Successful living donor liver transplantation of fulminant liver failure due to isoniazid prophylaxis.

Progressive liver failure is rarely seen in tuberculosis chemoprophylaxis with isoniazid. We present a case of a 32-year-old woman admitted to our clinic reporting abdominal pain, nausea and vomiting for 2 days. The initial diagnosis was fulminant toxic hepatitis due to isoniazid chemoprophylaxis, which was treated successfully with living donor transplantation. Tuberculosis continues to be a significant public health problem. Isoniazid-related hepatotoxicity is extremely rare in adults. The only treatment in cases of fulminant liver failure is orthotopic liver transplantation from a deceased or living donor. If a deceased donor is not available or the patient refuses this treatment, living donor transplantation is the only choice. Although rare, isoniazid used as protective therapy for pulmonary tuberculosis can lead to fulminant liver failure. When cadaveric liver transplantation is not available, living donor liver transplantation is vital.

A pancreatic pseudopapillary tumor enucleated curatively.

INTRODUCTION: Pseudopapillary tumors (PPT) of the pancreas are very rare, comprising 0.3-2.7% of all pancreatic tumors, and they occur mostly in young women. Generally, they are benign, but in rare cases they can enlarge, invade adjacent organs, and metastasize distantly. Radiological assessments and biochemical markers are important for diagnosing tumor characteristics. The main treatment is tumor resection. PRESENTATION OF CASE: An 18-year-old female was referred to our department suffering from abdominal discomfort and upper quadrant abdominal pain. Abdominal computed tomography (CT) revealed a 6-×5-cm mass between the pancreatic head and right adrenal gland (Fig. 1). The histological assessment was a solid PPT of the pancreas with intact surgical borders. DISCUSSION: PPT are very rare, comprising approximately 5% of cystic pancreatic tumors and ∼1% of exocrine pancreatic neoplasms and present mainly during the second and third decades of life. PPTs are usually indolent tumors. As such, they tend to produce vague nonspecific symptoms or may be detected incidentally on imaging. Complete surgical resection (R0) is the most effective therapy for PPT. CONCLUSION: Although PPT is a very rare, benign tumor, it has the potential to metastasize to adjacent and distant organs. Consequently, they should be detected early, so that they can be treated surgically before malignant conversion.