Rare association of solitary necrotic nodule of the liver with rheumatoid arthritis and systemic lupus erythematosus.

Solitary necrotic nodule of the liver (SNNL) is a rare benign lesion with uncertain etiology characterized by a "completely necrotic core" and a hyalinized capsule containing elastin fibers (Journal of Clinical Pathology 36:1181-1183, 1983). We report herein a 26-year-old woman with a previous diagnosis of rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome and no history of malignancy who presented with a complaint of diarrhea of 1-year duration. In the abdominal ultrasound, multiple paraaortic, portocaval, and ileal lymphadenopathies (LAPs) have been found with the largest one being 2 cm in size. The biopsy of the iliac LAP showed reactive nodular hyperplasia. An abdominal CT disclosed an incidental hypoechoic, heterogenous mass sized 27 × 27 mm close to segment VI of the liver. A trucut biopsy of this lesion was made, and clinicopathologic features of the specimen were compatible with a solitary necrotic nodule of the liver. Here, we discuss the diagnosis and the clinical course of this rare entity in light of current literature.

Hepatocellular adenomas in the Turkish population: reclassification according to updated World Health Organization criteria.

AIMS: Hepatocellular adenoma (HCA) is an uncommon liver neoplasm, and studies of HCA subtypes have been primarily limited to France, the USA, and Japan. The aim of this study was to describe the clinicopathological features of HCA subtypes in Turkey. METHODS AND RESULTS: The resection specimens of 59 cases diagnosed as 'hepatocellular adenoma' collected from 15 institutions were reviewed to confirm the diagnosis and to classify them according to the current World Health Organization 2019 classification. Immunostaining for glutamine synthetase, liver fatty acid-binding protein, C-reactive protein, ß-catenin and reticulin was performed. Of the 59 cases, 48 (81%) were diagnosed as HCA. We identified 24 (50%) hepatocyte nuclear factor 1α (HNF1α)-inactivated HCAs, five (10%) inflammatory HCAs, 15 (32%) ß-catenin-activated HCAs, three (6%) ß-catenin-activated inflammatory HCAs, and one (2%) unclassified HCA. HCA patients were predominantly female (female/male ratio of 5:1); they had a median age of 34 years and a median tumour diameter of 60 mm. In the ß-catenin-activated HCA group, nine cases (19%) showed cytoarchitectural atypia, and were also referred to as atypical hepatocellular neoplasms. In the ß-catenin-activated HCA group, three cases (6%) showed focal areas supportive of transition to HCA. The original diagnosis of HCA was changed to well-differentiated hepatocellular carcinoma in nine cases and to focal nodular hyperplasia in two cases. CONCLUSION: In our series, the major HCA subtype was HNF1α-inactivated HCA. We found a low incidence of inflammatory-type HCA. Our data also showed that ß-catenin-activated hepatocellular neoplasms, including cases with atypical histology, constituted a relatively high proportion of the cases. These findings are in contrast to those of most other studies of HCA subtypes.

Successful treatment of pediatric post-liver transplant Kaposi`s sarcoma with paclitaxel.

BACKGROUND: Kaposi`s sarcoma (KS) is a complication of immunosuppressive therapy for transplant recipients. Unlike adult recipients, KS in pediatric organ transplantation is quite rare. Treatment is usually withdrawal of immunosuppression; non-responders often receive chemotherapy. CASE: We have reported a child with post-liver transplant visceral KS which has progressed despite withdrawal of immunosuppressive therapy, who has been treated with Paclitaxel for three weeks. KS has regressed completely after four cycles of Paclitaxel. CONCLUSION: Paclitaxel should be considered as an effective first line treatment option for patients with posttransplant KS.

Endoscopic ultrasound-guided liver biopsy using a 20-gauge fine needle biopsy needle with the wet-heparinized suction technique.

OBJECTIVES: The primary aim of this study was to evaluate the histological adequacy of the liver tissue specimens obtained with a 20-gauge fine-needle biopsy needle and the secondary aim was to test the safety endoscopic ultrasound-guided liver biopsy with a 20-gauge fine-needle biopsy needle with the wet-heparinized suction technique. METHODS: Forty patients who underwent endoscopic ultrasound-guided liver biopsy were included in the study. A 20-gauge fine-needle biopsy needle was used with the wet-heparinized suction technique to make one pass each from the left and the right lobe. Histologic characteristics of the specimens were evaluated, and patients were observed after the procedure in order to intervene in case of an adverse event. RESULTS: The median longest core fragment was 22 mm from the left lobe [first quartile-third quartile 20-25 mm, interquartile range (IQR) 5 mm], and 20 mm (first quartile-third quartile 17-22 mm, IQR 5 mm) from the right lobe. The median cumulative core length per patient was 103 mm (91-108 mm, IQR 17 mm). The median cumulative number of complete portal triads per patient was 69.50 (52.25-82.25, IQR 30). The rate of diagnostic yield was 100%. Post-biopsy self-limiting abdominal pain was reported in two patients (5%). The most common histologic diagnosis was fatty liver disease (25%). CONCLUSION: Endoscopic ultrasound-guided liver biopsy with the wet-heparinized suction technique using a 20-gauge fine-needle biopsy needle is a safe alternative method in clinical practice.

The Assessment of Hepatosteatosis in Living-Donor Liver Transplant: Comparison of Liver Attenuation Index and Histopathologic Results.

OBJECTIVES: The purpose of the study was to determine the diagnostic value of computed tomography densitometry in the quantification of hepatosteatosis. MATERIALS AND METHODS: Fifty-one potential liver donors, ranging in age from 19 to 52 years (mean age: 32.4 years ± 10.2), participated in the study. The mean hepatic attenuation and mean splenic attenuation were determined using regions of interest measurements. The difference between the mean hepatic attenuation and mean splenic attenuation (or liver attenuation index), with liver attenuation index = mean hepatic attenuation - mean splenic attenuation were calculated. Computed tomography densitometric parameters were correlated with histopathologic results. RESULTS: From the histopathologic analysis, the degree of macrovesicular hepatosteatosis was 0% to 8% (mean: 1.1% ± 2%). Seven donors (13.7%) had a degree of macrovesicular steatosis of > 5%, and 12 donors (23.5%) had ≥ 2%. Of the 29 normal donors with histopathologic verification, computed tomography densitometry predicted ≤ 5% of the hepatosteatosis in 27 donors, and ≤ 2% hepatosteatosis in 2 subjects. The liver attenuation index was significantly correlated to the histopathologic results. The mathematical relation between liver attenuation index and the degree of histopathologic hepatosteatosis was calculated using the least-squares methods, which provided quadratic polynomials. CONCLUSIONS: Computed tomography densitometry is a rapid, robust, noninvasive technique for the assessment of hepatosteatosis. When used in conjunction with clinically stable reference measurements of spleen, the density measurements of liver correctly predicted the presence of fatty infiltration with significant sensitivity (77%) and specificity (75%). This technique, which was refined during the course of our liver transplant program, minimizes the need for highly invasive percutaneous liver biopsies.

Osteofibrous dysplasia-like adamantinoma in a 3-month-old male infant: a case report.

We report a case of a very rarely seen osteofibrous dysplasia-like adamantinoma (OFDLA) of the lower leg in a 3-month-old male infant, making it the youngest case in the literature. OFDLA is typically regarded as a benign lesion; however, due to its convertibility into classical adamantinoma, it is recommended to evaluate it as a pre-malignant lesion. After OFDLA diagnosis with biopsy, our case underwent surgical resection and reconstruction with a large allograft. Patient experienced good outcomes and did not experience any local relapse in the 3-year follow-up.

Primary malignant melanoma of the esophagus.

Primary malignant melanoma of the esophagus (PMME) comprises only 0.1-0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ultrasonography findings and management of a PMME case.

Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn.

PURPOSE: To evaluate the effects of resveratrol and bevacizumab on experimental corneal neovascularization. METHOD: A corneal alkali burn was performed in 62 eyes of 31 male white Vienna rabbits. Resveratrol (group 1), dimethyl sulfoxide (group 2), bevacizumab (group 3) and 0.9% NaCl (group 4) were administered to both eyes of the rabbits by subconjunctival injection for 7 days. Corneal photos were taken at 15 days after alkali injury. Inflammatory index scores and neovascularization areas were calculated. RESULTS: In bevacizumab group both inflammatory index scores and the calculation of the corneal neovascularization area was significantly less than the groups. CONCLUSION: The subconjunctival administration of bevacizumab inhibits corneal neovascularization effectively in the rabbit corneal alkali burn model. No effect of resveratrol to the corneal neovascularization on experimental model of the corneal alkali burn was seen at the doses of usage.

Beneficial effects of aminoguanidine on skin flap survival in diabetic rats.

Random flaps in DM patients have poor reliability for wound coverage, and flap loss remains a complex challenge. The protective effects of aminoguanidine (AG) administration on the survival of dorsal random flaps and oxidative stress were studied in diabetic rats. Two months after the onset of DM, dorsal McFarlane flaps were raised. Forty rats were divided into four groups: (1) control, (2) AG, (3) DM, and (4) DM + AG groups. Flap viability, determined with the planimetric method, and free-radical measurements were investigated. In addition, HbA1c and blood glucose levels, body weight measurements, and histopathological examinations were evaluated. The mean flap necrotic areas (%) in Groups I to IV were 50.9 ± 13.0, 32.9 ± 12.5, 65.2 ± 11.5, and 43.5 ± 14.7, respectively. The malondialdehyde (MDA) and nitric oxide (NO) levels were higher in the DM group than in the nondiabetic group, while the reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity were reduced as a result of flap injury. In the diabetic and nondiabetic groups, AG administration significantly reduced the MDA and NO levels and significantly increased GSH content and SOD enzyme activity. We concluded that AG plays an important role in preventing random pattern flap necrosis.

Ocular surface and dry eye in Graves' disease.

PURPOSE: To evaluate the tear function tests and the ocular surface damage in Graves' disease (GD) patients either with or without thyroid associated orbitopathy (TAO). METHODS: Forty-two eyes of 21 randomly selected patients with GD, and 30 eyes of 15 healthy subjects were included in this prospective study. The presence of TAO was evaluated clinically. The palpebral fissure height, degree of proptosis, ocular surface disease index (OSDI), Schirmer tear test, tear break-up time (TBUT), and conjunctival impression cytology were assessed. The results were first compared between the patient and the control groups. Results were then compared between the patients with TAO (group I) and without TAO (group II). RESULTS: The mean OSDI score in the patient group was 44.79 ± 11.83 and it was 21.17 ± 9.89 in the control group (p = 0.001). The mean Schirmer tear test score was 14.4 ± 8.32 mm and 24.9 ± 3.57 mm in the patient and control group, respectively (p = 0.001). The mean TBUT in the patient group was 7.1 sec. In the control group it was significantly increased to 10 sec (p = 0.003). The mean proptosis and interpalpebral distance did not show any difference between the GD patients and controls (p > 0.05). The patients with GD showed significant ocular surface damage in which 75.71% had grade 2-3 squamous metaplasia in temporal interpalpebral conjunctiva. Twenty-four (57%) eyes composed group I. There were no differences in the mean OSDI score, Schirmer tear test score, TBUT, and the amount of ocular surface damage between group I and group II (p > 0.05). CONCLUSIONS: Dry eye findings and the ocular surface damage in GD were most likely associated with the ocular surface inflammation. Before the development of the classic findings of TAO, ocular surface inflammation can be the only presenting clinical sign in GD.

A rare benign laryngeal tumor: angiomyolipoma.

Angiomyolipoma is a mesenchymal neoplasm containing adipose tissue, blood vessels, and smooth muscle fibers. Arising most frequently in the kidney, the tumor may exceptionally be at the head and neck region. The literature has 1 single published report of laryngeal angiomyolipoma, which was resected through laryngofissure. In this study, a 58-year-old man presented with laryngeal angiomyolipoma with swallowing discomfort. The tumor was removed by an endolaryngeal approach.

Effect of leflunomide on liver regeneration after partial hepatectomy in rats.

PURPOSE: Partial hepatectomy (PH) can be an inevitable surgical therapy in some conditions, such as hepatic malignancies, trauma or partial liver transplantation. Its capacity for regeneration distinguishes the liver from other essential organs. Regeneration is a complex process involving growth factors, cytokines, transcription factors, hormones, and oxidative stress products. In the event of ineffective or total absent liver regeneration, the life threatening picture of acute liver failure may supervene. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and antiinflammatory agent against autoimmune disease, on hepatic regeneration after PH in Wistar Albino rats. METHODS: Thirty-five Wistar albino rats were divided into five groups: group 1, control; group 2, sham; group 3, drug control (was treated with leflunomide 10 mg/kg/d/i.g.); group 4, PH; group 5, PH + leflunomide. As for PH, approximately 70% of the rat liver was surgically removed under general anesthesia. On postoperative day 3, all rats were humanely killed. Catalase (CAT), superooxide dismutase (SOD) and myeloperoxidase (MPO) activities with malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were determined in remnant liver tissue. Inflammatory process and liver regeneration were evaluated with H&E and KI67, respectively. RESULTS: The tissue levels of MDA, PC and MPO were lower in group 5 than levels in group 1. PH significantly decreased the enzymatic activity of CAT (p < 0.05) and SOD. This reduction was significantly improved by the treatment with leflunomide. Histopathologically the enhancement of the liver parenchymal regeneration in the group 5 was significantly greater than the group 4. CONCLUSION: The findings imply that oxidative stress products play a preventive role in liver regeneration after PH and leflunomide ameliorates the regeneration probably by the radical scavenging and antioxidant activities.

The expression of matrix metalloproteinases in intrahepatic cholangiocarcinoma, hilar (Klatskin tumor), middle and distal extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma: role of matrix metalloproteinases in tumor progression and prognosis.

BACKGROUND/AIMS: Carcinomas of the biliary tree are rare tumors of the gastrointestinal tract, with an increasing incidence in recent years. Biliary neoplasms are classified into intra- and extrahepatic cholangiocarcinoma (Klatskin tumor, middle and distal extrahepatic tumors), gallbladder adenocarcinoma, and ampullary carcinoma. We aimed to determine the expression profile of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-14 in the biliary neoplasms classified according to their localization and the relation with the prognosis. METHODS: Ten gallbladder adenocarcinoma, 8 distal bile duct carcinomas (distal cholangiocarcinoma), 8 Klatskin tumors, 8 intrahepatic cholangiocarcinomas and 10 ampullary carcinomas were included in the study. The immunohistochemical expression of MMP-2, MMP-9 and MMP-14 was detected in the nontumoral, metaplastic, dysplastic and tumoral epithelia. The tumor differentiation, angiolymphatic and perineural invasion of the tumor, and presence of lymph node and distant metastasis were determined. Survey of the patients was noted from the patient follow-up data. RESULTS: The nontumoral epithelia of the gallbladder, intrahepatic ducts, and Klatskin tumor did not express MMP-2. MMP-2 expression was detected in the distal part of the biliary ducts, in 75% (6/18) of cases and in the nontumoral epithelia of the ampullary region in 50% (5/10) of cases. The metaplastic and dysplastic epithelia were positively stained in all of the gallbladder adenocarcinoma, distal cholangiocarcinoma and ampullary tumors. In the intrahepatic cholangiocarcinoma, the hepatocytes were positively stained but the infiltrative tumors were spared. Klatskin tumors were also not stained with MMP-2. The gallbladder adenocarcinoma, distal cholangiocarcinoma and ampullary carcinomas expressed MMP-2 in 30%, 37% and 40% of the cases, respectively. MMP-9 and MMP-14 were expressed in normal, metaplastic, and dysplastic epithelium and tumoral cells in all of the cases of the groups. Expressions of MMPs were higher in subjects with neural invasion, but there was no correlation between MMP expression and tumor differentiation or angiolymphatic invasion. CONCLUSIONS: When tumors of the biliary system are divided as intrahepatic and extrahepatic cholangiocarcinomas, MMP-2 expression was present in the extrahepatic cholangiocarcinomas including gallbladder carcinomas. Like the intrahepatic cholangiocarcinoma, Klatskin tumors also did not express MMP-2. This can be related with its characteristic growth pattern. MMP-9 and MMP- 14 were present in metaplasia, dysplasia carcinoma sequence in all of the bile tract tumors, suggesting that MMPs play an important role in carcinogenesis. The higher expression of the MMPs with neural invasion suggests the significant role of those tumors in the invasion activity.

Does leflunomide attenuate the sepsis-induced acute lung injury?

The organ that is affected first and most severely in intraabdominal sepsis is the lung. Oxygen radicals and active neutrophils in the lung are important sources for severe pulmonary inflammation leading to acute lung injury (ALI)/acute respiratory distress syndrome. The aim of this study was to investigate the effects of leflunomide, an immunomodulatory agent, on oxidant/antioxidant status with nitric oxide (NO) level and myeloperoxidase (MPO) activity in rats with sepsis-induced ALI. Fifty male Wistar albino rats were divided into five groups: control, sham, sepsis, leflunomide (10 mg/kg, intragastrically for two doses with an 8 h interval prior to the experiment) and sepsis + leflunomide. After the animals were anesthetized with ketamine and xylazine, the abdominal cavity was opened and ligated just below the ileocaecal valve with 3-0 silk. The antimesentric surface of the cecum was perforated and the cecum was gently compressed until fecal matter was extruded to induce sepsis. None of the rats received antibiotics during the experimental procedures. The experiment was ended 24 h after cecal ligation puncture (CLP) with the cervical dislocation under anesthesia. The lung tissues were removed for analysis of biochemical parameters and light microscopic investigation. The lung superoxide dismutase (SOD), catalase and glutathione peroxidase activities were decreased in the sepsis group as compared to the group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and SOD activity were significantly higher in group sepsis + leflunomide than sham, control, leflunomide and sepsis group (P < 0.05). The lung MPO, malondialdehyde (MDA), protein carbonyl and NO levels were higher in the sepsis group when compared to group control, sham, leflunomide and sepsis + leflunomide (P < 0.05), and MPO, MDA and NO levels were higher in the sepsis + leflunomide group than in the sham, control and leflunomide group (P < 0.05). The light microscopic evaluation showed that pulmonary architecture was preserved, and infiltration of neutrophil and edema decreased in sepsis + leflunomide group. The grade of alveolar damage was significantly decreased in sepsis + leflunomide group in comparison with sepsis group (P < 0.05). Our findings suggested that leflunomide attenuated the lung injury after CLP-induced sepsis by inhibition of neutrophils accumulation and increasing endogenous antioxidant capacity.

Expression of matrix metalloproteinases in gallbladder carcinoma and their significance in carcinogenesis.

The correlation between matrix metalloproteinase (MMP)-2, MMP-9, and MMP-14 expression on the prognostic parameters of gallbladder carcinoma (GBC) and their role in carcinogenesis were evaluated. Carcinomas of the gallbladder (n=20) and chronic cholecystitis (n=10) were studied for the expression of MMP-2, MMP-9, and MMP-14 by immunohistochemistry. In all of the cases, metaplastic and dysplastic epithelial alterations, and (in GBC histologic type, grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, and lymph node involvement were noted. MMP-2, MMP-9, MMP-14 were expressed in tumor epithelium in 9 (45%), 20 (100%), and 20 (100%) of the cases, respectively. MMP stromal expression including muscle layer, vascular endothelium, fibroblasts, and lymphoid cells were detected in all cases. MMP-2 was not expressed in normal, metaplastic, and dysplastic epithelia. In contrast, MMP-9 and MMP-14 immunoreactivities were present in antral-type metaplastic areas as moderate (grade 2) and strong in dysplastic epithelia (grade 3). Only in mucinous-type GBC was the expression of the MMPs lower than in the other types. No significant correlation was detected with the grade of differentiation, level of infiltration, perineural and angiolymphatic invasion, liver invasion, or lymph node involvement. These data suggest that MMP-9 and MMP-14 overexpression may have an important role in tumorigenesis. MMP-2, MMP-9, and MMP-14 were expressed in GBC epithelium but also the expression in the stromal component may be essential for the malignant potential of GBC.

Kaposi's sarcoma after liver transplantation from a donor with a history of ventriculoperitoneal shunt and craniotomy for primary central nervous system lymphoma: report of a case.

The transplantation of organs from donors who have undergone shunt surgery or craniotomy for a malignant central nervous system (CNS) tumor is controversial. We report a case of Kaposi's sarcoma (KS) developing as a result of immunosuppression in the recipient of a liver transplant from a donor who underwent craniotomy and ventriculoperitoneal shunt surgery for primary CNS lymphoma. Polymerase chain reaction assay did not isolate human herpes virus-8 in the Kaposi lesions. To our knowledge, this is the only case ever reported of KS developing after liver transplantation from a donor with lymphoma. Thus, with appropriate screening to exclude possible dissemination, patients with a history of high-grade primary CNS lymphoma treated by ventriculoperitoneal shunt and craniotomy may be accepted as donors.

The effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats.

OBJECTIVE: This study evaluates the effects of granulocyte colony-stimulating factor on the healing of tracheal anastomosis following radiation therapy in rats. METHODS: Fifty-six male Wistar rats were divided into four groups. Group 1 underwent tracheal anastomosis. Group 2 underwent radiation therapy followed by tracheal anastomosis. Group 3 underwent radiation therapy followed by tracheal anastomosis and received granulocyte colony-stimulating factor. Group 4 underwent sham radiation therapy followed by sham tracheal anastomosis. At 10 days following radiation therapy, the trachea was dissected for histopathological, mechanical and biochemical evaluation. RESULTS: Median scores for inflammation were three points for Group 1, two points for Group 2, two points for Group 3 and one point for Group 4. Median scores for angiogenesis were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for connective tissue regeneration were four points for Group 1, two points for Group 2, three points for Group 3 and one point for Group 4. Median scores for epithelial regeneration were two points for Group 1, one point for Group 2, one point for Group 3 and one point for Group 4. Mean anastomotic bursting pressures were 853 mmHg for Group 1, 293 mmHg for Group 2, 417 mmHg for Group 3 and 966 mmHg for Group 4. Mean hydroxyproline concentrations were 159 microg/mg for Group 1, 177 microg/mg for Group 2, 120 microg/mg for Group 3 and 117 microg/mg for Group 4. CONCLUSIONS: This study suggests that granulocyte colony-stimulating factor contributes to the healing of tracheal anastomosis following radiation therapy through improved connective tissue regeneration.

Role of matrix metalloproteinase-7 in colorectal adenomas.

Matrix metalloproteinases (MMPs) degregade and remodel the extracellular matrix. They are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. In our prospective study we measured the overexpression of MMP-7 immunohistochemically in various types of colonic adenomas. Although MMP-7 has already been shown to be overexpressed in various types of colonic adenomas, tubular versus villous adenomas had not been further seperated to date. Seventy-six patients had either normal mucosa (n=15) or tubular (n=32), tubulovillous (n=16), or villous (n=13) colonic adenoma. MMP-7 expression was classified into three categories, as negative, weakly stained, or strongly stained, depending on the percentage of cells stained. Each adenoma was graded according to the percentage of strongly stained areas in the adenoma as G0, G1, G2, or G3. Sixty-nine percent of villous adenomas showed grade 3 staining of MMP-7, versus none of the tubular adenomas. G0 and G1 staining was not detected in the villous adenomas. The results of the study show that the degrees of overexpression of the three subtypes of colonic adenomas were statistically significantly different. In conclusion, MMP-7 overexpression is thought to be an early event in the adenoma-carcinoma pathway.

Hepatic damage in biliary-obstructed rats is ameliorated by leflunomide treatment.

Cholestasis, or impaired bile flow, occurs in a wide variety of liver diseases and causes hepatic damage by retention and accumulation of toxic hydrophobic bile salts inducing persistent inflammation and oxidative stress. In the present research, we studied the effect of leflunomide, a novel immunosuppressive and anti-inflammatory agent against autoimmune disease, on hepatic damage produced by double ligature of the extrahepatic biliary duct in Wistar Albino rats. Cholestasis was done by double ligature and section of the extrahepatic biliary duct (BDL). Leflunomide was given i.g. 10 mg/kg/day. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and levels of direct bilirubin. Malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO), catalase (CAT) and superoxide dismutase (SOD) were determined to the oxidative status in the liver tissue. Myeloperoxidase (MPO) activity and levels of tissue hydroxyproline (HPR) were determined to neutrophil activation and collagen accumulation, respectively. Further, histological changes were studied. Treatment with leflunomide markedly reduced serum transaminase activities as compared to BDL rats. At the same time leflunomide significantly inhibited increases in liver MDA, PC and NO levels and also attenuated the depletion of CAT and SOD in the liver after bile duct ligation. Similarly, increase in tissue MPO activity and HPR due to BDL was also attenuated by leflunomide treatment. These findings were supported by histopathological findings. These findings suggested that leflunomide can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress and inflammatory process.

Resveratrol, a red wine constituent polyphenol, protects gastric tissue against the oxidative stress in cholestatic rats.

This experimental study was designed to determine the effects of resveratrol on the level of malondialdehyde (MDA), reduced glutathione (GSH), and nitric oxide (NO) in gastric tissue after bile duct ligation (BDL). Swiss albino rats were divided into three groups: Group 1, sham (n = 7); Group 2, BDL (BDL only group; n = 7); and Group 3, BDL plus resveratrol (n = 7). Animals in the resveratrol group were treated with 10 mg/kg resveratrol (i.p.) once a day throughout 28 days. In the resveratrol group, levels of MDA and NO in gastric tissue were significantly lower than in the BDL-only group (P < 0.001). The level of GSH in the resveratrol group was significantly higher than in the BDL-only group (P < 0.001). The present study demonstrates that intraperitoneal administration of resveratrol maintains antioxidant defenses and reduces oxidative gastric damage. This effect of resveratrol may be useful to preserve gastric tissue under oxidative stress due to cholestasis.