Effects of grapeseed extract on doxorubicin-induced cardiotoxicity in rats.

BACKGROUND: Doxorubicin (DX) is used for the treatment of many types of cancer; however, a side effect of this agent is cardiotoxicity, which may lead to cardiomyopathy or cardiac failure. Oxidative stress is thought to play a major role in the development of cardiotoxic effects. Proanthocyanidins found in grapeseed (GS) extract may inhibit chemically induced lipid peroxidation and apoptosis caused by oxidative stress. We aimed to investigate the cardioprotective effects of GS extract against DX-induced cardiotoxicity. METHODS: A total of 28 male Sprague Dawley rats were grouped to receive: (a) standard nutrition (n = 7); (b) standard nutrition with an additional dose of 10 mg/kg DX (n = 7); (c) standard nutrition plus 100 mg/kg/day of GS (n = 7); (d) standard nutrition with 100 mg/kg/day of GS plus a single dose of 10 mg/kg DX. After 35 days the rats were decapitated and blood samples were taken for biochemical testing. Cardiac tissue samples were prepared for microscopy and histopathological evaluation. RESULTS: Rats in the DX group exhibited significant elevations in biomarkers such as troponin and NT-proBNP as well as in oxidative stress markers compared with all other groups. Histopathological examination corroborated these findings by demonstrating significant and severe structural injury in the cardiac tissue of DX rates. Moreover, rats in the DX + GS group had significantly lower cardiac injury than rats in the DX group according to both biochemical (troponin and NT-proBNP) and histopathological analyses. Serum malondialdehyde levels (a marker of oxidative stress) in the DX + GS rats were significantly lower than in the DX rats. CONCLUSION: Our findings suggest that GS may reduce the severity of DX-induced cardiotoxicity and thus has the potential to prevent cardiac injury in this setting.

Wnt signaling pathway activities may be altered in primary Sjogren's syndrome

Background/aim: Sjögren's syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The wingless (Wnt)/ß-catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and to evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS. Materials and methods: This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically. Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group. Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt/ß-catenin pathway activities may be altered in case of glandular inflammation.

Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model.

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.

Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer.

Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01-4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50-4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28-0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14-0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95-6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.

Assessment of Liver Fibrosis with Diffusion-Weighted Magnetic Resonance Imaging Using Different b-values in Chronic Viral Hepatitis.

OBJECTIVE: To examine the effectiveness of apparent diffusion coefficient (ADC) values and to compare the reliability of different b-values in detecting and identifying significant liver fibrosis. SUBJECTS AND METHODS: There were 44 patients with chronic viral hepatitis (CVH) in the study group and 30 healthy participants in the control group. Diffusion-weighted magnetic resonance imaging (DWI) was performed before the liver biopsy in patients with CVH. The values of ADC were measured with 3 different b-values (100, 600, 1,000 s/mm2). In addition, liver fibrosis was classified using the modified Ishak scoring system. Liver fibrosis stages and ADC values were compared using areas under the receiver-operating characteristic (ROC) curve. RESULTS: The study group's mean ADC value was not statistically significantly different from the control group's mean ADC value at b = 100 s/mm2 (3.69 ± 0.5 × 10-3 vs. 3.7 ± 0.3 × 10-3 mm2/s) and b = 600 s/mm2 (2.40 ± 0.3 × 10-3 vs. 2.5 ± 0.5 × 10-3 mm2/s). However, the study group's mean ADC value (0.99 ± 0.3 × 10-3 mm2/s) was significantly lower than that of the control group (1.2 ± 0.1 × 10-3 mm2/s) at b = 1,000 s/mm2. With b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s for the diagnosis of liver fibrosis, the mean area under the ROC curve was 0.702 ± 0.07 (p = 0.0015). For b = 1,000 s/mm2 and the cutoff ADC value of 0.0011 mm2/s to diagnose significant liver fibrosis (Ishak score = 3), the mean area under the ROC curve was 0.759 ± 0.07 (p = 0.0001). CONCLUSION: Measurement of ADC values by DWI was effective in detecting liver fibrosis and accurately identifying significant liver fibrosis when a b-value of 1,000 s/mm2 was used.

Use of asprosin and subfatin for differential diagnosis of serous ovarian tumors.

Asprosin (ASP) and subfatin are hormones that regulate glucose metabolism. The role of ASP and subfatin in serous ovarian tumors has not been investigated. We investigated the expression of subfatin and asprosin in 30 serous benign, 30 serous borderline, 30 malignant and 30 control ovarian tissues. We investigated ASP and subfatin immunoreactivity and quantification was achieved using an ELISA method. ASP and subfatin were localized in the epithelial parts of normal ovarian tissues; however, in cancer tissues, immunoreactivity was detected in the parenchymal areas. Biochemical analysis of ovarian tissues revealed significantly decreased ASP and subfatin compared to the control. We propose that ASP and subfatin are promising candidates for biomarkers to distinguish serous benign, serous borderline and malignant ovarian cancers.

Prevention of doxorubicin-induced experimental cardiotoxicity by Nigella sativa in rats.

INTRODUCTION: Doxorubicin (DOX) is an anthracycline cytotoxic chemotherapeutic drug that is commonly used in cancer treatment. A major side effect limiting the clinical use of DOX is cardiotoxicity due to oxidative injury. Nigella sativa (NS) is an annual flowering plant with antioxidant properties. Its seeds contain several bioactive constituents such as saturated and unsaturated fatty acids, thymoquinone, dithymoquinone, thymohydroquinone, and thymol. In this study, we investigated the effect of NS extract on DOX-induced cardiotoxicity. METHODS: The experimental study animals consisted of 28 male Sprague Dawley rats weighing between 300 and 400 g. Four study groups each of seven rats were defined: controls; NS extract; DOX; and DOX+NS. Control and DOX rats received standard food, while each rat in the NS and DOX+NS groups also received 100 mg/kg NS extract orally. At day 28 of follow-up, rats in the DOX groups were administered a single 10 mg/kg intraperitoneal dose of DOX, while rats in the control and NS groups received a single 10 mg/kg dose of physiological saline solution. All animals were monitored for 35 days. On day 35, the rats were decapitated and serum and cardiac tissue samples were obtained. Troponin and NT-proBNP levels were measured in blood sera, while malondialdehyde (MDA), nitric oxide, total antioxidant capacity (TAC), and total oxidative stress (TOS) levels were quantified in sera and tissue samples. Histological alterations that were assessed in cardiac tissue included myocyte disarray, small vessel disease, myocyte hypertrophy, and fibrosis. RESULTS: The DOX group had significantly higher NT-proBNP, TOS, and MDA, with greater histopathological derangement. TAC was significantly elevated in the DOX+NS group, which also exhibited significantly lower troponin, TOS, and MDA, as well as significantly higher TAC compared to the DOX group. Histopathological examination showed that the significant structural derangement observed in DOX rats was markedly and significantly reduced in DOX+NS rats. CONCLUSION: Our results suggest that NS extract may prevent DOX-induced cardiotoxicity and thus represents a promising cardioprotective agent.

Tofacitinib and metformin reduce the dermal thickness and fibrosis in mouse model of systemic sclerosis.

Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is important in the process of inflammation and fibrosis. The adenosine 5'-monophosphate-activated protein kinase (AMPK) enzyme can affect JAK/STAT pathway. Tofacitinib is a pan-JAK inhibitör. Metformin activates AMPK enzyme. We aimed to investigate the therapeutic efficacy of tofacitinib and metformin on IL-17 and TGF-ß cytokines, skin fibrosis and inflammation in mouse model of systemic sclerosis (SSc). 40 Balb/c female mice were divided into 4 groups: (control, sham (BLM), tofacitinib and metformin). The mice in the tofacitinib group received oral tofacitinib (20 mg/kg/daily) and mice in the metformin group received oral metformin (50 mg/kg/day) for 28 days. At the end of 4th week, all groups of mice were decapitated and tissue samples were taken for analysis. Histopathological analysis of skin tissue was performed, and mRNA expressions of collagen 3A, IL-17 and TGF-ß were assessed by real-time PCR and ELISA. Repeated BLM injections had induced dermal fibrosis. Moreover, the tissue levels of collagen 3A, IL-17 and TGF-ß were elevated in the BLM group. Tofacitinib and metformin mitigated dermal fibrosis. They reduced dermal thickness and tissue collagen 3A, IL-17 and TGF-ß levels. Tofacitinib and metformin demonstrated anti-inflammatory and anti-fibrotic effects in the mouse model of SSc.

Diet-induced obesity suppresses ghrelin in rat gastrointestinal tract and serum.

The aims of the present study were to examine ghrelin expression in serum and gastrointestinal tract (GIT) tissues, and to measure tissue ghrelin levels and obesity-related alterations in some serum biochemical variables in rats with diet-induced obesity (DIO). The study included 12 male rats, 60 days old. The rats were randomly allocated to two groups (n = 6). Rats in the DIO group were fed a cafeteria-style diet to induce obesity, while those in the control group were fed on standard rat pellets. After a 12 week diet program including an adaptation period all rats were decapitated, tissues were individually fixed, ghrelin expression was examined by immunohistochemistry , and tissue and serum ghrelin levels were measured by radioimmunoassay. Serum biochemical variables were measured using an autoanalyzer. When the baseline and week 12 body mass index and GIT ghrelin expression were compared between DIO and control rats, BMI had increased and ghrelin expression decreased due to obesity. The RIA results were consistent with these findings. Serum glucose, LDL cholesterol, and total cholesterol levels were elevated and HDL cholesterol significantly decreased in the DIO group. A comparison of GIT tissues between the control and obese groups demonstrated that ghrelin was decreased in all tissues of the latter. This decrease was brought about a decline in the circulating ghrelin pool. This suggests that rather than being associated with a change in a single tissue, obesity is a pathological condition in which ghrelin expression is changed in all tissues.

Multiple cystic pulmonary chondroid hamartomas colonized by Aspergillus species: report of a case.

Pulmonary hamartoma is the most common benign neoplasm of the lung, but the cystic form is very rare. This report presents the case of a 31-year-old woman with two cystic pulmonary lesions. She was radiologically and clinically diagnosed to have multiple ruptured hydatid cysts, and underwent a thoracotomy. The pathological investigation revealed that these lesions were cystic chondroid hamartomas, and one of the cysts was colonized by Aspergillus. Multilocular pulmonary cystic hamartomas are exceptionally rare and should be differentiated from other cystic pulmonary lesions. This is the first case of cystic pulmonary hamartomas colonized by Aspergillus species.

Secukinumab and metformin ameliorate dermal fibrosis by decreasing tissue interleukin-17 levels in bleomycin-induced dermal fibrosis.

Although the pathogenesis of systemic sclerosis is not exactly known, it is thought that immune activation has prominent roles in pathogenesis. Secukinumab is a monoclonal antibody against interleukin (IL)-17A. Metformin, a widely used antidiabetic medication, has anti-proliferative, immunomodulating and anti-fibrotic activities. The purpose of our study is to determine the therapeutic efficacy of secukinumab and metformin on bleomycin (BLM) induced dermal fibrosis. Fifty Balb/c female mice were divided into 5 groups: (group 1 control, 2 sham, 3 secukinumab, 4 metformin and 5 secukinumab + metformin). The mice in the control group received 100 µL phosphate-buffered saline (PBS), while the mice in other groups received 100 µL (100 µg) BLM in PBS subcutaneously (sc) every day for 4 weeks. In addition, mice in groups 3 and 5 received secukinumab at a dose of 10 mg/kg/wk sc, and mice in the groups 4 and 5 received oral metformin 50 mg/kg/d for 28 days. All groups of mice were sacrificed at the end of the 4th week and tissue samples were taken for analysis. In addition to histopathological analysis, skin tissue messenger RNA (mRNA) expressions of IL-17 and collagen 3A were measured by real-time polymerase chain reaction. Repeated BLM injections had caused dermal fibrosis. In addition, the mRNA expressions of IL-17 and collagen 3A were increased in the BLM group. Secukinumab and metformin ameliorated dermal fibrosis. They decreased dermal thickness and tissue IL-17A and collagen 3A mRNA levels. Secukinumab and metformin exhibit anti-fibrotic effects in the BLM-induced dermal fibrosis.

The effects of sponges soaked with chlorhexidine gluconate and metronidazole on safety of colonic anastomosis in an experimental model of peritonitis.

BACKGROUND: The present study aims to evaluate the use of the chlorhexidine gluconate and metronidazole impregnated compresses concerning anastomosis safety in the left colonic anastomosis in the presence of peritonitis. METHODS: This study was conducted on 21 Wistar-Albino-rats divided into three equal groups. After median laparotomy, the whole layer of the left colon was cut 2 cm over the pelvic peritoneum. The faeces were spread around the injury for fecal contamination. Then, fasia and skin were closed with 3/0 silk. After one day period, relaparatomy was performed. The abdomen was cleared isotonic sodium chloride with impregnated material before starting colonic anastomosis in the first group and then double layer colonic anastomosis was performed. In the second Group-II, abdomen was cleared with the metronidazole impregnated compresses then double layer colonic anastomosis was performed. In the group-III, abdomen was cleared with the chlorhexidine gluconate impregnated compresses then double layer colonic anastomosis was performed. Tissue hydroksiproline levels and anastomosis bursting pressures were measured and histopathologic findings on the anastomosis line were evaluated on the postoperative tenth day by performing relaparatomy. RESULTS: The highest anastomosis bursting pressure was found in Group-III (p<0.05). The highest tissue hydroksiproline level was found in Group-III (p<0.005 Group I-III, Group II-III). When histopathologic findings were evaluated by comparing the three groups in this study, the healing of the intestine tissue score was statistically insignificant between group-II and III, for both group-II and III, healing score was statistically significant higher than Group-I (p<0.05 Group I-III and Group I-II). CONCLUSION: Cleaning the abdomen before the anastomosis using antibacterial soaked material increased resection safety in the presence of peritonitis and anastomosis safety in primary anastomosis.

Pleural liposarcoma mimicking carcinoma in pleural effusion cytology: a case report.

BACKGROUND: Primary pleural liposarcoma is extremely rare, and its most common subtype is the myxoid subtype. To the best of our knowledge, the number of cases reported up to now is <20. It is primarily a disease ofindividuals 50 years of age and it is more common in men. It has no specific symptoms except for cough and chest pain. CASE: A 56-year-old female presented complaining of chest pain and dyspnea for 4 months. An increase in homogeneous density on the left hemithorax, from the apex to basal area, with blurring of the borders of the heart and the diaphragm, was revealed by lung radiography. Thoracic computed tomography revealed a diffuse pleural effusion causing compressive atelectasis at the base of the left hemithorax. Cytologic examination of the pleural fluid demonstrated tumoral cells forming papillary structures with complex branching and fine fibrovascular core. The tumor cells were relatively uniform and had vacuolar cytoplasm with hyperchromatic nuclei. Upon finding CA-125 positive in the immunocytochemical examination, the case was reported as "consistent with malignancy, possibility of ovarian origin, cannot be excluded". As the gynecologic examination was normal, exploratory thoracotomy was performed to take a biopsy. The case was diagnosed as liposarcoma (myxoid type) by histopathologic examination. CONCLUSION: Cytologic diagnosis of pleural liposarcoma is difficult due to its rarity and resemblance to malignant mesothelioma. Cytologic properties of liposarcoma in pleural fluid should be well known and considered in the differential diagnosis.

P2X7 receptor as an independent prognostic indicator in gastric cancer.

Gastric cancer (GC) is one of the foremost causes of cancer-related death around the world. The P2X7 receptor (P2X7R), a member of the P2X7R subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers, and recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human GC specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes (TILs) (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced tumor, node, metastasis stage (p < 0.001). Moreover, univariate (hazard ratio [HR] 3.98; 95% confidence interval (CI) 1.89-11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53-12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for GC.

Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders.

Nesfatin-1 and ghrelin are the two recently discovered peptide hormones involved in the control of appetite. Besides its main appetite-control function, ghrelin also has anticonvulsant effects, while nesfatin-1 causes depolarization in the paraventricular nucleus (PVN). The aims of this study, therefore, were to investigate: (i) whether there are differences in the concentrations of nesfatin-1 and ghrelin in saliva and serum samples between eplilepsy patients and normal controls and (ii) whether salivary glands produce nesfatin-1. The study included a total of 73 subjects: 8 patients who were newly diagnosed with primary generalized seizures and had recently started antiepileptic drug therapy; 21 who had primary generalized seizures and were continuing with established antiepileptic drug therapy; 24 who had partial seizures (simple: n = 12 or complex: n = 12) and were continuing with established antiepileptic drug therapy; and 20 controls. Salivary gland tissue samples were analyzed for nesfatin-1 expression by immunochemistry and ELISA. Saliva and serum ghrelin levels were measured by ELISA and RIA, and nesfatin-1 levels by ELISA. Nesfatin-1 immunoreactivity was detected in the striated and interlobular parts of the salivary glands and the ducts. The nesfatin-1 level in the brain was around 12 times higher than in the salivary gland. Before antiepileptic treatment, both saliva and serum nesfatin-1 levels were around 160-fold higher in patients who are newly diagnosed with primary generalized epilepsy (PGE) than in controls; these levels decreased with treatment but remained about 10 times higher than the control values. Saliva and serum nesfatin-1 levels from patients with PGE and partial epilepsies who were continuing antiepileptic drugs were also 10-fold higher than control values. Serum and saliva ghrelin levels were significantly (twofold) lower in epileptic patients before treatment than in controls; they recovered somewhat with treatment but remained below the control values. These results suggest that the low ghrelin and especially the dramatically elevated nesfatin-1 levels might contribute to the pathophyisology of epilepsy. Therefore, serum and saliva ghrelin and especially the remarkably increased nesfatin-1 might be candidate biomarkers for the diagnosis of epilepsy and for monitoring the response to anti-epileptic treatment.

Fascioliasis: A Rare Parasitic Infection-Mimicking Tumor in the Liver: Report of Two Cases.

Fascioliasis is a rarely encountered parasitic infection in Turkey that mainly affects the liver and bile ducts. Other defined localizations of the parasite are the lungs, gastrointestinal system, and subcutaneous fatty tissue. Two cases of female patients who presented to the hospital with abdominal pain and whose physical examination and laboratory findings were normal except peripheral eosinophilia, were detected to have liver masses with necrotic areas. Segmental hepatectomies were performed in both cases with the preliminary diagnosis of liver tumors. Upon microscopic examinations of the resection materials, necrotic granulomatous inflammation with eosinophilic reaction at the periphery and the parasite (Fasciola hepatica) were seen. Both cases were reported to be fascioliasis according to these findings. Two cases of fascioliasis mimicking malignancy in the liver are presented here together with literature findings.

Is excision repair cross-complementation Group1 expression a biological marker in nasopharynx carcinoma?

OBJECTIVE: To determine the prognostic value of excision repairs cross-complementation group1 (ERCC1) gene in cases with nasopharyngeal carcinoma (NPC) treated with platinum-containing chemotherapy (PCT). SUBJECTS AND METHODS: The present study was included 33 cases in local advanced stage with NPC. ERCC1 expression was evaluated by using immunohistochemical staining in biopsy specimens. We evaluated the relationship between the degree of ERCC1 expression and clinicopathological features, response to therapy, survival rates in cases with NPC, retrospectively. RESULTS: ERCC1 expression was not observed in 5 (15.15%) of all cases. Thirteen (39.9%) cases weakly positive (+1, +2) and 15 (45.5%) cases of all them were rather strongly positive (+3). There was no statistically significant difference between the degree of ERCC1 expression and clinicopathological features, response to treatment, survival rates (P > 0.05) in cases with NPC. CONCLUSIONS: ERCC1 expression has no predictive value for survival in cases locally advanced stage with NPC. Evaluation of ERCC1 expression is not appropriate with a biomarker to detect cases who can benefit from PCT in NPC.

Epigallocatechin gallate attenuates experimental non-alcoholic steatohepatitis induced by high fat diet.

BACKGROUND AND AIM: In the present study, we examined the preventive role of epigallocatechin gallate (EGCG) in an experimental non-alcoholic steatohepatitis model induced by a high fat diet. METHODS: The study included 21 male Sprague-Dawley rats, which were equally divided into three groups. The first group was fed on a standard rat diet, the second group on a high fat diet (HFD), and the third group on a HFD + EGCG. The study concluded after 6 weeks. Histopathological examination was performed. Plasma and tissue MDA levels, glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, triglyceride, and cholesterol levels were studied. Insulin resistance was calculated by the homeostasis model of insulin resistance method. RESULTS: Steatosis, inflammation, ballooning degeneration, and necrosis increased significantly in the HFD group, compared to the control group (P < 0.01). Steatosis and inflammation decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.05, for each). There was a significant decline in ALT (P < 0.01), triglyceride (P < 0.01), insulin (P < 0.05), and glucose (P < 0.05) levels in the HFD + EGCG group, when compared to the HFD group. Plasma and liver MDA levels in the HFD + EGCG group were lower than those of the HFD group; the difference was significant (P < 0.01 for each). Glutathione levels in the HFD + EGCG group was significantly higher those in the HFD group. CYP 2E1 and alpha-smooth muscle actin expression decreased in the HFD + EGCG group, in comparison to the HFD group (P < 0.01, P < 0.05, respectively). CONCLUSION: EGCG reduces the development of experimental non-alcoholic steatohepatitis induced by a high fat diet. It seems to exercise this effect through its effect on lipid metabolism and antioxidant characteristics.

Effect of unfiltered coffee on carbon tetrachloride-induced liver injury in rats.

To assess the role of unfiltered coffee upon carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. All rats were randomly divided into control group, CCl(4)-treated, unfiltered coffee-treated and CCl(4)/unfiltered coffee-treated. Hepatic damage was induced by repeated intraperitoneal injections of CCl(4) every other day. Unfiltered coffee was given as drinking fluid for 8 days starting the day before CCl(4) administration. Liver enzymes, plasma and liver tissue malondialdehyde were analyzed. Histopathological evaluation of liver sections was performed. Serum aminotransferase level significantly increased in CCl(4)/unfiltered coffee-treated group compared to CCl(4)-treated group, as well as, lipid peroxidation products in the plasma and liver tissue. In addition, histopathological findings including inflammation and necrosis were significantly confirmed these findings. Unfiltered coffee potentiates acute liver injury in rats with CCl(4)-induced hepatotoxicity.

Hepatoprotective effect of infliximab, an anti-TNF-alpha agent, on carbon tetrachloride-induced hepatic fibrosis.

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-alpha agent, on the carbon tetrachloride (CCl(4))-induced hepatic fibrosis in rats. Rats were randomized into three groups (n=9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl(4) (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p<0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of alpha-smooth muscle actin were lower in the infliximab-treated group than the CCI(4)-treated group (p<0.01, p<0.001, p<0.01, p<0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-alpha levels, while infliximab relatively reduced the level of transforming growth factor-beta(1) (373.0+/-153.1 vs. 280.8+/-127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI(4)-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.