Mehmet Bilici

Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers

Indomethacin is an indol derivative, non-steroidal, anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other non-steroidal anti-inflammatory drugs (NSAIDs). There have been several conflicting reports about the ulcerogenic mechanism of indomethacin; the mechanism is still unclear. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2), bicarbonate, and mucus; increasing aggressive factors like acid; and increasing oxidant parameters while decreasing antioxidant parameters. Classic antiulcer drugs are known to produce antiulcer effects by activating against indomethacin (increasing PGE2, mucus, and bicarbonate production; inhibiting acid secretion; decreasing oxidant parameters; and increasing antioxidants). However, some antiulcer drugs have been shown to inhibit indomethacin-induced ulcers without affecting acid and mucus secretion or oxidant parameters, as well as to inhibit the production of protective factors like COX-1, PGE2, and bicarbonate, and to reduce antioxidant parameters. In order to resolve the contradictions in the abovementioned data, this review hypothesized a relationship between indomethacin-induced ulcers and α 2 adrenergic receptors. It is suggested that blockage of α 2 adrenergic receptors may be responsible for the increase in the aggressive factors induced by indomethacin, and stimulation of α 2 adrenergic receptors may be responsible for the increase of protective factors induced by antiulcer drugs.

Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue

BackgroundAlthough many drugs are available for the treatment of gastric ulcers, often these drugs are ineffective. Many antidepressant drugs have been shown to have antiulcer activity in various models of experimental ulcer. One such drug, the antidepressant mirtazapine, has been reported to have an antiulcer effect that involves an increase in antioxidant, and a decrease in oxidant, parameters. To date, however, there is no information available regarding the antiulcer activity for a similar antidepressant, fluvoxamine. This study aimed to investigate the antiulcer effects of fluvoxamine and to determine its relationship with antioxidants.MethodsGroups of rats fasted for 24 h received fluvoxamine (25, 50, 100 and 200 mg/kg), ranitidine (50 mg/kg) or distilled water by oral gavage. Indomethacin (25 mg/kg) was orally administered to the rats as an ulcerative agent. Six hours after ulcer induction, the stomachs of the rats were excised and an ulcer index determined. Separate groups of rats were treated with the same doses of fluvoxamine and ranitidine, but not with indomethacin, to test effects of these drugs alone on biochemical parameters. The stomachs were evaluated biochemically to determine oxidant and antioxidant parameters. We used one-way ANOVA and least significant difference (LSD) options for data analysis.ResultsThe 25, 50, 100 and 200 mg/kg doses of fluvoxamine exerted antiulcer effects of 48.5, 67.5, 82.1 and 96.1%, respectively, compared to the control rat group. Ranitidine showed an 86.5% antiulcer effect. No differences were observed in the absence of indomethacin treatment for any dose of fluvoxamine or for ranitidine. The levels of antioxidant parameters, total glutathione and nitric oxide, were increased in all fluvoxamine groups and in the ranitidine group when compared with the indomethacin-only group. In addition, fluvoxamine and ranitidine decreased the levels of the oxidant parameters, myeloperoxidase and malondialdeyhyde, in the stomach tissues of the rats when compared to indomethacin group.ConclusionWe conclude that fluvoxamine has antiulcer effects, and that these occur by a mechanism that involves activation of antioxidant parameters and inhibition of some toxic oxidant parameters.

Serum Adiponectin Levels in Patients with Esophageal Cancer

OBJECTIVE The aim of the study was to investigate a possible relationship between serum levels of adiponectin and clinicopathological characteristics in esophageal cancer. This is the first report evaluating serum adiponectin levels in patients with esophageal cancer. METHODS Sixty-two patients with esophageal cancer and thirty healthy subjects were included in the study. Adiponectin levels were determined by an enzyme-linked immunosorbent assay kit. RESULTS The mean serum adiponectin level in the cancer group was significantly low compared with the adiponectin level in the healthy control group. Furthermore, adiponectin levels of the patients gradually decreased with increase in tumor stage. The patients with adenocarcinoma of the esophagus had significantly lower values of serum adiponectin than patients with squamous cell carcinoma. CONCLUSION We concluded that decreased circulating adiponectin levels may play a role in the progression and/or development of esophageal cancers. However, for clinical use of serum adiponectin in terms of early diagnosis and treatment, further studies should be performed.

Antioxidant Enzyme Activities and Lipid Peroxidation Levels in Erythrocytes of Patients with Oesophageal and Gastric Cancer

In this study, levels of lipid peroxidation and antioxidant enzyme activities were investigated in the erythrocytes of patients with oesophageal and gastric cancers. Erythrocytes were obtained from 17 patients with oesophageal cancer, 37 patients with gastric cancer and 20 healthy controls. Levels of malondialdehyde (MDA), a lipid peroxidation marker, and activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined using spectrophotometric methods. MDA levels and CuZn-SOD activity were significantly higher and GPx and CAT activities significantly lower in patients with oesophageal and gastric cancer than in controls. There were no statistically significant differences in the parameters measured in relation to disease stage in either patient group. These results indicate significant changes in the antioxidant defence system in patients with oesophageal and gastric cancer. It is postulated that this may lead to enhanced action of oxygen radicals, resulting in lipid peroxidation.

Morphological alterations produced by zinc deficiency in rat sciatic nerve : A histological, electron microscopic, and stereological study

Zinc (Zn) is an essential trace element for humans and animals. It is required for normal growth, gene expression, wound healing, protein metabolism, immune function, and membrane integrity. In this study, unbiased stereological methods have been used to quantify the effects of Zn deficiency on the sectioned surface area and the number of myelinated axons in the sciatic nerve of rats. Animals were fed a Zn-deficient or Zn-sufficient diet for a period of 4 weeks. At the end of this time, the samples of sciatic nerves were removed from the animals, processed for electron microscopy and embedded in resin. The Zn-deficient group of rats was found to have a lower body weight compared to rats in the control group (P < 0.05). The sectioned surface area of nerve cross-section and myelinated axon number in Zn-deficient rats decreased by 20% and 29%, respectively, compared to the control group. A significant correlation between sectioned surface area and myelinated axon number was also determined. Morphological findings were as follows: on light microscopy, it was determined that certain abnormalities occur specifically in the experimental group, such as collapsed nerve fascicles, irregular profiles of and degeneration in myelin sheaths, and on electron microscopy, extensive myelin damage was seen in Zn-deficient groups compared with control groups. This study suggests that peripheral nerves require Zn for development and preservation of their structure.

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

Tumour necrosis factor-α levels in hepatitis B virus-related chronic active hepatitis and liver cirrhosis and its relationship to Knodell and Child-Pugh scores

Although both chronic active hepatitis‐B (CAH‐B) and liver cirrhosis (LC) are characterised by various degrees of inflammation and hepatocyte necrosis, in advanced stage cirrhosis, marked fibrosis develops and inflammation and tissue necrosis diminishes.

Prognostic Value of Baseline Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in Local and Advanced Gastric Cancer Patients

BACKGROUND We aimed to investigate the prognostic value of baseline neutrophil, lymphocyte, and platelet counts along with the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in local and advanced gastric cancer patients. MATERIALS AND METHODS In this retrospective cross-sectional study, a total of 103 patients with gastric cancer were included. For all, patient characteristics and overall survival (OS) times were evaluated. Data from a complete blood count test including neutrophil, lymphocyte, monocyte, white blood cell (WBC) and platelet (Plt) count, hemoglobin level (Hb) were recorded, and the NLR and PLR were obtained for every patient prior to pathological diagnosis before any treatment was applied. RESULTS Of the patients, 53 had local disease, underwent surgery and were administered adjuvant chemoradiotherapy where indicated. The remaining 50 had advanced disease and only received chemotherapy. OS time was 71.6±6 months in local gastric cancer patients group and 15±2 months in the advanced gastric cancer group. Univariate analysis demonstrated that only high platelet count (p=0.013) was associated with better OS in the local gastric cancer patients. In contrast, both low NLR (p=0.029) and low PLR (p=0.012) were associated with better OS in advanced gastric cancer patients. CONCLUSIONS This study demonstrated that NLR and PLR had no effect on prognosis in patients with local gastric cancer who underwent surgery and received adjuvant chemoradiotherapy. In advanced gastric cancer patients, both NLR and PLR had significant effects on prognosis, so they may find application as easily measured prognostic factors for such patients.

Effect of Mirtazapine on MNNG-Induced Gastric Adenocarcinoma in Rats

OBJECTIVE In this study, anticancer effects of mirtazapine on rats were investigated in an adenocarcinoma model induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and compared with those of cisplatin. MATERIALS AND METHODS For this purpose, 10 mg/kg doses of mirtazapine were administered orally to one group of rats, while 1 mg/kg doses of cisplatin were administered intraperitoneally to another group. At 1 hour after administration, 200 mg/kg doses of MNNG were given orally to both groups. MNNG administration was repeated once every 10 days through 3 months, after which period, gastric tissue was taken and pathologically evaluated. RESULTS Mirtazapine prevented adenocarcinoma induction by MNNG in rats to a greater extent than cisplatin. Some of the rats receiving cisplatin demonstrated severe dysplasia in gastric samples and others exhibited mild dysplasia. Rats given mirtazapine were not observed to suffer severe dysplasia, only mild dysplasia being observed. CONCLUSION For adenocarcinoma induced by MNNG on rats, mirtazapine was determined more effective than cisplatin. In order to make statement about mechanism of anticancer activity of mirtazapine, wider studies are required.

Analysis of HLA class I and II alleles regarding to lymph node and distant metastasis in patients with non-small cell lung cancer

The aim of this study was to investigate the relation of HLA alleles in patients with non-small cell lung cancer (NSCLC). The incidence of class I and II HLA alleles of 63 patients with NSCLC were prospectively compared with the incidence of class I and II HLA alleles with 88 healthy controls. The number of cases with stage I and II (early stage) was 12 and there were 51 cases with stage III and IV (advanced stage). Metastasis rates of the regional lymph node in patients were as follow; N(0): n=10; N(1): n=13; N(2): n=26 and N(3): n=14. Lymph node metastasis was detected by pathological staging in 15 cases and by clinical staging in 48 cases. Lymph node metastasis was searched in all patients by a helical thorax CT. All distant metastasis were investigated by thorax CT, abdominal CT, brain CT or MRI and bone scintigraphy, and distant organ metastasis was detected in 25 cases. The patients and healthy controls were typed for HLA class I and II alleles. HLA-A2 was an independent risk factor for both critical lymph node (N(2 and 3)) involvement and distant metastasis. HLA-B44, -CW6 and -CW7 frequencies appear to be significant in controls compared to patients. HLA-A2 frequency was higher in patients with advanced stage than early stage, while HLA-A26, -B35 and -CW4 frequencies were more expressed in patients with early stage than in patients with advanced stage. Compared with controls, frequency of HLA-DRB1*07, -DQ02 and -DQ07 were lower expressed in patients. Compared patients with advanced stage, HLA-DRB1*07 was higher in patients with early stage. HLA-A2 was an independent risk factor for lymph node and distant metastasis, and the allele was significantly higher in patients with critical lymph node for surgery and distant metastasis. HLA-A26 appeared to be a significance protective allele against to metastases.