Arzu Sungur

The effects of bosentan, aminoguanidine and L-canavanine on mesenteric blood flow, spleen and liver in endotoxaemic mice

The modulatory effects of a non-selective endothelin receptor antagonist, bosentan, were investigated together with those of relatively selective inducible nitric oxide synthase inhibitors, aminoguanidine and L-canavanine, on mesenteric blood flow decrease, liver and spleen injury elicited by endotoxaemia. Swiss albino mice (20-40 g) were administered intraperitoneally bosentan (3, 10 or 30 mg kg(-1)), aminoguanidine (15 mg kg(-1)) or L-canavanine (20 or 100 mg kg(-1)) 10 min before they received saline or Escherichia coli endotoxin (10 mg kg(-1)). After 4 h, the mice were anaesthetized, mesenteric blood flow values were measured, spleen and liver weight/body weight ratios were determined and the organs were examined histopathologically. Endotoxin decreased mesenteric blood flow (ml min(-1), saline: 3.0 +/- 0.2; endotoxin: 2.2 +/- 0.2: n = 10, P < 0.05), increased the weight of liver (g per kg body weight, saline: 47.5 +/- 2.0; endotoxin: 60.8 +/- 1.9: n = 10, P < 0.05) and spleen (g per kg body weight, saline: 3.9 +/- 0.5; endotoxin: 8.6 +/- 0.9; n = 10, P < 0.01) while it inflicted significant histopathological injury to both organs. Bosentan was ineffective at 3 mg kg(-1) but at 10 and 30 mg kg(-1) doses, it abolished all the deleterious effects of endotoxin without exception. Aminoguanidine blocked most of the effects of endotoxin except those on spleen. In contrast, L-canavanine blocked only the endotoxin-induced increase in liver weight but itself increased spleen weight and failed to block any other effects of endotoxin. Thus, it can be speculated that the beneficial effects of aminoguanidine are produced largely by mechanisms other than selective inducible nitric oxide synthase inhibition since L-canavanine was not fully effective. The beneficial effects of endothelin inhibition by using bosentan in endotoxaemia can be further exploited for the understanding and the therapy of sepsis-related syndromes.

PCR on disseminated tuberculosis in bone marrow and liver biopsy specimens : Correlation to histopathological and clinical diagnosis

Disseminated tuberculosis with negative pulmonary findings is a diagnostic problem. Histopathological studies of bone marrow (BM) and liver (LV) biopsies are the most reliable methods for diagnosis in such cases; however, their sensitivity is limited. In this retrospective study, 41 BM and 7 LV paraffin-embedded biopsy specimens from clinically (clinical response to antituberculous treatment after 6 months follow-up) and/or histopathologically diagnosed tuberculosis were analysed for the detection of Mycobacterium tuberculosis DNA by polymerase chain reaction (PCR). Two different primer sets, one based on the repeated IS6110 sequence of M. tuberculosis and the other based on the mtp40 gene region, were used for amplification. Histopathological and PCR studies were positive for M. tuberculosis in 12/41, and 30/41 in BM and 4/7, and 6/7 in LV biopsy specimens, respectively. As the control group, 17 BM biopsy specimens obtained from patients with a positive Mantoux skin test but no active tuberculosis were analysed. One BM biopsy out of 17 control cases was positive with PCR while none was consistent with TB histopathologically. In conclusion, PCR might be applicable and more reliable than histopathological studies for detection of tuberculosis in BM and LV biopsy specimens.

Infratemporal hydatid cyst – unusual location of echinococcosis

Hydatid disease is an important medical problem in countries of the temperate zones. Only occasional cases are reported in the head and neck region. An unusual location for hydatid disease in the infratemporal fossa is presented. Characteristics of this rare disease together with treatment modalities are discussed.

Langerhans cell histiocytosis: retrospective analysis of 217 cases in a single center.

Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and pathogenesis, which is characterized by abnormal clonal proliferation and accumulation of langerhans cells at various tissue and organs. A total of 217 patients with LCH were evaluated retrospectively for clinicopathological features, laboratory findings, treatment modalities, long-term outcome, and factors affecting the outcome. Median age at the time of diagnosis was 3.5 years and male/female ratio was 1.8. The most common complaint at presentation was a bone lesion-related symptom. Fifty percent of the patients younger than 2 years had organ dysfunction (OD). Treatment consisted of surgery, chemotherapy, and radiotherapy alone or in combination. Vinblastine with or without prednisolone was the most common used chemotherapy regimen. Overall (OS) and event-free survival (EFS) rates were 84% and 51.5%, respectively, at an 8-year median follow-up time. Overall survival was significantly lower in patients younger than 2 years of age and patients with OD. The age at diagnosis, pulmonary, liver, or hematological involvement, and elevated acute-phase reactants were found to have a statistically significant effect on the OS or EFS rates.

Vibrational Spectroscopic Studies of 4,4′-Bipyridyl Metal(II) Tetracyanonickelate Complexes and their Clathrates

The infrared spectra of M(4,4′-bipyridyl)Ni(CN)4 complexes (M=Ni or Cd) and their dioxane, benzene, toluene, aniline andN,N-dimethylaniline clathrates are reported. Additional information regarding the structure of the host lattice is obtained from the Raman spectra of the M=Cd complex. It is shown that the structure of the host lattice consists of infinite polymeric layers of {M-Ni(CN)4}∞ analogous to those of Hofmann type clathrates that have tetragonal symmetry. Bidentate 4,4′-bipyridyl molecules form bridges between the metal atoms {M} in the adjacent {M-Ni(CN)4}∞ layers. It is found that the 4,4′-bipyridyl molecules are centrosymmetric in this structure.

C-Met Overexpression in Supraglottic Laryngeal Squamous Cell Carcinoma and its Relation to Lymph Node Metastases:

BACKGROUND: The c-met oncogene encodes the receptor for the hepatocyte growth factor/scatter factor (HGF/SF), which is known to have the effects of stimulation of cell motility, dissociation of epithelial sheets, invasion of cellular matrix, and induction of angiogenesis. Many studies in solid tumors have indicated a role for c-met and HGF/SF in the progression of the disease. METHODS: The expression of c-met in tissue specimens was studied by immunohistochemical examination in 60 patients with supraglottic laryngeal squamous cell carcinoma. Patients were chosen such that there were 30 with lymph node metastases in the neck and 30 without metastases. TNM staging, differentiation, lymphovascular and perineural invasion, and growth pattern for tumors were also recorded, and their relation to lymph node metastases was analyzed. RESULTS: Overexpression of c-met was observed in 90% of the cases at the primary site and in 83% of the cases with lymph node metastases in the neck. Lymphovascular invasion (P = 0.005) and the N stage (P = 0.001) were found to be related to lymph node metastases, but other variables—c-met over-expression, the T stage, perineural invasion, and growth pattern—were found to have no relation to lymph node metastases in multivariate analysis of the data with linear regression. CONCLUSIONS: c-met overexpression is observed in both the primary site and the neck in supraglottic laryngeal squamous cell carcinoma. We believe that it may have a role in the progression of malignancy, but we were unable to find a definite relation between c-met expression and lymph node metastases. (Otolaryngol Head Neck Surg 2004;130:698-703.)

Solid tumor chemotherapy and in vivo distribution of fluorouracil following administration in poly(L-lactic acid) microspheres.

The physicochemical properties and in vivo distribution of poly(L-lactide) (L-PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent evaporation method were evaluated for potential use in the treatment of liver cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da) and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean particle size of the microspheres was 3-6 microns, and there was a direct relationship between the mean particle size and the molecular weight of the polymers. The drug release behavior from microspheres exhibited a diffusion mechanism in different dissolution media, with the molecular weight of the polymer being a major factor in controlling the drug release and degradation rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in the liver. The disappearance rate of radioactivity from the tissue was very slow in comparison to that of free 5-FU. The results were confirmed by histological examination of liver tissue following administration of fluorescein particles. In addition, growth of a human liver tumor as first transplant generation under the renal capsule of immunocompetent rats and antitumor activity of L-PLA2 microspheres were investigated. Histological examination by optical microscopy showed that there was no neoplastic tissue of the kidney or in other tissues examined after treatment.

PTEN and p27 expression in mature T-cell and NK-cell neoplasms

PTEN is a tumor suppressor gene located on chromosome 10q23 and is amongst the most commonly mutated genes in human cancers. The lipid phosphatase activity of Pten enables it to dephosphorylate PIP3, thereby antagonizing growth factor stimulated PI3-kinase signaling mediated by AKT/PKB. The growth inhibition effect of PTEN has been shown to be mediated by p27 which is one of the important effector molecules downstream of the AKT pathway. Recently the importance of the Pten and AKT pathway in the regulation of the immune system and development of hematological malignancies has been shown. Loss of Pten and p27 expressions were examined immunohistochemically in 45 patients with peripheral T- and NK-cell lymphoma. Partial or complete loss of Pten was detected in 66.7% of the cases of anaplastic large cell lymphoma (ALCL) compared to only 12.5% of all other mature T-/NK-cell lymphomas combined. Loss of p27 was identified in 64.9% of cases, which showed a positive correlation with Pten loss. In this study, we showed that loss of Pten is more frequent in ALCL as compared to other mature T-/NK-cell lymphomas, which strongly correlates with the loss of p27 expression. Our findings provide further evidence for the importance of the deregulation of the PI3K-AKT pathway in ALCL.

Histopathological predictors of occult lymph node metastases in supraglottic squamous cell carcinomas.

Abstract Lymph node metastasis appears to be the most important factor determining survival in patients with squamous cell carcinoma of the larynx. Supraglottic laryngeal carcinomas have a known tendency to metastasize to cervical lymph nodes because of the extensive lymphatic network present. This retrospective cohort study was conducted to define possible histopathological parameters affecting cervical lymph node metastasis and then using these parameters to create a scale to predict occult lymph node metastasis in supraglottic squamous cell carcinoma. The pathological slides of 61 operated patients were reevaluated for tumor grade, lymphatic-vascular invasion, invasion pattern of tumor margins, perineural invasion and lymphocytic infiltration. Grade (P < 0.001), lymphatic-vascular invasion (P < 0.001) and tumor margins (P = 0.007) were found to be closely associated with neck metastasis. To define the risk factors for occult metastasis, a grading scale was created by using grade (G), lymphatic-vascular invasion (L) and tumor margin (M) findings of patients. None of the patients with a GLM value of zero developed occult metastasis. On the other hand occult metastasis was found in 58.8% of N0 patients with a GLM value that was more than zero. These findings indicate that patients with high-grade tumors having infiltrating borders and lymphatic-vascular invasion have a high risk for occult metastasis so that elective treatment of the neck either by neck dissection or radiotherapy should be added to therapy. Serial sections of specimens are needed to avoid missing metastatic loci of disease.

C-Myc And Bcl-2 Expression In Supraglottic Squamous Cell Carcinoma of the Larynx

OBJECTIVES: To evaluate the expression and prognostic significance of c-myc and bcl-2 oncogenes in squamous cell carcinoma (SCC) of the supraglottic larynx. STUDY DESIGN: A retrospective cohort study of 61 patients who underwent surgery for SCC of the supraglottic larynx. Gender, age, TNM status, operative procedure, recurrences, and disease-free survival periods were recorded. METHODS: Hematoxylin and eosin-stained sections were reexamined for grade, invasion of tumor margins, lymphovascular invasion, lymphocyte infiltration, and perineural invasion. Immunohistochemical detection of c-myc and bcl-2 oncogenes was performed using monoclonal antibodies. RESULTS: No correlation was observed between either c-myc or bcl-2 and the clinical and histopathologic parameters. Survival analysis revealed no correlation of either c-myc (P = 0.88) or bcl-2 (P = 0.85) with the disease-free survival. c-myc expression was found to be significantly higher in bcl-2-positive patients (P = 0.001). CONCLUSION: Neither c-myc nor bcl-2 had shown to be prognostic factor for laryngeal carcinoma in this present study. Correlation between c-myc and bcl-2 supports the experimental observations of cooperative action between these two genes in tumorigenesis.