Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study.

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection --Group II (n = 9), infection-cholesterol rich diet--Group III (n = 12), infection-cholesterol rich diet-cefepime--Group IV (n = II); infection-cholesterol rich diet-diclofenac potassium--Group V (n = 9); infection-cholesterol rich diet and red wine--Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However antibiotics and anti-inflammatory agents could be useful in prevention.

Effect of a cholesterol rich diet, recurrent infection and possible treatment modalities on the pulmonary vascular system: an experimental study / Efecto de la dieta rica en colesterol, la infección recurrente, y las posibles modalidades de tratamiento sobre el sistema vascular pulmonar: un estudio experimental

OBJECTIVE: Infection may lead to inflammation, atherosclerosis and thrombotic vascular events. The atherosclerotic effect of hypercholesterolaemia on the vascular system is well-known. However, limited studies were done on the therapeutic and preventative agents. The aim of this study was to investigate the effects of infection and cholesterol rich diet combined with an antibiotic, anti-inflammatory agent and red wine on the pulmonary vascular system. METHODS: Fifty-nine rats were evaluated. Six groups were created: Control-Group I (n = 10); infection - Group II (n = 9), infection-cholesterol rich diet - Group III (n = 12), infection-cholesterol rich dietcefepime - Group IV (n = 11); infection-cholesterol rich diet-diclofenac potassium - Group V (n = 9); infection-cholesterol rich diet and red wine - Group VI (n = 8). Blood samples of rats were collected for cholesterol analysis every month. Sections of central pulmonary arteries were examined for thickness of the intima and medial wall by computerised image analysis. RESULTS: There was a statistically significant difference in serum cholesterol levels and in thickness of the intima between the groups (p = 0.000). The rest of the groups had more intimal thickening than Group I (p = 0.000). Group III had thicker intima than Groups IV and V (p = 0.009, p = 0.011 respectively). There was no significant difference between the groups in thickness of media (p = 0.432). CONCLUSION: Infection and cholesterol rich diet have a synergistic effect on atherosclerosis in pulmonary arteries. However, antibiotics and anti-inflammatory agents could be useful in prevention.

OBJETIVO: La infección puede conducir a inflamación, ateroesclerosis y eventos vasculares trombóticos. El efecto aterosclerótico de la hipercolesterolemia en el sistema vascular es bien conocido. Sin embargo, se hicieron estudios limitados sobre los agentes preventivos y terapéuticos. El objetivo de este estudio fue investigar los efectos de la infección y la dieta rica en colesterol, combinados con agentes antibióticos, anti-inflamatorios, y vino tinto, sobre el sistema vascular pulmonar. MÉTODOS: Cincuenta y nueve ratas fueron evaluadas. Se hicieron seis grupos: grupo-control I (n = 10), grupo-infección II (n = 9), grupo infección-dieta rica en colesterol III (n = 12), grupo-infección-dieta rica en colesterol-cefepima IV (n = 11), grupo-infección-dieta rica en colesterol-diclofenaco potásico V (n = 9), grupo-infección-dieta rica en -vino tinto VI (n = 8). Se tomaron muestras de sangre de ratas para analizar el colesterol cada mes. Se examinaron secciones de las arterias pulmonares centrales para determinar el grosor de la pared íntima y media mediante análisis computarizado de imágenes. RESULTADOS: Hubo una diferencia estadísticamente significativa en los niveles de colesterol en suero y el grosor de la íntima entre los grupos (p = 0.000). El resto de los grupos tenía más engrosamiento de la íntima que el grupo I (p = 0.000). El grupo III tenía una íntima más gruesa que los grupos IV y V (p = 0,009, p = 0.011 respectivamente). No hubo ninguna diferencia significativa entre los grupos en cuanto al espesor de la media (p = 0.432). CONCLUSIÓN: La infección y la dieta rica en colesterol tienen un efecto sinérgico sobre la aterosclerosis en las arterias pulmonares. Sin embargo, los antibióticos y los agentes antiinflamatorios podrían ser útiles para la prevención.

Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study.

BACKGROUND: Expressions of various biomarkers in non-small cell lung cancer (NSCLC) have been linked with the prognosis and involvement of mediastinal lymph nodes. METHODS: In this study, we utilized recursive partitioning analysis (RPA) by using P53, c-erb-B2, and P-glycoprotein (PGP) expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC. RESULTS: In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged <75 and with >/=4 mediastinal lymph nodes removed that, high PGP expression frequency (>/=20%) predicted an increased likelihood of the N2 involvement (46.7%, R(2) = 0.25). Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation) were associated with the metastasis to N2 lymph nodes (chi(2) = 17.59, p = 0.0005, and chi(2) = 2.40, p = 0.0654, respectively). Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (chi(2) = 14.63, p = 0.0022). CONCLUSION: This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.

Differential expression of VASP in normal lung tissue and lung adenocarcinomas.

BACKGROUND: Vasodilator stimulated phosphoprotein (VASP) is associated with focal adhesions and is thought to have an important role in actin filament assembly and cell motility. We hypothesise that an increase in the expression of VASP is involved in the progression and invasion of lung adenocarcinomas in parallel to tumour progression. A study was undertaken to analyse VASP expression in normal lung tissue and lung adenocarcinomas. METHODS: Human lung tissues with adenocarcinomas (n = 26) were used. Normal lung tissue specimens (n = 14) were taken from areas a standard distance (3 cm) from resected adenocarcinomas of patients who underwent surgical lung resection. Adenocarcinomas were classified according to pathological staging and histopathological grades. Tissues were stained for VASP using immunohistochemistry. RESULTS: Normal lung pneumocytes showed no VASP expression while alveolar macrophages had the strongest immunoreactivity for VASP. Bronchial epithelium (surface epithelium, goblet cells) and bronchial gland cells had a very weak immunoreactivity for VASP. Adenocarcinomas had significantly greater VASP expression than normal epithelium (p < 0.001). Moreover, VASP expression in adenocarcinomas increased significantly with more advanced tumour stage (p < 0.001). CONCLUSIONS: The spatial and differential expression of VASP in normal lung tissue and lung adenocarcinomas suggests that it is likely to be involved in the differentiation of normal lung cells to adenocarcinomas. The significant increase in the expression of VASP in adenocarcinomas in parallel to pathological staging suggests that it may regulate the invasive behaviour of lung adenocarcinomas as adenocarcinoma invasion is increased in more advanced tumours.

Effect of chronic Pseudomonas aeruginosa infection on the development of atherosclerosis in a rat model.

In order to investigate the possible relationship between atherosclerosis and chronic Pseudomonas aeruginosa infection, 66 Wistar rats were given five separate intratracheal inoculations of either P. aeruginosa or sterile saline at 4-week intervals. The rats were divided into four groups: group 1 was infected with P. aeruginosa and fed a diet containing cholesterol 1% w/v; group 2 was infected with P. aeruginosa and fed a normal diet; group 3 was not infected and was fed a diet containing cholesterol 1% w/v; and group 4 (the control group) was not infected and was fed a normal diet. One month after the final inoculation, the rats were killed humanely; computerised image analysis was used to evaluate sections of the aorta and heart, and the maximal wall thickness of the aorta and coronary artery. The aortic wall thickness was significantly greater for group 1 (329.53 +/- 58.06 microm) compared to groups 2 (190.59 +/- 27.81 microm; p < 0.0001), 3 (262.90 +/- 61.12 microm; p < 0.0004) and 4 (158.00 +/- 30.30 microm; p < 0.0001). Similarly, the coronary artery wall thickness was significantly greater for group 1 (72.96 +/- 10.67 microm) compared to groups 2 (35.07 +/- 8.53 microm; p < 0.0001), 3 (41.45 +/- 10.22 microm; p < 0.0001) and 4 (32.30 +/- 5.27 microm; p < 0.0001). These findings strengthen the hypothesis that chronic infection plays a role in the pathogenesis of atherosclerosis.

Drug resistance in epithelial ovarian cancer: P-glycoprotein and glutation S-transferase. Can they play an important role in detecting response to platinum-based chemotherapy as a first-line therapy.

OBJECTIVE: Drug resistance is important for the treatment of ovarian cancer. P-glycoprotein and glutation S-transferase as resistance markers play an important role in the effectivity of chemotherapeutical agents. The role of P-glycoprotein and glutation S-transferase in the treatment of epithelial ovarian cancer is not well understood. We investigated the relation between P-glycoprotein and glutation S-transferase level for response to platinum-based chemotherapy in epithelial ovarian cancer. MATERIAL AND METHODS: We reviewed 30 cases diagnosed as epithelial ovarian cancer and treated with platinum-based chemotherapy in the Department of Obstetrics and Gynecology, Akdeniz University School of Medicine. The material was attained from initial parafin-embeded blocks stained for P-glycoprotein and glutation S-transferase. The cases that were diagnosed and treated before attending our clinic were not enrolled in the study. RESULTS: Mean age was 58.2 (25-70) and mean gravida 4.1 (0-10). Twenty-four patients (80%) were glutation S-transferase positive. Three cases (10%) out of 30 had positive reaction for P-glycoprotein. No difference was revealed regarding chemotherapy response rate among the cases showing glutation S-transferase positivity and P-glycoprotein negativity. CONCLUSION: Detection of glutation S-transferase and P-glycoprotein levels in epithelial ovarian cancer tissue is not important for response to platinum-based chemotherapy as a first line.

Protective effect of vitamin E on gastric mucosal injury in rats with biliary obstruction.

Patients with liver disease display increased susceptibility to gastric mucosal damage. A role of free radicals has been suggested in the development of gastric mucosal damage in normal subjects. The effects of antioxidant vitamin E treatment on the liver and stomach in cirrhotic rats were examined. Fifty rats were divided into three groups. Cirrhosis was induced by bile duct ligation in 40 of 50 rats. Controls underwent a sham operation. Gastric mucosal lesions were produced by intragastric administration of 1 mL of 95% ethanol in all three groups. Twenty bile duct-ligated rats were injected intramuscularly with vitamin E (100 mg/kg/day). Liver and stomach histology, and stomach malondialdehyde and glutathione levels were determined. Portal hypertension was measured. Macroscopic and microscopic gastric mucosal injury were significantly greater in the control and common bile duct-ligated groups than in the vitamin E-pretreated group (P<0.05). The tissue malondialdehyde and glutathione levels were significantly decreased in the vitamin E-administrated group compared with the common bile duct-ligated group (P<0.001). Vitamin E administration may be cytoprotective for both the liver and gastric mucosa in bile duct-ligated rats.

Immunohistochemical staining properties of PCNA, Ki-67, p53, beta-hCG and HPL in trophoblastic disease.

OBJECTIVE: In this study proliferating markers PCNA (proliferating cell nuclear antigen) Ki-67 and mutation of supressor gene p53 were investigated in gestational trophoblastic disease (GTL). These markers were tested by using immunostaining with beta subunits of human chorionic gonadotropin (hCG) and human placental lactogen (HPL). MATERIAL AND METHODS: Twenty curetting samples, 20 spontaneous abortions, 16 hydatidiform moles and two choriocarcinomas were studied and compared. Hydatidiform moles were subdivided into 10 complete and six partial moles by using flow cytometry analysis. All slides were stained with PCNA, Ki-67, p53, hCG, and HPL immunohistochemically. PCNA and Ki-67 stained slides were studied quantitatively to determine the PCNA and Ki-67 index. Other slides that were stained with p53, hCG, HPL were evaluated according to staining percentage and intensity. Staining properties of all groups were compared with each other. Variance analysis and the Mann Whitney U test were used for statistical analysis. Choriocarcinomas were not included in the statistical analysis. Ki-67 and the PCNA index in two choriocarcinoma cases found 81.4% and 41%, and 44% and 64%, respectively. One case was stained in 70% with (++) intensity by p53. While both were stained in 80% with (++) intensity by hCG, one was stained in 30% field (+) intensity by HPL. RESULTS: The four groups of complete and incomplete diagnosed hydatiform moles, spontaneous abortions and retention curettage were matched in pairs and evaluated according to the PCNA index. This index showed significant differences among the groups. The differences among the Ki-67 index, p53, hCG and HPL staining properties were not statistically significant. CONCLUSION: Our findings showed that PCNA is a significant and useful marker for trophoblastic diseases and can be used as a prognostic factor.

Experimental cirrhosis of the liver and cytoprotective effects of alpha tocopherol.

OBJECTIVE: To investigate whether alpha tocopherol (alpha-T) treatment influences liver cirrhosis induced by carbon tetrachloride (CCl4) in the rat. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Turkey. SUBJECTS: Fifty rats were divided into three groups. Group I consisted of ten controls; Group II: twenty CCl4 induced cirrhotic rats and Group III: twenty cirrhotic rats treated with Vitamin E. INTERVENTIONS: Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4 ml CCl4 (diluted 1:4 with olive oil) per kilogram body weight twice a week for 12 weeks. MAIN OUTCOME MEASURES: Histopathologically evaluation of liver, liver malondialdehyde and glutathione peroxidase levels and aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT) and gamma-glutamyltranspeptidase (GGT) levels. RESULTS: Histopathologic evaluation of liver samples demonstrated cirrhotic changes in CCl4 treated groups. The enzyme levels in Group II were significantly increased (p < 0.05) but it was insignificantly lower in the alpha tocopherol treated group III. In Group II, statistically significant increase in liver malondialdehyde levels was determined (p < 0.001). CONCLUSION: Our results demonstrate that alpha-T administration may protect liver against CCl4 induced cirrhosis.

The protective effect of vitamin E on gastric mucosal injury in rats with cirrhosis of the liver.

OBJECTIVE: To evaluate the functional and morphologic features of stomach in liver cirrhosis model and the cytoprotective effects of Vitamin E. METHODS: Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4 ml CCl4 (diluted 1:4 with olive oil) per kilogram of body weight twice a week for 12 weeks. Rats were divided into three groups. Group 1 was control. Group 2 consisted cirrhotic rats induced by CCl4 and Group 3 cirrhotic rats treated with Vitamin E (intramuscularly 100 mg/kg per day during study). At the end of 12 weeks, gastric mucosal injury was produced by instillation of absolute alcohol via an orogastric tube. After 3 hours, each animal was sacrificed. The stomachs were macroscopically, microscopically and biochemically analyzed. RESULTS: Macroscopic and microscopic area of gastric mucosal injury were significantly larger in cirrhotic rats (P < 0.05). Gastric mucosal injury was more serious in cirrhotic rats as compared with Group 1. With vitamin E treatment, tissue Malondialdehyde (MDA) and glutathione [GSH (X)] levels were significantly lower in group 3 as compared with group 2 (P < 0.001). CONCLUSION: Gastric mucosa in cirrhotic rats has distinctive histological and functional abnormalities. These abnormalities can be reversed by Vitamin E or other antioxidants.

Cytoprotective effects of alpha tocopherol against liver injury induced by extrahepatic biliary obstruction.

There are several important aetiologies of extrahepatic biliary obstruction (EBO). If EBO is surgically reconstructed in the critical time period, liver damage can be halted or reversed. In this golden period, lipid peroxidations significantly intensify liver defects. We hypothesised that alpha tocopherol (alpha-T) could protect the liver from the damage caused by response to EBO. In standard conditions, albino rats of Wistar strain were divided into two groups. All rats underwent double ligations and divisions of common bile ducts (CBD). One of these groups received alpha-T (CBDL-alpha-T). The other CBDL animals received intramuscular injections of normal saline (CBDL-NS). Serum samples were taken for biochemical analyses by light microscopy. The data showed a decrease in plasma bilirubin and liver enzyme levels in CBDL-alpha-T group, when compared with CBDL-NS (p < 0.05). Morphologic analyses showed better results for CBD-alpha-T. Serum levels of Malonyldialdehyd (MDA) in the CBDL-alpha-T group was 9.2 +/- 3.4 nmol/g compared to that in CBDL-NS, 12.3 +/- 4.4 nmol/g (p < 0.05). In conclusion, a dramatic protective effect of alpha-T on functional and structural features of the liver in rats with EBO was demonstrated. The data suggest that EBO may cause liver damage by stimulation of lipid peroxidation and that alpha-T may slow down liver damage in this setting.

Cytogenetic findings in thirty lung carcinoma patients.

Primary tissue cultures of human lung tumors were prepared from 30 cases of which 16 were diagnosed as squamous cell carcinoma, six adenocarcinoma, four adenosquamous cell carcinoma, three large cell carcinoma, and one small cell lung carcinoma. Chromosomal abnormalities were observed in 26 cases by cytogenetic studies with a GTG banding technique. Specific chromosome bands frequently involved in structural abnormalities were seen on 1p11, 1q11, 2p10, 6p10, 7q11, 7q22, 7q32, 8q22, 9q22, 11q11, 21q10, and Xq24. We assumed that especially i(2)(p10), i(9)(p10), i(21)(q10), t(11;12), t(14;15), del(X)(q24), and loss of the Y chromosome may play a role in the development of lung cancer as secondary changes. In this way, our cytogenetic findings provide evidence that multiple genetic lesions are associated with the pathogenesis of lung cancer.

Bronchioloalveolar carcinoma in progressive systemic sclerosis. Report of a case diagnosed by fine needle aspiration cytology.

BACKGROUND: Progressive systemic sclerosis (PSS) is a systemic disorder involving many internal organs, including the lungs. The occurrence of a pulmonary tumor has occasionally been reported, especially in long-standing cases. Bronchioloalveolar carcinoma is the most prevalent histologic type. CASE: A 35-year-old male with a 12-year history of PSS presented with exertional dyspnea and pain in the left side of the chest. Fine needle aspiration cytology (FNAC) showed abundant cellular material with large, monolayered sheets and papillary structures. The neoplastic cells had uniform round to oval nuclei and spacious cytoplasm. Some had intranuclear vacuoles. Phosphotungstic acid-hematoxylin (PTAH) stain revealed structures in the form of prominent cell membranes rimming the free surfaces of the tumor cells. The overall cytologic picture was interpreted as consistent with bronchioloalveolar carcinoma. The patient's condition did not permit surgery. CONCLUSION: In this case the development of bronchioloalveolar carcinoma occurred over a 12-year period following the diagnosis of PSS. This case emphasizes diagnosis of the tumor solely by FNAC. PTAH stain was also helpful in the cytologic diagnosis.

[Female genital tract tuberculosis]. / Kadin genital sistem tüberkülozu.

The frequency of female genital tract tuberculosis exhibits a parallelism that of pulmonary tuberculosis in the population. It is generally found in reproductive women, but also occurs in postmenopausal ones. Its frequency has declined since the introduction of specific treatment, but it is discovered incidentally during the course of an investigation for infertility. The most common location is in fallopian tubes. In the Department of Pathology from the Medical School of Cumhuriyet University 11 female genital tract tuberculosis have been described between the years of 1984 and 1990. In this study, age, symptoms, localizations and pathological findings of these cases have been reviewed.