The use of concurrent hormonotherapy and radiotherapy does not deteriorate radiation-induced cardiac toxicity.

Postmenopausal patients with breast cancer have two options for adjuvant endocrine therapy, tamoxifen and aromatase inhibitors (AIs) as well as radiotherapy (RT) and chemotherapy. However, there is limited data regarding the optimal sequencing of RT and tamoxifen/AIs. Thus, we aimed to evaluate the effects of tamoxifen and AIs on radiation-induced cardiotoxicity. Eighty ovariectomized rats were divided into eight groups (G). G1 was defined as a control group; G2, G3, G4, and G5 were RT, tamoxifen, anastrozle, and letrozole groups, respectively; G6, G7, and G8 were RT plus tamoxifen, anastrozle, and letrozole groups, respectively. Drugs were started 1 week before RT and continued until the animals were killed 16 weeks after RT. The heart tissues were then dissected and examined with light microscopy to determine endocardial thickness and cardiac fibrosis. The endocardial thickness scores of both RT alone and the tamoxifen groups as well as the cardiac fibrosis score of RT alone were higher than that the control group ( p < 0.05 for all). There was no difference in the endocardial thickness and cardiac fibrosis scores of the RT-only group and the RT plus hormonotherapy groups ( p > 0.05 for all). Concurrent administration of RT and hormonal therapy with either tamoxifen or AIs did not further amplify radiation-induced cardiac toxicity. This issue warrants further study.

Assessment of concomitant versus sequential trastuzumab on radiation-induced cardiovascular toxicity.

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.

Expression of cyclin A, cyclin E and p27 in normal, hyperplastic and frankly malignant endometrial samples.

Cellular growth is under the control of certain molecules such as cyclins and cyclin dependent kinases. Dysregulation of these proteins disrupt cell cycle and may trigger malignant transformation. Cyclins and kinase inhibitors also play essential roles in endometrial cellular proliferation. But the exact roles of these mediators in the disease process is not clear. We evaluated expression of cyclin A, cyclin E and p27 in normal, hyperplastic and malignant endometrial samples assuming different expression patterns in physiological and pathological processes. A total of 75 patients with histopathological diagnosis of normal proliferative, hyperplastic or malignant endometrial samples were evaluated with different cellular proliferation markers, cyclin A, cyclin E and p27. For cyclin E, endometrial cancer samples had higher rate of immunoreactivity than normal proliferative and hyperplastic endometrial samples. Staining properties for cyclin A were comparable for three groups. However, p27 immunoreactivity decreased progressively as lesions progress from proliferative benign endometrium to frank carcinoma. Further large-scale studies with clinical follow-up will reveal the exact role of cyclins on endometrial carcinogenesis.

Serum homocysteine, arginine, citrulline and asymmetric dimethyl arginine levels, and histopathologic examination of the abdominal aorta in rats exposed to acrylamide.

We investigated serum homocysteine, arginine, citrulline and asymmetric dimethyl arginine (ADMA) levels and conducted a histopathologic examination of the abdominal aorta in rats given acrylamide (AA) for long periods. We used 25 male and 25 female Wistar rats. Females were divided into three groups; two were experimental groups and one was the control group. Each experimental group consisted of ten animals and each control group consisted of five animals; male animals were divided in the same way. AA, 2 or 5 mg/kg/day, was administered to the experimental groups in drinking water for 90 days. At the end of the experiment, serum samples were analyzed for homocysteine, arginine, citrulline and ADMA using high performance liquid chromatography. Serum homocysteine, citrulline and ADMA levels were significantly higher than controls in both female and male rats when AA was administered at a concentration of 5 mg/kg/day. Serum citrulline levels also were significantly higher than controls when administered AA at a concentration of 2 mg/kg/day in female rats. There was no difference in serum arginine levels among the groups. Histopathologic examination of the abdominal aorta revealed degeneration of the external elastic lamina in rats treated with 5 mg/kg/day AA. Our findings show that long term ingestion of high dose AA with food might contribute to the development of atherosclerosis.

Oxidative stress and prolidase activity in women with uterine fibroids.

The aim of this study was to investigate oxidative stress markers and prolidase activity in serum and tissue samples of women with uterine fibroids, with further analysis on position and size. Lipid hydroperoxide, ceruloplasmin, catalase, arylesterase, free sulfhydryl group activity and prolidase activity levels were measured in fibroid tissue, myometrial tissue and serum of the same patients (n = 51), at the same time. Results show that ceruloplasmin, catalase, arylesterase, free sulfhydryl group and prolidase activities were higher in fibroid tissue than those in myometrial tissue (p = 0.003, 0.009, 0.004, 0.02, 0.008, respectively). Serum levels of catalase and prolidase were lower, and arylesterase and free sulfhydryl groups were higher in the fibroid group than those in the control group (p < 0.001 for all). Fibroid volume in submucosal subgroup of the fibroid group yield significant correlation with ceruloplasmin, catalase, arylesterase and prolidase activities (r = 0.84, p = 0.02; r = 0.93, p < 0.001; r = 0.63, p = 0.049 and r = 0.87, p = 0.01, respectively). Despite the lack of statistical significance, the highest levels of prolidase activity were found in fibroid samples, especially in submucosal ones. It is concluded that this study demonstrated increased antioxidative repair system in the fibroid tissue compared to the myometrium and serum of the same patients. Additionally, higher pathophysiological potential of the submucosal fibroids over intramural and subserosal fibroids were shown with the levels of oxidative stress markers and prolidase activity levels.

Histological effects of zinc and melatonin on rat testes.

BACKGROUND: The objective of this study is to examine the histological effects of zinc and melatonin, alone or in combination, on rat testes. METHODS: For this purpose four study groups of ten Sprague-Dawley male rats were formed and treated for one month as follows: (1) Controls; (2) Rats injected with 3 mg/kg/day zinc, as zinc sulfate; (3) Rats injected with 3 mg/kg/day melatonin and (4) Rats injected with 3 mg/kg/day each zinc and melatonin. RESULTS: After four weeks the rats treated with melatonin showed inhibited spermatogenesis, testicular tubular degeneration and necrosis, obstruction of tubular lumen and lymphocytic infiltration. The two zinc-treated groups showed no histological differences to controls but the melatonin-only group showed inhibited spermatogenetic activity, tubular degeneration and necrosis, as well as obstruction of tubule lumens and lymphocytic infiltration. CONCLUSION: The obtained results suggest that 4-week treatment with melatonin leads to histological and physiological impairments of testis and that zinc supplementation might offset these damaging effects (Tab. 2, Fig. 4, Ref. 12).

Gallbladder motor function in patients with different thyroid hormone status.

Hypothyroidism and hyperthyroidism are known to affect cholesterol metabolism, bile acid synthesis and bile content. There are previous studies reporting increased prevalence of gallstone and common bile duct stone formation in hypothyroidism. The aim of this study was to compare gallbladder (GB) motor function between euthyroid, hypothyroid and hyperthyroid subjects by conventional ultrasonography. Eighteen euthyroid, 14 hypothyroid and 20 hyperthyroid, age, sex and body mass index matched subjects were included in the study. Etiology of hypothyroidism comprised of thyroidectomy, Hashimoto's thyroiditis and previous radioactive iodine therapy. Hyperthyroid group included patients with toxic nodular goitre and Graves' disease. Patients who have diseases or are under drug treatment known to affect biliary function were not included in the study. Fasting and post-stimulus GB volumes were measured by real-time conventional ultrasonography and computer unit (Aloka UST-979, 3.5 mHz electronic convex probe, Japan). No significant differences were noted for fasting, post-stimulus GB volumes and GB ejection fraction between euthyroid, hypothyroid and hyperthyroid subjects. Measuring GB motility accurately is not straightforward because besides being not static during fasting, after a meal, intermittent emptying and refilling of GB occurs. Ultrasonography is affected by GB filling and measures "net" GB emptying. Although cumbersome, additional evaluation with cholescintigraphy which detects "absolute" GB emptying and is not affected by GB filling may provide complete assessment of motor function and may be more informative in evaluating subjects with different thyroid hormone status.

Assessment of serum paraoxonase and arylesterase activities in early pregnancy failure.

QUESTIONS UNDER STUDY: Paraoxonase-1 (PON1) is an HDL-bound enzyme system which plays a key role in the protection of LDL and HDL from oxidation by hydrolysing activated phospholipids and lipid peroxide products. Oxidative stress has been involved in the pathogenesis of many complications of human pregnancy, including early pregnancy failure (EPF), preeclampsia and preterm labour. The purpose of this study was to determine serum paraoxonase/arylesterase activities and lipid hydroperoxide (LOOH) levels as an oxidative stress indicator in women with EPF. METHOD: Paraoxonase/arylesterase activities and LOOH levels were assessed in women with EPF (n = 40) and healthy continuum pregnant women without EPF (n = 38) before 12 weeks' gestation. Serum basal and salt-stimulated paraoxonase/arylesterase activities were measured spectrophotometrically. LOOH levels were measured by ferrous oxidation with a xylenol orange assay. Student's t-test and the Pearson correlation were used for statistical analysis. RESULTS: We found that basal and salt-stimulated paraoxonase/arylesterase activities were significantly lower in women with EPF than in women without EPF (all p <0.05), while LOOH levels were significantly higher (p = 0.009). CONCLUSION: Our study showed that decreased paraoxonase/arylesterase activities and increased LOOH levels may play a role in ethiopathogenesis through increased susceptibility to lipid peroxidation in women with EPF.

Correlation between osteopontin protein expression and histological grade of astrocytomas.

Osteopontin is a ligand for the integrin proteins, which are cell surface receptors that mediate the physical and functional interactions between a cell and the extracellular matrix. The expression of osteopontin is reportedly increased in a number of transformed cell lines and tumor tissues. Furthermore, increased expression of osteopontin results in some infiltrative features of tumors. The aim of the study is to demonstrate that expression of osteopontin in human astrocytomas correlates with histological tumor grade. The expression of osteopontin in human astrocytomas was determined with immunohistochemistry. Median osteopontin expression levels were 1%, 7.5%, 60%, and 50% in grade I, II, III, and IV tumors, respectively. Osteopontin staining was significantly higher in high grade (grade III-IV) than low grade (grade I-II) tumors. These findings indicate that osteopontin immunoreactivity in human astrocytomas may correlate with the grade of a tumor.

Assessment of serum paraoxonase and arylesterase activity in patients with endometrial cancer.

PURPOSE OF INVESTIGATION: Serum paraoxonase (PON 1) is one of the most important enzymatic antioxidants that hydrolyzes lipid peroxidation, an indicator of carcinogenic activity. The aim of this study was to compare the serum levels of paraoxonase and arylesterase activity in patients with endometrial cancer to those of healthy controls. METHODS: Serum paraoxonase and arylesterase activities, total free sulphydryl (-SH) groups and lipid hydroperoxide (LOOH) levels were measured in patients with endometrial cancer (n = 20) and controls (n = 23). RESULTS: Serum paraoxonase, arylesterase activities and total -SH group levels were significantly lower in patients compared to controls (p < 0.05, p < 0.05 and p < 0.001; respectively), while LOOH levels were significantly higher (p < 0.001). Among patients, serum paraoxonase and arylesterase activities were inversely correlated with LOOH levels (r = -0.680, p < 0.05; r = -0.708, p < 0.001; respectively), while these were positively correlated with the total -SH group (r = 0.526, p < 0.05; r = 0.508, p < 0.05; respectively). CONCLUSION: Reduced serum PON 1 activity might contribute to an impaired antioxidant defense system which plays a critical role in carcinogenesis in patients with endometrial cancer.

A rare cause of ileus: invagination due to ectopic pancreas.

INTRODUCTION: Invagination is seen rarely as a cause of ileus in adults. The cause of invagination in children differs from that in adults. In adults it is mostly due to organic lesions (tumour). CASE REPORT: In a 49 years old patient, with 3 months of intermittant abdominal pain, radiologic investigations suspected a of small bowel tumour. The patient was operated on. At exploration, there was an ileo-ileal invagination on the terminal ileum over 40 cm distance A totally necrosed ileum segment was resected and an end-to-end anastomosis was performed. Inside the excised ileal loop their was a polyp-like lesion originating from submucosa, bordered by the wall but not protruding to the lumen. The pathological examination of the lesion revealed ectopic pancreatic tissue between the muscular layers of the bowel wall. RESULT: Intestinal invagination must be got in mind as a rare cause of ileus in adults. During it's clinical course their is enough time to reach the diagnosis. So unnecessory resections and postoperative complications can be prevented.

Protective role of zinc pretreatment in hepatotoxicity induced by halothane.

BACKGROUND AND OBJECTIVE: This study was designed to determine the protective effects of zinc on halothane induced hepatotoxicity. METHODS: Forty-five male Sprague-Dawley rats were divided into three groups. The halothane group received normal drinking water and diet; the zinc-halothane group received 227 mg L(-1) zinc sulphate in the drinking water and diet for 2 weeks; and the control group received normal diet and water. At the end of 2 weeks, rats were housed in an anaesthesia box and 1 MAC (minimum alveolar concentration)halothane was administered at 6 L min(-1) in room air for 2 h. This was repeated 48 h later. After the rats were sacrificed, we measured alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gammaglutamyl transpeptidase, glutathione-S-transferase, serum electrolytes and bilirubin in samples. The degree of liver toxicity was assessed by light microscopic examination. RESULTS: We demonstrated a reduction of alanine aminotransferase, aspartate amino transferase, glutathione-S-transferase levels and a reduction in liver damage in the zinc-halothane group. CONCLUSION: The study concludes that zinc has the potential to alleviate the toxic effects of halothane in rat liver.

A comparison of liquid-based cytology with conventional cytology.

OBJECTIVE: To evaluate the 2 methods of cytologic screening to detect abnormalities of the cervical epithelium. METHODS: This study with 3 groups of women was performed at Selcuk University Meram Medical School between January 2004 and March 2006. In one group (paired sample for specimen collection) women were screened with conventional cytology; in another group (paired sample for specimen collection) they were screened with liquid-based cytology; and in the third group (split sample for specimen collection) they were screened by both methods. RESULTS: The rate of unsatisfactory results was lower in the liquid-based than in the conventional cytology group (6.1% vs. 2.6%; P<0.05). More smears containing atypical squamous cells of undetermined significance were detected by the liquid-based method, but the difference was not statistically significant. Also, no statistically significant differences between liquid-based and conventional cytology were observed in the detection of other epithelial abnormalities (P>0.05). CONCLUSION: The liquid-based and conventional cytology methods were found to be equivalent in the detection of cervical epithelial abnormalities.

[Quality of life and voice handicap of laryngectomees using tracheoesophageal substitute voice]. / Lebensqualität und Stimmbeeinträchtigung Laryngektomierter mit Stimmventilprothesen.

BACKGROUND: Health-related quality of life (QoL) and subjective health have become popular constructs for the evaluation of both efficacy and efficiency of diagnostic and therapeutic procedures in medicine. QoL is considered a multidimensional construct encompassing physical, mental and social facets of life. It is an accepted outcome parameter not only in international classification systems such as ICIDH and ICF, but as well in clinical guidelines and disease management programs. Measuring quality of life allows for comparison of different diseases though it certainly lacks disease specific aspects. Thus, it has to be assumed that in patients with distinct functional deficits QoL cannot cover all aspects that are important for the individual patient. This study focuses on laryngectomies and their self-evaluation of post-laryngectomy speech. It is well known that these patients experience a decreased QoL compared to patients after partial laryngectomy or healthy persons. In this study, the impact of voice restoration on the laryngectomies' QoL was evaluated. PATIENTS AND METHODS: In 20 male laryngectomies aged 62 +/- 8 years, relations between QoL and voice handicap were evaluated using two instruments as proposed in the international literature, i. e. the Short-Form Health Survey (SF-36) and the Voice Handicap Index (VHI). All patients had successfully been using tracheoesophageal substitute voice for at least one year. Complete data sets were available from all patients. Data were analysed using Microsoft Excel and Sigma Plot, Jandel Corp. software packages. RESULTS: Results of both the SF-36 and the VHI reveal wide interindividual ranges. There are statistically significant correlations (p < 0.05) between the SF-36's scales General Health and Vitality and the VHI, whereas no correlations were found between social and psychological scales and the voice handicap. DISCUSSION: Wide ranges of the data obtained reveal that obviously both health related quality of life and voice handicap are not affected in a group specific way. So, both tests are of clinical value to depict individual aspects of wellbeing after laryngectomy. The combination of VHI and SF-36 illuminates correlations between general and special subjective aspects. Strikingly, the laryngectomies' social and psychological status is not related to their voice handicap. Data allow for conclusion that laryngectomies' substitute voice problems do not affect social aspects of quality of life in a disease specific way, at least as long as voice restoration was successful at all.