Safiye Aktas

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

Tubular dysplasia and carcinoma in situ: precursors of renal cell carcinoma

OBJECTIVES To identify the dysplastic changes in tubules adjacent to or remote from renal cell carcinoma (RCC) and to assess proliferating cell nuclear antigen (PCNA) expression of normal tubule and carcinoma cells. METHODS The study analyzed 62 kidneys with RCC that were removed by radical nephrectomy. Pathologic sections were stained with hematoxylin-eosin and evaluated for the presence of dysplasia. Sections that contained dysplasia were then stained by the avidin-biotin immunoperoxidase technique after epitope retrieval for PCNA. RESULTS Dysplastic changes in normal kidney were identified in 14 cases (23%). Dysplastic changes were adjacent to the tumor in 10 cases. Dysplasia was adjacent to the tumor and diffuse in 6 cases (3 clear cell [CRCC], 2 chromophobe [ChRCC], 1 sarcomatoid RCC [SRCC]), adjacent to the tumor and focal in 4 cases (2 CRCC, 1 papillary RCC, 1 SRCC), remote and focal in 3 cases (1 granular RCC, 1 ChRCC, 1 SRCC), and remote and diffuse in 1 case (CRCC). The lesions represented a focus that could be defined as carcinoma in situ in 3 cases. PCNA immunostaining in dysplastic epithelia was more intense than that in normal tubules and was as intense or even more intense than that in carcinoma cells. CONCLUSIONS Dysplasia of tubular epithelium is probably a biologic precursor of at least some RCC. Tubular dysplasia warrants further study as an important phase that will provide new insights into the pathogenesis, biologic behavior, and natural history of RCC. Its impact on the surgical management of small unilateral RCC needs to be investigated.

Protective effect of acetyl‐l‐carnitine against cisplatin ototoxicity: role of apoptosis‐related genes and pro‐inflammatory cytokines

Cisplatin is an anti‐neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl‐l‐carnitine would have protective effects on cisplatin‐induced ototoxicity in vitro, and if present, to reveal roles of apoptotic gene expressions and pro‐inflammatory cytokines.

Sex determination from the sternal end of the rib by osteometric analysis

BACKGROUND The aim of this study was to establish a sample group of Turkish population to determine sex from the sternal end of the ribs. Sex determination from the human skeleton bones is a simple and specific method. MATERIALS AND METHODS The specimens consisted of right fourth (4th) ribs of 78 females and 173 males of known age, sex and race during 1994-1997 in Izmir, Turkey. A discriminant function analysis showed that the most helpful parameter in the young group was superior-inferior height (SIH), and both SIH and anterior-posterior breadth (APB) in the older group. Modified discriminant score formulae for both young and old groups to determine sex for Turkish population was calculated. RESULTS The results indicated that the accuracy of sex determination was 88.6% in the young group (phase 1-4, age 15-32), 86.5% in the older group (phase 5-8, age 33-89). CONCLUSIONS This study indicates that sexual dimorphism can be assessable by using a single rib, right fourth rib in a Turkish population from ages 13 to 89. SIH of the rib is the most reliable parameter; APB follows it.

Evaluation of the Effect of Acetyl L-Carnitine on Experimental Cisplatin Ototoxicity and Neurotoxicity

Introduction: Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent for pediatric tumors, and ototoxicity is one of the dose-limiting side effects. Objective: It was the aim of our study to investigate the effect of acetyl L-carnitine (ALCAR) on experimental CDDP ototoxicity by audiologic tests, histomorphologic, immunohistochemical and ultrastructural examinations and to investigate the apoptotic pathways. Materials and Methods: Wistar albino rats (n = 28) were studied. Baseline audiological tests were performed in 4 groups: group 1, control; group 2, ALCAR; group 3, CDDP; group 4, CDDP + ALCAR-administered rats. Control audiological tests were performed on the 3rd day, and then the rats were sacrificed. Ear and brain specimens were examined by transmission electron microscopy, and caspase 3, 8 and 9 activities were investigated. Results: The CDDP-administered rats showed significant auditory brainstem response threshold shifts using all stimuli (clicks, 6-kHz and 8-kHz tone burst) compared with the control groups. The CDDP + ALCAR-administered rats showed significant auditory brainstem response threshold shifts by only click stimuli compared with the control groups. In the brain, spiral ganglion and organ of Corti, ultrastructural damage was prominent in group 3; the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase 3, 8 and 9 immunostaining cells was significantly high in group 3. Conclusion: ALCAR improves CDDP-induced auditory impairment, and also antioxidative and antiapoptotic properties of ALCAR on CDDP ototoxicity were supported by the findings.

Expression profiling reveals MSX1 and EphB2 expression correlates with the invasion capacity of Wilms tumors.

Wilms tumor is the most common pediatric renal malignancy, but the parameters that are important to its invasion capacity are poorly understood. The aim of this study was to identify new proteins associated with the invasion capacity of Wilms tumor.

Promoting effects of sanguinarine on apoptotic gene expression in human neuroblastoma cells.

Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK- N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

Becker's naevus and segmental naevus depigmentosus: An example of twin spotting?

A 12‐year‐old girl presented with a 1‐year history of a Beckers naevus involving the right posterior thigh and gluteal area. In addition, three hypopigmented macules of naevus depigmentosus distributed in a segmental pattern on the medial aspect of the right posterior thigh had been present since birth. We suggest that their unusual coexistence in close proximity may represent an example of twin spotting.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity

Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem.

Experience of the Izmir Pediatric Oncology Group on Neuroblastoma: IPOG-NBL-92 Protocol

This multicentric study aimed to bring neuroblastoma patients together under IPOG-NBL-92 protocol and evaluate the results within the period between 1992 and 2001 in Izmir. Sixty-seven neuroblastoma patients from 4 pediatric oncology centers in Izmir were included in the study. IPOG-NBL-92 protocol modified from German Pediatric Oncology (GPO)-NB-90 protocol was applied: Patients in stage 1 received only surgery, while surgery plus 4 chemotherapy courses (cisplatin, vincristine, ifosfamide) were given in stage 2 and surgery plus 6 chemotherapy courses (cisplatin, vincristine, ifosfamide, epirubicin, cyclophosphamide) were given in stages 3 and 4 patients. In patients who were kept in complete remission (CR), a maintenance therapy of one year was applied. Radiotherapy was given to the primary site following induction chemotherapy plus surgery in stages 3 and 4 patients with partial remission (PR). The stages of the patients were as follows: 5% in stage 1, 39% in stage 3, 49% in stage 4, and 7% in stage 4S. Primary tumor site was abdomen in 88% of cases. CR rates were as 100% in stage 1, 76% in stage 3, 35% in stage 4, and 75% in stage 4S. Relapse was observed in 32% of patients in a median of 19 months. The median follow-up time for survivors was 33 (17-102) months. Five-year OS rate was 31% and the EFS rate was 30% in all patients. Five-year overall and event-free survival rates were 63 and 30% in stage 3, but 6 and 5%, respectively, in stage 4 patients. Univariate analysis established that the age, stage, primary tumor site, and high LDH and NSE levels conferred a significant difference. The IPOG-NBL-92 protocol has proved to be satisfactory with tolerable toxicity and reasonable CR and survival rates. However, more effective treatments suitable to Turkeys social and economic conditions are urgently needed for children over 1 year of age with advanced neuroblastoma.