Nadir Korkmazer

Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid

Valproic acid (VPA) is an antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including anorexia and nausea, and hepatoxicity. As to its dose-dependent side effects are the weight loss, tremor, skin eruption and the alopecia. In this study we aimed to put forward the biotinidase deficiency considered as a possible cause of alopecia in the rats administered with valproic acid, and the correlation between liver and serum biotinidase enzyme activities (BEA) and transaminases, albumin and serum valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver biotinidase enzyme activities, serum AST, ALT, albumin, and valproic acid levels were measured. Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver biotinidase enzyme activities and the serum valproic acid levels, and the negative correlation between the liver tissues biotinidase activities and the serum valproic acid levels were noted, respectively. As a conclusion, the partial alopecia which is an initial symptom of reduced biotinidase activity may also be created depending on the reduction of biotinidase activity during valproic acid therapy. The alopecia which may further be observed in the patients receiving valproic acid therapy may be prevented by means of administration of biotin in a dose of 10 mg/day.

The effect of melatonin on procarbazine induced testicular toxicity on rats

Abstract Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects.

Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury.

BACKGROUND Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity.

Raynaud's phenomenon in a child with medulloblastoma as a late effect of chemotherapy

There are a lot of early or late side effects of chemotherapies. One of them is Raynauds phenomenon (RP). Vascular toxicity associated with antineoplastic agents is notified in bleomycin alone therapy or in combination with cisplatin, vinblastine, and vincristine. The mechanism of RP associated with antineoplastic agents is unknown. All children receiving vinblastine, vincristine, bleomycin and cisplatin therapy, are followed and questioned about their complaint on RP. Long-term follow-up of surviving patients is recommended. Oncologists should be aware of the potential late toxic effects of antineoplastic drugs.

Clofarabine associated capillary leak syndrome in a child with lymphoma successfully treated with intravenous immunoglobulin

Clofarabine is an effective drug in relapsed leukemia and lymphoma that has some adverse effects which can be fatal like capillary leak syndrome (CLS). Identification and management of CLS is important that may result in mortality. Although prophylactic treatment with steroids may prevent CLS and improve survival, intravenous immunoglobulins are used in the treatment with great success in steroid resistant cases. However, the knowledge about the effects and the dose of intravenous immunoglobulins (IVIG) in pediatric patients is limited. Herein, we reported a patient with relapsed lymphoma who developed CLS successfully and was treated with IVIG.

Ozone Ameliorates Doxorubicine-Induced Skin Necrosis - results from an animal model.

Doxorubicin (DXR) extravasation result with serious morbidity like skin ulceration and necrosis. The purpose of this study is to determine the protective effects of ozone, olive oil, dimethyl sulfoxide (DMSO), and coenzyme Q10 in the treatment of DXR-induced skin ulcers on rats. After an intradermal injection of DXR on a basis of an animal extravasation model, the materials were topically applied. The ulcer sizes were measured, and a punch biopsy was taken from the extravasation site in which the skin ulcers formed at the end of the experiment. The samples were analyzed for tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL1β), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) enzymes, and examined histopathologically. The ulcer sizes clearly decreased in the study groups, including DMSO, olive oil, ozone plus coenzyme Q10, and ozone plus olive oil groups in comparison with the control group with the exception of the coenzyme Q10 group. The malondialdehyde levels were lower in the DMSO, olive oil, ozone plus olive oil, and ozone plus coenzyme Q10 groups than they were in the control group, but they were not significantly different. The TNF-α level was lower in the DMSO, ozone plus olive oil, coenzyme Q10, and ozone plus coenzyme Q10 groups in comparison with the control group. There was no significant change in the SOD, GSH-Px, and IL1β levels in the study groups in comparison with the control and the sham groups. The ozone plus olive oil group could be considered to be an alternate therapy for skin ulcers due to DXR extravasation.

The timing of autologous stem cell transplantation and the prognostic factors affecting the prognosis in children with relapsed Hodgkin lymphoma.

Although ASCT is used as a standard treatment following second remission for adults in oncology practice, data are lacking for relapsed childhood HL. Therefore, we evaluated the exact timing of the ASCT treatment, as well as factors affecting the prognosis in children with relapsed HL who underwent ASCT. Patients were divided into two groups (Group 1: ASCT after second remission [n = 6], Group 2: ASCT after >2 remissions [n = 3]). Overall, DFS rate was 64.8% at 24 months after ASCT. In Group 1, post‐transplant DFS and OS were 83.3% and 75%, respectively, and the post‐transplant response without event rate was 5/6 (83.3%). However, in Group 2 this was 1/3 (33.3%). Nonetheless, the timing of ASCT was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.21 and p = 0.73, respectively). Median follow‐up time was 21 months after transplant, and DFS and OS were 62.5% and 75% in early relapse group (n = 6) at 24 months. DFS and OS were both 66.7% in late relapse (n = 3). In addition, response rates of ASCT without event were 66.7% for both early and late relapse groups. Relapse types (early: 3–12 months, late: >12 months) was not a significant prognostic factor for DFS and OS in univariate analyses (p = 0.96 and p = 0.92). While we found ASCT to be a useful treatment following second remission, it does not demonstrate better success in early relapse cases, when compared to late relapse cases. Therefore, after second remission for relapsed HL, ASCT is advisable regardless of the time of relapse.

Small intestinal lactoferrin and calprotectin levels in different stages of necrotizing enterocolitis in a rat model

PURPOSE Necrotizing enterocolitis (NEC) is a severe disease of mostly premature infants with high morbidity and mortality rates. There is no reliable biomarker for detecting newborns at risk for NEC development. We aimed to investigate small intestinal lactoferrin (LF) and calprotectin (CAL) levels as predictors and indicators of disease severity in an experimental newborn rat model. MATERIALS AND METHODS Newborn pups were randomly divided into two groups, NEC and control. The NEC group pups were decapitated on the second, third and fourth days of the experiment for an assessment of the different stages of NEC. In the study group, hypoxia-reoxygenation model used to induce NEC. As biochemical parameters, small intestinal LF and CAL levels were measured with an enzyme-linked immunosorbent assay technique and intestinal injury scoring was evaluated as a pathologic parameter. RESULTS Small intestinal levels of both LF and CAL increased in the second and the third day groups, but began to decrease by the fourth day. The first, second and third day levels of LF and CAL were higher than controls. The intestinal injury scores of all NEC groups were significantly higher than the control group. CONCLUSION Small intestinal lactoferrin and calprotectin were good markers for demonstrating NEC. However, instead of spot testing, monitoring the levels of these markers may be more informative.