Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69?M?×?10^?5 at 24th hour and 3.93?M?×?10^?6 at 48th hour. IC50 dose for pioglitazone was 1.61?M?×?10^?3 at 24th hour and 2.85?M?×?10^?4 at 48th hour. Although cells were treated the dose of 40,225?mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.     

Aplastic Anemia Frequency and Management in Pediatric Liver Transplantations Due to Non-A-E Hepatitis

Background: Hepatitis-associated aplastic anemia (HAAA) is a rare complication that presented with bone marrow failure after acute hepatitis. HAAA usually occurs in adolescent men within 1-6 months following hepatitis. Most of HAAA’s etiology has non-A-E viral hepatitis.Methods: Our retrospective study included patients with acute fulminant hepatitis who had been treated in Ege University Pediatric Gastroenterology, Hepatology and Nutrition Department and İzmir Kent Hospital Clinical, laboratory, and epidemiological data of the patients were collected from the files.Results: In this study, 499 children underwent liver transplantation (LT) in two pediatric transplantation centers. Sixty-eight (13.6%) out of 499 patients, underwent liver transplantation due to fulminant hepatic failure (FHF). Therefore, a total of 64 patients (34 girls, 30 boys) with a diagnosis of FHF have included in the study. Thirty-two (50.0%) of 64 FHF were due to non-A-E hepatitis and 4 out of the 64 patients (6.2%) with FHF developed HAAA. All of the patients received prednisolone as immunosuppression treatment after LT. Three patients were also given Tacrolimus and 1 received an additional mycophenolate mofetil. One of the patients was given prednisolone and cyclosporine treatment without tacrolimus. Bone marrow transplantation was performed in 1 patient (25.0%). Two of the patients received immunosuppressive treatment including rabbit-derived anti-thymocyte globulin, cyclosporine, and initially prednisolone.Conclusion: In children who underwent liver transplantation for non-A-E FHF are at high risk to develop aplastic anemia. The clinicians should be alert after orthotropic liver transplantation patient could develop aplastic anemia and early treatment with immunosuppressive therapies result in a more successful outcome.     

Spinal metastasis of occult lung carcinoma causing cauda equina syndrome.

Cauda equina syndrome (CES) may be caused by tumor, herniated disc, trauma and spinal infections. However, CES due to occult lung cancer has not been reported in the literature. A 50-year-old man presented with a subacute CES caused by an intradural metastasis of an adenocarcinoma of the lung to the lumbosacral cauda fibers. His lumbosacral magnetic resonance imaging (MRI), showed a well-demarcated, intradural extramedullary mass lesion resembling a neurinoma at the L4/5 level. The patient underwent an L4-L5 laminectomy. The operative findings were also suggestive of neurinoma with involvement of three nerve roots, and a well-demarcated tumor without infiltration into the subarachnoid space. Although the findings of the operation were suggestive of neurinoma, final pathological diagnosis revealed metastatic carcinoma. Immunohistochemistry revealed clear cell adenocarcinoma metastasis. Chest X-ray and high resolution contrasted pulmonary computed tomography were normal. Positron emission tomography (PET) showed a lung mass, at the left apex. The patient was treated with chemotherapy and post-operative spinal radiotherapy was also performed. The CES resolved after the operation and the patient was followed up for 2 years with no recurrence. MRI of intradural cauda equina metastasis may be similar to that of intradural nerve sheath tumor. Surgery and postoperative radiotherapy may be effective for the treatment of CES due to lung carcinoma. Definitive diagnosis is by histopathological examination with immunohistochemistry. If the primary cancer cannot be detected by conventional radiological techniques, PET may be helpful.     

Effect of sensory training of the posterior thigh on trunk control and upper extremity functions in stroke patients

Neurological Sciences - Some studies show that sensorial rehabilitation is effective on functionality. The aim of this study is to investigate the effect of sensory training of the posterior thigh...     

Tumor-Resident CD8+ T-cell: The Critical Catalyst in IL-12-Mediated Reversal of Tumor Immune Suppression

Tumor-resident T cells display a functionally impaired effector/memory (Tem) phenotype. Sustained intratumoral administration of IL-12, on the other hand, can restore cytolytic function to pre-existing CD8⁺ Tem, resulting in effective tumor kill. Whereas cytotoxic T lymphocytes (CTL) are generally assumed to mediate tumor regression via direct tumor cytotoxicity, recent work revealed that activated CD8⁺ Tem mobilize a systemic, multi-component effector cascade that includes both innate and adaptive immune mechanisms. Here we summarize these mechanisms, review how tumor-resident CD8⁺ Tem orchestrate this cascade and discuss the potential clinical implications of these findings.     

Antioxidant actions and early ultrastructural findings of thiopental and propofol in experimental spinal cord injury

Thiopental and propofol are effective antioxidant agents. The current study was undertaken to examine the neuroprotective effects of a single intraperitoneal dose of thiopental and propofol. Effects of the drugs were evaluated by lipid peroxidation and ultrastructural findings. Fifty male Wistar rats were divided into five groups. Group 1 was the control group. Rats underwent laminectomy only, and nontraumatized spinal cord samples were obtained 1 hour after surgical intervention. All other rats sustained a 50-g/cm contusion injury by the weight drop technique. Group 2 rats underwent spinal cord injury alone, group 3 rats received 1 mL intralipid solution intraperitoneally immediately after trauma as the vehicle group, group 4 rats received a 15-mg/kg single dose of thiopental, and group 5 rats received a 40-mg/kg single dose of propofol intraperitoneally following the trauma. Samples from groups 2, 3, 4, and 5 were obtained 1 hour after injury. Lipid peroxidation was determined by measuring the concentration of malondialdehyde in the spinal cord tissue. The ultrastructure of the spinal cord was determined by electron microscopy. The contusion injury was associated with a rise in lipid peroxidation. Compared with the trauma group there was significant attenuation in lipid peroxidation of groups 4 and 5. Ultrastructural findings showed that the rats of group 4 sustained minor damage after spinal cord injury, but there was more evident damage in group 5 rats. These results indicate that thiopental decreases lipid peroxidation and improves ultrastructure, whereas propofol decreases lipid peroxidation without improving ultrastructure 1 hour after spinal cord injury in rats.     

The effects of methidathion on lipid peroxidation and some liver enzymes: role of vitamins E and C

Methidathion (MD) [ O, O-dimethyl S-(2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadiazol-3-ylmethyl) phosphorodithioate] is one of the most widely used organophosphate insecticides (OPIs) in agriculture and public health programmes. We have, therefore, examined the in vivo and in vitro effects of MD on the serum activities of cholinesterase (ChE), enzymes concerning liver damage and lipid peroxidation (LPO; only in vivo), and have evaluated the ameliorating effects of a combination of vitamins E and C against MD toxicity. The in vivo experimental groups were: control group, MD-treated group (MD), and a group treated with MD plus vitamin E plus vitamin C (MD+Vit). The MD and MD+Vit groups were treated orally with a single dose of 8 mg MD/kg body weight at 0 h. Vitamin E and vitamin C were injected at doses of 150 mg/kg body weight i.m. and 200 mg/kg body weight i.p., respectively, 30 min after the treatment with MD in the MD+Vit group. Blood samples were taken 24 h after the MD administration. For in vitro study, venous blood samples were obtained from volunteers, and serum recovered. The activities of serum enzymes were determined in each sample and these served as 0 h values. Each sample was divided into four portions, each of which served as one of the experimental groups, as follows: control group, vitamin E plus vitamin C group (Vit), MD-treated group (MD) and MD plus vitamin E plus vitamin C group (MD+Vit). Vitamin E and vitamin C were added at doses of 7.5 and 10 micro g/ml, respectively, into the Vit and MD+Vit groups. MD was added at doses of 0.4 mg/ml into the MD and MD+Vit groups. The activities of serum enzymes were determined in each sample at 24 h. The results of the in vivo experiment demonstrated that thiobarbituric acid reactive substances were increased in the MD group compared with the control group, and decreased in the MD+Vit group compared with MD group. ChE activity was decreased in both MD and MD+Vit groups compared with controls and increased in the MD+Vit group compared with the MD group. The activities of aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) were increased in both the MD and MD+Vit groups compared with the control group. AST activity was decreased in MD+Vit group compared with the MD group. Alanine aminotransferase (ALT) activity was decreased in both the MD and MD+Vit groups compared with control group. The results of in vitro experiment showed that all enzyme activities remained unchanged in both the control and Vit groups compared with values at 0 h. The activities of ChE, ALT and LDH were decreased in both the MD and MD+Vit groups compared with 0 h values. There was no significant difference between the MD and MD+Vit groups. The activities of AST, ALP and GGT remained unchanged in all groups. From these results, it can be concluded that MD caused liver damage, and LPO may be one of the molecular mechanisms involved in MD-induced toxicity. Single-dose treatment with a combination of vitamins E and C after the administration of MD can reduce LPO caused by MD.