Kemal Deniz

The protective effect of royal jelly against cisplatin-induced renal oxidative stress in rats

BackgroundThe aim of this study was to investigate the effects of royal jelly on cisplatin-induced nephrotoxicity and oxidative stress in rats.MethodsAdult male Wistar albino rats were randomly divided into eight groups: the control, cisplatin, royal jelly, and royal jelly plus cisplatin groups. Biochemical and histopathological methods were utilized for evaluation of the nephrotoxicity. Blood was collected and analyzed for blood urea nitrogen (BUN), alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, uric acid, total bilirubin, and total protein levels. The kidney samples were stored for the measurement of malondialdehyde (MDA), glutathione peroxidase (GSHPx), superoxide dismutase (SOD), and catalase (CAT) activities and processed for histopathological examinations.ResultsAdministration of cisplatin to rats induced a marked renal failure, characterized with a significant increase in serum BUN and uric acid concentrations, and they had higher kidney MDA and lower GSH-Px, SOD, and CAT activities. In the groups that were administered RJ in association with CP, improvement was observed in some oxidative stress parameters and certain other biochemical parameters, pre-treatment with RJ being more effective.ConclusionsThe CP-induced changes in histopathologic findings of kidneys were partially reversed by treatment with royal jelly. The results provide further insight into the mechanisms of CP-induced nephrotoxicity and confirm the antioxidant potential of royal jelly.

Stromal vascular fraction improves deep partial thickness burn wound healing.

OBJECTIVE The practice of early burn wound excision and wound closure by immediate autologous skin or skin substitutes is the preferred treatment in extensive deep partial and full-thickness burns. To date there is no proven definite medical treatment to decrease burn wound size and accelerate burn wound healing in modern clinical practice. Stromal vascular fraction is an autologous mixture that has multiple proven beneficial effects on different kinds of wounds. In our study, we investigated the effects of stromal vascular fraction on deep partial-thickness burn wound healing. METHODS In this study, 20 Wistar albino rats were used. Inguinal adipose tissue of the rats was surgically removed and stromal vascular fraction was isolated. Thereafter, deep second-degree burns were performed on the back of the rats by hot water. The rats were divided into two groups in a randomized fashion. The therapy group received stromal vascular fraction, whereas the control group received only physiologic serum by intradermal injection. Assessment of the burn wound healing between the groups was carried out by histopathologic and immuno-histochemical data. RESULTS Stromal vascular fraction increased vascular endothelial growth factor, proliferating cell nuclear antigen index, and reduced inflammation of the burn wound. Furthermore, vascularization and fibroblastic activity were achieved earlier and observed to be at higher levels in the stromal vascular fraction group. CONCLUSIONS Stromal vascular fraction improves burn wound healing by increasing cell proliferation and vascularization, reducing inflammation, and increasing fibroblastic activity.

Circulating microRNAs in patients with non-alcoholic fatty liver disease

AIM To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). METHODS Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR-181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. RESULTS Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.

Sarcomas With Cic-rearrangements are a Distinct Pathologic Entity With Aggressive Outcome: A Clinicopathologic and Molecular Study of 115 Cases.

CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available. However, most studies reported so far include small series with limited follow-up information, which preclude a more definitive assessment. The present work investigates the clinicopathologic features of a large cohort of sarcomas with CIC gene rearrangement, to define their clinical presentation, morphologic spectrum, and outcome. Our study further examines the overall survival of the CIC-positive cohort compared with a control group of EWSR1-rearranged Ewing sarcoma matched for age and stage. The study cohort included 115 patients, with a mean age of 32 years and a slight male predominance. Most tumors occurred in the soft tissue (86%), predominantly deep-seated and equally divided among trunk and extremity, followed by visceral locations (12%) and rarely in the bone (3%). Microscopically, most tumors showed round to ovoid cytomorphology but half of the cases showed also focal areas of spindling and epithelioid/rhabdoid phenotype, with frequent myxoid stromal changes. Variable CD99 reactivity was seen in 84% cases, with a diffuse pattern only in 23% of cases, whereas nuclear WT1 was seen in 92%. A CIC-DUX4 fusion was detected in 57% of cases, with either DUX4 on 4q35 (35%) or on 10q26 in 25 (22%) cases. No FOXO4 gene rearrangements were present in 39 cases tested. Clinical follow-up was available in 57 patients, with a 5-year survival of 43%, which was significantly lower than the 77% 5-year survival in the control Ewing sarcoma group (P=0.002). Our findings show that CIC-DUX4 sarcomas occur most commonly in young adults within the somatic soft tissues, having a wide spectrum of morphology including round, epithelioid and spindle cells, and associated with an aggressive clinical course, with an inferior overall survival compared with Ewing sarcoma. The results support the classification of CIC-rearranged tumors as an independent molecular and clinical subset of small blue round cell tumors distinct from Ewing sarcoma.

Cholestatic Liver Injury Associated with Whey Protein and Creatine Supplements

We present a case of acute cholestatic liver injury associated with the combination of whey protein and creatine supplements. The difficulty of diagnosing drug-induced liver injury is emphasized. The patient is a healthy, 27-year-old man who presented with painless jaundice. He had no occupational exposures to solvents, was not taking prescription medications, and did not use recreational drugs or alcohol. He was an enthusiastic weight-lifter and had been taking creatine for 8 to 9 months and whey protein supplements for 4 weeks prior to the development of symptoms. Laboratory tests revealed elevated total bilirubin (54.7 mg/dL) and alkaline phosphatase (436 U/L), minimally elevated transaminases, and a creatinine of 3.1 mg/dL. Serologic work-up was negative for viral hepatitis and autoimmune liver disease, and Wilsons disease was ruled out. Magnetic resonance cholangiopancreatogram was unremarkable, but a liver biopsy showed marked cholestasis with ductular proliferation. He had dramatic clinical improvement with intravenous fluids and discontinuation of the nutritional supplements. In patients with acute liver injury, clinicians should inquire about dietary supplement usage and consider immediate discontinuation of all unnecessary products. We describe a case of profound jaundice related to a commonly used and reportedly safe combination of such supplements.

Ewing sarcoma with ERG gene rearrangements: A molecular study focusing on the prevalence of FUS‐ERG and common pitfalls in detecting EWSR1‐ERG fusions by FISH

The genetics of Ewing sarcoma (ES) are characterized by a canonical fusion involving EWSR1 gene and a member of the ETS family of transcription factors, such as FLI1 and ERG. In fact, ERG gene rearrangements represent the second most common molecular alteration, with EWSR1‐ERG being identified in 5–10% of cases, while only a handful of reports document a FUS‐ERG fusion. In this study, we focus on ES with ERG gene abnormalities, specifically to investigate the prevalence and clinicopathologic features of FUS‐ERG fusions in a large cohort of small blue round cell tumors (SBRCTs) and compare to the eight reported FUS‐positive ES. Among the 85 SBRCTs tested, seven (8.2%) cases harbored FUS gene rearrangements; six fused to ERG and one with FEV. During this investigation we came across a number of ERG‐rearranged ES lacking both EWSR1 and FUS abnormalities by FISH. In one case, RNA sequencing identified an EWSR1‐ERG transcript despite the negative EWSR1 rearrangements by FISH. Additional 3‐color FISH fusion assay demonstrated the fusion of EWSR1 and ERG signals in all four cases negative for break‐apart EWSR1 FISH. These results emphasize a potential pitfall of relying on EWSR1 FISH assay alone for diagnosis of ES. In cases with classic morphology and/or strong CD99 and ERG immunoreactivity, additional molecular testing should be applied, such as ERG FISH or RT‐PCR/next generation sequencing, for a more definitive diagnosis. Although our study group is small, there were no differences noted between the clinical, morphologic features and immunoprofile of the different subsets of ERG‐rearranged SBRCTs.

Familial nodular lymphocyte predominant Hodgkin lymphoma: Successful treatment with CHOP plus rituximab

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare tumor type distinct from classical Hodgkin lymphoma and its familial form is unusual. The two cases (mother at age 48 and son at age 30 years) of NLPHL in advanced clinical stage are described. The patients were successfully treated with an immunochemotherapy schedule consisting CHOP plus rituximab (CHOP-R). This chemotherapy was well tolerated and the patients reached complete remission. These remissions were for 34 and 40 months for mother and son, respectively. In patients with NLPHL, CHOP-R regimen should be used as an alternative treatment regimen to obtain a good long-lasting response without any adverse events.

Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD has a strong association with metabolic syndrome and its component like insulin resistance (IR). Cardiovascular disease has a relation with NAFLD. Platelet volume is an indicator of platelet function and activation. Mean platelet volume (MPV) has been reported as a risk factor for atherothrombosis. In our study, we aimed to investigate the relation of MPV with NAFLD and IR in the NAFLD patients. A total of 54 patients with histologically proven NAFLD and 41 healthy age-matched control subject were enrolled in this study. The NAFLD subjects were divided into two subgroups: 42 patients in the insulin resistant group (median age 39.5, females 22 [52%]) and 12 patients in the insulin sensitive group (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD group in univariate analysis (p < 0.05). In the NAFLD patients, we did not find any relation between steatosis grade, lobular inflammation, hepatocellular ballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin resistant and sensitive groups in the NAFLD patients MPV values were similar. The results of this study showed that MPV, an indicator of platelet activation, increased in biopsy proven NAFLD patients but MPV is not correlated with the increase of IR in NAFLD patients. MPV is not related with inflammation and steatosis degree, hepatocellular ballooning and fibrosis in NAFLD patients.

Solitary Necrotic Nodule of the Liver: Always Benign?

ObjectiveSolitary necrotic nodule of the liver (SNNL) is a rare lesion and accepted as a benign entity. The aim of this study is to investigate the possible causes for the development of solitary necrotic nodules.MethodsTwenty-two retrospective solitary necrotic nodule specimens were examined to evaluate histologic features. The clinical records of these patients were reviewed, and clinical data were obtained for all patients.ResultsHistologically, 17 of the 22 nodules were necrotic with surrounding fibrosis, and the remaining five nodules were completely fibrotic. Four of the 22 cases were found to have specific lesions within the nodules which may put light on the pathogenesis. Foci of metastatic carcinoma were identified in two of these four cases, and cuticle fragments of the hydatid cyst were identified in the other two cases. Clinical data showed that half of the cases with solitary necrotic nodule have an associated malignancy mainly involving the gastrointestinal system.ConclusionsSNNL is not always benign. The possible causes of this lesion include parasites and metastatic tumors. It is important to identify the minute foci of metastatic carcinoma for the appropriate management of this lesion.

Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats.

Abstract: Background: The protective effect of ischemic preconditioning (IPC) has been reported on improvement of survival, reduction of liver necrosis and enhancement of the regenerative capacity of hepatocytes after partial hepatectomy. This study was undertaken to confirm that IPC has a significant impact on regeneration of hepatocytes after partial hepatectomy in ischemically damaged liver. In addition, we sought to examine the role of adenine nucleotides in this process.