Acute brucella melitensis M16 infection model in mice treated with tumor necrosis factor-alpha inhibitors

Introduction: There is limited data in the literature about brucellosis related to an intracellular pathogen and anti-tumor necrosis factor alpha (anti-TNFα) medication. The aim of this study was to evaluate acute Brucella infections in mice receiving anti-TNFα drug treatment. Methodology: Anti-TNFα drugs were injected in mice on the first and fifth days of the study, after which the mice were infected with B. melitensis M16 strain. Mice were sacrificed on the fourteenth day after infection. Bacterial loads in the liver and spleen were defined, and histopathological changes were evaluated. Results: Neither the liver nor the spleen showed an increased bacterial load in all anti-TNFα drug groups when compared to a non-treated, infected group. The most significant histopathological findings were neutrophil infiltrations in the red pulp of the spleen and apoptotic cells with hepatocellular pleomorphism in the liver. There was no significant difference among the groups in terms of previously reported histopathological findings, such as extramedullary hematopoiesis and granuloma formation. Conclusions: There were no differences in hepatic and splenic bacterial load and granuloma formation, which indicate worsening of the acute Brucella infection in mice; in other words, anti-TNFα treatment did not exacerbate the acute Brucella spp. infection in mice. © 2015 Kutlu et al

Diffüz büyük B-hücreli lenfomanın farklı immünofenotipik profillerinde apoptozis, proliferasyon durumu ve O6 metilguanin DNA metiltransferaz metilasyon profillerinin tespiti

Objective: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immunophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL). Materials and Methods: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. Results: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). Conclusion: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles

Ki-67, p53, Bcl-2 and Bax expression in urothelial carcinomas of urinary bladder

Objective: The most important predictive parameter for the biological behavior of urothelial carcinomas except depth of invasion is the histological grade of the tumor. However, crucial discordances arise between pathologists because of subjectivity in histological grading schemes and these discordances cause difficulties especially in low-grade tumors. The number of studies aiming to predict the risk of recurrence and progression in urothelial carcinomas has therefore increased in recent years. Our aim in this study was to evaluate the relation of histopathological and clinical characteristics of urothelial carcinomas with proliferation and apoptosis markers and to determine predictive parameters for their biological behavior. Material and Method: This study included 84 previously diagnosed cases of urothelial carcinoma of the urinary bladder. Immunohistochemical expressions of Ki-67, p53, Bcl-2, and Bax were examined in each case. Results: Expressions of Ki-67 and p53 determined a significant relationship between pathological stage and histological grade of the cases. There was no significant relationship between the other apoptotic markers (Bcl-2, and Bax) and clinical or morphological parameters. Conclusion: We concluded that the evaluation of Ki-67 and p53 expression combined with pathological stage and histological grade may give more accurate information about the biological behavior of urothelial carcinomas of the urinary bladder

Primary malignant fibrous histiocytoma of the kidney: Report of a case

Primary renal malignant fibrous histiocytoma is extremely rare. The prognosis is generally poor because of the high rate of local recurrence even if radical surgery is performed. We report a case of primary renal malignant fibrous histiocytoma in a 43-year-old woman. A well-defined renal mass (10x9x7cm) with lobulated contour was revealed by abdominal ultrasonography and computerized tomography in our patient who presented with left-flank pain. The contralateral kidney and renal functions were normal. No other primary tumor focus was detected by screening performed to exclude a metastasis to the kidney. However, a nodule consistent with metastasis was identified in the liver. The patient underwent left radical nephrectomy. A huge, yellowish-white, partly necrotic neoplasm infiltrating the renal parenchyma, perirenal fat and adrenal tissue was revealed by gross examination. Microscopically, the tumor was composed of pleomorphic spindle to polygonal cells arranged in fascicles and storiform structures with extensive necrosis. Twelve mitotic figures were noted in 10 high power fields. Immunohistochemical staining for vimentin and CD68 were positive whereas pan-cytokeratin, smooth muscle actin, S-100, HMB-45 and desmin were negative. "A pleomorphic type of malignant fibrous histiocytoma" was diagnosed based on both the microscopic and immunohistochemical findings. The patient presented with multiple bilateral lung metastasis three years after nephrectomy. Histopathological examination is essential since malignant fibrous histiocytoma cannot be differentiated clinically and radiologically from other lesions with kidney involvement. The overall prognosis is unfavorable with a recurrence rate of more than 50% and the 5-year-survival rate is only 14%

The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model.

PURPOSE: The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model. MATERIALS AND METHODS: A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples. RESULTS: Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected. CONCLUSIONS: Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans

The determination of relationship between "excision repair cross-complementing group 1" (ERCC1) gene T19007C and C8092A single nucleotide polymorphisms and clinicopathological parameters in non-small cell lung cancer

DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5′ incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P = 0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P = 0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC. © 2011 Springer Science+Business Media B.V

Acute Brucella melitensis M16 infection model in mice treated with tumor necrosis factor-alpha inhibitors.

INTRODUCTION: There is limited data in the literature about brucellosis related to an intracellular pathogen and anti-tumor necrosis factor alpha (anti-TNFα) medication. The aim of this study was to evaluate acute Brucella infections in mice receiving anti-TNFα drug treatment. METHODOLOGY: Anti-TNFα drugs were injected in mice on the first and fifth days of the study, after which the mice were infected with B. melitensis M16 strain. Mice were sacrificed on the fourteenth day after infection. Bacterial loads in the liver and spleen were defined, and histopathological changes were evaluated. RESULTS: Neither the liver nor the spleen showed an increased bacterial load in all anti-TNFα drug groups when compared to a non-treated, infected group. The most significant histopathological findings were neutrophil infiltrations in the red pulp of the spleen and apoptotic cells with hepatocellular pleomorphism in the liver. There was no significant difference among the groups in terms of previously reported histopathological findings, such as extramedullary hematopoiesis and granuloma formation. CONCLUSIONS: There were no differences in hepatic and splenic bacterial load and granuloma formation, which indicate worsening of the acute Brucella infection in mice; in other words, anti-TNFα treatment did not exacerbate the acute Brucella spp. infection in mice

Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. MATERIALS AND METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040). CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ