Sex dichotomy in the course of experimental latent toxoplasmosis.

Toxoplasma gondii is an opportunistic zoonotic protozoan that exceeds neurological and congenital impact sequence to reactivating latent toxoplasmosis especially under immunosuppression. Sex-associated hormones influence the severity of Toxoplasma infection. Thus, our study aimed to compare toxoplasmosis associated morbidity in both male and female mice and to monitor the response to anti-Toxoplasma therapeutics fortified with sex hormones in comparison to presently used drugs. Twenty male and 20 female mice were infected with ME49 Toxoplasma strain. The morbidity was assessed in the chronic stage in both sexes by estimating brain cyst burden, brain histopathological examination and monitoring serum anti-Toxoplasma IL-12 using ELISA method. Another 40 male and 40 female mice were infected with ME49 Toxoplasma strain then after 6 weeks received different treatment regimens including Atovaquone, Spiramycin, Metronidazole, Estradiol benzoate and Testoserone propionate either as a monotherapy or as a combination. Treatment response was monitored by scoring mice activity and brain cyst burden. This study showed that female mice demonstrated higher cyst burden and manifested more pathological reactions than male mice. While, the IL-12 serum level was significantly higher in male than female mice. Also, it is proved that the Toxoplasma cyst number was reduced significantly when used testosterone/atovaquone, or testosterone/spiramycin/metronidazole combined regimen in female mice groups. While for male mice, the combined therapy of spiramycin/metronidazole was the superior one. Accordingly, combined therapy with sex hormones is a promising strategy for discovering new therapeutic regimens for treating latent toxoplasmosis especially in female.

Expression of pRb, Ki67 and HER 2/neu in gastric carcinomas: Relation to different histopathological grades and stages.

Gastric carcinoma is one of the aggressive malignancies with poor prognosis. The expression of pRb, Ki67, Her-2 in relation to tumor grade and stage in gastric carcinoma still needs more exploration. This study was performed aiming to study the immunohistochemical expression of altered retinoblastoma encoding protein (pRb), Ki67 and Her-2 in gastric carcinoma and to investigate their clinical and pathological significance. We studied tumor tissue specimens from 48 patients with gastric carcinoma. Paraffin sections were submitted for immunohistochemistry using pRb, Ki67 and Her-2. Statistical analysis was performed for clinical and pathological data of all studied cases. Altered pRb was expressed in 79% of the studied tumors, inversely correlated with tumor invasion and stage with no significant relation with tumor grade, age, and gender and tumor size. Ki67 LI was significantly associated with tumor grade and stage but not related to sex, age, tumor size, site, depth of invasion and lymph node metastasis. Her2 was expressed in 75% of studies tumors with significant association with tumor grade, the depth of invasion, lymph node metastasis and higher tumor stage. However, there was no significant association between Her-2 expression and gender, tumor site and size. In conclusion, altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. Ki67 expression in gastric carcinoma is directly correlated with the tumor grade and depth of invasion. Her2 expression is significantly correlated with tumor grade, depth of invasion and stage.

Effects of aluminum oxide (Al2O3) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid.

The objectives of present study were to examine the effects of aluminum oxide (Al2O3) nanoparticles on myocardial functions, electrical activities, morphology, inflammation, redox state, and myocardial expression of connexin 43 (Cx43) and the effect of gallic acid (GA) on these effects in a rat animal model. Forty male albino rats were divided into 4 equal groups: the control (normal) group; the Al2O3 group, rats received Al2O3 (30 mg·kg(-1), i.p.) daily for 14 days; the nano-alumina group, rats received nano-alumina (30 mg·kg(-1), i.p.) daily for 14 days; and the nano-alumina + GA group, rats received GA (100 mg·kg(-1) orally once daily) for 14 days before nano-alumina administration. The results showed disturbed ECG variables and significant increases in serum levels of LDH, creatine phosphokinase (CPK), CK-MB, triglycerides (TGs), cholesterol and LDL, nitric oxide (NO), and TNF-α and myocardial concentrations of NO, TNF-α, and malondialdehyde (MDA), with significant decreases in serum HDL and myocardial GSH, SOD, catalase (CAT), and Cx43 expression in the nano-alumina group. Pretreatment with GA improved significantly all parameters except serum and myocardial NO. We concluded that chronic administration of Al2O3 NPs caused myocardial dysfunctions, and pretreatment with GA ameliorates myocardial injury induced by nano-alumina, probably through its hypolipidaemic, anti-inflammatory, and antioxidant effects and upregulation of Cx43 in heart.

Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4-Related Disease.

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.

Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.

Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

Cisplatin-induced testicular toxicity in rats: the protective effect of arjunolic acid.

In the present study, the effect of arjunolic acid on testicular damage induced by intraperitoneal injection of rats with 7 mg/kg cisplatin was studied. Cisplatin induced a significant reduction in testicular weights, plasma testosterone, and testicular reduced glutathione levels in addition to a significant elevation of testicular malondialdehyde levels and testicular gene expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and p38 mitogen-activated protein kinase (MAPK) when compared with the control group (p < 0.05). Lower tubular diameters and depletion of germ cells and irregular small seminiferous tubules with Sertoli cells only were observed in the cisplatin group. Arjunolic acid administration significantly corrected the changes in both biochemical and histopathological parameters. Arjunolic acid plays a significant protective role against cisplatin-induced testicular injury by attenuating oxidative stress parameters along with downregulation of iNOS, TNF-α, and p38-MAPK testicular expressions.

Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.

Oligoclonal band versus chitinase-3-like protein-1 in CSF of newly diagnosed relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune-mediated demyelinating disease of the central nervous system (CNS) that is usually associated with varying degrees of progressive disability. Chitinase-3-like protein-1 (CHI3L1) has attracted growing attention as a marker of ongoing inflammation and oncogenic transformation. The aim of this work was to assess the diagnostic accuracy of CHI3L1 versus IgG oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) of newly diagnosed relapsing remitting MS (RRMS) patients to throw light on a new simpler non subjective potential diagnostic marker in MS. This cross-sectional study of MS patients was carried at Ain Shams University Hospitals during the period from January 2021 till January 2022. Subjects included in this study were 40 patients diagnosed as having RRMS, based on their magnetic resonance imaging (MRI) findings, clinical presentation and according to the revised McDonald criteria 2017. The group included 10 males and 30 females; their ages ranged from 20 to 45 years. We found a significant correlation between CSF CHI3L1 levels and presence of oligoclonal bands (p=0.001), and that a cut off value of 30 ng/ml could be used for diagnosis of MS with sensitivity 84.85% and specificity 85.71%. A significant association was also found between CHI3L1 levels in CSF and Expanded Disability Status Scale (EDSS) score (p=0.002). We concluded that there were high levels of CHI3L1 in the CSF of MS patients and there was a significant correlation between CHI3L1 and oligoclonal bands and that CHI3L1 may be considered a promising diagnostic marker of MS.

Recoverability of renal functions after relief of partial ureteric obstruction of solitary kidney: impact of ferulic acid.

UNLABELLED: What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney. OBJECTIVE: To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney. METHODS: Male mongrel dogs (n = 32) were classified into three groups: sham (eight), control (12) and study (12). A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO. Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction. Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment. RESULTS: Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction. In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD. Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction. CONCLUSION: Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.

Myocardial and metabolic dysfunction in type 2 diabetic rats: impact of ghrelin.

Diabetes mellitus (DM) is commonly associated with metabolic and cardiac dysfunctions. The aim of this study was to examine the effect of ghrelin on metabolic and cardiac dysfunctions in a type-2 diabetes mellitus (T2DM) rat model. For this, 48 male adult Sprague-Dawley rats were divided equally into 4 groups: Group I, fed normal chow, served as normal control group; Groups II-IV, were fed a high-fat diet for 2 weeks followed by injection of streptozotocin (STZ) (35 mg/kg body mass) to create a model of T2DM; Group II, were not treated; Group III, were treated with the vehicle (saline); Group IV, were treated with ghrelin (40 µg/kg body mass) twice daily for 10 days. The untreated diabetic rats showed a significant increase in serum fasting blood glucose, insulin homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), total serum cholesterol (TC), and body mass, with a decrease in high-density lipoprotein cholesterol (HDL-C) (p < 0.05). Hearts isolated from diabetic rats showed a significant increase in myocardial fat content, a significant decrease in GLUT4, and an increase in acyl-CoA oxidase enzyme mRNA (p < 0.05). Ghrelin administration for 10 days caused a significant improvement in lipid profile, HOMA index, and body mass, and significantly corrected the myocardial mass, significantly reduced the fat content of the myocardium, significantly increased GLUT4, and decreased acyl CoA oxidase mRNA (p < 0.05). Thus, ghrelin improves both the metabolic functions and the disturbed energy metabolism in the cardiac muscle of obese diabetic rats.

Subtyping of high grade serous ovarian carcinoma: histopathological and immunohistochemical approach.

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is classified into four molecular subtypes; mesenchymal, proliferative, immunoreactive, and differentiated, with suggested different prognosis. Addressing the presence of histopathological and immunohistochemical differences in HGSOC that parallel the molecular subtypes can help in tailoring the management protocol to improve therapeutic response and patient outcome. METHODS: This retrospective study was conducted on 85 specimens for cases of HGSOC. Cases were classified according to histopathological findings into mesenchymal, proliferative, immunoreactive, and differentiated subtypes. Cases were immunostained with ER, PR, Ki67, CD8, E-cadherin, and vimentin. RESULTS: By applying histopathological data, cases were subdivided into 4 groups; mesenchymal type represented by 25 cases, proliferative type which included 14 cases, the immunoreactive type included 14 cases, and differentiated type represented by 32 cases; 13 of them had SET features and 19 had papillary architectural features. A significant correlation was found between Ki67 and proliferative subtype, as well as between CD8 and immunoreactive subtype. ER showed significantly higher expression in proliferative subtype in the group treated by primary debulking. CD8 showed a significant correlation with solid endometroid transitional (SET) pattern in the group that underwent interval debulking. In terms of prognosis, the shortest median progression-free survival (PFS) was for mesenchymal subtype, while the longest median PFS was for differentiated subtype with SET architectural pattern with statistically significant correlation. No correlation was found between any of the studied parameters and overall survival. CONCLUSION: Histopathological features and immunohistochemistry can help to stratify HGSOC into prognostic distinct groups.

Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status.

OBJECTIVE: Programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) are currently considered as prognostic markers and therapeutic targets in many human cancers. This study aims to evaluate immunohistochemical (IHC) expression of PD-L1 in gastric cancer (GC) and explore its prognostic role in terms of association with HER2 expression, different clinico-pathological variables, in particular density and cluster designation (CD)8 positivity in tumor infiltrating lymphocytes (TILs) and with patients' disease-free and overall survival (DFS, OS). METHODS: This retrospective cohort study included 111 diagnosed primary GC patients who underwent surgical resection at the Gastrointestinal Surgery Center (GISC), Faculty of Medicine, Mansoura University, Egypt. After demographic, clinicopathological and survival data collection, histopathological evaluation was done for GC typing, staging and assessment of the histopathological prognostic parameters. IHC was performed for PD-L1, HER2 and CD8. PDL-1 was scored using the Combined Positive Score (CPS). RESULTS: PD-L1 was expressed in 43.2% of GCs at a CPS cut-off value ≥ 1. PDL-1 positivity was significantly associated with high TILs and CD8+ TILs (p=0.008, 0.016 respectively), indicating its contribution to tumor microenvironment along with the TILs. Multivariate analysis spotted PD-L1 positivity as an independent prognostic predictor for shorter OS in GC (p=0.013), with a tendency toward shorter DFS. Only 9.9% GCs were HER2 positive (score +3) with no significant association with PD-L1. CONCLUSION: PDL-1 is a promising prognostic and therapeutic target in GC that may direct the selection of patients for immunotherapy and checkpoint-blockade (pembrolizumab) therapy.

Role of combination of L-arginine and α-tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model.

UNLABELLED: What's known on the subject? and What does the study add? Renal ischaemia/reperfusion (I/R) injury is an inevitable consequence of kidney transplantation. It contributes to delayed graft function (DGF), acute renal failure and graft rejection. The present study investigates for the first time the impact of a combination of L-arginine and alpha tocopherol on the renal ischemia/reperfusion injury in a rodent model of kidney transplantation. We found that concomitant administration of L-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys. OBJECTIVES: To investigate the role of L-arginine and α-tocopherol in ischaemia/reperfusion injury in a kidney transplanted rat model. MATERIALS AND METHODS: In total, 40 male Sprague-Dawley rats subjected to renal transplantation received FK506 (tacrolimus) to overcome early acute rejection episodes. Animals were divided randomly into four groups (ten rats each). Group I were treated with FK506 (2 mg/kg/bw/day) and served as the control group. Group II were treated with L-arginine 300 mg/kg/bw. Group III were treated with α-tocopherol 30 mg/kg/bw. Group IV were treated with L-arginine and α-tocopherol. Urine and blood samples were taken at 0 (before operation), 2, 7 and 14 days post-transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium and blood urea nitrogen. Histological examination and measurement of malondialdehyde in kidney tissues were also performed. RESULTS: Serum creatinine and blood urea nitrogen significantly decreased in L-arginine and α-tocopherol, as well as combination groups, compared to the control group. Malondialdehyde was significantly decreased in the combination group compared to L-arginine and α-tocopherol alone. Histological examination of the control group showed that acute tubular necrosis was markedly decreased in transplanted kidneys treated with a combination of both L-arginine and α-tocopherol. CONCLUSIONS: Concomitant administration of l-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.

Celecoxib, a selective cyclooxygenase-2 inhibitor, attenuates renal injury in a rat model of Cisplatin-induced nephrotoxicity.

BACKGROUND: Cisplatin is an effective chemotherapeutic agent successfully used in the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has restricted its clinical use. Recent studies have strongly suggested that inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. Celecoxib, a selective cyclooxygenase-2 inhibitor used as anti-inflammatory, may therefore have a protective effect on cisplatin-induced renal injury. METHODS: In the present study, rats were injected intraperitoneally with a single dose of cisplatin (7 mg/kg) and/or celecoxib (30 mg/kg) for 5 days. RESULTS: Nephrotoxicity manifested biochemically by elevations in serum creatinine, blood urea nitrogen, and proteinuria, and an increase in kidney weight as a percentage of total body weight. In addition, a marked decrease in serum albumin was observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde level and glutathione content, which were increased and depleted, respectively. Administration of celecoxib with cisplatin attenuated cisplatin-induced changes in kidney function parameters and oxidative stress markers. Histopathological examination of the kidney confirmed these results. CONCLUSION: In conclusion, this study indicates that celecoxib may be a promising drug for clinical use as a nephroprotectant against cisplatin-induced nephrotoxicity.

The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity.

BACKGROUND: The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined. RESULTS: Cisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats. CONCLUSIONS: The BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Valproate-induced liver injury: modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen.

BACKGROUND: The polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA. METHODS AND RESULTS: VPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor necrosis factor-alpha (TNFα) levels, as well as myeloperoxidase (MPO) activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250 mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides, TNFα, and MPO activity, while raising serum albumin and hepatic GSH levels. DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly increased the latency in convulsion evoked by VPA, beyond their individual responses. Lastly, pharmacokinetic studies revealed that joint DHA administration did not alter serum VPA concentrations. CONCLUSIONS: DHA substantially ameliorated liver injury induced by VPA, while also markedly boosted its pharmacologic effects. DHA manipulated definite cellular machinery to curb liver oxidative stress and inflammation, without affecting VPA plasma levels. Collectively, these protective and synergy profiles for DHA propose a superior VPA-drug combination regimen.

Is combination therapy interferon and ribavirin in patients with chronic hepatitis C infection toxic for eyes?

BACKGROUND: Many side effects of combination therapy using pegylated interferon (IFN) and ribavirin for treatment of chronic hepatitis C virus (HCV) infection have been well described. Ocular complications are fairly common. Diabetes mellitus (DM) and systemic hypertension are possible suggested risk factors for development of these complications. PURPOSE: To determine the frequency of retinopathy and its risk factors in patients treated with combined pegylated IFN and ribavirin for chronic hepatitis C infection. METHODS: Eligible 98 patients for HCV treatment with pegylated IFN a-2a, a-2b, and ribavirin between October 2011 and March 2012 were included. All patients underwent a baseline full ophthalmological examination, and any visual complaints during treatment prompted a repeat eye examination. RESULTS: Out of the eligible 98 patients, 48 (48.78%) patients received pegylated IFN alpha-2a, and the other 50 (51.21%) patients were treated with pegylated IFN alpha-2b. Out of 98 patients, 21 (21.42%) had diabetes; 19 (19.38%) patients had hypertension and 16 (16.32%) patients had both diabetes; and hypertension. Only 8 patients (8.16%) had documented retinopathy [2 had DM; one had hypertension; 4 had both hypertension and diabetes; and one patient without DM or hypertension]. Univariate logistic regression analysis revealed that diabetic, hypertensive patients are at increased risk for development of IFN-associated retinopathy (IAR) (P=0.007, Odds ratio=6.5, 95% confidence interval=1.56-27. CONCLUSION: Retinopathy in chronic HCV-infected patients undergoing treatment with combination of pegylated IFN-alpha and ribavirin therapy appears to be relatively low, and treatment cessation is rarely needed. Diabetic, hypertensive patients are at increased risk for IAR and are recommended to be ophthalmologically followed-up.

Survivin expression in medulloblastoma: a possible marker for survival.

UNLABELLED: Medulloblastomas are highly invasive tumors which are generally disseminated at the time of diagnosis. High and continued morbidity and mortality have prompted the search for new biologic markers that might be used for targeted therapy to minimise treatment related side effects. In this work, we studied the positive expression of survivin in medulloblastoma and investigated its relation to clinical, pathologic data and survival. Tumor tissue specimens from 47 patients with medulloblastoma who underwent primary surgical treatment from June 2002 to June 2006 at the Mansoura university hospital, Egypt were collected. Paraffin sections of all samples were submitted for immunohistochemistry using anti-survivin antibody. The relation between the percentage of positive survivin cells with clinical, pathological and survival data was evaluated. RESULTS: In 47 cancer tissue specimens, one case large-cell-anaplastic (1.12 %), tweleve cases desmoplastic (25.53 %) and 34 cases classic medulloblastomas (72.34 %). The immunohistochemical expression of survivin was nulear with moderate intensity. It does not correlate with either age or sex. There was a significant negative correlation of survivin expression with survival (p < 0.001), where negative survivin immunostaining was associated with prolonged overall and disease free survival, while survivin expression was associated with shortened survival. CONCLUSION: Survivin expression correlate with the clinical outcome with poor prognosis and could be a potential predictive factor for recurrence or metastasis.

Impact of Hepatitis C Virus (HCV) infection on biomolecular markers influencing the pathogenesis of bladder cancer.

OBJECTIVE: The present study was designed to determine the possible impact of hepatitis C virus (HCV) infection on the expression of telomerase (TERT), retinoblastoma (RB1), E2F3, TP53, CDKN1A (p21) and fibroblast growth factor receptor- 3 (FGFR3) genes in patients with bladder cancer (BC). MATERIALS AND METHODS: 100 patients with bladder cancer (15 female and 85 male) were divided into 2 groups; Group I: 50 HCV negative subjects (age range 36-79), and Group II: 50 HCV positive subjects (age range 42-80). Expressions of the telomerase, retinoblastoma (Rb), E2F3, TP53 and FGFR3 genes were tested by immunohistochemistry and real time PCR in tumour tissues and healthy bladder tissues. Also, telomerase activity was assessed by telomeric repeats amplification protocol (TRAP). RESULTS: Bladder tumors associated with HCV infection were of high grade and invasive squamous cell carcinomas (SCCs). Expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as telomerase activity were significantly higher in bladder tissues of HCV-infected patients compared with bladder tissues of non infected patients (p<0.05). On the contrary, CDKN1A (p21) expression was significantly lower in bladder tissues of HCV-infected patients compared to bladder tissues of non infected patients (p<0.05). CONCLUSION: The expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as the activity of telomerase were significantly high in malignant bladder tissues associated with HCV infection. On the other hand, CDKN1A (p21) expression was low in bladder tissues of HCV-infected subjects. Moreover, there was a positive correlation between HCV infection and expression of telomerase, E2F3, TP53 and FGFR3. There was a negative correlation between HCV infection and expression of Rb and p21.