Impact of latent toxoplasmosis on the fertility indices of male rats.

Infertility is a prevalent condition affecting approximately 70 million people worldwide and male factor contributes to about fifty percent of the issues. Studies on infectious agents as a possible cause of infertility has become prominent in the past decade. Toxoplasma gondii has emerged as a prime candidate as it has been found in the reproductive organs and semen of males of many animal species and humans. The aim of this study is to assess the effect of latent toxoplasmosis on experimental rat fertility. Ninety Toxoplasma infected rat were used as the experimental group besides, thirty control naïve ones. Both groups were observed clinically. Weekly assessment of fertility indices starting from the 7th week post infection till the 12th week were done by recording rat body weight, weight of testes, semen analysis and histo-morphometric analysis of the testes. Toxoplasma infected rats exhibited significant gradual loss of body weight and the absolute weight of the testes. The sperm characteristic parameters including percentage of motile sperm, percentage of viable sperm and sperm concentration in Toxoplasma infected rats showed highly significant decrease throughout the observation period in comparison to the control group with recording highly significant increase in the percentage of abnormal sperm forms. Pathological insults in tests of the infected rat group were denoted. Our findings demonstrated that Toxoplasma gondii is accused for affecting male rat main reproductive parameters and is implicated in the male reproductive disorders.

Accuracy and Upgrading of CNB and BI-RADS Diagnoses Compared to Excision: A Clinicopathological-Radiological Correlation of Papillary Breast Lesions and Neoplasms.

BACKGROUND: Papillary breast lesions and neoplasms (PBLs/Ns) are diagnostically challenging lesions in both core needle biopsy (CNB) and radiology. AIM: To determine the accuracy and upgrade rate of CNB and BI-RADS diagnosis of PBLs/Ns compared to final excision diagnosis and the factors linked to upgrade. METHODS: The favored CNB diagnosis and BI-RADS category for 82 PBLs/Ns were assessed based on histopathology, myoepithelial marker immunohistochemistry, mammographic/ultrasonographic findings. The radiological findings were compared to the pathological diagnoses. The accuracies of CNB and BI-RADS were compared to the excision diagnosis of the corresponding PBLs/Ns. The upgrade rates to malignancy were evaluated for both CNB and BI-RADS. RESULTS: The presence of solid, irregular masses in breasts with composition A/B with calcification in radiology was significantly associated with the diagnosis of suspicious/malignant CNB, and malignant excision specimens (p<0.05). CNB was more accurate (90%), sensitive and specific with high positive and negative predictive values than BI-RADS. Combined CNB/BI-RADS accuracy was 90.2%. Overall upgrade rate came up to 9.8%. Upgrade rates to carcinoma were 7.3% for CNB and 8.5% for BI-RADS. Factors linked to upgrade were the age, lesion-size, BI-RADS category 4A and C, and histopathological/radiological discordance. All the upgraded PBLs/Ns were diagnosed as benign lesions in CNB with present/focally present myoepithelial diagnosis reflecting a sampling error. CONCLUSION: Up to 9.8% of PBLs/Ns diagnosed on CNB and BI-RADS undergo upgrading upon final excision, despite the high diagnostic accuracy. These evidences should be considered for final decision on whether to excise the lesion or not.

Fluconazole as Schistosoma mansoni cytochrome P450 inhibitor: In vivo murine experimental study.

Schistosomiasis is a chronic disease caused by blood flukes of the Schistosoma spp. New approaches against this morbid infection are needed. In this study, we investigated fluconazole (FLZ) as an inhibitor of Schistosoma mansoni cytochrome P450 (S. mansoni CYP450) enzyme at different life cycle stages. We compared FLZ (10 mg/kg for two days) effects when administrated early 5 days post-infection (dpi) (Early I) and 21 dpi (Early II) versus late administration 60 dpi on S. mansoni CYP450 gene expression. These different FLZ treatment regimens were evaluated in experimentally infected mice with S. mansoni. This study showed that administration of FLZ, whether early or late during schistosomal infection, resulted in significant inhibition of S. mansoni CYP450 expression in the adult stage (P < 0.001). Early exposure to FLZ during the first week of infection significantly decreased the number of schistosomula that reached the adult stage compared to the infected control group and resulted in significant inhibition of S. mansoni CYP450 expression (P < 0.001) in the adult stage. In the Early I group, the fewest number of eggs per liver tissue gram was recorded. Our data suggested that FLZ is a S. mansoni CYP450 gene expression inhibitor with greater effect on schistosomula stages.

Podoplanin expression in salivary gland carcinomas and its clinical significance. An immunohistochemical study.

Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland carcinomas (SGCs). Aim: the present study aimed to investigate the immunohistochemical expression of podoplanin in SGCs and to correlate its expression with the clinicopathological parameters and patients' survival. Forty-nine SGC cases were electronically selected. Demographic, clinical, laboratory, and survival data were reviewed and tabulated. Immunohistochemistry was performed using antipodoplanin. Cases were divided into low and high expression based on a scoring system. A score of 0 and 1 was considered low expression, while > 1 was considered high expression. Podoplanin high expression was seen in 46.9% of cases, and 53.1% of cases showed low expression. Significant statistical associations were seen between podoplanin expression and tumour grade ( p ≤ 0.001), tumour-nodal- metastasis (TNM) stage (p ≤ 0.001), tumour size (p ≤ 0.001), nodal metastasis (p ≤ 0.001), tumour type (p = 0.03), prognosis (p ≤ 0.001), and mortality (p ≤ 0.001). The overall survival and progression-free survival differed significantly in cases with high and low expression (p ≤ 0.001). Podoplanin overexpression might be a significant prognostic indicator for patients with SGCs, implicating that it is a potential therapeutic target to improve survival in these cancer patients.

Isolated Myeloperoxidase Immunohistochemical Expression in Bone Marrow Biopsy Depicts Clinical Outcomes in Adults with Typical B-Acute Lymphoblastic Leukemia.

INTRODUCTION: Recently, isolated myeloperoxidase expression (isoMPO) has been documented in B-acute lymphoblastic leukemia (B-ALL) and several contradictory studies addressed its clinical significance in pediatric patients. AIM: In this study, isoMPO was evaluated in bone marrow biopsies (BMB) from adults with B-ALL using immunohistochemistry (IHC) in relation to a number of risk-stratification factors and patients' outcomes. METHODS: Sixty B-ALL adult patients were selected upon electronic database search. Demographic, clinical, laboratory, therapy and survival data were reviewed and tabulated. Flowcytometry (FCM), histopathology and IHC available material were reviewed to confirm the diagnostic criteria according to our standard laboratory protocols. IHC was performed on BMB using antiMPO. Cases were divided into MPO+ve and MPO-ve based on a 3% blast cell staining threshold. RESULTS: Using IHC, 26.7% of B-ALLs were MPO+ve, in most of which ≥10% of blasts were stained. Among standard risk-stratification factors, isoMPO was associated with a mean WBC count above 30x109/L. MPO+ patients achieved therapeutic complete remission at lower rates and were more prone to progressive/refractory disease and relapse. There was a concordant expression of MPO in FCM and IHC. All of the aforementioned parameters reached the level of significance when compared to the MOP-ve group. Kaplan-Meier curves revealed a significantly lower survival probability for the MPO+ group than the MOP-ve one (p= 0.0066; Log-rank test) and also when separating MPO+ and -ve patients by gender (p= 0.0033; Log-rank test). CONCLUSION: isoMPO occur in a considerable percentage of B-ALL in adults contributing to misdiagnosis. It depicts poor outcomes and might be introduced as a B-ALL risk-stratification factor.
.

High FOXA1 immunohistochemical expression level associates with mucinous histology, favorable clinico-pathological prognostic parameters and survival advantage in epithelial ovarian cancer.

BACKGROUND: Forkhead box (FOX) A1 is a potential therapeutic biomarker that has been investigated in various human cancers. Limited data exist about FOXA1 biologic role in epithelial ovarian cancer (EOC). AIM: This study assessed FOXA1 immunohistochemical (IHC) expression and evaluated its association with clinico-pathological parameters in EOC including overall and disease-free survivals (OS, DFS) and patient's outcome. METHODS: Patient's socio-epidemiologic, clinical, radiological, laboratory, surgical, and follow-up data were collected. After histopathologic typing, grading and staging, FOXA1 IHC expression was scored in 98 EOC specimens. Clinico-pathological associations were investigated in high-and low-FOXA1 expression groups using appropriate statistical methods. Kaplan-Meier method was used for survival analysis. RESULTS: FOXA1 tumor cell nuclear staining was detected in 63.3% of EOC with weak, moderate and strong scores (28.6%, 12.2% and 22.5% respectively). Comparing high- and low-expression groups (34.7% and 65.3% respectively), high FOXA1 was associated with larger tumors, low mean serum CA-125, tumor histopathology (mucinous and low-grade serous), type I EOC, limited tumor's anatomical extent, absence of nodal or distant metastases and omental nodules, earlier FIGO stages, non-recurrent tumors and survival advantage with longer and OS and DFS (all p ≤ 0.05). Independent predictors of high FOXA1 expression included: omental nodules, tumor's anatomical extent and tumor's size (p ≤ 0.001, = 0.046 and = 0.023 respectively). CONCLUSION: FOXA1 is frequently expressed in EOC notably mucinous and low-grade serous carcinomas in association with favorable prognostic clinico-pathological parameters and longer OS and DFS. It likely has a suppressor function in EOC and could be recommended as a prognostic and therapeutic biomarker.

Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors.

Neutrophil extracellular traps (NETs) are incriminated in several immune and inflammatory diseases including ulcerative colitis (UC). Analysis of colonic tissues for NETs-related markers in UC carries prognostic and therapeutic implications. This work aims to evaluate the immunohistochemical (IHC) expression of NETs-associated-protein arginine deaminase 4 (PAD4) in colonic biopsies from UC patients in comparison to normal colon (NC). Association between PAD4 expression level and histopathologic grade, patient's therapeutic response and other clinicopathological prognostic predictors in UC are determined. This cohort study included biopsies from 42 UC patients and 11 NC controls. Clinicopathological data including patient's age at diagnosis, gender, presenting symptoms, anatomical disease extent, extra-intestinal manifestations, type and response to therapy and surgical interventions were recorded and tabulated. Histopathological grading of disease activity and associated epithelial changes were assessed. PAD4 immunostaining was conducted using Horseradish Peroxidase technique and scored semiquantitatively considering intensity and percentage of nuclear staining of lamina propria inflammatory cells. Appropriate statistical tests were applied. Anti-PAD4 was localized mainly in the nuclei of lamina propria infiltrating neutrophils. It was expressed more significantly in UC (95.2 %) compared to NC (p 0.001). Increased PAD4 expression level was significantly associated with increasing histopathologic grade, anatomical disease extent, lacking response to therapy and subjection to radical surgery (p:0.001, = 0.038, 0.046, 0.046 respectively). Age, gender, presenting symptoms, extra-intestinal manifestations and epithelial changes showed insignificant associations. This study characterizes a subset of UC patients with high histopathological grade of activity, pancolonic involvement, strong/moderate PAD4 expression levels and who are unresponsive to routine medical therapeutic regimens rendering them candidates for radical surgery. In conjunction with histopathological grading, IHC evaluation of PAD4 in UC is recommended to guide patient's selection for targeted therapy using the novel-discovered selective PAD4 inhibitors.