Background: Microscopic colitis (MC) is a recognized cause of chronic diarrhea and is often underestimated when a colonoscopy appears normal. This study aims to accurately diagnose chronic diarrhea through histopathological examination of colonoscopic mucosal biopsies and assess the prevalence of microscopic colitis and the diagnostic value of biomarkers. Methods: A hospital-based cohort study was conducted on 116 patients with chronic diarrhea. Colonoscopies and colonic mucosal biopsies were performed and analyzed, along with various tests including fecal calprotectin (FC) level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), stool analysis, routine laboratory tests, and clinical data related to nocturnal diarrhea, abdominal pain, and unexplained weight loss. Results: In the study group, 32.8% had MC, with 25.9% having lymphocytic colitis (LC) and 6.9% having collagenous colitis (CC). Patients with MC had significantly higher FC, ESR, and CRP levels than those without colitis (p < 0.001). Factors associated with MC included nocturnal diarrhea (OR = 4.26; 95% CI [1.64–11.08]; p-value = 0.003) and abdominal pain (OR = 4.62; 95% CI [1.85–11.54]; p-value = 0.001). ESR at a cutoff >14 mm/h and FC at a cutoff >64 mcg/g showed excellent validity in diagnosing MC with area under the curve (AUC) values of 0.94 and 0.97, respectively. Conclusions: Microscopic colitis, particularly LC-type, is not an uncommon cause of chronic diarrhea, especially when accompanied by symptoms such as abdominal pain and nocturnal diarrhea, warranting further investigation, including inflammatory markers and colonic biopsy. Inflammatory markers can be useful in diagnosing MC with proper values and approaches; however, further studies are needed.

Background: Gliomas are considered the most prevalent malignancies of the central nervous system. These tumors are diffusely infiltrative and behave destructively toward the nearby brain tissue. Based on histological grading, gliomas were previously categorized. Histopathology and molecular characteristics are now included in the classification of brain tumors. Glioma prognosis can be predicted, which allows patients to choose an effective course of treatment. It is crucial to look for fresh prognostic indicators in cancer biopsy samples that might indicate prognosis. IDH mutation is a crucial component for the subclass categorization of diffuse gliomas and is just one of many molecular parameters. Significantly, all forms of IDH-mutant gliomas seem to have much better prognosis than malignant diffuse IDH wild type (IDH-wt) gliomas such as glioblastoma. Conclusion: We concluded that IDH1 and MMR genes immunohistochemical expression could help in the prediction of gliomas outcome. More large-scale multicenter investigations are needed to back up our findings.

Aim: PI3K/AKT/GSK-30/0-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract that has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z.Main methods: Twenty-four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells.Key findings: Parthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-30, P/total GSK-30, and n0-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth.Significance: Our findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-30/n0-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin and reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.

BACKGROUND:Tacrolimus is a calcineurin inhibitor widely used for immunological disorders. However, there is significant controversy regarding its effect on the liver. The present study was conducted to evaluate the anticancer effects of tacrolimus on an induced murine hepatocellular carcinoma (HCC) model and its possible hepatotoxicity at standard therapeutic doses.METHODS:Fifty-four male mice were divided into five groups: a control healthy group, control HCC group, tacrolimus-treated group, doxorubicin (DOXO)-treated group, and combined tacrolimus- and DOXO-treated group. The activity of liver enzymes, including alkaline phosphatase, gamma- glutamyl transferase, lactate dehydrogenase, alanine transaminase, and aspartate transaminase, was determined. Serum vascular endothelial growth factor (VEGF) was measured using an enzyme- linked immunosorbent assay. A quantitative real time- polymerase chain reaction (qRTPCR) was conducted to measure the expression of proliferating cell nuclear antigen (PCNA), Bax, and p53 mRNA. Immunohistochemical staining for cyclin D1 and VEGF was performed.RESULTS:Mice that received combined treatment with tacrolimus and DOXO exhibited the best improvement in all parameters when compared with the groups that received DOXO or tacrolimus alone (p < 0.001).CONCLUSION:The combination of DOXO and tacrolimus was more effective in the management of HCC compared with either agent alone. This improvement was detected by the reduction of liver enzymes and the improvement of the histopathological profile. The involved mechanisms included significant apoptosis induction demonstrated by upregulation of bax along with a reduction in angiogenesis demonstrated by downregulation of VEGF. This was accompanied by inhibition of cell cycle progression mediated by upregulated p53 and downregulated PCNA and cyclin D1.

Introduction:We aimed to evaluate the outcome of treatment with docetaxel plus androgen deprivation therapy (ADT) in newly diagnosed patients with metastatic high tumor burden hormone-sensitive prostate cancer (mHSPC) and correlated the outcome with hemoglobin, albumin, lymphocyte and platelets (HALP) score. Material and methods:Six cycles of docetaxel plus ADT were given to 50 patients with high burden mHSPC. Baseline HALP score was calculated and disease outcome was tabulated; moreover, the prognostic impact of the HALP score in response to treatment and survival was calculated. Results:We found a significant association between high HALP score and response to treatment where a higher rate of complete response occurred in patients with a high HALP score than in patients with a low HALP score (53.8% vs. 5.4% respectively, p-value = 0.001). Patients with ≥ 12-month-duration castration-resistant prostate cancer (CRPC) had a significantly higher HALP score compared to patients with a lower HALP score (84.6% vs. 35.1% respectively, p-value = 0.002); 18-month-duration CRPC-free survival was significantly greater in patients with higher HALP score than patients with a lower HALP score (23.1% and 5.4% respectively, p-value < 0.001). Patients with a high HALP score had insignificantly higher mean overall survival than patients with a low HALP score (mean: 22.91 and 20.66 months respectively, p-value = 0.230). Conclusions:Our results confirmed the benefits of treatment with docetaxel plus ADT in high-burden mHSPC with accepted tolerance. HALP score was found to be an independent predictive factor for benefit from therapy; we can apply it as an easy way to stratify patients for appropriate selection of treatment for better tolerance and outcome.

Pancreatic cancer (PC), a lethal condition with poor prognosis and aggressive behavior, ranks fourth among the most common causes of cancer-related mortality as early diagnosis of PC is so difficult, consequently, most cases at the time of initial diagnosis already harbor metastasis. The early detection and survival of PC cases depend mainly on the improvement of diagnostic approaches. This review spots light on the role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a minimally invasive method in the early diagnosis of PC and differentiation between different pancreatic lesions. The discovery of new diagnostic and prognostic markers for PC will raise the accuracy of proper diagnosis and in turn, patients will gain better survival and prognosis. Insulin-like growth factor II mRNA binding protein3 (IMP3) is overexpressed in several malignant tumors, including pancreatic cancer, which may raise its role in diagnosis and prognosis as well as its therapeutic benefit for PC.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype, where no effective therapies have been established for it. Searching for therapeutic targets for TNBC patients is the aim of the current research. Poly adenosine diphosphate ribose polymerase (PARP1) inhibitors are promising antitumor therapy that have a high potency in BRCA1-deficient breast cancers. Materials and methods: Forty TNBC patients who received neoadjuvant chemotherapy (NAC) were enrolled in this study, and evaluated for PARP1, BRCA1, and Androgen receptor (AR) immunohistochemical expression before and after receiving NAC. Data of patients' clinical and pathological responses to the chemotherapy were collected and finally analyzed. Results: The immunohistochemical results revealed 10 cases (25%) positive for AR, while 18 cases (45%) and 22 cases (55%) expressed PARP1 at low and high levels, respectively. Twelve cases (30%) and 28 cases (70%) expressed BRCA1 at low and high levels, respectively. There was a significant difference between PARP1 expression in normal and malignant tissues (P < 0.001). Higher PARP1 expression was correlated with a better overall clinical response (OAR) and pathological complete response (pCR) (P = 0.018, 0.01 respectively). Co-expression of both PARP1 & BRCA1 was correlated with OAR and pCR. Chemotherapy decreases PARP1 protein levels in matched patient samples (P = 0.015). Positive AR expression was correlated with BRCA1 overexpression. Conclusion: PARP1 is highly expressed in TNBC with a better OAR and pCR especially in cases with high BRCA1, so it might be considered as a therapeutic target for this risky group. (c) 2021 SESPM. Published by Elsevier Espana, S.L.U. All rights reserved.

Introduction: Although the molecular profile of the breast provides prognostic indicators, risk stratification in breast cancer continues to be a challenge. Therefore, it is mandatory to seek new prognostic markers that could aid the early diagnosis of potential metastases in biopsy samples from breast cancer; among these are increased Snail-1 and Claudin-4 expression. Objectives: The aim of this study was to analyze the correlation between Snail-1 and Claudin-4 with other clinical-pathological parameters and distinct molecular subtypes. Methods: This study included 110 patients with invasive ductal carcinoma from 2009 to January 2015. Snail-1 and Claudin-4 were assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissue blocks and the data were correlated with clinical-pathological data and survival. Results: A total of 65 patients (68.2%) were positive for Snail-1 and 85 patients (77.3%) were positive for Claudin-4. High Snail-1 and high Claudin-4 were detected in high-grade tumors and were associated with lymphovascular infiltration and lymph node metastases (p < 0.001 for each). There was a highly significant correlation between Snail-1, Claudin-4 expression and the molecular subtype of breast cancer (p < 0.001), with higher Snail-1 expression in TNBC and Her 2/neu cases (p = 0.001). Claudina-4 expression in the Her2/neu enriched subtype, Snail-1-positivity and high Claudin-4 expression were associated with recurrence (p = 0.001; 0.004 respectively) among the cases studied. Snail-1 and Claudin-4 were inversely related with overall survival (p = 0.001) and disease-free survival (p = 0.001). Conclusion: High Snail-1 and Claudin-4 levels were associated with adverse outcomes in patients with breast cancer.

Background Poor prognosis and short survival of patients harboring pancreatic cancer emerge how advanced disease it is. In a trial to achieve the earliest and most accurate diagnosis to manage this progressive disease, we proposed that using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with an adjuvant diagnostic immunohistochemical marker would give better diagnostic results. IMP3 has gained recently wide attention, as many studies found that IMP3 has not only diagnostic but also prognostic role in different types of malignancies. Aim of the Study This prospective work is to assess the diagnostic role of EUS-FNA combined with the immunohistochemical expression of IMP3 on different benign and malignant pancreatic lesions. Material and Method The included pancreatic lesions ( n = 140) were obtained by EUS-FNA technique and stained for IMP3 immunohistochemically. Paraffin blocks from patients who underwent excision ( n = 92) or core biopsies ( n = 48) were performed for confirming diagnosis. Results The combined method for diagnosis showed that IMP3 was positive in 78.7%, 91.7%, 100% PAC, mucinous neoplasm with high grade dysplasia, and IPMN with high grade dysplasia, respectively, while almost all benign lesions showed negative IMP3. Also, this method showed sensitivity (78.26%), specificity (95.83%), and accuracy (84.3%). Conclusion EUS-FNA cytology with IMP3 could be a reliable diagnostic tool especially for assessment of malignant pancreatic lesions.

OBJECTIVES:Background: Tumor-infiltrating lymphocytes (TILs) reflect the antitumor response of the host. This study aimed to assess the value of TILs in predicting pathological response after neoadjuvant chemotherapy (NAC) and survival outcomes in patients with triple-negative breast cancer (TNBC).METHODS:A retrospective analysis conducted between February 2012 and December 2015. Patients with stage I, II, and III TNBC patients were enrolled. TILs were assessed in haematoxylin and eosin-stained sections from true cut needle biopsies before NAC. According to international TILs working group, we had three groups; low (0-10%), intermediate (11-59%), and high TILs (= 60%).RESULTS:A total of 159 patients was included, 56% were premenopausal and 76.1% were less than 60 years. The main bulk of patients had histological grade III, high Ki 67, and high TILs (74.2%, 84.3%, and 72.3%), respectively. The pre-treatment high TILs was significantly correlated with high Ki-67 (p = 0.001), pCR (p<0.001), and late relapse (p<0.001). Other clinico-pathological features such as age, menopausal status, tumor size, histological grade, lymph node involvement and lympho-vascular invasion weren't significantly correlated with TILs levels. 71.3% of enrolled patients having high TILs achieved pCR, vs 27.8% in the intermediate group and 30.8% in low group. After a median follow-up of 45.3 months, patients with high TILs were significantly associated with longer DFS and OS as compared to intermediate and low TILs (27.2 vs 15.9 vs11.4 months for DFS and 70.2 vs 34.3 vs 27.6 months for OS)p<0.001).CONCLUSIONS:Pre-treatment level of TILs had a predictive and prognostic value in TNBC patients receiving NAC. TILs may be integrated into the basic laboratory for TNBC prognostication as a credible biomarker.

Introduction: Immune system plays an important role in behavior of cancer. Breast cancer and its stroma display high levels of immune-cell infiltrates (tumor-infiltrating lymphocytes TILs). Programmed cell death-ligand 1 (PD-L1) is one key inhibitor mechanism for TILs. Potential of TILs and PD-L1 as predictive factors for chemotherapy response in breast cancer is a promising field of study. The aim of this work is to investigate the correlation of PD-L1, TILs and pathologic response following neoadjuvant chemotherapy (NAC) in breast cancer patients and effect of NAC on PD-L1 expression and TILs in residual tumor mass.Methods: Thirty patients with invasive duct carcinoma diagnosed by core biopsy and received NAC were enrolled in this prospective study from November 2018 to October 2020. PD-L1 expres-sion was evaluated by immunohistochemistry and relates this to TILs, clinical characteristics, and response to neoadjuvant chemotherapy and then re-evaluated in residual masses after surgery.Results: PD-L1 expression was observed in 40% of cases in the tumor cells. High stromal TILs were detected in 46.7%. Also, 64.3% and 58.3% of patients expressed TILs and PD-L1 (respec-tively) in their core biopsies gained complete clinical and pathologic responses with significant difference (p value < 0.001; 0.013). High PD-L1 expression and high TILs were observed in triple negative breast cancer (TNBC) and Her2 enriched cases but without significant difference.Conclusion: High TILs and PD-L1 are associated with complete clinical and pathologic responses in breast cancer patients who receiving NAC.(c) 2021 SESPM. Published by Elsevier Espan similar to a, S.L.U. All rights reserved.

Patients with breast cancer are appropriate candidates for neoadjuvant chemotherapy (NAC) to facilitate conservative surgery. The chemotherapeutic agents may exert their action by inducing the anti-tumor immune response. This study aimed to evaluate the tumor immune microenvironment including PD-L1, Foxp3+ Tregs, and TILs count in early stages TNBC patients (stage T1, T2) before and after neoadjuvant chemotherapy and their correlation with the clinical and pathological response. Fifty patients of TNBC patients were enrolled in this study; all of them received neoadjuvant chemotherapy. TILs count, Foxp3+ Tregs, and PD-L1 immunohistochemical expression were investigated in all cases before NAC and then evaluated in residual masses after surgery. Data on the clinical and pathological response to NAC were collected and then statistically analyzed. PDL1 expression was detected in 24% of all studied cases, all of them were node-positive (P < 0.002); while Foxp3+ Tregs expressed in 50% and high TILs in 28%. Pathological complete response (pCR) was achieved in 40% of patients and was associated with high TILs expression (P < 0.02) and absence of Foxp3+ Tregs and PDL1 (P < 0.001 for each). In conclusion, Pathologic complete response to NAC was associated with the immunological profile of TNBC. High TILs expression with concomitant decreased PD-L1 expression and low FOXP3+ Tregs is associated with favorable tumor prognosis. Combined therapeutic approaches aiming to PD-L1 block and Tregs depletion might improve treatment efficacy in TNBC.

Toxoplasmosis is one of the widest spread parasitic infections which is caused by Toxoplasma gondii protozoon. Many experimental studies have evaluated the effect of aminoguanidine upon parasitic load and inflammatory process. However, few reports have illustrated the impact of combining aminoguanidine with spiramycin in the treatment of toxoplasmosis. Therefore, our study aimed to explore the possible effects of spiramycin used alone and combined with aminoguanidine against the avirulent (ME49) Toxoplasma gondii strain in experimental toxoplasmosis. Fifty-five Swiss albino mice were included in the study and were divided into five groups: (GI): non-infected control group; (GII): infected untreated control group; (GIII): infected- spiramycin treated group; (GIV): infected-aminoguanidine treated group; (GV): infected and received combination of spiramycin and aminoguanidine. Obtained results exhibited a significant increase in brain cysts numbers in aminoguanidine treated groups compared to infected untreated control groups. Histopathological studies denoted that combination between spiramycin and aminoguanidine improved the pathological features only in liver and heart tissues of the studied groups. Moreover, it was noticed that spiramycin administered alone had no effect on nitric oxide expression, whereas its combination with aminoguanidine had an inhibitory effect on inducible nitric oxide synthase enzyme in brain, liver and heart tissues of different study groups. In conclusion, the combination of spiramycin and aminoguanidine significantly reduced the parasitic burden, yet, it failed to resolve the pathological sequels in brain tissues of Toxoplasma gondii infected mice.

BACKGROUND:There is growing evidence that the response to chemotherapy may be affected by Androgen Receptor (AR) expression suggesting that triple-negative breast cancers (TNBC) AR+ and quadruple negative breast cancer (QNBC) subtypes may have different diseases behavior.METHODOLOGY:We retrospectively estimated the predictive value of the AR expression in stage II and stage III TNBC patients treated with neoadjuvant chemotherapy (NAC) and correlated with the rate of pathological response (pCR).RESULTS:Of 89 TNBC patients, 29 patients (32.6%) were TNBC AR+ and 60 patients (67.4) were QNBC. Most of the patients were less than 60 years old. Of note, approximately 62% in the QNBC group were less than 40 years old compared with 39 % in the TNBC AR+ group. The Ki-67 expression was higher in the QNBC in comparison with TNBC AR+ being 86.7% and 65.5%, respectively. QNBC subgroup showed higher rates of pCR compared with TNBC; 60% and 24%, respectively. Higher Ki-67 expression, higher grade, and lymph node involvement were statistically significantly correlated with the rate of pCR in the QNBC group (p=0.02, p=0.04, and p=0.03, respectively). In contrast, no significant association was observed between pCR and clinical-pathological features in the TNBC AR+ group.CONCLUSION:Our results suggested that the AR expression in TNBC may be applied as a predictive marker for NAC. TNBC AR+ had a lower rate of pCR compared with QNBC, suggesting that this subtype may have a partial chemoresistance.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease which has an unpredictable risk of progression to muscle-invasive bladder cancer (MIBC). The selection of patients who may benefit from early radical intervention is a challenge. To define the useful prognostic markers for progression, we analyzed the immunohistochemical expression of fatty acid synthase (FASN), Her2/neu, and E2F1 in 60 cases of NMIBC who underwent TURBT and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Their predicting role for tumor recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. High FASN expression was observed in 56.7% (34/60) of NMIBC cases, and FASN expression was significantly associated with the tumor size, grade, and tumor stage (p = 0.003, p < 0.001, p < 0.0001 respectively). Positive Her2/neu was noted in 18.3% (11/60) of the cases, and its expression was significantly associated with the tumor size, histologic grade, and tumor stage (p = 0.001, p = 0.002, p = 0.011 respectively). High E2F1 expression was detected in 40% of the cases, and it was associated with tumor size, histologic grade, and tumor stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high FASN, positive Her2/neu, and high E2F1 expression exhibited a potent relation with tumor progression, shorter RFS, and poor PFS. Conclusions: High FASN, Her2/neu, and E2F1 are considered as adverse prognostic factors of tumor recurrence and progression in NMIBC and these patients should be followed carefully. Therefore, we suggest that FASN, Her2/neu, and E2F1 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients.

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries andclinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to checkthe possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL)instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequentimprovement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC andBCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathologicalfeatures and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detectedin 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL andDHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high InternationalPrognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DELand DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their proteinexpression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated withDEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significantcorrelation between protein overexpression and gene rearrangement may open the door for the possibility to use IHCinstead of RT-PCR in developing countries.

Although toxoplasmosis is worldwide spread, the available medications have low efficacy and high toxicity.This research aims to study the effect of artesunate loaded nanofiber and its combination with spiramycin as an alternative treatment for murine toxoplasmosis.Two groups of male Swiss albino male mice were used for acute and chronic phases of Toxoplasma infection.Mice were infected with 100 viable tachyzoites of RH type-1 virulent strain intraperitoneally and orally with 100 viable tissue cysts of ME 49 Toxoplasma strain.They were orally treated with the drugs.The doses of the drug were administered from the first to the fifth day post-infection in acute infection and after six weeks in chronic one.Tachyzoites in peritoneum and cysts burden in the brain were subjected for parasitological analysis, Histopathological study and ultrastructural study by Scanning Electron microscopy (SEM).Liver enzymes analysis was done for biochemical assessment drugs.The combination artesunate loaded nanofiber and spiramycin gave the least number of tachyzoites ( 139) and brain tissue cysts (125) with the highest percentage reductions (85%, 84.3%) consequently.SEM revealed a reduction in the size of tachyzoites with surface irregularity and abnormal protrusions in the treated group with the drug combination.Brain tissue cyst of the same group showed a distortion in the shape and size with patches all over the surface.

Cryptosporidium species the Apicomplexa protozoan parasites, causing diarrheal disease in man and animals, due to the lack of a licensed vaccine and resistance to the available effective therapy.This study explored the curative and the prophylactic effect of the cinnamon and ginger methanolic extracts separately and combined with nanazoxide on the experimentally infected mice with Cryptosporidium.Ninety Swiss albino mice, weight of 23-25gm, aged 7-8 weeks were divided into nine groups to assess the therapeutic and the prophylactic effect of cinnamon and ginger methanolic extracts separately then combined with nanazoxide.The result was assessed parasitologically, histopathlogically and by TEM.The best efficacy was three weeks post infection in all groups.Therapeutic effect of ginger was better than cinnamon extract, but combined ginger and nanazoxide gave the least oocyst shedding.The prophylactic dose of ginger and cinnamon methanolic extracts showed marked decrease in oocysts shedding and ginger was the best.Histopathological sections showed immune cells infiltration with a decrease in number of tissue parasite that was absent in the prophylactic groups given ginger extract.The results were confirmed by transmission electron microscopy explored a great improvement in the small intestinal brush border of the same groups.

Background: Classical β-blockers usually reduce renal blood flow thus, worsening renal function in hypertensive patients with renal impairment. However, vasodilator b-blockers with biased agonist activity on b-arrestin, at least theoretically, could protect the kidney against ischemia. Objectives: To compare the effect of prophylactic administration of carvedilol, nebivolol, nadolol on the kidneys. Materials & Methods: Rats were divided into five groups: Group1: sham-operated; Group2: Untreated hypertensive; Group3: Carvedilol pre-treated; Group4: Nebivolol pre-treated; Group5: Nadolol pre-treated. MABP, serum urea, creatinine, renal level of TNFα, BAX and pERK1/2 to non-pERK1/2 ratio were measured, besides renal histopathology and Bax immunohistochemistry. Results: In carvedilol and nebivolol groups, MABP, Bax, TNFα and pERK1/2 to non-pERK1/2 ratio were not only significantly (P<0.05) lower than that of the untreated group; but also, not significantly different from that of the sham; except significantly higher pERK1/2 to non-pERK1/2 ratio. In the nadolol pre-treated rats, MABP and the pERK1/2 to non-pERK1/2 ratio were significantly lower than that of the untreated hypertensive rats, however, they were significantly higher than that of the carvedilol, nebivolol pre-treated groups and the sham-operated group. Furthermore, Bax and TNFα were not significantly different from that of the untreated hypertensive group; in the meantime, they were significantly higher compared to sham, carvedilol and nebivolol pretreated groups. Serum urea& creatinine levels were significantly higher in nadolol pre-treated group compared to other groups. Conclusion: Carvedilol and nebivolol have renal protective effect which is nearly equal in contrast to the deterioration caused by nadolol.