Fructose improves titanium dioxide nanoparticles induced alterations in developmental competence of mouse oocytes.

AIMS: We investigated the effects of intraperitoneal injections of titanium dioxide nanoparticles (TiO2 NPs, 100 mg/kg) for 5 consecutive days on the developmental competence of murine oocytes. Furthermore, study the effects of TiO2 NPs on antioxidant and oxidative stress biomarkers, as well as their effects on expression of apoptotic and hypoxia inducing factor-1α (HIF1A) protein translation. Moreover, the possible ameliorating effects of intraperitoneal injections of fructose (2.75 mM/ml) was examined. MATERIALS AND METHODS: Thirty sexually mature (8-12 weeks old; ~ 25 g body weight) female mice were used for the current study. The female mice were assigned randomly to three treatment groups: Group1 (G1) mice were injected intraperitoneal (ip) with deionized water for 5 consecutive days; Group 2 (G2) mice were injected ip with TiO2 NPs (100 mg/kg BW) for 5 consecutive days; Group 3 (G3) mice were injected ip with TiO2 NPs (100 mg/kg BW + fructose (2.75 mM) for 5 consecutive days. RESULTS: Nano-titanium significantly decreased expression of GSH, GPx, and NO, expression of MDA and TAC increased. The rates of MI, MII, GVBD and degenerated oocytes were significantly less for nano-titanium treated mice, but the rate of activated oocytes was significantly greater than those in control oocytes. TiO2 NPs significantly increased expression of apoptotic genes (BAX, Caspase 3 and P53) and HIF1A. Intraperitoneal injection of fructose (2.75 mM/kg) significantly alleviated the detrimental effects of TiO2 NPs. Transmission electron microscopy indicated that fructose mitigated adverse effects of TiO2 NPs to alter the cell surface of murine oocytes. CONCLUSION: Results of this study suggest that the i/p infusion of fructose for consecutive 5 days enhances development of murine oocytes and decreases toxic effects of TiO2 NPs through positive effects on oxidative and antioxidant biomarkers in cumulus-oocyte complexes and effects to inhibit TiO2-induced increases in expression of apoptotic and hypoxia inducing factors.

Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study.

BACKGROUND: Screening of ß thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of ß thalassemia carriers and iron deficiency anemia among relatives of ß thalassemia patients in Mid Delta, Egypt. METHODS: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with ß thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. RESULTS: The total prevalence of iron deficiency anemia among close relatives of confirmed ß thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al-Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al-Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). ß thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). CONCLUSION: More than one-third of relatives of patients with ß thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with ß thalassemia in Egypt.

The interrelation between lipid profile in chronic HCV patients and their response to antiviral agents.

OBJECTIVES: This study aims to assess the changes of lipid profile in chronic HCV patients; before, during, and after treatment with DAAs and their association with treatment response. METHODS: 301 chronic HCV patients who received SOF-based therapy were included. Serum lipid profile was assessed at different check points; baseline, 6 weeks on treatment, end of treatment (EOT) and 12 weeks after EOT; and compared between SVR and non-SVR groups. RESULTS: SVR group had significantly higher baseline lipid parameters compared to non-SVR group with significant increase in lipid parameters at different time points apart from HDL-C. Non-SVR group showed non-significant change in lipid parameters apart from LDL-C. On week6 on treatment, cholesterol level > 125 mg/dl was 92.8% sensitive, 97.3% specific with 95.5% NPV, and AUC of 0.989 in prediction of SVR. Similarly, LDL > 57 mg/dl was 83.7% sensitive, 100% specific with 93.3%, NPV and AUC of 0.952. Baseline cholesterol and LDL were significantly associated with SVR. CONCLUSION: Higher baseline lipid parameters and their further elevation starting from week 6 on treatment are good predictors of SVR in HCV patients. Successful HCV therapy with DAAs is associated with a significant increase in lipid parameters.

Study of Serum Soluble Programmed Death Ligand 1 as a Prognostic Factor in Hepatocellular Carcinoma in Egyptian Patients.

BACKGROUND: The expression of programmed cell death ligands on tumor cells has a role in the suppression of antitumor immunity, resulting in tumor immune evasion. OBJECTIVE: In this study, we evaluated the prognostic value of the soluble form of programmed death-ligand1 (sPD-L1) in Egyptian hepatocellular carcinoma (HCC) patients. METHODS: This prospective cohort study was performed between November 2016 to November 2018 on 85 individuals (25 HCC patients, 25 HCC with vascular invasion and/or extrahepatic metastasis, 25 patients with liver cirrhosis, 10 healthy controls). The levels of sPD-L1 were determined in all subjects and compared in different groups and stages of cirrhosis and HCC. The association between sPD-L1 levels and overall survival (OS) was assessed. RESULTS: Significant statistical difference in sPD-L1 was detected between different study groups. The cut-off value for normal sPD-L1 was defined by high sPD-L1 levels determined in a healthy control cohort. It was 2.522 ng/ml. In HCC patients, cut-off value was 7.42 ng/ml (sensitivity 88%, specificity 100%). In HCC with vascular invasion or metastasis, cut-off value was 9.62 ng/ml (sensitivity 88%, specificity 88%). Patients with high serum sPD-L1 or serum bilirubin concentrations had an increased risk of mortality. CONCLUSION: High sPD-L1 level could be a possible prognostic indicator for a poor outcome in liver cirrhosis and HCC patients. The predictive value of sPD-L1 levels for a successful anti- PD1/PD-L1 therapy should be investigated in the future.

Reuse of Biopsy Forceps may be Associated with Risk of Transmission of HCV in Egyptian Patients Undergoing Gastrointestinal Endoscopy.

BACKGROUND AND AIMS: Hepatitis viruses are not transmitted via gastrointestinal endoscopy except if there are any mistakes in sterilization and disinfection of the endoscope that disrupt the infection control measures. So we aimed to measure the risk of transmitting HCV by GI endoscopy at department of Tropical Medicine and infectious Diseases, in a major University hospital in Egypt. METHODS: Our study was conducted on four hundred patients with exclusion of those with HCV, HBV, and/or HIV positive antibodies. An ethical committee approval and a given consent were taken prior to enrollment on the study. Our patients are grouped into the following; 100 patients undergoing upper GI endoscopy without biopsy as group I; 100 patients undergoing upper GI endoscopy with biopsy as group II; 100 patients undergoing lower GI endoscopy without biopsy as group III and 100 patients undergoing lower GI endoscopy with biopsy as group IV. HCV antibodies were done 3 months after endoscopy with exclusion of other risks of HCV infection by a detailed questionnaire. RESULTS: Only one case was reported positive after 3 months of procedure; it was after colonoscopy with biopsy using reusable forceps. CONCLUSIONS: Strict infection control measures of the GI endoscopes despite being effective in preventing HCV transmission, the reuse of disinfected biopsy forceps may be associated with a risk of transmission. So, we recommend using disposable forceps for every patient to omit the risk of HCV transmission during endoscopy.

Copeptin as a novel marker predicting prognosis of liver cirrhosis and its major complications.

OBJECTIVES: The aim of the work was to assess the level of copeptin as a surrogate marker predicting the severity of liver diseases and its major complications. PATIENTS AND METHODS: This was a cross-sectional study that included 40 patients and 10 controls and was performed in Tanta University Hospital between June 2016 and November 2016. The studied cases were divided into five groups: group I (10 patients): compensated cirrhosis; group II (10 patients): cirrhosis with gastrointestinal hemorrhage due to portal hypertension; group III (10 patients): cirrhosis with hepatorenal syndrome; group IV (10 patients): cirrhosis with liver cell failure; and group V (10 controls): normal healthy individuals. RESULTS: Regarding serum copeptin in the studied groups, copeptin showed a significant decrease in group I vs group II' group I vs group III, and group I vs group IV; and there was a significant increase in group II vs group III' group II vs group IV' group II vs control' group III vs control, and group IV vs control. No significance was detected between group I vs control and group III vs group IV. CONCLUSIONS: Copeptin is a novel marker for the determination of prognosis of liver cirrhosis. There is significant association between serum level of copeptin and complications of liver cirrhosis.

Diagnostic Value of Glypican-3 for Hepatocellular Carcinomas

Background: Hepatocellular carcinoma (HCC) is a common and dangerous malignancy in many parts of the world, and especially in Egypt. Early diagnosis is the most important step in successful HCC management. However most cases are detected at late stage making effective intervention impossible. Aim: The aim of this study was to evaluate the potential of Glypican-3 (GPC-3) to aid in diagnosis of HCC, especially in patients with low serum alpha-fetoprotein (AFP). Subjects and methods: Serum GPC-3 was assessed by flow-cytometry and serum AFP by enzyme-linked immunosorbent assay (ELISA) in 40 HCC patients with AFP< 400ug\l. (GI), 40 HCC patients with AFP> 400ug\l. (GII) and 20 healthy controls (GIII). Results: GPC-3 was found to be significantly elevated in HCC as compared to healthy subjects (GI 38.2±22. 5, GII 50.2±22.6, and GIII 2.24±1.19), with sensitivities of 85% for GI and 84% for GII and specificities of 95% for GI and 92% for GII. AFP showed respective sensitivities of 50% and 79%, and specificities of 80% and 90%, for HCC diagnosis. The combination of GPC-3 with AFP achieved the highest sensitivity (98.5%) and specificity (97.8%). Conclusion: Serum GPC-3 has a better sensitivity than AFP for the diagnosis of HCC. Combination of two markers appears warranted for greatest accuracy.

Role of Serum Soluble CD163 in the Diagnosis, Risk of Bleeding, and Prognosis of Gastro-Esophageal Varices in Cirrhotic Patients.

Research is continuous for noninvasive tools for the prediction of portal hypertension than upper gastrointestinal endoscopy. Serum sCD163 correlates with hepatic venous pressure gradient, aiding in the prediction of portal hypertension. We aimed at investigating the role of sCD163 in the prediction of the presence and size of varices as well as a stratification tool for surveillance or prophylaxis by assessment of prognosis and risk of bleeding. Two hundred forty-three cirrhotic patients were divided into 3 groups: group I: no varices, group II: small-sized varices, and group III: medium-sized and large-sized varices. Serum sCD163 levels were assessed and correlated with abdominal ultrasound and laboratory investigations. Follow-up for 1 year was conducted to assess the risk of bleeding, and band ligation was performed for significant varices with follow-up of obliteration. sCD163 levels were significantly higher in patients with varices requiring prophylactic interventions (P = 0.03) and in large varices (P = 0.012), patients at risk of bleeding (P = 0.04), and the bleeder patients (P = 0.001). No relationship between the sCD163 levels and the rate of variceal obliteration was reported. sCD163 levels were positively correlated with the Child score (P = 0.05), the portal vein diameter (P = 0.02), and the splenic size (P = 0.04). Although sCD163 level cannot predict the development of varices, it serves as a good predictor for the detection of size of varices (large varices), the need of prophylactic interventions, and risk of variceal bleeding. sCD163 level is a helpful indicator with the progression of cirrhosis and portal hypertension.

Progesterone suppresses interferon signaling by repressing TLR-7 and MxA expression in peripheral blood mononuclear cells of patients infected with hepatitis C virus.

This study aimed at investigating the effect of progesterone on interferon signaling pathways in peripheral blood mononuclear cells (PBMCs) of patients infected with hepatitis C virus (HCV). PBMCs were isolated from peripheral blood of 38 treatment-naïve HCV-infected patients, pooled, and stimulated with progesterone in the presence and absence of its receptor antagonist, mifepristone, along with interferon alpha (IFN-α) or imiquimod. Toll-like receptor (TLR) 7 and myxovirus resistance protein A (MxA) were quantified in PBMCs using RT-qPCR. Imiquimod alone or combined with progesterone did not change MxA expression in HCV-infected PBMCs. Progesterone decreased the inducing effect of IFN-α on TLR-7 expression in both males and females. Moreover, progesterone stimulation prior to IFN-α treatment attenuated the Jak/STAT pathway, which was reflected by decreased expression of MxA in females. Progesterone showed a negative impact on the IFN signaling pathway in HCV-infected PBMCs as it decreased the expression of TLR-7 in both genders, while MxA expression was decreased only in females.

Incidence and risk factors of retinopathy in Egyptian patients with chronic hepatitis C virus treated with pegylated interferon plus ribavirin.

BACKGROUND: Data are scarce on ocular complications in Egyptian patients with chronic hepatitis C treated with pegylated interferon and ribavirin therapy. The aim of this study was to investigate the development of retinal lesions induced by interferon therapy for chronic hepatitis C. METHODS: We prospectively analyzed 84 patients with chronic hepatitis C (total 168 eyes), who underwent combination pegylated interferon and ribavirin therapy for 48 weeks. Visual acuity, color vision, and visual field were measured, and a fundus assessment was made at baseline, at 12, 24, and 48 weeks post the commencement of treatment, and at follow-up, 1 month after treatment. Past medical and ocular histories, visual symptoms, and the results of a full ophthalmologic assessment were recorded for each patient. RESULTS: Twenty-two patients (26%) developed retinopathy. Retinal hemorrhage was observed in eight patients. Four patients complained of visual disturbance. Retinopathy disappeared in 16 patients (73%) despite the continuation of combination therapy. However, retinopathy persisted in six patients with retinal hemorrhage and three of them stopped treatment. A comparison of the clinical backgrounds between the patients with and without retinopathy showed no significant differences with regard to gender, HCV RNA level, white blood cell count, platelet count, hemoglobin level, or fibrosis score. However patients with retinopathy were of older age, had a higher prevalence of hypertension and diabetes mellitus, and more often did not respond to therapy. Multiple logistic regression analysis revealed that hypertension and diabetes were factors predicting retinopathy. CONCLUSION: Retinopathy associated with interferon α-2a and ribavirin combination therapy tends to develop in patients of older age with hypertension and diabetes.

Role of Foxp3 and regulatory CD4+CD25+ T-lymphocytes in bronchial asthma.

Regulatory T cells (Tregs) are thought to have a critical role in the suppression of immune responses. In addition to the prevention of the development of autoimmunity, they are thought to have a role in the prevention of allergic responses to environmental allergens. Foxp3 is transcription factor (Foxp3), which is predominantly expressed by CD4+ CD25+ T cells, and may correlates with the suppressive activity of these cells. This study assesses the immunoregulatory role of CD4+CD25+ T-lymphocytes in peripheral blood of asthmatic children and possible role of Foxp3 mRNA expression. The study included thirty children, 10 with acute asthmatic exacerbation, 10 during rest state with no asthma manifestation and 10 apparently healthy children. T-regs, and Foxp3 mRNA were investigated using Flowcytometry and RT-PCR respectively. Early morning sputum was also collected for determination of eosinophillia. Significant increase in the percent of CD4+CD25+ was found in acute asthmatic as compared to stable asthmatic cases (23.3 +/- 3.74% vs 13.97% +/- 1.18%), and in acute asthmatic group than control group (13.97% +/- 1.18% vs 8.12 +/- 1.65%), (P < 0.001). Similarly, significant increase in Foxp3 mRNA expression was found in acute asthmatic cases as compared to stable and control children (P < 0.001). A significant positive correlation was found between Foxp3 mRNA expression and the percent of CD4+CD25+ T cells in all studied groups (r = 0.91 P = 0.01). It is concluded that regulatory CD4+CD25+ T-cells may play a critical role in maintaining suppression and protection against allergic bronchial asthma and that Foxp3 may be important in the development of these cells.