CYP1B1 and myocilin gene mutations in Egyptian patients with primary congenital glaucoma

Purpose: Primary congenital glaucoma (PCG) accounts for 26–29% of childhood blindness in Egypt. The identification of disease causing mutations has not been extensively investigated. We aimed to examine the frequency of CYP1B1 and MYOC mutations in PCG Egyptian patients, and study a possible genotype/phenotype correlation.Methods: Ninety-eight patients with PCG diagnosed at the Ophthalmology department ofAlexandria Main University Hospital were enrolled. Demographic and phenotypic characteristics were recorded. Patients and 100 healthy subjects (control group) were screened for two mutations in CYP1B1 gene (G61E, R368H) and one mutation in MYOC gene (Gln48His) using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Phenotypic characteristics pertaining to disease severity were compared.Results: Nineteen patients (19%) with PCG were found positive for one or more of the mutations screened for. Seven patients (7%) were homozygous for the G61E mutation. Ten patients (10%) were heterozygous; 6 for the G61E mutation, 2 for the R368H mutation and 2 for the Gln48His mutation. Two patients (2%) were double heterozygotes harboring a R368H as well as a Gln48His mutation. The most common mutation observed was the G61E in 13 patients; 7 homozygotes and 6 heterozygotes for the mutation. The control group were negative for all mutations screened for. No significant correlations between the mutations and phenotype severity were detected. A statistically significant positive correlation however was found between the different mutations andeach of the IOP and the cup/disk ratio.Conclusion: The current study further endorses the role of CYP1B1 mutations in the etiology of PCG among Egyptian patients and is the first study to report MYOC gene mutation in Egyptian patients with PCG

Monitoring EPR Effect Dynamics during Nanotaxane Treatment with Theranostic Polymeric Micelles

Cancer nanomedicines rely on the enhanced permeability and retention (EPR) effect for efficient target site accumulation. The EPR effect, however, is highly heterogeneous among different tumor types and cancer patients and its extent is expected to dynamically change during the course of nanochemotherapy. Here the authors set out to longitudinally study the dynamics of the EPR effect upon single- and double-dose nanotherapy with fluorophore-labeled and paclitaxel-loaded polymeric micelles. Using computed tomography-fluorescence molecular tomography imaging, it is shown that the extent of nanomedicine tumor accumulation is predictive for therapy outcome. It is also shown that the interindividual heterogeneity in EPR-based tumor accumulation significantly increases during treatment, especially for more efficient double-dose nanotaxane therapy. Furthermore, for double-dose micelle therapy, tumor accumulation significantly increased over time, from 7% injected dose per gram (ID g–1) upon the first administration to 15% ID g–1 upon the fifth administration, contributing to more efficient inhibition of tumor growth. These findings shed light on the dynamics of the EPR effect during nanomedicine treatment and they exemplify the importance of using imaging in nanomedicine treatment prediction and clinical translation

Alleviation of Fatty Liver by Using Soy Proteins in Rat

The purpose of the current investigation is to determine how soy isoflavone (ISF) and genistein (GS) affects oxidative stress, IL1-ß and PPARγ signaling pathways in liver of obese rats and how this pathway is involved in controlling the formation of hepatic fat. The study included 60 male Sprague Dawley rats that were allocated to six groups (n = 10rats) :(I) Fatty liver was induced in rats were daily fed  (60% fat energy, high fat diet (HFD)) for 12 weeks ; (II) (Fatty liver + ISF group)  rats were daily fed with HFD and 10 mg/Kg ISF  intragastrical for 12 weeks ;(III) (Fatty liver + GS group)  rats were given HFD and 16 mg/Kg GS in 0.1%  DMSO once daily by intragastric tube for 12 weeks; (IV) (Normal control group) rats were fed with normal balanced diet for 12 weeks; (V)(Normal diet + ISF group) rats were fed with normal diet and 10 mg/Kg ISF  intragastrical for 12 weeks; (VI) (Normal diet + GS group)  rats were fed with normal diet and 16 mg/Kg GS for 12 weeks. All rats allowed water whereas rats got HFD were accompanied by 18% sucrose solution freely. Also, weight was measured weekly. At the end of the experiments lipid profile and liver function were analyzed. Moreover, the levels of MDA, SOD, CAT, and GSH, and the gene expression of IL1-ß and PPARγ genes were detected.  Our study showed that fat content was significantly lowered in the liver of ISF and GS  -fed obese rats, accompanied by a reduction in hepatocellular vacuolation when compared to the fatty liver control. In ISF and GS fatty liver treated groups SOD, CAT and GSH activities were significantly increased in comparison to the Fatty liver untreated group in addition to that MDA level decreased in ISF and GS groups.IL1-ß expression and PPARγ expressions was dowenregulated in Fatty liver  + ISF and  Fatty liver+  GS treated rats when compared with Fatty liver one,however the results in Fatty liver+  GS treated rats was significantly Improved over ISF +  Fatty liver.Genistein administration alleviated fatty liver  through the down-regulation of PPARγ and IL-1 β  and up-regulation the activity of oxidative stress marker ( SOD , CAT and GSH)

Alleviation of Fatty Liver by Using Soy Proteins in Rat

The purpose of the current investigation is to determine how soy isoflavone (ISF) and genistein (GS) affects oxidative stress, IL1-ß and PPARγ signaling pathways in liver of obese rats and how this pathway is involved in controlling the formation of hepatic fat. The study included 60 male Sprague Dawley rats that were allocated to six groups (n = 10rats) :(I) Fatty liver was induced in rats were daily fed  (60% fat energy, high fat diet (HFD)) for 12 weeks ; (II) (Fatty liver + ISF group)  rats were daily fed with HFD and 10 mg/Kg ISF  intragastrical for 12 weeks ;(III) (Fatty liver + GS group)  rats were given HFD and 16 mg/Kg GS in 0.1%  DMSO once daily by intragastric tube for 12 weeks; (IV) (Normal control group) rats were fed with normal balanced diet for 12 weeks; (V)(Normal diet + ISF group) rats were fed with normal diet and 10 mg/Kg ISF  intragastrical for 12 weeks; (VI) (Normal diet + GS group)  rats were fed with normal diet and 16 mg/Kg GS for 12 weeks. All rats allowed water whereas rats got HFD were accompanied by 18% sucrose solution freely. Also, weight was measured weekly. At the end of the experiments lipid profile and liver function were analyzed. Moreover, the levels of MDA, SOD, CAT, and GSH, and the gene expression of IL1-ß and PPARγ genes were detected.  Our study showed that fat content was significantly lowered in the liver of ISF and GS  -fed obese rats, accompanied by a reduction in hepatocellular vacuolation when compared to the fatty liver control. In ISF and GS fatty liver treated groups SOD, CAT and GSH activities were significantly increased in comparison to the Fatty liver untreated group in addition to that MDA level decreased in ISF and GS groups.IL1-ß expression and PPARγ expressions was dowenregulated in Fatty liver  + ISF and  Fatty liver+  GS treated rats when compared with Fatty liver one,however the results in Fatty liver+  GS treated rats was significantly Improved over ISF +  Fatty liver.Genistein administration alleviated fatty liver  through the down-regulation of PPARγ and IL-1 β  and up-regulation the activity of oxidative stress marker ( SOD , CAT and GSH)