Haplotypes and mutations of the PAH locus in Egyptian families with PKU

A high degree of molecular heterogeneneity at the phenylalanine hydroxylase (PAH) locus was established by examining RFLP haplotypes and PAH mutations in the families of 13 Egyptians with phenylketenouria (PKU). Thirteen different haplotypes were unequivocally determined in these kindreds. Haplotypes 1.8, 3.9, 4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with normal chromosomes, whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned 73.9, and two as yet incomplete but novel haplotypes were found segregating with the mutant chromosomes. There was no particular preference for a single haplotype among normal or mutant chromosomes. Nine different mutations were also identified among the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c (4/26), R261Q (3/26), R176X (2/26), Y206D (2/26), S231P (2/26), Y198fs [593-614del22bp]; (2/26), G46fs [136/137delG]; (1/26), and E178G (1/26). Six of these mutations (IVS 2nt5g-c, R176X, Y198fs, R261Q, S231P, and IVS 10nt11g) are common to other Mediterranean populations. Two mutations not previously reported in the Mediterranean basin were also observed (Y206D and G46fs). These intriguing preliminary findings confirm IVS 10nt11g as a major mutation among Mediterranean mutations and demonstrate the need for a more comprehensive study of Arab populations to confirm the uniqueness of the two novel mutations to the Egyptian population.     

Disturbances of Haemostasis in Diabetes Mellitus

Diabetes mellitus is associated with disturbances in haemostasis that could contribute to the development of thrombotic complications.The present study was undertaken to determine the behavior of coagulation variables and fibrinolytic system in diabetes mellitus. Forty five diabetic patients and forty five matched controls were evaluated by doing the following haemostatic parameter, prothrombin time, partial thromboplastin time, thrombin time, coagulation factors assay II, VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, a₂- antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of fibrinogen, a₂- antiplasmin, & PAI and lower level of protein C. Other haemostatic parameters did not show statistically significant difference between diabetic patients and control group. Significantally elevated levels of PAI, a₂- antiplasmin together with low protein C level in diabetic patients may result in the disturbance of haemostatic balance favoring thrombotic events. Conclusion: High levels of plasma fibrinogen, a₂A- antiplasmin with low plasma protein C activity could lead to a prothrombotic tendency in insulin dependent diabetic patients. Moreover, in non-insulin dependent diabetic patients, the above mentioned parameters together with high levels of ADP-induced platelet aggregation and plasminogen activator inhibitor may increase the risk of thrombotic complications. Obesity can be considered as an additional risk factor for development of thrombosis in diabetic patients.     

Evaluation of Photon Interaction Parameters of Some Antioxidants for Food Irradiation Applications

This study aimed to investigate the interaction parameters of antioxidant molecules in some spices and vegetables with gamma radiation. At first, mass attenuation coefficients (MACs, cm²/g) of gingerol, rosmarinic acid, quercetin, curcumin, eugenol, piperine, allicin, and capsaicin molecules were determined at the photon energies (13–1332 keV) emitted from the radioactive isotopes Am-241, Ba-133, Co-60, and Cs-137 with the help of the EpiXS and WinXCOM programs. The smallest and largest MAC values were found as 1.20 and 8.48 cm²/g at 13 keV and 0.059 and 0.058 cm²/g at 1332 keV for eugenol and allicin, respectively. It was observed that both results support each other. Using the MAC values, the effective atomic number and electron density (Z_eff and N_eff) values of the molecules were derived. The Z_eff values for gingerol and allicin were obtained in the range of 5.79–3.40 and 13.85–4.53, respectively. The variation of the buildup factors of antioxidants in the range of 0.015–15 MeV depending on the chemical composition and penetration depth were also examined. It was noticed that the photon accumulation was the lowest in allicin and the highest in gingerol and eugenol. The results obtained from this study will make an essential contribution to dose calculations in food irradiation studies.     

Superior quality chemically reduced graphene oxide for high performance EMI shielding materials

The chemical reduction process of graphene oxide combined with a mild and controllable thermal treatment under vacuum at 200 °C for 4 hours provided a cost-effective, scalable, and high-yield route for Reduced Graphene Oxide (RGO) industrial production and became a potential candidate for producing electromagnetic interference (EMI) shielding. We investigated graphite, and RGO using l-ascorbic acid and Sodium borohydride before and after thermal treatment by carefully evaluating the chemical and morphological structures. The thermally treated l-ascorbic Acid reduction route (TCRGOL) conductivity was 2.14 × 10³ S m⁻¹ and total shielding efficiency (SET) based on mass loadings per area of shielding was 94 dB with about one-tenth less graphite weight and surpassing other graphene reduction mechanisms in the frequency range of 8.2–12.4 GHz, i.e., X-band, at room temperature while being tested using the waveguide line technique. The developed treatment represents valuable progress in the path to chemical reduction using a safe reducing agent and offering superior quality RGO rarely achieved with the top-down technique, providing a high EMI shielding performance.

The developed two-step protocol offers a superior reduced graphene oxide TCRGOL quality (7 layers), and its SET was 94 dB over the X-band.     

The Osborn wave: what have we learned?

The Osborn wave is a deflection with a dome-shaped configuration at the R-ST junction of the electrocardiogram. It is mainly encountered in hypothermic states but is also recognized in other nonhypothermic conditions. It has important prognostic implications that warrant its recognition by various health-care providers. Most important is its arrhythmogenic potential especially when observed in patients with myocardial ischemia where it was found to be a precursor of malignant ventricular arrhythmias. Herein, we provide a comprehensive review of the history, causes, electrocardiographic and electrophysiologic characteristics, as well as diagnostic and prognostic significance of the Osborn wave.     

Mutants of type II heat-labile enterotoxin LT-IIa with altered ganglioside-binding activities and diminished toxicity are potent mucosal adjuvants

The structure and function LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, are closely related to the structures and functions of cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies demonstrated that mutant LT-IIa(T34I), which exhibits no detectable binding activity as determined by an enzyme-linked immunosorbent assay, with gangliosides GD1b, GD1a, and GM1 is a very poor adjuvant. To evaluate whether other mutant LT-IIa enterotoxins that also exhibit diminished ganglioside-binding activities have greater adjuvant activities, BALB/c mice were immunized by the intranasal route with the surface adhesin protein AgI/II of Streptococcus mutans alone or in combination with LT-IIa, LT-IIa(T14S), LT-IIa(T14I), or LT-IIa(T14D). All three mutant enterotoxins potentiated strong mucosal immune responses that were equivalent to the response promulgated by wt LT-IIa. All three mutant enterotoxins augmented the systemic immune responses that correlated with their ganglioside-binding activities. Only LT-IIa and LT-IIa(T14S), however, enhanced expression of major histocompatibility complex class II and the costimulatory molecules CD40, CD80, and CD86 on splenic dendritic cells. LT-IIa(T14I) and LT-IIa(T14D) had extremely diminished toxicities in a mouse Y1 adrenal cell bioassay and reduced abilities to induce the accumulation of intracellular cyclic AMP in a macrophage cell line.     

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.