Evaluation of an experimental dental porcelain

The aim of this study was to evaluate fracture toughness, hardness, ceramic/metal bond strength and microstructure of experimental dental porcelain and compare it with commercial type. Specimens of specific dimensions were prepared. Fracture toughness was assessed by a three-point bending test. The Vickers hardness was measured using a microhardness tester. The ceramometal bond strength was measured using a universal testing machine. The load was applied at the porcelain/metal interface via a chisel edged blade with a crosshead speed of 2.0 mm/min until fracture. The polished specimens of dental porcelain were chemically etched and the microstructure was analyzed with a scanning electron microscope. The results showed comparable fracture toughness and bond strength for both materials, while the experimental porcelain exhibited higher hardness. The experimental porcelain showed uniform cohesive failure while the commercial type showed mixed mode of failure. The microstructure of the experimental porcelain was tetragonal leucite crystals dispersed randomly in a glass matrix. The leucite crystals exist in two forms, acicular and rod like structures. It was concluded that the experimental porcelain has adequate fracture toughness and ceramic/metal bond strength that can resist the rapid crack propagation and its consequent catastrophic failure, which indicates a material serviceability in the oral cavity.     

Murine neutralizing antibody response and toxicity to synthetic peptides derived from E1 and E2 proteins of hepatitis C virus

Introduction

The highest estimated prevalence of HCV infection has been reported in Egypt, nearly 12% mostly type 4. Currently, a commercial vaccine to protect this high risk population as well as global HCV infected patients is not available.

Objectives

In the present study, we aim at: (1) examining the viral binding capacities of purified monospecific polyclonal murine antibodies raised against genetically conserved viral protein sequences, i.e. synthetic peptides derived from those sequences located within envelope proteins and (2) assessment of immunogenic properties and safety parameters of those peptides individually and in a vaccine format in mice.

Methods

Purified IgG Abs from immunized mice were used in immunocapture RT-PCR experiments to test viral neutralization by Abs raised against each of 4 peptides termed p35 (E1), p36 (E2), p37 (E2) and p38 (E2). Swiss mice were immunized with each of the 3 peptides (p35, p37 and p38) which generated neutralizing antibodies in immunocapture experiments. Antibody responses to corresponding peptides were determined using different routes of administration, different adjuvants, different doses and at different time points post-injection. To explore the dose range for future pharmacological studies, three doses namely 50 ng, 10 μg and 50 μg/25 gm mouse body weight were tested for biochemical and histopathological changes in several organs.

Results

Murine Abs against p35, p37 and p38 but not p36 showed HCV neutralization in immunocapture experiments. Subcutaneous injection of peptides elicited higher responses than i.m. and i.p. Immunization with Multiple Antigenic Peptide (MAP) form or coupled to Al PO4 elicited the highest Ab responses. Peptide doses of 50 ng/25 gm body weight or less were effective and safe, however dose assessment still requires further study. Histopathological changes were observed in animals that received doses ∼1000 times higher than the potential therapeutic dose.

Conclusion

Exploration of humoral immunogenicity, neutralization capacity and safety suggested that the peptides presented herein are candidate vaccine components for further preclinical assessment.     

Association between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection

AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients.METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease BsmI and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of this single nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy.RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient’s sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient’s sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibrosis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.     

Association between serum 25 (OH) vitamin D level at birth and respiratory morbidities among preterm neonates

Objectives: To determine the association between 25-hydroxyvitamin D [25(OH)D] levels on first day of life with respiratory distress syndrome (RDS), need and duration of mechanical ventilation, and subsequent development of bronchopulmonary dysplasia (BPD) among preterm neonates.

Study design: In this case–control study, serum 25(OH)D was measured on first day of life in 65 preterm neonates <34 weeks: 40 with RDS and 25 without RDS and compared between them. Serum 25(OH)D levels were categorized into normal (above 30?ng/ml), insufficiency (20–30?ng/ml), moderate deficiency (10–20?ng/ml), and severe deficiency (<10?ng/ml). Neonates with different 25(OH)D levels were compared as regard grade of RDS, initial pH, initial CO₂, need and duration of mechanical ventilation, development of BPD, and mortality.

Results: Only one of 65 studied preterm neonates had normal vitamin D level. Neonates with RDS had significantly lower mean serum 25(OH)D level than controls (10.6 versus 13.9?ng/dl) (p?=?.028). Neonates with severe 25(OH)D deficiency developed more BPD than those with moderate deficiency (29.4 versus 8.7%) but did not reach significant level (p value?=?.08). There is no correlation between serum 25(OH)D level and duration of mechanical ventilation. Logistic regression analysis shows that low serum 25(OH)D level is an independent risk factor for RDS.

Conclusion: Low 25(OH)D level is far frequent among Egyptian preterm neonates. Vitamin D deficiency is an independent risk factor for development of RDS in preterm neonates.     

Mycobacterium tuberculosis infection in systemic lupus erythematosus patients

Aim of the work

To estimate prevalence of tuberculosis (TB) infection in systemic lupus erythematosus (SLE) patients; to study its relation to disease duration, activity, damage and treatment as well as to compare the performance of interferon gamma (IFN-γ) release assay and tuberculin skin test (TST) in detection of TB infection.

Serum tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and leptin as biomarkers of accelerated atherosclerosis in patients with systemic lupus erythematosus and antiphospholipid syndrome

Background

Patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are at increased risk of atherosclerosis, and occurs much earlier compared to the general population even after accounting for traditional risk factors.

Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt

Topical therapy is usually of limited benefit in the treatment of severe atopic dermatitis (AD), and the need for a safe and effective systemic treatment may be required in certain cases especially in children. We evaluated the efficacy and safety of methotrexate and cyclosporine in the treatment of 40 children with severe AD. Patients were divided into two groups (each consisting of 20 patients); group A was treated with methotrexate (7.5 mg/week) while group B was treated with cyclosporine (2.5 mg/kg/day). The severity scoring for atopic dermatitis (SCORAD) was used to indicate efficacy of treatment. In group A, the mean SCORAD score at the beginning of the study was 57.90?±?3.21 that was reduced at the end of the treatment period to reach 29.35?±?6.32 with a mean absolute reduction of 26.25?±?7.03. In group B, the mean SCORAD score was 56.54?±?4.82 at the start of treatment and was 31.35?±?8.89 at the end of 12 weeks of treatment. The mean absolute reduction was 25.02?±?8.21. There was no statistically significant difference in the reduction of SCORAD score between both groups (P?±?0.93). Mild and temporary adverse effects were reported in some patients in both groups. Conclusion: Methotrexate or cyclosporine in low doses can be considered as effective, relatively safe, and well-tolerated treatments for severe AD in children.     

Potential role of acid ceramidase in conversion of cytostatic to cytotoxic end-point in pancreatic cancer cells

Purpose

Acid ceramidase (AC) occupies an important place in the control of cancer cell proliferation. We tested the influence of AC inhibition on the effects of PSC 833, a P-glycoprotein antagonist with potent ceramide-generating capacity, to determine whether AC could be a therapeutic target in pancreatic cancer.

Methods

Ceramide metabolism was followed using ³H-palmitate, and molecular species were determined by mass spectroscopy. Apoptosis was measured by DNA fragmentation, autophagy by acridine orange staining, and cell cycle was assessed by flow cytometry and RB phosphorylation. AC was measured in intact cells using fluorescent substrate.

Results

Exposure of human PANC-1 or MIA-PaCa-2 cells to PSC 833 promoted increases in de novo (dihydro)ceramides, (dihydro)glucosylceramides, and (dihydro)sphingomyelins, demarking ceramide generation and robust metabolism. Despite the multifold increases in (dihydro)ceramide levels, cells were refractory to PSC 833. However, PSC 833 produced a dose-dependent decrease in DNA synthesis and dose- and time-dependent decreases in RB phosphorylation, consistent with cell cycle arrest as demonstrated at G1. Cytostatic effects of PSC 833 were converted to cytotoxic end-point by acid ceramidase inhibition. Cytotoxicity was accompanied by formation of acridine orange-stained acidic vesicles and an increase in LC3 expression, indicative of autophagic response. Cell death was not reversed by preexposure to myriocin, which blocks PSC 833-induced ceramide generation.

Conclusion

Although the role of ceramide in end-point cytotoxicity is unclear, our results suggest that acid ceramidase is a viable target in pancreatic cancer. We propose that AC inhibition will be effective in concert with other anticancer therapies.