Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms.

BACKGROUND: Children with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA. METHODS: OPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below - 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI). RESULTS: Patients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children. CONCLUSIONS: Egyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

Potential Antigenic Candidates for the Development of Peptide-Based Vaccines to Induce Immunization against Helicobacter pylori Infection in BALB/c Mice.

Helicobacter pylori (H. pylori) has been identified as a group-1 definite carcinogen. As of yet, there is no available vaccine for this microorganism. Our study aimed to identify antigenic peptides in H. pylori using an in silico proteomic approach, and to evaluate their effectiveness as potential vaccine candidates. Four different peptide sequences were prioritized using the reverse vaccinology, namely, CagA1, CagA2, VacA, and SabA. Peptides emulsified with Freunde's adjuvant were used to immunize BALB/C mice. Subcutaneously immunized mice were challenged by oral administration of H. pylori. IgG, IgA, IL4, and IL17 were detected in mice sera. Histopathology of the dissected stomach of vaccinated and control mice were assessed using H&E stain. IgG was significantly higher in mice vaccinated with SabA. IL-4 was significantly increased in CagA1, CagA2, VacA, and SabA vaccinated mice compared to the adjuvant group. Additionally, histopathological examination of gastric tissue showed a protective effect in the vaccinated groups compared to adjuvant and PBS groups. Our findings indicate a promising effect of the tested epitopes, particularly the SabA antigen, to induce an immune response against H. pylori.

Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms.

OBJECTIVES: This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). METHODS: Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes' frequencies were compared between cases and controls and between patients with BMD z-scores above and below -2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). RESULTS: The patients aged 14.01 ± 2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below -2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below -2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below -2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). CONCLUSIONS: This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617 T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

Tumor necrosis factor receptor II and PTPN22 genes polymorphisms and the risk of systemic lupus erythematosus in Egyptian children.

BACKGROUND: Many genes have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) is a potent cytokine stimulator acting through 2 cell surface receptors (TNFR I and II). TNFRII gene which controls expression of these receptors has been linked to SLE susceptibility through promoting apoptosis. Also; Protein tyrosine phosphatase non receptor 22 (PTPN22) gene enhances intrinsic phosphatase activity of T lymphocytes leading to their dysregulation and stimulates autoimmune process of lupus and its rs2476601 has been linked to susceptibility to thyroiditis in SLE patients in few studies. OBJECTIVES: (i) to investigate the correlation between 2 SNPs of TNFR II and PTPN22 genes and SLE susceptibility in a cohort of Egyptian children compared to controls (ii) and to investigate their possible association with different clinical presentations of the disease in children. SUBJECTS AND METHODS: Typing of TNFR II rs1061622 and PTPN22 rs2476601 SNPs were done using polymerase chain reaction-restriction fragment length polymorphism for 74 children with SLE and 100 matched healthy controls. RESULTS: Children with SLE had more frequent G allele and GG genotype of TNFR II rs1061622 (p < 0.001) and more T allele and TT genotype of PTPN22 rs2476601 (p = 0.012 and <0.001, respectively) compared to controls. Only 6 patients (8%) had thyroiditis (hypothyroidism) with T allele and TT genotype of PTPN22 1858 T more prevalent in those patients versus those without thyroiditis (p ≤ 0.001). Apart from, thyroiditis, no significant association was found between genotypes and alleles frequencies of the 2 studied SNPs and other clinical manifestations of the disease. CONCLUSION: The G allele and GG genotype of TNFR II rs1061622 and T allele and TT genotype of PTPN22 rs2476601 genes polymorphism can be considered as risk factors for the development of SLE. The presence of the T allele of PTPN22 rs2476601 may increase the risk of concomitant thyroiditis in Egyptian children with SLE but further studies are required to confirm this finding as thyroiditis was reported only in few cases in this study.

In-vivo assessment of the osteo-protective effects of eugenol in alveolar bone tissues.

Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.

Academic advising and student support: Help-seeking behaviors among Saudi dental undergraduate students.

OBJECTIVE: The purpose of this study was to assess the use of and satisfaction with the academic-advising and student-support systems available to undergraduate students in the College of Dentistry at the University of Dammam. In addition, the study aimed to also identify factors that explained the help-seeking behavior of students which they used to solve academic issues. MATERIALS AND METHODS: Students enrolled in the five-year Bachelor of Dental Surgery (BDS) program in 2012-13 and 2013-14 first-year students were invited to respond to a self-administered questionnaire. RESULTS: The results showed that 66.2% of students had discussed academic issues with their advisor at least once, with a frequency ranging from zero to six times. Most students reported that their advisors were readily available, listened intently to their needs and questions, and helped them solve their problems. However, only 7.6% of students relied primarily on advisors for help with academic issues, whereas 51% depended first on colleagues and 13.8% did not seek help and relied on themselves. In total, 17.2% of students were very or somewhat satisfied with the academic advising system. Males had lower odds of discussing issues with their advisors, and the odds were higher with advisors who were more available (OR = 0.25 and 3.74, respectively). Alerting students to important dates in the academic calendar significantly increased the odds that a student would depend primarily on academic advisors for advice related to academic issues (OR = 6.53). CONCLUSIONS: Few students were satisfied with the academic support system. We need to train advisors to help them develop their skills and knowledge and to enable them to provide the support needed by the students.

Therapeutic efficacy of plasmonic photothermal nanoparticles in hamster buccal pouch carcinoma.

OBJECTIVES: The objective of this study was to assess the short-term effect of plasmonic photothermal therapy (PPTT) on induced hamster buccal pouch (HBP) carcinoma. STUDY DESIGN: Seventy-six Syrian golden male hamsters were used. The induced HBP carcinomas were directly injected with ∼30 nm gold nanospheres followed by 15 min laser exposure (PPTT). RESULTS: PPTT caused rapid growth cessation and dramatic decrease in tumor sizes after 4 weeks of treatment (P < .05) compared to controls. Microscopic and immunohistochemical examination of the tumor biopsies revealed significant differences in the cellular apoptotic index (AI) value and proliferating cell nuclear antigen (PCNA) immunoexpression in PPTT-treated tumor tissue sections compared to controls (P < .05). Survival probability of the treated animals was increased compared to controls (P < .05). CONCLUSION: PPTT proved to be a successful method for treating superficially located HBP carcinomas.