Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.

Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5-79; P < 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7-50·7; P < 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3-14; P < 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1-8·9; P < 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9-18·9; P = 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0-0·8; P = 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06-1·03; P = 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06-8·3; P = 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.

Possible neuroendocrine role for oxytocin in bone remodeling.

OBJECTIVE: The present study was carried out to evaluate the assumption that oxytocin (OT) plays a neuroendocrine role in bone remodeling. For this purpose the changes in serum calcium, serum RANKL and OPG levels were detected in addition to morphological examination of the bone. METHODS: Two regimes for OT administration were used: 1. one group of rats was treated with a high OT dose of 40 microIU/kg b.w. for 6 weeks; 2. second group was treated with a low OT dose of 8 microIU/kg b.w. for a longer period of treatment (12 weeks). To evaluate the possible role of OT in bone remodeling, the changes in serum calcium, serum RANKL (sRANKL--Receptor Activator of Nuclear factor K-beta Ligand) and OPG (Osteoprotegerin) levels were detected and sRANKL/OPG ratio was calculated. To confirm the biochemical data, a histological and ultrastructural study of rat bone samples, before and after injection with oxytocin, was also performed. RESULTS: In general, the present study shows that intramuscular injection of OT at both concentrations and durations of treatment caused a significant decrease in serum calcium and sRANKL levels and a significant increase in OPG level. The sRANKL/OPG ratio was decreased as well. Morphological observations showed that both OT treatments induced a slight effect on bone remodeling in favor of bone formation. CONCLUSION: Oxytocin was found to posses a growth promoting effects on bone. The results also clearly showed that treatment with a high OT dose for a short duration was more effective than the low dose for a longer period of treatment.

Phospholipases in biology and medicine.

Phospholipases, a group of enzymes that catalyze the hydrolysis of membrane phospholipids, are classified according to the bond cleaved in a phospholipid into PLA1 (EC 3.1.1.3), PLA2 (EC 3.1.1.4), PLB (EC 3.1.1.5), PLC (EC 3.1.4.3), and PLD (EC 3.1.4.4). This paper reviews source and structure of PLA2 and the involvement of PLA2 and PLC in several biological phenomena, such as, signal transduction, photoreception, biosynthesis of lung surfactant, sperm motility, and fertilization. New assays for PLA2 activity and concentration in biological fluids are discussed. Phospholipases are involved in many inflammatory reactions by making arachidonate available for eicosanoid biosynthesis. The determination of PLA2 activity and mass concentration in plasma is useful in the diagnosis and prognosis of pancreatitis and of septic shock. Naturally occurring phospholipase inhibitors, such as lipocortins act as second messengers in the anti-inflammatory response to steroids. Lipocortins may be valuable therapeutic agents, because they are more specific in their anti-inflammatory action than glucocorticoids; therefore, they are less likely to produce harmful side effects.