Discovery of a 2-hydroxyacetophenone derivative as an outstanding linker to enhance potency and ß-selectivity of liver X receptor agonist.

Our research found that the 2-hydroxyacetophenone derivative is an outstanding linker between the 1,1-bistrifluoromethylcarbinol moiety and the imidazolidine-2,4-dione moiety to enhance the potency and ß-selectivity of liver X receptor (LXR) agonist in our head-to-tail molecular design. The incorporation of this linker is 20-fold more potent than our previous compound (2) for LXR ß agonistic activity (EC50) in a GAL-4 luciferase assay. Furthermore, we also identified 5-[5-(1-methylethoxy)pyridyl-2-yl]-5-methylimidazoline-2,4-dione (54), which lowers the lipophilicity of 2-hydroxyacetophenone derivative. We revealed that a combination of our newly developed linker and hydantoin (54) plays a pivotal role in improving the potency and selectivity of LXRß. The optically separated (-)-56 increases high-density lipoprotein cholesterol levels without elevating plasma triglyceride levels and results in a decrease of the lipid accumulation area in the aortic arch in a high-fat- and cholesterol-fed low-density lipoprotein receptor knock-out mice. In this manuscript, we report that (-)-56 is a highly potent and ß-selective LXR agonist for use in the treatment of atherosclerosis.

Comparison of morphological features in the femur between femoral neck fractures and femoral intertrochanteric fractures.

PURPOSE: The purpose of this study is to make proximal femur fracture types more predictable by considering morphological features of an acetabulum as well as of a proximal femur in the Japanese population. METHODS: A retrospective review of radiographs of the proximal femoral fractures was conducted in patients registered from 2010 to 2012, dividing into patients with femoral neck fractures; Group Neck (n = 101), and patients with femoral intertrochanteric fractures; Group IT (n = 99). Intergroup comparison was conducted: age, sex, height, weight, the ratios of femoral intertrochanteric length (IT Length), femoral neck length (Neck Length), femoral neck width (Neck Width), lateral offset length (Offset) to femoral head diameter, neck-shaft angle (N-S angle), and center-edge angle of the acetabulum (C-E angle), adjusting for age. Multiple logistic regression analysis was conducted among these parameters. RESULTS: The Group IT showed significantly older age than the Group Neck. Greater C-E angle in Group IT was observed in the patients in their 80s and 90s years of age. The Group Neck showed greater N-S angle only in the patients in their 80s years of age. In multiple logistic regression analysis, the impact of the age and the C-E angle on the fracture types was similar (odds ratio 1.08, 1.09, respectively, p < 0.01 both). CONCLUSIONS: Age, N-S angle, and C-E angle could be independent predictors for determining the proximal femur fracture types.

Surgical treatment of scoliosis associated with central core disease: minimizing the effects of malignant hyperthermia with provocation tests.

We report the case of a 7-year-old boy with thoracolumbar scoliosis and central core disease who had a history of malignant hyperthermia. He had scoliosis with Cobb's angle deteriorating to 67 degrees (thoracic) and 59 degrees (lumbar). A provocation test of general anesthesia was performed to confirm no hyperthermic reaction. Then, he underwent surgical correction by a posterior approach. The thoracic curve was reduced to 38 degrees and the lumbar curve to 42 degrees . He has been followed up for 2 years without any complications. This is the first report with a detailed description of perioperative management on surgical treatment of scoliosis associated with central core disease.

Crystal structures of (S)-(+)-5-(3-bromo/chloro-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione.

In (S)-(+)-5-(3-bromo-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione, C13H15BrN2O3, (I), the hydantoin groups are connected via inter-molecular N-H⋯O hydrogen bonds, forming a terraced sheet structure. In the chloro analogue, (S)-(+)-5-(3-chloro-4-isopropoxyphen-yl)-5-methyl-imidazolidine-2,4-dione, C13H15ClN2O3, (II), the inter-molecular N-H⋯O hydrogen-bonding network forms a flat sheet. Comparison of the crystal structures reveals that (II) is more loosely packed than (I).

Acetabular perforation after medial migration of the helical blade through the femoral head after treatment of an unstable trochanteric fracture with proximal femoral nail antirotation (PFNA): a case report.

The proximal femoral nail antirotation is a new generation of intramedullary device for the treatment of trochanteric femoral fractures, having a helical blade rather than a screw for suggested better purchase in osteoporotic bone. However, it is not free of complications. Few reports are available on postoperative perforation of the helical blade through the femoral head as a unique complication of proximal femoral nail antirotation. We report a 79-year-old woman with acetabular perforation after migration of the helical blade through the femoral head after an unstable trochanteric fracture, which was fixed with a proximal femoral nail antirotation.