Search for an optimal atherogenic lipid risk profile: from the Framingham Study

Recent guidelines have targeted low-density lipoprotein (LDL) cholesterol for treatment of dyslipidemia. A lack of clear demarcation of potential coronary heart disease (CHD) cases solely on the basis of LDL cholesterol indicates the need to consider the dyslipidemic risk in the context of a lipid and risk factor profile. We prospectively examined the influence of individual lipids and their ratios on 20-year CHD development in 2,439 men and 2,812 women participating in the Framingham Offspring Study. The influence of the total/high-density (HDL) cholesterol ratio on CHD risk was examined in tertiles of LDL cholesterol and total cholesterol levels. During the 20-year period, 566 CHD events occurred in men and 327 events in women. The CHD risk increased stepwise two- to threefold in men and women from the first to third tertile of total/HDL cholesterol ratio, irrespective of the level of total or LDL cholesterol level. In men, the LDL cholesterol level reflected the lowest risk factor adjusted quintile 5 to quintile 1 relative risk (1.85), and the total/HDL cholesterol ratio predicted the greatest risk (relative risk 2.9). In women, LDL cholesterol imparted the highest risk of the individual lipids (relative risk 3.9), and this was not exceeded by the lipid ratio (relative risk 3.8). In conclusion, the levels of components of the total/HDL cholesterol ratio have little influence on its prediction of CHD. In men, elevated LDL need not be treated aggressively if the total/HDL cholesterol ratio is low. Conversely, modest elevations of LDL may warrant more aggressive treatment if the ratio is high. In women, the ratio is also a good CHD predictor, but a combination of a high ratio accompanied by high LDL cholesterol may warrant more aggressive therapy.     

Bioactive and degradable hybridized nanofibers of gelatin-siloxane for bone regeneration

Organic-inorganic hybridized nanofibers constituted of gelatin and siloxane were generated by the electrospinning technique for use as bone regeneration matrices. The composition of the nanofibers selected was to be both degradable and bioactive. Precursors of gelatin and siloxane were dissolved in a modified acidic solvent composed of acetic acid, ethyl acetate, and distilled water. The hybridized nanofibers with various compositions (gelatin/siloxane = 1/2, 1, and 2 by weight fraction) were successfully electrospun under the adjusted processing conditions. Compared to the pure gelatin nanofiber, the hybridized nanofibers showed improved chemical stability in a saline solution. This was attributed to the cross-linking effect of the siloxane with the gelatin chains. Osteoblastic cells were observed to attach, spread, and populate actively on the hybridized nanofiber matrices. In particular, the cells on the hybridized nanofibers were recruited to elicit better osteoblastic activity (alkaline phosphatase) with respect to those on the pure gelatin. The newly-developed hybridized nanofiber is considered to be useful as a bone regeneration matrix, due to its nanofibrous structural trait as well as its degradability and bone cell activity.     

Severe Disease Activity Based on the Paris Classification Is Associated with the Development of Extraintestinal Manifestations in Korean Children and Adolescents with Ulcerative Colitis

BackgroundThere are limited data regarding the extraintestinal manifestations (EIMs) associated with pediatric inflammatory bowel disease (IBD) in Korea. We aimed to investigate the clinical features and factors associated with the development of EIMs in Korean children and adolescents with IBD.MethodsThis multicenter, retrospective study was conducted from 2010 to 2017. Baseline clinicodemographic, laboratory findings, disease activity, disease phenotypes, and EIMs were investigated.ResultsA total of 172 patients were included. One-hundred thirty-seven (79.7%) had Crohn''s disease (CD), and 35 (20.3%) had ulcerative colitis (UC). EIMs occurred in 42 patients (24.4%). EIMs developed in 34/137 diagnosed with CD (24.8%), and in 8/35 diagnosed with UC (22.9%), during a median follow-up duration of 3.2 (interquartile range, 1.9–5.4) years for CD and 3.0 (1.0–4.0) years for UC, respectively. Arthritis/arthralgia was most commonly observed (n = 15, 35.7%), followed by stomatitis/oral ulcer (n = 10, 23.8%), hepatitis (n = 5, 11.9%), nephritis (n = 4, 9.5%), pancreatitis (n = 2, 4.8%), erythema nodosum (n = 2, 4.8%), pyoderma gangrenosum (n = 1, 2.4%), primary sclerosing cholangitis (n = 1, 2.4%), uveitis (n = 1, 2.4%), and ankylosing spondylitis (n = 1, 2.4%). A significant difference in disease severity based on the Paris classification (P = 0.011) and ESR at diagnosis (P = 0.043) was observed between the EIM positive and negative group in patients with UC. According to logistic regression analyses, S1 disease severity based on the Paris classification was the only factor that was significantly associated with the development of EIMs (odds ratio, 16.57; 95% confidence interval, 2.18–287.39; P = 0.017).ConclusionSevere disease activity based on the Paris classification in pediatric patients with UC was significantly associated with EIM development. As disease severity in the Paris classification is a dynamic parameter, treatment should be focused on disease control to minimize the occurrence of EIMs in Korean children and adolescents with UC.     

Studies on the synthesis andin vitro antitumor activity of the isoquinolone derivatives

3-Arylisoquinolin-1(2H)-ones (2) are possible bioisosteres of the 5-[4'-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a]iso quinoline (1) which is in clinical evaluation for the treatment of cancer. Structure-activity relationship studies of 3-arylisoquinolin-1(2H)-ones (2) led to the synthesis of 3-arylquinolin-2(1H)-ones (3). A number of 3-phenyl substituted quinolin-2(1H)-ones were synthesized and tested for their in vitro antitumor activity against four different human tumor cell lines and 3-phenyl-N-benzyl-3,4-dihydroquinolin-2(1H)-one (12) showed the most potent activity.