This model predicted the probability of successful guidewire crossing within 30 min very well and can be applied for difficulty grading.

Serum melatonin concentrations were determined by RIA in 81 healthy humans, aged 1-92 yr. The daytime (0900-1100 h) serum levels of melatonin decreased progressively with advancing age. No sex difference was noted. The nocturnal rise of serum melatonin in the aged group was significantly reduced compared with that in the young group. These results suggest that serum melatonin may be secreted under the agerelated neural control of pineal metabolism. (J Clin Endocrinol Metab 55: 27, 1982) T HE PHYSIOLOGICAL role of melatonin in man has not been defined. However, the characteristic circadian periodicity of serum melatonin, with a prominent peak during the night, has been found in humans (1-4). Additional factors other than the light-dark cycle, such as the sleep-wake cycle (1, 3, 5), the menstruation cycle (6), and season of the year (7), have been shown to modulate serum melatonin levels in man. Whether serum melatonin levels vary with aging was determined during our studies to estimate the serum melatonin levels in relation to age and sex and to examine its diurnal variations in young and aged persons. Materials and MethodsEighty-one human subjects (44 men and 37 women), aged 1-92 yr, were studied for the determination of the daytime concentration of melatonin. Five young men (mean ± SEM, 26.4 ± 2.3 yr; young group) and 5 aged men (84.8 ± 1.8 yr; aged group) were studied for the examination of the diurnal variations.

Most CTO lesions can be safely and successfully treated with PCI utilizing contemporary advanced techniques. Invasiveness and potential risks of these strategies, which have been the greatest concerns of CTO treatment, may be acceptable in the majority of cases considering the actual incidences of related adverse events and the procedural success rates.

To evaluate the influence of changes in liver function on serum levels of melatonin, we measured serum levels and MCR of the hormone in patients with liver cirrhosis and in healthy control subjects. Daytime (0900-1100 h) serum levels of melatonin in patients with liver cirrhosis were significantly elevated compared to those in healthy subjects. Significant positive correlations of the daytime serum levels of melatonin with the serum retention rate of indocyanine green dye and serum levels of total bilirubin were noted. The clearance of melatonin from blood showed a biphasic first-order kinetic pattern. The half-life of each phase was significantly prolonged in patients with cirrhosis compared to healthy subjects. Our data indicate that the elevated daytime serum levels of melatonin in patients with liver cirrhosis are due to decreased clearance, probably related to decreased liver blood flow, lowered activity of 6 beta-hydroxylase, and competition with bilirubin in the intrahepatic transport system.

Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.

Aim: A previous phase 2 study of patients undergoing non-urgent PCI treated with SCH530348 plus aspirin and clopidogrel tended to reduce MACE without increased bleeding. This study evaluated the safety of SCH530348 in Japanese patients with NSTE ACS. Methods: Subjects (117), in whom PCI was planned, received standard-of-care (aspirin, ticlopidine, and heparin) and were randomized 4:1 to receive either SCH530348 (20 or 40 mg loading dose followed by 1 mg/d or 2.5 mg/d for 60 days) or placebo. The key safety endpoint was TIMI major and minor bleeding in the PCI cohort (n 92). The key exploratory efficacy endpoint was MACE and death within 60 days. Addition of SCH530348 to standard-of-care did not significantly increase the rate of TIMI major and minor bleeding (or non-TIMI bleeding) in the primary cohort. Results: Incidence (non-MACE) and discontinuation of AEs were similar across groups. PCI subjects treated with SCH530348 plus standard-of-care experienced a significant reduction in periprocedural MI compared with standard-of-care alone (16.9% vs 42.9%, respectively; p 0.013). There were no deaths or any other MACE. Conclusion: SCH530348 added to standard-of-care did not result in excess bleeding in Japanese subjects with NSTE ACS but significantly reduced the incidence of periprocedural MI in subjects undergoing urgent PCI. J Atheroscler Thromb, 2010; 17:156-164.

No abstract

Bacillus subtilis CwlC is a cell wall lytic N-acetylmuramoyl-l-alanine amidase that plays an important role in mother-cell lysis during sporulation. The enzyme consists of an N-terminal catalytic domain with C-terminal tandem repeats. The repeats [repeat 1 (residues 184-219) and repeat 2 (residues 220-255)] are termed CwlCr. We report on the solution structure of CwlCr as determined by multidimensional NMR, including the use of 36 (h3)J(NC)'-derived hydrogen bond restraints and 64 residual (1)D(NH) dipolar couplings. Two tandem repeats fold into a pseudo-2-fold symmetric single-domain structure consisting of a betaalphabetabetaalphabeta-fold containing numerous contacts between the repeats. Hydrophobic residues important for structural integrity are conserved between the repeats, and are located symmetrically. We also present NMR analysis of the circularly permuted repeat mutant of CwlCr. Secondary structure content from the chemical shifts and hydrogen bonds derived from (h3)J(NC)' show that the mutant folds into a structure similar to that of the wild type, suggesting that the repeats are exchangeable. This implies that conserved hydrophobic residues are crucial for maintaining the folding of the repeats. While monitoring the chemical shift perturbations following the addition of digested soluble peptidoglycan fragments, we identified two peptidoglycan interaction sites of CwlCr at the edges of the protein symmetrically, and they are located approximately 28 A from each other.