Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24,000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with i.v. infusions of 0.1-10 micrograms/kg/min of 23m in anesthetized dogs, with 10 micrograms/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

Objective: Adipocytokine genes encoding adiponectin (ADIPOQ) and the leptin receptor (LEPR) affect glucose and fatty acid metabolism. The purpose of this study was to examine the association between early-onset type 2 diabetes mellitus (T2DM) and variability within these two genes in the Han Chinese population of Taiwan. Subjects: A cross-sectional study of 999 patients from the Han Chinese population of Taiwan with early-onset T2DM (n ¼ 264; age at diagnosis, 20 to o45 years) and late-onset T2DM (n ¼ 735; age at diagnosis, X45 years) was performed. Blood samples from T2DM patients were taken for DNA extraction, and levels of serological markers were measured at enrollment. Seven single-nucleotide polymorphisms (SNPs) were selected for genotyping (three SNPs in AIDPOQ and four SNPs in LEPR) by polymerase chain reaction in each patient. Results: Polymorphisms at the position rs10937273 in ADIPOQ and at the positions rs1892534 and rs2211651 in LEPR were statistically associated with early-onset T2DM (P ¼ 0.0246, 0.0014 and 0.0012, respectively). C-reactive protein levels were significantly different among the early-onset T2DM patients with different genotypes at the SNPs rs1892534 and rs2211651 in LEPR (P ¼ 0.003 and P ¼ 0.004, respectively). In addition, fasting glucose levels were also significantly different among different genotypes at the SNP rs1892534 in LEPR (P ¼ 0.038). Conclusion: We conclude that the polymorphisms in the adipocytokine genes ADIPOQ and LEPR are significantly associated with the age at diagnosis of T2DM in the Han Chinese population of Taiwan.

This study shows increased bioavailability in all patients converted to CsA-ME, with the greatest increase seen in patients with the lowest initial cyclosporine bioavailability. The tolerability was similar between the two formulations during this study.

The predialysis CCI, instead of SDI, determines an increased risk for mortality in lupus patients treated with PD. The prognosis of lupus patients treated with PD largely depends on the severity of predialysis comorbidity, especially cardiovascular diseases.