Experiences of high-dose mizoribine as antimetabolite immunosuppressants for kidney transplantation.

We have used low doses of mizoribine (MZ) or mycophenolate mofetil (MMF) as induction and maintenance immunosuppressants, but since 2009 have employed a high dose of MZ. We reviewed the efficacy and side effects of MZ compared with MMF. It is difficult to compare graft survivals between these periods because of different patient demographics, though the high dose of MZ cohort showed no significant difference from MMF. High doses of MZ serum to prevent acute rejection episodes as the induction and maintenance therapy. MZ controlled with blood concentrations showed less side effects, suggesting that high MZ doses could be safely used for an induction and maintenance antimetabolite.

[Effects of nicorandil on coronary collateral circulation depend on the donor arteries].

The effects of nicorandil on coronary collateral circulation during exercise-induced ischemia were compared between the different donor arteries in 13 patients with effort angina, 7 with complete obstruction of the left anterior descending artery (LAD) with well-developed collateral vessels from the right coronary artery (RCA) (LAD group), and 6 with complete occlusion of the RCA (segment 2-3) with well-developed collateral vessels from the LAD (RCA group). Initial percentage thallium (%TI) uptake (thallium-201 single photon emission computed tomography) and washout rate were measured in the anterior, septal and posterior regions during ergometer exercise. The submaximal treadmill exercise test was also performed using a cardiopulmonary monitoring system to measure Vo2 at anaerobic threshold (AT). After the controls were obtained, nicorandil (15 mg/day) was administered for 4 weeks, during which ergometer exercise and treadmill exercise tests were carried out repeatedly. A significant improvement of initial %TI uptake on exercise was observed in the LAD group with nicorandil therapy, but no improvement was shown in the RCA group. The AT significantly increased after nicorandil treatment in the LAD group (13.9 +/- 0.38-->16.8 +/- 1.18 ml/min/kg), reflecting the improvement of cardiac function through the increased collateral flow. However, in the RCA group, it remained unchanged, suggesting no improvement of cardiac function. Nicorandil was effective to increase collateral flow from the RCA, but ineffective on that from the LAD. Nicorandil is an effective coronary dilator and is reported to affect both large and small coronary arteries. The effect on the collateral circulation is dependent on the donor artery supplying different areas. The vasodilator effect of nicorandil is mainly on the LAD, which is large enough to supply blood to a wider area of the heart, rather than the RCA.

Effect of levofloxacin on glycosaminoglycan and DNA synthesis of cultured rabbit chondrocytes at concentrations inducing cartilage lesions in vivo.

We investigated the toxic effect of levofloxacin (LVFX), a quinolone antibacterial agent, on cartilage by examining aspects of its in vivo toxicokinetics and effect on the function of cultured chondrocytes of the femoral articular cartilage from juvenile New Zealand White rabbits. Repeated administration of LVFX (100 mg/kg) orally for 7 days induced focal necrosis and superficial erosion in the articular cartilage of the femoral condyle, but 30 mg/kg did not. Concentrations of LVFX in the cartilage were highest at the first sampling point (30 min) after a single administration, being 4.93 and 12.2 micrograms/g in the 30- and 100-mg/kg groups, respectively. The arthropathic concentration of LVFX in the cartilage was then shown to be 12.2 micrograms/g or more. For an in vitro study, chondrocytes were separated from the articular cartilage of the rabbit femoral condyle and cultured for 7 days until confluence. 35SO4 uptake by cultured chondrocyte sheets was most susceptible to LVFX, decreasing at drug concentrations of 5 micrograms/ml or more in 24- and 48-h cultures but not in a 72-h culture. Furthermore, 3H-thymidine uptake was decreased at concentrations of 10 micrograms/ml or more in a 48-h culture but not in 24- and 72-h cultures. Rhodamine 123 accumulation was susceptible to inhibition in cultured chondrocytes at an LVFX concentration of 10 micrograms/ml or more. These results suggest that LVFX inhibits glycosaminoglycan synthesis initially and DNA synthesis and mitochondrial function secondarily at actual arthropathic concentrations in cultured rabbit chondrocytes but that these changes are reversible and not enough to kill the cells.

[HLA study in 108 Japanese patients with Crohn's disease].

We attempted to clarify the association between HLA and Crohn's disease. HLA-A, -B, -C, -DR and -DQ locus antigens in 108 Japanese patients with Crohn's disease were analyzed and the results were compared with findings of 472 healthy Japanese. In patients with Crohn's disease there was a strong positive association with HLA-DR4 (chi 2 = 14.086, Pc less than 0.005, RR = 2.231), and a weak positive association with HLA-B51, -Bw54, -DRw12, -DRw13 and -DRw52. While there was a strong negative association with HLA-DR2 (chi 2 = 10.194, Pc less than 0.025, RR = 0.435), DQw1 (chi 2 = 14.680, Pc less than 0.001 RR = 0.442) and DQw3 (chi 2 = 7.760 Pc less than 0.025 RR = 0.549), and a weak negative association with HLA-B7. In conclusion, susceptibility to Crohn's disease may relate to HLA-DR4, especially HLA-DR4.1, in Japanese patients.