Oxidative addition of (HO)2B−XH3 to M(PH3)2 (X = C, Si, Ge, or Sn; M = Pd or Pt) was theoretically investigated with MP2-MP4(SDQ) and CCSD(T) methods. (HO)2B−XH3 easily undergoes oxidative addition to Pt(PH3)2 with a moderate activation energy for X = C and either a very small barrier or no barrier for X = Ge, Si, and Sn. Also, (HO)2B−SiH3, (HO)2B−GeH3, and (HO)2B−SnH3 undergo oxidative addition to Pd(PH3)2 with either a very small barrier or no barrier. Only the oxidative addition of (HO)2B−CH3 to Pd(PH3)2 cannot take place, but the reductive elimination of (HO)2B−CH3 from Pd(CH3)[B(OH)2](PH3)2 occurs with no barrier. The transition states (TS) of these oxidative additions are nonplanar except for the nearly planar TS of the oxidative addition of (HO)2B−CH3 to Pt(PH3)2. This TS structure is very sensitive to steric and electronic factors; for instance, the TS becomes nonplanar by substituting PH2(C2H5) for PH3, to decrease the steric repulsion between (HO)2B−CH3 and PH2(C2H5). A noteworthy feature of these reactions is that the TS is much stabilized by the charge-transfer interaction between M d and B(OH)2 pπ orbitals, which is the main reason for the high reactivity of (HO)2B−XH3 in the oxidative addition reaction. Pt−B(OH)2 and Pd−B(OH)2 bonds are much stronger than Pt−XH3 and Pd−XH3 bonds, respectively. This is because the M−B(OH)2 bond is stabilized by the π-back-donating interaction between the empty pπ orbital of B(OH)2 and the doubly occupied dπ orbital of Pt and Pd. Also, it should be noted that the trans influence of the boryl group is stronger than the very strong trans influence of silyl group.

Rituximab, a chimeric murine/human monoclonal anti-CD20 antibody, was licensed for the treatment of B-cell lymphoma and has also shown efficacy against autoimmune diseases such as immune thrombocytopenic purpura (ITP). It is relatively safe; however, about 1-20% of patients were reported to have developed rituximab-induced serum sickness, which is more common among patients with autoimmune conditions than among those with hematologic malignancies. Here we describe a pediatric patient with steroid-dependent chronic ITP who presented with arthralgia and fever ten days after the second infusion of rituximab (on day 10), and presented with malaise and maculopapular rash on day 21. Oral prednisolone was started and his symptoms resolved. He had an elevated level of human anti-chimeric antibody (HACA) on day 27; thereafter, the HACA level slowly decreased. To our knowledge, among pediatric patients who received rituximab for chronic ITP, this is the sixth documented case of serum sickness and the only one who manifested an elevated level of HACA. Rituximab is a beneficial treatment option against chronic ITP; however, the risk of serum sickness should be considered. Steroid, usually used for the treatment of serum sickness, may prevent the development of severe serum sickness when administered during and after rituximab treatment.

The rat sciatic nerve was locally frozen, and changes in the nerve, motor endplates, and the soleus muscle were examined for up to 6 weeks by light and electron microscopy. The wet weights of denervated soleus muscles compared with contralateral values progressively declined to a minimum at 2 weeks after injury (60.7 +/- 2.5%) and began to reverse following 3 weeks. The sciatic nerve thoroughly degenerated after freezing. However, numerous regenerated myelinated and thin nerve fibers were observed at 3 weeks. They were considerably enlarged but still smaller than normal counterparts at 6 weeks postoperatively. Nerve terminals containing synaptic vesicles of endplates disappeared at day 1 and mostly reappeared at 3 weeks (about 70% of the endplates). All endplates examined were reinnervated at 4, 5, and 6 weeks. On the other hand, postsynaptic folds of muscle fibers seemed to be only slightly influenced by denervation or reinnervation. Ultrastructural alterations of myofibrils, in particular the loss of register, immediately appeared after denervation, spread progressively, peaked at 2 weeks, ameliorated following reinnervation, and became significantly normalized at 6 weeks after freezing. The proportion of type II fibers in the soleus muscle similary showed an increase and a decrease with a short delay in response to denervation and reinnervation, respectively. This study clearly demonstrated that the nerve supply affects the ultrastructural integrity of skeletal muscles. In addition, changes in the endplates and the soleus muscle evaluated in this study after short-term denervation are largely reversible following reinnervation.

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High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.