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High-sensitivity quantitative analysis reveals the non-linear relationship between the dose and deposition of diphenylarsinic acid in the rat central nervous system following its subchronic exposure

In the year 2003, the residents of Kamisu, Japan, were exposed to pentavalent organic arsenic diphenylarsinic acid (DPAA[V]) via their normal drinking water. Following the exposure, they developed cerebellar and brainstem symptoms. Although the relatively high dose of DPAA(V) is assumed to have caused their symptoms, the relationship between the exposed dose of DPAA(V) and the level of their deposition in the central nervous system (CNS) remains unclear. Using liquid chromatography–tandem mass spectrometry, we examined the deposition of DPAA(V) and its pentavalent metabolites in the CNS tissues of Crl:CD(SD) rats following the administration of DPAA(V) for 28 days. We found that the concentrations of DPAA(V) in the CNS were very high, given a dose of 5.0 mg/kg/day. However, very low concentrations of DPAA(V) were detected at a dose of 0.3 or 1.2 mg/kg/day, suggesting the absence of a linear dose-response relationship between the dose and deposition of DPAA(V). We also found that this non-linear relationship was commonly observed in various non-CNS tissues, including the excretory system. Our study showed for the first time the exact relationship between the dose and tissue deposition of the organic arsenic following its subchronic administration

H dibaryon in the QCD sum rule

The QCD sum rule is applied to the H dibaryon and is compared to the flavor non-singlet di-nucleon. We find that the H dibaryon is almost degenerate to the di-nucleon in the $SU(3)_{flavor}$ limit and therefore is not deeply bound as far as th\ e threshold parameter is adjusted not to have a di-nucleon bound state. After introducing the $SU(3)_{f}$ breaking effects, the H dibaryon is found to be bound by $40 MeV$ below the $\Lambda \Lambda$ threshold.Comment: 10 pages 4 uuencoded figures containe

Long-term accumulation of diphenylarsinic acid in the central nervous system of cynomolgus monkeys

Diphenylarsinic acid (DPAA) is an organic arsenic compound used for the synthesis of chemical weapons. We previously found that the residents of Kamisu city in Ibaraki Prefecture, Japan, were exposed to DPAA through contaminated well water in 2003. Although mounting evidence strongly suggests that their neurological symptoms were caused by DPAA, the dynamics of DPAA distribution and metabolism after ingestion by humans remain to be elucidated. To accurately predict the distribution of DPAA in the human body, we administrated DPAA (1.0 mg/kg/day) to cynomolgus monkeys (n = 28) for 28 days. The whole tissues from these monkeys were collected at 5, 29, 170, and 339 days after the last administration. The concentration of DPAA in these tissues was measured by liquid chromatography–mass spectrometry. We found that DPAA accumulated in the central nervous system tissues for a longer period than in other tissues. This finding would extend our knowledge on the distribution dynamics and metabolism of DPAA in primates, including humans. Furthermore, it may be useful for developing a treatment strategy for patients who are exposed to DPAA

Time to Bone Union after Hybrid Closed-Wedge High Tibial Osteotomy

Medial open- and lateral closed-wedge high tibial osteotomy (hybrid CWHTO) can overcome the limitations of conventional CWHTO and open-wedge HTO (OWHTO) for medial compartmental osteoarthritis (OA) of the knee. Hybrid CWHTO increases stability by using a rigid locking plate and allows early full weight-bearing. However, the literature contains no information about time to bone union after this new procedure. The aim of this study is to evaluate the time to bone union after hybrid CWHTO. We reviewed 44 knees treated with hybrid CWHTO. Patients were able to stand on both legs on the day after surgery and walked with full weight-bearing within 4 weeks of the procedure. The time to achievement of bone union at the osteotomy site was defined as the number of months until bone union was confirmed on radiographic imaging. The mean time to radiographic confirmation of bone union was 4.5±1.5 months after surgery. Eleven knees (25.0%) required 6 months or more. Radiographic analysis and JOA score improved significantly between before and 1 year after surgery (p<0.01). Hybrid CWHTO is a very useful method for treating medial OA, but radiographic bone union requires 4.5 months on average. We must be aware of bone union after hybrid CWHTO

Two Cases of High Tibial Osteotomy in Patients with Rheumatoid Arthritis Treated with Biologic Disease-modifying Anti-rheumatic Drugs

High tibial osteotomy (HTO) procedure is generally contraindicated in rheumatoid arthritis (RA) patients because synovial inflammation may exacerbate joint damage post-surgery. The natural course of joint destruction in RA changed dramatically with new treatment strategies and the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDs). We report the cases of two RA patients who underwent HTO and whose disease activities were well controlled by bDMARDs. Despite their short follow-up periods, they showed acceptable objective and subjective clinical results. We believe that the combination of bDMARDs and HTO can be indicated for selected RA patients before total knee arthroplasty

In situ proliferation and differentiation of macrophages in dental pulp

The presence of macrophages in dental pulp is well known. However, whether these macrophages proliferate and differentiate in the dental pulp in situ, or whether they constantly migrate from the blood stream into the dental pulp remains unknown. We have examined and compared the development of dental pulp macrophages in an organ culture system with in vivo tooth organs to clarify the developmental mechanism of these macrophages. The first mandibular molar tooth organs from ICR mice aged between 16 days of gestation (E16) to 5 days postnatally were used for in vivo experiments. Those from E16 were cultured for up to 14 days with or without 10% fetal bovine serum. Dental pulp tissues were analyzed with immunohistochemistry to detect the macrophages and with reverse transcription and the polymerase chain reaction (RT-PCR) for the detection of factors related to macrophage development. The growth curves for the in vivo and in vitro cultured cells revealed similar numbers of F4/80-positive macrophages in the dental pulp. RT-PCR analysis indicated the constant expression of myeloid colony-stimulating factor (M-CSF) in both in-vivo- and in-vitro-cultured dental pulp tissues. Anti-M-CSF antibodies significantly inhibited the increase in the number of macrophages in the dental pulp. These results suggest that (1) most of the dental pulp macrophages proliferate and differentiate in the dental pulp without a supply of precursor cells from the blood stream, (2) M-CSF might be a candidate molecule for dental pulp macrophage development, and (3) serum factors might not directly affect the development of macrophages