Clinical Evaluation of Adenosine Triphosphate Disodium Hydrate (ATP-2Na) for Asthenopia

To investigate the effect and the safety of Adenosine triphosphate disodium hydrate (ATP-2Na) for asthenopia. 40 subjects [35 females and 5 males, 25~87 years old (average: 62.5 years old)] with asthenopia ingested 200~300 mg/day ATP-2Na for 3 months. Before and after 1 and 3 months ingestion, subjects completed a questionnaire to determine their asthenopia symptom and fatigue symptom by visual analog scale (VAS). The scores were compared between before and after ingestion. 31 subjects completed a questionnaire for 1 month. The scores of asthenopia symptom before ingestion, 1 and 3 months were 4.05 ± 3.22, 2.67 ± 2.19 and 2.41 ± 2.16, respectively. The scores of fatigue symptom were 4.76 ± 3.05, 3.08 ± 2.93 and 3.10 ± 3.19, respectively. Both scores were significantly decreased (p < 0.005) at 1 month compared before ingestion. Three subjects had side effects (diarrhea for two, nausea for one), and all subjects improved by oral discontinuation. These results suggest that ATP-2Na is relatively early effective in improving asthenopia and accompanying fatigue symptoms

競走馬における浅屈腱炎発症の危険因子の解析

[諸言]　アスリートである競走馬は、運動器疾患の発生が多い動物種である。本研究では、サラブレッド競走馬に好発する浅屈腱炎に着目し、浅屈腱炎によって出走できなくなる馬を減らすことを目的に、第１章で浅屈腱炎についての文献調査を、第２章で浅屈腱炎発症の危険因子の解析を行った。　第1章では、馬の浅屈腱炎の病態、診断、治療について調査した。馬の浅屈腱炎とは、浅指屈筋腱の腱中心部に変性、出血が生じる運動器疾患である。運動負荷による腱組織内の温度上昇、循環血液量低下が変性の原因である。しかし、競走馬であるゆえ、運動は避けて通ることはできないことが現実である。休養によって、腱の損傷部位は最終的に瘢痕組織に置換されるが、腱組織の弾力性は失われ、運動再開による浅屈腱の損傷は容易に発生する。そのため、馬の臨床現場では、浅屈腱炎は再発率の高い疾患と認識されている。超音波検査によって診断は可能であるものの、腱組織に回復したか、瘢痕組織に置換されたままかの判断はできないので、調教再開の判断は困難である。また、浅屈腱炎に効果のある治療方法は確立しておらず、内科治療、外科治療、再生医療のいずれも長期間の休養が必要である。これらのことから、浅屈腱炎は経済的損耗が大きく、発症を未然に防止することが重要であると考えられた。 　第2章では、競走馬の浅屈腱炎の発症危険因子について解析した。2011年から2015年までの5年間の大井競馬場の医療記録から、浅屈腱炎と診断された馬292頭を症例馬群として選出した。対照馬は、浅屈腱炎を発症した症例馬と同じ調教師、同時期に出走、同じ年齢であることを選出の条件とし、浅屈腱炎の症例馬1頭に対して、対照馬を2頭、合計584頭を選出した。症例馬および対照馬のレース記録は、オンラインデータベースから収集した。解析項目は、馬場状態（良馬場、稍重、重、不良）、出走時の天候（晴、曇、雨、雪）、着順、レース距離、馬券の人気、出走時の体重、前回出走からの体重の増減、性別、直前３および６レースの競走距離、前回出走からの出走間隔とし、症例馬と対照馬の比較は、student-t検定によって、有意差検定を実施した。また、浅屈腱炎発症馬のオッズ比（ORs）は、カイ二乗検定により実施した。これらの統計学的解析は、危険率5％未満をもって有意差ありと判断した。 　馬場関連の危険因子では、不良馬場は良馬場よりも、浅屈腱炎のオッズ比は有意に高かった（OR= 1.69; P <0.01）。出走時の天候は、症例馬群と対照馬群との間に差を認めなかった。レース関連の危険因子では、着順は、症例馬群が対象馬群よりも有意に悪かった（P < 0.01）。着順が10着以下であった場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 2.50; P < 0.01）。また、競走距離は、1,300m未満であった場合に浅屈腱炎のオッズ比は有意に高かった（OR = 1.45; P < 0.05）。さらに、馬券の人気が8番より悪かった場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.49; P < 0.05）。馬関連の危険因子では、出走時の馬の体重は、症例馬群が対照馬群よりも有意に重かった（P < 0.01）。また、浅屈腱炎発症馬の体重は470kgより重い場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.55; P < 0.01）。さらに、前回出走から体重5kg以上減少していた場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.59; P < 0.05）。雄と去勢雄は、雌よりも浅屈腱炎のオッズ比は有意に高かった（雄：OR= 1.35; P<0.05、去勢雄：OR=3.09; P < 0.01）。競走歴関連の危険因子では、直近3レースの競走距離は、症例馬群が対照馬群よりも有意に短かった（P < 0.01）。直近3レースの競走距離が4、000メートル未満であった場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.40; P < 0.05）。また、直近6レースの競走距離は、症例馬群が対照馬群よりも有意に短かった（P < 0.05）。直近6レースの競走距離が8,000メートル未満であった場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.47; P < 0.05）．前回出走からの出走間隔は、症例馬群が対照馬群よりも有意に長かった（P < 0.05）。出走間隔が90日以上であった場合に、浅屈腱炎のオッズ比は有意に高かった（OR = 1.75; P < 0.05）。病歴関連の危険因子では、病歴の有無は、浅屈腱炎発症に関連はなかった。　以上、不良馬場状態、短い競走距離、出走時の重い体重、前回出走からの体重の減少、長い出走間隔が、浅屈腱炎発症における危険因子であることが明らかとなった。獣医師、調教師、馬主がとれる浅屈腱炎を未然に防ぐ対策として、不良馬場であった場合には、騎手はレース中のコース取りに注意することを指導する。また、走行速度の速い短距離のレースは避け、比較的走行速度の遅い長距離のレースを選ぶことを提案する。 　本研究の結果を馬主、調教師に啓発することで、浅屈腱炎によって出走できなくなる馬を一頭でも減らすことに貢献できると考える。　Racehorses are a specific species of athletic horses that frequently develop orthopedic diseases. In this study, we focused on superficial digital flexor (SDF) tendinopathy, which is prevalent among thoroughbred racehorses. In chapter 1, literature discussing the pathology, diagnosis, and treatment of SDF tendinopathy is reviewed.SDF tendinopathy is an orthopedic disease that causes degeneration and bleeding in the SDF tendon. Eventually, the damaged areas of the SDF are replaced by scar tissue, and recurrence becomes more frequent because of the loss of toughness associated with scar tissue development. In addition, the treatment for SDF tendinopathy requires a long time. Furthermore, diagnosing whether the injury has been completely healed can be difficult, and no reliable treatment method has been established so far. Therefore, preventing the onset of this disease is essential to avoid great economic loss.　In chapter 2, an analysis was performed to identify risk factors associated with the development of SDF tendinopathy in racing horses. The authors selected racehorses (n = 292) diagnosed with SDF tendinopathy based on the medical records from a racetrack. Among the track-related variables that were identified as risk factors, a sloppy track surface was associated with a significantly higher risk of SDF tendinopathy than a standard track surface (odds ratio: OR = 1.69; P < 0.01). No significant differences in the weather conditions at race times were identified between racehorses with SDF tendinopathy and control racehorses. Among the race-related variables that were identified as risk factors, the OR for SDF tendinopathy was significantly increased for the following variables: (i) when the horse finished in 10th place or worse (OR = 2.50; P < 0.01); (ii) when the racehorse ran a short race (<1,300 m) (OR = 1.45; P < 0.05); and (iii) when the racehorses’ favorites were worse than or equal to the 8th place (OR = 1.49; P < 0.05). Among the racehorse-related variables that were identified as risk factors, the body weights of racehorses with SDF tendinopathy, for the race during which SDF tendinopathy occurred, was significantly heavier than the body weights of control racehorses (P < 0.01). When the body weight at race time was ≥ 470 kg, the SDF tendinopathy OR increased significantly (OR = 1.55; P < 0.01). A decrease in body weight ≥ 5 kg compared with the body weight recorded in the previous race significantly increased the SDF tendinopathy OR (OR = 1.59; P < 0.05). In addition, male and gelding horses had higher SDF tendinopathy ORs (OR = 1.35; P < 0.05 and OR =3.09; P < 0.01, respectively) compared with female horses. No significant differences were identified in horse ages between SDF tendinopathy and control racehorses. Among the race career-related variables that were identified as risk factors, When the total race distance for the last 3 races was < 4,000 m and the total race distance for the last 6 races was < 8,000 m, the SDF tendinopathy OR increased significantly (OR = 1.40; P < 0.05 and OR = 1.47; P < 0.05, respectively). When the number of days since the previous race was ≥ 90-days, the SDF tendinopathy OR increased significantly (OR = 1.75; P < 0.05). No significant differences were identified with respect to a history of other diseases between SDF tendinopathy and control horses. A total of 0.69% of the studied horses (2/292) had a history of SDF tendinopathies.　As a countermeasure for the prevention of SDF tendinopathy, sloppy track surfaces should be avoided, and horses should be guided toward more solid track surfaces. Selecting long-distance races with slower speeds, if possible, could also reduce the risks of horses developing SDF tendinopathy. Informing horse owners and trainers of the results of this analysis will contribute to reducing the number of racehorses whose active lives are disrupted by the development of SDF tendinopathy博士(獣医学)麻布大

Heme-dependent autophosphorylation of a heme sensor kinase, ChrS, from Corynebacterium diphtheriae reconstituted in proteoliposomes

AbstractCorynebacterium diphteriae employs the response regulator, ChrA, and the sensor kinase, ChrS, of a two-component signal transduction system to utilize host heme iron. Although ChrS is predicted to encode a heme sensor, the sensing mechanism remains to be characterized. In this report, ChrS expressed in Eshcherichia coli membranes was solubilized and purified using decylmaltoside. ChrS protein incorporated into proteoliposomes catalyzed heme-dependent autophosphorylation by ATP. Other metalloporphyrins and iron did not stimulate kinase activity. The UV–Vis spectrum of hemin in the ChrS–proteoliposomes indicated that heme directly interacts with ChrS. This is the first functional reconstitution of a bacterial heme-sensing protein

Essential Role of NMDA Receptor Channel ε4 Subunit (GluN2D) in the Effects of Phencyclidine, but Not Methamphetamine

Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, increases locomotor activity in rodents and causes schizophrenia-like symptoms in humans. Although activation of the dopamine (DA) pathway is hypothesized to mediate these effects of PCP, the precise mechanisms by which PCP induces its effects remain to be elucidated. The present study investigated the effect of PCP on extracellular levels of DA (DAex) in the striatum and prefrontal cortex (PFC) using in vivo microdialysis in mice lacking the NMDA receptor channel ε1 or ε4 subunit (GluRε1 [GluN2A] or GluRε4 [GluN2D]) and locomotor activity. PCP significantly increased DAex in wildtype and GluRε1 knockout mice, but not in GluRε4 knockout mice, in the striatum and PFC. Acute and repeated administration of PCP did not increase locomotor activity in GluRε4 knockout mice. The present results suggest that PCP enhances dopaminergic transmission and increases locomotor activity by acting at GluRε4

Differential responses of serum gamma-glutamyltransferase to alcohol intake in Japanese males.

We studied the association of gamma-glutamyltransferase (GGT) and other serum markers of liver injury with daily alcohol consumption in a healthy population of 1,043 Japanese males. A positive correlation between daily alcohol consumption and biochemical markers, such as log GGT (r = 0.432), log AST (r = 0.244) or log LAP (r = 0.246), was seen in all drinkers. However, there was a negative correlation, such as log GGT (r = -0.434), log AST (r = -0.424) or log LAP (r = -0.430), in heavy drinkers who consumed more than 70 g ethanol a day. On the other hand, a positive correlation, such as log GGT (r = 0.426), log AST (r = 0.247) or log LAP (r = 0.216) was found in moderate drinkers who consumed less than 70 g ethanol a day. Interestingly, there was a tendency toward negative association between alcohol consumption and the Tokyo University ALDH2 Phenotype Screening Test (TAST) score in the heavy drinkers, and there was a tendency toward positive association between GGT and TAST score in this group. Our results suggest that there are 2 groups of drinkers, those with elevated GGT (good responders) and those with normal GGT (poor responders) despite heavy drinking.</p

Changes in the deep vasculature assessed using anterior segment OCT angiography following trabecular meshwork targeted minimally invasive glaucoma surgery

The effect of trabecular meshwork (TM)-targeted minimally invasive glaucoma surgery (MIGS) on the vasculature assessed using anterior segment (AS)-optical coherence tomography angiography (OCTA) has not been established. In this prospective, longitudinal study, we investigated changes in the deep vasculature following TM-targeted MIGS using AS-OCTA for open-angle glaucoma in 31 patients. AS-OCTA images of the sclera and conjunctiva at the nasal corneal limbus were acquired preoperatively and 3 months postoperatively, and the vessel densities (VDs) of the superficial (conjunctival) and deep (intrascleral) layers were calculated. The VDs before and after MIGS were compared, and the factors associated with the change in VD following MIGS were analyzed. The mean deep VD decreased from 11.98 ± 6.80% at baseline to 10.42 ± 5.02% postoperatively (P = 0.044), but superficial VD did not change (P = 0.73). The multivariate stepwise regression analysis revealed that deep VD reduction was directly associated with IOP reduction (P < 0.001) and preoperative IOP (P = 0.007) and inversely associated with preoperative deep VD (P < 0.001). The deep VD reduction following MIGS was significant in the successful group (21 eyes) (P = 0.032) but not in the unsuccessful group (10 eyes) (P = 0.49). The deep VDs assessed using AS-OCTA decreased following TM-targeted MIGS, especially in the eyes with good surgical outcomes

Regulation of the Poly(A) Status of Mitochondrial mRNA by Poly(A)-Specific Ribonuclease Is Conserved among Land Plants

Regulation of the stability and the quality of mitochondrial RNA is essential for the maintenance of mitochondrial and cellular functions in eukaryotes. We have previously reported that the eukaryotic poly(A)-specific ribonuclease (PARN) and the prokaryotic poly(A) polymerase encoded by AHG2 and AGS1, respectively, coordinately regulate the poly(A) status and the stability of mitochondrial mRNA in Arabidopsis. Mitochondrial function of PARN has not been reported in any other eukaryotes. To know how much this PARN-based mitochondrial mRNA regulation is conserved among plants, we studied the AHG2 and AGS1 counterparts of the liverwort, Marchantia polymorpha, a member of basal land plant lineage. We found that M. polymorpha has one ortholog each for AHG2 and AGS1, named MpAHG2 and MpAGS1, respectively. Their Citrine-fused proteins were detected in mitochondria of the liverwort. Molecular genetic analysis showed that MpAHG2 is essential and functionally interacts with MpAGS1 as observed in Arabidopsis. A recombinant MpAHG2 protein had a deadenylase activity in vitro. Overexpression of MpAGS1 and the reduced expression of MpAHG2 caused an accumulation of polyadenylated Mpcox1 mRNA. Furthermore, MpAHG2 suppressed Arabidopsis ahg2-1 mutant phenotype. These results suggest that the PARN-based mitochondrial mRNA regulatory system is conserved in land plants