大腿四頭筋の等尺性収縮は、膝蓋上外側アプローチによる膝関節内注射の正確性を向上する

Background: Intra-articular injection is an important technique for treating rheumatoid arthritis and osteoarthritis of the knee. However, medication is often inaccurately injected outside of the joint. We devised an intra-articular injection method in which the needle is inserted into the suprapatellar bursa while the patient maintains isometric contraction of the quadriceps. This isometric contraction method is based on the concept that isometric contraction of the quadriceps induces contraction of the articularis genus muscle, thus expanding the lumen of the suprapatellar bursa. Methods: Intra-articular injections were performed on 150 osteoarthritic knees without effusion. The knees were alternately assigned to the isometric quadriceps method group (75 knees) and non-activated quadriceps method group (75 knees). Prior to joint injection, the anterior-posterior dimension of each suprapatellar bursa was measured to ascertain its expansion. The isometric quadriceps method was performed with the quadriceps and the articularis genus muscle maintained in a contracted state. The non-activated quadriceps method was performed in a relaxed state. Ultrasound guidance was not used for either method. Subsequently, an ultrasonic probe was used only to confirm whether the intra-articular injections were successful. We compared the accuracy of injections performed between the 2 groups. Results: Suprapatellar expansion was significantly larger (p < 0.001) using the isometric quadriceps method (2.1 ± 1.4 mm [range, 0 to 5 mm]) than using the non-activated quadriceps method (0.8 ± 0.7 mm [range, 0 to 2 mm]). The percentage of accurate intra-articular injections was significantly higher (p = 0.0287) using the isometric quadriceps method (93%) compared with the non-activated quadriceps method (80%). Conclusions: In comparison with the non-activated quadriceps method, the isometric quadriceps method led to a larger expansion of the suprapatellar bursa, which should lead to more accurate intra-articular injections. The isometric quadriceps method is effective in reducing inaccurate injections into the synovium or surrounding fatty tissues. Clinical relevance: Putting force on the quadriceps muscle increases the success rate of intra-articular injection of the knee. The results of this study could provide a clinically relevant injection technique for future treatment.博士（医学）・乙第1448号・令和元年12月5日Copyright © 2018 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

Zinc Supplementation with Polaprezinc Protects Mouse Hepatocytes against Acetaminophen-Induced Toxicity via Induction of Heat Shock Protein 70

Polaprezinc, a chelate compound consisting of zinc and l-carnosine, is clinically used as a medicine for gastric ulcers. It has been shown that induction of heat shock protein (HSP) is involved in protective effects of polaprezinc against gastric mucosal injury. In the present study, we investigated whether polaprezinc and its components could induce HSP70 and prevent acetaminophen (APAP) toxicity in mouse primary cultured hepatocytes. Hepatocytes were treated with polaprezinc, zinc sulfate or l-carnosine at the concentration of 100 µM for 9 h, and then exposed to 10 mM APAP. Polaprezinc or zinc sulfate increased cellular HSP70 expression. However, l-carnosine had no influence on it. Pretreatment of the cells with polaprezinc or zinc sulfate significantly suppressed cell death as well as cellular lipid peroxidation after APAP treatment. In contrast, pretreatment with polaprezinc did not affect decrease in intracellular glutathione after APAP. Furthermore, treatment with KNK437, an HSP inhibitor, attenuated increase in HSP70 expression induced by polaprezinc, and abolished protective effect of polaprezinc on cell death after APAP. These results suggested that polaprezinc, in particular its zinc component, induces HSP70 expression in mouse primary cultured hepatocytes, and inhibits lipid peroxidation after APAP treatment, resulting in protection against APAP toxicity

Polaprezinc Protects Mice against Endotoxin Shock

Polaprezinc (PZ), a chelate compound consisting of zinc and l-carnosine (Car), is an anti-ulcer drug developed in Japan. In the present study, we investigated whether PZ suppresses mortality, pulmonary inflammation, and plasma nitric oxide (NO) and tumor necrosis factor (TNF)-α levels in endotoxin shock mice after peritoneal injection of lipopolysaccharide (LPS), and how PZ protects against LPS-induced endotoxin shock. PZ pretreatment inhibited the decrease in the survival rate of mice after LPS injection. PZ inhibited the increases in plasma NO as well as TNF-α after LPS. Compatibly, PZ suppressed LPS-induced inducible NO synthase mRNA transcription in the mouse lungs. PZ also improved LPS-induced lung injury. However, PZ did not enhance the induction of heat shock protein (HSP) 70 in the mouse lungs after LPS. Pretreatment of RAW264 cells with PZ suppressed the production of NO and TNF-α after LPS addition. This inhibition likely resulted from the inhibitory effect of PZ on LPS-mediated nuclear factor-κB (NF-κB) activation. Zinc sulfate, but not Car, suppressed NO production after LPS. These results indicate that PZ, in particular its zinc subcomponent, inhibits LPS-induced endotoxin shock via the inhibition of NF-κB activation and subsequent induction of proinflammatory products such as NO and TNF-α, but not HSP induction

Geranylgeranylacetone Ameliorates Inflammatory Response to Lipopolysaccharide (LPS) in Murine Macrophages: Inhibition of LPS Binding to The Cell Surface

We investigated whether pretreatment with geranylgeranylacetone (GGA), a potent heat shock protein (HSP) inducer, could inhibit proinflammatory cytokine liberation and nitric oxide (NO) production in lipopolysaccharide (LPS)-treated murine macrophages. The levels of NO and tumor necrosis factor-α (TNF-α) released from murine macrophage RAW 264 cells were increased dose- and time-dependently following treatment with LPS (1 µg/ml). GGA (80 µM) treatment 2 h before LPS addition significantly suppressed TNF-α and NO productions at 12 h and 24 h after LPS, respectively, indicating that GGA inhibits activation of macrophages. However, replacement by fresh culture medium before LPS treatment abolished the inhibitory effect of GGA on NO production in LPS-treated cells. Furthermore, GGA inhibited both HSP70 and inducible NO synthase expressions induced by LPS treatment despite an HSP inducer. When it was examined whether GGA interacts with LPS and/or affects expression of Toll-like receptor 4 (TLR4) and CD14 on the cell surface, GGA inhibited the binding of LPS to the cell surface, while GGA did not affect TLR4 and CD14 expressions. These results indicate that GGA suppresses the binding of LPS to the cell surface of macrophages, resulting in inhibiting signal transduction downstream of TLR4

Strategic use of new generation antidepressants for depression: SUN(^_^) D protocol update and statistical analysis plan

Background: SUN(^_^)D, the Strategic Use of New generation antidepressants for Depression, is an assessor-blinded, parallel-group, multicenter pragmatic mega-trial to examine the optimum treatment strategy for the first- and second-line treatments for unipolar major depressive episodes. The trial has three steps and two randomizations. Step I randomization compares the minimum and the maximum dosing strategy for the first-line antidepressant. Step II randomization compares the continuation, augmentation or switching strategy for the second-line antidepressant treatment. Step III is a naturalistic continuation phase. The original protocol was published in 2011, and we hereby report its updated protocol including the statistical analysis plan. Results: We implemented two important changes to the original protocol. One is about the required sample size, reflecting the smaller number of dropouts than had been expected. Another is in the organization of the primary and secondary outcomes in order to make the report of the main trial results as pertinent and interpretable as possible for clinical practices. Due to the complexity of the trial, we plan to report the main results in two separate reports, and this updated protocol and the statistical analysis plan have laid out respective primary and secondary outcomes and their analyses. We will convene the blind interpretation committee before the randomization code is broken. Conclusion: This paper presents the updated protocol and the detailed statistical analysis plan for the SUN(^_^)D trial in order to avoid reporting bias and data-driven results. Trial registration: ClinicalTrials.gov: NCT01109693(registered on 21 April 2010)

Evidence for migration of metamorphosing larvae of Anguilla japonica in the Kuroshio

Two sampling surveys of the R/V Tansei Maru were conducted in the Kuroshio region south of Kyushu Island of Japan and to the south in the western North Pacific, to study the distribution patterns of the larval stages of the Japanese eel Anguilla japonica as they approach their recruitment areas in East Asia. Nine fully-grown premetamorphic leptocephali (49.5-58.3mm TL) were collected during November 1996 to the east of Taiwan. During November and December 2000, nine early stage glass eels (51.3-57.0mm TL, pigmentation stage II-IV) that were still in the late metamorphosis stages were collected in the Kuroshio. These findings suggest that metamorphosing Japanese eel leptocephali that recruit to the northern part of their species range migrate in the Kuroshio. They may detrain from the Kuroshio at the pigmentation stage IV-VA and begin their coastal migration

Genotype determination of the OPN1LW/OPN1MW genes: novel disease-causing mechanisms in Japanese patients with blue cone monochromacy

Blue cone monochromacy (BCM) is characterized by loss of function of both OPN1LW (the first) and OPN1MW (the downstream) genes on the X chromosome. The purpose of this study was to investigate the first and downstream genes in the OPN1LW/OPN1MW array in four unrelated Japanese males with BCM. In Case 1, only one gene was present. Abnormalities were found in the promoter, which had a mixed unique profile of first and downstream gene promoters and a −71A > C substitution. As the promoter was active in the reporter assay, the cause of BCM remains unclear. In Case 2, the same novel mutation, M273K, was present in exon 5 of both genes in a two-gene array. The mutant pigments showed no absorbance at any of the wavelengths tested, suggesting that the mutation causes pigment dysfunction. Case 3 had a large deletion including the locus control region and entire first gene. Case 4 also had a large deletion involving exons 2–6 of the first gene. As an intact LCR was present upstream and one apparently normal downstream gene was present, BCM in Case 4 was not ascribed solely to the deletion. The deletions in Cases 3 and 4 were considered to have been caused by non-homologous recombination

Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects.</p> <p>Methods</p> <p>Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning.</p> <p>Results</p> <p>Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference.</p> <p>Conclusions</p> <p>The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.</p