Rocuronium has a suppressive effect on platelet function via the p2y12 receptor pathway in vitro that is not reversed by sugammadex

Rocuronium is an aminosteroid nondepolarizing neuromuscular blocker that is widely used for anesthesia and intensive care. In this study, we investigated the effect of rocuronium on human platelet functions in vitro. The effects of rocuronium on platelet aggregation, P-selectin expression, and cyclic adenosine monophosphate (cAMP) levels in platelets were measured using an aggregometer, an enzyme immunoassay, and flow cytometry, respectively. Rocuronium inhibited ADP-induced platelet aggregation, P-selectin expression and suppression of cAMP production. These effects were not antagonized by equimolar sugammadex, a synthetic γ-cyclodextrin derivative that antagonizes rocuronium-induced muscle relaxation by encapsulating the rocuronium molecule. Morpholine, which constitutes a part of the rocuronium molecule but is not encapsulated by sugammadex, inhibited ADP-induced platelet aggregation. Vecuronium, which has a molecular structure similar to that of rocuronium but does not possess a morpholine ring, had no significant effect on ADP-induced platelet aggregation. These results indicate that rocuronium has a suppressive effect on platelet functions in vitro that is not reversed by sugammadex and suggest that this effect is mediated by blockade of the P2Y12 receptor signaling pathway via the morpholine ring of rocuronium

Use of argatroban in combination with nafamostat mesilate in open-heart surgery for a pediatric patient with heparin-induced thrombocytopenia type II: a case report

[Background]Heparin-induced thrombocytopenia type II (HIT II) is a rare, immune-mediated complication of heparin therapy and can cause life-threatening thromboembolism. However, perioperative anticoagulation therapy for patients with a complication of HIT II has not been established. [Case presentation]A 6-year-old boy with tetralogy of Fallot underwent radical intracardiac repair with administration of argatroban at 1 year old due to positive HIT antibody. Reoperation was scheduled for pulmonary valve insufficiency, using argatroban and nafamostat mesilate as anticoagulants. Argatroban has a long onset time and the activated coagulation time (ACT) requires 7–26 h to return to the preadministration level, making hemorrhage control difficult, while half-life of nafamostat mesilate is shorter than that of argatroban. Celite ACT reflects the effects of both argatroban and nafamostat mesilate, but kaolin ACT reflects only the effect of argatroban. Due to the early termination of argatroban administration based on Celite and kaolin ACTs, ACT recovered to ≤ 200 s at 5 h after the end of argatroban administration. [Conclusion]Celite and kaolin ACTs can be used as markers to obtain close control of the required dose of argatroban in combination with nafamostat mesilate for the management of HIT II patients

A case of left ventricular free wall rupture after insertion of an IMPELLA® left ventricular assist device diagnosed by transesophageal echocardiography

[Background]The IMPELLA® is a minimally invasive left ventricular assist device. We report a case in which transesophageal echocardiography (TEE) was useful in diagnosis of left ventricular rupture after IMPELLA® insertion. [Case presentation]A 75-year-old man presented to the emergency room with chest pain and underwent percutaneous coronary intervention for 100% stenosis of the left anterior descending branch #7. An IMPELLA® was inserted to stabilize the circulation, but hypotension persisted. Transthoracic echocardiography revealed increased pericardial effusion and suspicion of free wall left ventricular rupture, leading to emergency surgery. TEE revealed the IMPELLA® straying into the left ventricle apical wall and cardiac tamponade. Hemorrhage was observed from the thinning free wall and the tip of the IMPELLA® was palpable. The IMPELLA® was removed and the left ventricular wall was repaired. [Conclusions]The IMPELLA® requires implantation of the tip in the left ventricle, but it should be noted that a fragile ventricular wall can be easily perforated

Squamous Cell Carcinoma of the Hilar Bile Duct

We herein report a rare case of squamous cell carcinoma of the hilar bile duct. A 66-year-old Japanese male patient was admitted to our hospital because of appetite loss and jaundice. Abdominal computed tomography revealed an enhanced mass measuring 10 × 30 mm in the hilar bile duct region. After undergoing biliary drainage, the patient underwent extended right hepatic lobectomy with regional lymph nodes dissection. The tumor had invaded the right portal vein. Therefore, we also performed resection and reconstruction of the portal vein. Histopathologically, the carcinoma cells exhibited a solid structure with differentiation to squamous cell carcinoma with keratinization and intercellular bridges. Immunohistochemical staining of the tumor cells revealed positive cytokeratin staining and negative CAM 5.2 staining. Based on these findings, a definitive diagnosis of well-differentiated squamous cell carcinoma of the hilar bile duct was made

Agreement between continuous cardiac output measured by the fourth-generation FloTrac/Vigileo system and a pulmonary artery catheter in adult liver transplantation

In liver transplantation for end-stage liver failure, monitoring of continuous cardiac output (CCO) is used for circulatory management due to hemodynamic instability. CCO is often measured using the minimally invasive FloTrac/Vigileo system (FVS-CCO), instead of a highly invasive pulmonary artery catheter (PAC-CCO). The FVS has improved accuracy due to an updated cardiac output algorithm, but the effect of this change on the accuracy of FVS-CCO in liver transplantation is unclear. In this study, we assessed agreement between fourth-generation FVS-CCO and PAC-CCO in 20 patients aged ≥ 20 years who underwent scheduled or emergency liver transplantation at Kyoto University Hospital from September 2019 to June 2021. Consent was obtained before surgery and data were recorded throughout the surgical period. Pearson correlation coefficient (r), Bland–Altman and 4-quadrant plot analyses were performed on the extracted data. A total of 1517 PAC-CCO vs. FVS-CCO data pairs were obtained. The mean PAC-CCO was 8.73 L/min and the mean systemic vascular resistance was 617.5 dyne·s·cm⁻⁵, r was 0.48, bias was 1.62 L/min, the 95% limits of agreement were − 3.04 to 6.27, and the percentage error was 54.36%. These results show that agreement and trending between fourth-generation FVS-CCO and PAC-CCO are low in adult liver transplant recipients

Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats

<p>Abstract</p> <p>Background</p> <p>The glial glutamate transporter GLT-1 is abundantly expressed in astrocytes and is crucial for glutamate removal from the synaptic cleft. Decreases in glutamate uptake activity and expression of spinal glutamate transporters are reported in animal models of pathological pain. However, the lack of available specific inhibitors and/or activators for GLT-1 makes it difficult to determine the roles of spinal GLT-1 in inflammatory and neuropathic pain. In this study, we examined the effect of gene transfer of GLT-1 into the spinal cord with recombinant adenoviruses on the inflammatory and neuropathic pain in rats.</p> <p>Results</p> <p>Intraspinal infusion of adenoviral vectors expressing the GLT-1 gene increased GLT-1 expression in the spinal cord 2–21 days after the infusion. Transgene expression was primarily localized to astrocytes. The spinal GLT-1 gene transfer had no effect on acute mechanical and thermal nociceptive responses in naive rats, whereas it significantly reduced the inflammatory mechanical hyperalgesia induced by hindlimb intraplantar injection of carrageenan/kaolin. Spinal GLT-1 gene transfer 7 days before partial sciatic nerve ligation recovered the extent of the spinal GLT-1 expression in the membrane fraction that was decreased following the nerve ligation, and prevented the induction of tactile allodynia. However, the partial sciatic nerve ligation-induced allodynia was not reversed when the adenoviruses were infused 7 or 14 days after the nerve ligation.</p> <p>Conclusion</p> <p>These results suggest that overexpression of GLT-1 on astrocytes in the spinal cord by recombinant adenoviruses attenuates the induction, but not maintenance, of inflammatory and neuropathic pain, probably by preventing the induction of central sensitization, without affecting acute pain sensation. Upregulation or functional enhancement of spinal GLT-1 could be a novel strategy for the prevention of pathological pain.</p

The Changes of Phenotypic and Gene Frequencies of Esterase-D Isozyme in Japanese Quail by Full-sib Mating

本研究は,全きょうだい交配によって近交世代を進めた場合の日本ウズラのエステラーゼDアイソザイムの表現型頻度と遺伝子頻度の変化について検討した. 材料は当研究室で無作為交配によって維持した閉鎖集団から作出した近交群と無作為交配群である. これらの交配群から得た成雌雄ウズラの血球エステラーゼDアイソザイムがデンプンゲル電気泳動法により検出された. 得られた結果は要約すると以下の通りである. 1.系統数,家系数は近交群では1世代目38系統38家系で出発したが,近交世代に伴い急激に減少し,5世代目では3系統12家系となった. これに対して,無作為交配群では40家系が維持された. 2.近交群では,FF型の表現型頻度は4世代まで近交世代に伴い徐々に増加する傾向がみられた. FS型の表現型頻度は2世代までは近交に伴い急激な減少がみられたが,その後の世代では増加する傾向が認められた. またSS型の表現型頻度は近交に伴いわずかに増加する傾向がみられたが,3代以降の世代では減少した. これに対して,無作為交配群では世代に伴う変化は認められなかった. 3.近交群では,Es-DFの遺伝子頻度は2世代目0.307から3世代目0.458となり,2世代から3世代目にかけて増加した. 一方Es-Dsの遺伝子頻度は2世代目0.693から3世代目0.542となり,3世代目では減少した. これに対して,無作為交配群ではいずれの遺伝子頻度も世代に伴う著しい変化は認められなかった. 4.近交群では,FF型の観察値は4世代まで期待値と適合した. またFS型とSS型の観察値は2世代までは期待値と適合したが,それ以後の世代では適合しなかった. これに対して,無作為交配群では観察値と期待値は適合した. 5.近交群では,生存系統が絶滅系統に比較してFS型のヘテロ接合体頻度は高く,一方SS型のホモ接合体頻度は低くなる傾向がみられた. 6.以上の結果から,日本ウズラにおいて近交世代を進めた場合エステラーゼDのヘテロ接合体はホモ接合体に比べて有利であること,および近交退化は遺伝子のホモ接合体の増加とポリジーン系のヘテロ性の低下に起因することが示唆された

Novel mechanism of photoinduced reversible phase transitions in molecule-based magnets

A novel microscopic mechanism of bi-directional structural changes is proposed for the photo-induced magnetic phase transition in Co-Fe Prussian blue analogues on the basis of ab initio quantum chemical cluster calculations. It is shown that the local potential energies of various spin states of Co are sensitive to the number of nearest neighbor Fe vacancies. As a result, the forward and backward structural changes are most readily initiated by excitation of different local regions by different photons. This mechanism suggests an effective strategy to realize photoinduced reversible phase transitions in a general system consisting of two local components.Comment: 4 pages, LaTex, 3 figures, to appear in Phys. Rev. Let

Tumor-Derived Microvesicles Induce Proangiogenic Phenotype in Endothelial Cells via Endocytosis

Background: Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). Our previous reports also showed that TEC were different from NEC. For example, TEC have chromosomal abnormality and proangiogenic properties such as high motility and proliferative activity. However, the mechanism by which TEC acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies have shown that TMV contain numerous types of bioactive molecules and affect normal stromal cells in the tumor microenvironment. However, most of the functional mechanisms of TMV remain unclear. Methodology/Principal Findings: Here we showed that TMV isolated from tumor cells were taken up by NEC through endocytosis. In addition, we found that TMV promoted random motility and tube formation through the activation of the phosphoinositide 3-kinase/Akt pathway in NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis inhibitor dynasore. Our results indicate that TMV could confer proangiogenic properties to NEC partly via endocytosis. Conclusion: We for the first time showed that endocytosis of TMV contributes to tumor angiogenesis. These findings offer new insights into cancer therapies and the crosstalk between tumor and endothelial cells mediated by TMV in the tumor microenvironment