Hemodynamic Analysis of a Microanastomosis Using Computational Fluid Dynamics

[Background] Technical issues in free flap transfer, such as the selection of recipient vessels and the positioning and method of anastomosis of the vascular pedicle, have been the subject of vigorous debate. Recent developments in computational fluid dynamics (CFD) have enabled the analysis of blood flow within microvessels. In this study, CFD was used to analyze hemodynamics in a microanastomosis. [Methods] In the fluid calculation process, the fluid domain modelizes microvessels with anastomosis. The inlet flow conditions were measured as venous waveform, and the fluid is simulated as blood. Streamlines (SL), wall shear stress (WSS), and oscillatory shear index (OSI) at the anastomosis were visualized and analyzed for observing effects from the flow field. [Results] Some flow disruption was evident as the SL passed over the sutures. The maximum recorded WSS was 13.37 Pa where the peak of a suture was exposed in the lumen. The local maximum value of the OSI was 0.182, recorded at the base of the anastomosis on the outflow side. [Conclusion] In the ideal anastomosis, the SL is disrupted as little as possible by the sutures. The WSS indicated that thrombus formation is unlikely to occur at suture peaks, but more likely to occur at the base of sutures, where the OSI is high. Tight suture knots are important in microanastomosis

Profile of Blood Glucose in Diabetic Patient Suffered from Diabetic Foot Osteomyelitis with Effective Low Carbohydrate Diet

The case was 52-year-old female with type 2 diabetes mellitus (T2DM) for 10-years. She complained of the decreased sensation of right lower foot, and revealed diabetic foot infection (DFI) and/or diabetic foot osteomyelitis (DFO) at right 1st proximal phalanx. Various data included body mass index (BMI) 33.3 kg/m2, HbA1c 11.4%, blood glucose 430 mg/dL, WBC 12100 /μL, C-reactive Protein (CRP) 13.5 mg/dL. On admission (day 1), she was started by 4 times of injection (Aspart and Glargin) with glucose profile 200-500 mg/dL. Surgical amputation of the right toe was performed between 1st metatarsal and proximal phalanx (day 17). Then, blood glucose profile decreased moderately. After discharge of the hospital, super-Low Carbohydrate Diet (LCD) was started without Aspart (day 37). Consequently, glucose profile was normalized with HbA1c 6.3% on (day 77). Consequently, LCD was evaluated to be effective for glucose variability in this case and some related discussion was described

Evaluation of transporter-mediated hepatobiliary transport of newly developed ¹⁸F-labeled pitavastatin derivative, PTV-F1, in rats by PET imaging

Quantitative evaluations of the functions of uptake and efflux transporters directly in vivo is desired to understand an efficient hepatobiliary transport of substrate drugs. Pitavastatin is a substrate of organic anion transporting polypeptides (OATPs) and canalicular efflux transporters; thus, it can be a suitable probe for positron-emission tomography (PET) imaging of hepatic transporter functions. To characterize the performance of [¹⁸F]PTV-F1, an analogue of pitavastatin, we investigated the impact of rifampicin (a typical OATP inhibitor) coadministration or Bcrp (breast cancer resistance protein) knockout on [¹⁸F]PTV-F1 hepatic uptake and efflux in rats by PET imaging. After intravenous administration, [¹⁸F]PTV-F1 selectively accumulated in the liver, and the radioactivity detected in plasma, liver, and bile mainly derived from the parent PTV-F1 during the PET study (∼40 min). Coadministration of rifampicin largely decreased the hepatic uptake of [¹⁸F]PTV-F1 by 73%. Because of its lower clearance in rats, [¹⁸F]PTV-F1 is more sensitive for monitoring changes in hepatic OATP1B function that other previously reported OATP1B PET probes. Rifampicin coadministration also significantly decreased the biliary excretion of radioactivity by 65%. Bcrp knockout did not show a significant impact on its biliary excretion.[¹⁸F]PTV-F1 enables quantitative analysis of the hepatobiliary transport system for organic anions

Serologic Markers in Relation to Parasite Exposure History Help to Estimate Transmission Dynamics of Plasmodium vivax

Plasmodium vivax infection has been gaining attention because of its re-emergence in several parts of the world. Southeastern Turkey is one of the places in which persistent focal malaria caused exclusively by P. vivax parasites occurs. Although control and elimination studies have been underway for many years, no detailed study has been conducted to understand the mechanisms underlying the ineffective control of malaria in this region. Here, for the first time, using serologic markers we try to extract as much information as possible in this region to get a glimpse of P. vivax transmission. We conducted a sero-immunological study, evaluating antibody responses of individuals living in Sanliurfa to four different P. vivax antigens; three blood-stage antigens (PvMSP119, PvAMA1-ecto, and PvSERA4) and one pre-erythrocytic stage antigen (PvCSP). The results suggest that a prior history of malaria infection and age can be determining factors for the levels and sustainability of naturally acquired antibodies. Significantly higher antibody responses to all the studied antigens were observed in blood smear-negative individuals with a prior history of malaria infection. Moreover, these individuals were significantly older than blood smear-negative individuals with no prior history of infection. These data from an area of sole P. vivax-endemic region may have important implications for the global malaria control/elimination programs and vaccine design

Generation of Tetrafluoroethylene–Propylene Elastomer-Based Microfluidic Devices for Drug Toxicity and Metabolism Studies

フッ素系エラストマー素材を用いた肝臓チップの開発と薬物代謝・毒性試験への応用. 京都大学プレスリリース. 2021-09-16.Drug testing on miniatured livers. 京都大学プレスリリース. 2021-09-17.Polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic organs-on-chips. Using these devices (PDMS-based devices), the mechanical microenvironment of living tissues, such as pulmonary respiration and intestinal peristalsis, can be reproduced in vitro. However, the use of PDMS-based devices in drug discovery research is limited because of their extensive absorption of drugs. In this study, we investigated the feasibility of the tetrafluoroethylene–propylene (FEPM) elastomer to fabricate a hepatocyte-on-a-chip (FEPM-based hepatocyte chip) with lower drug absorption. The FEPM-based hepatocyte chip expressed drug-metabolizing enzymes, drug-conjugating enzymes, and drug transporters. Also, it could produce human albumin. Although the metabolites of midazolam and bufuralol were hardly detected in the PDMS-based hepatocyte chip, they were detected abundantly in the FEPM-based hepatocyte chip. Finally, coumarin-induced hepatocyte cytotoxicity was less severe in the PDMS-based hepatocyte chip than in the FEPM-based hepatocyte chip, reflecting the different drug absorptions of the two chips. In conclusion, the FEPM-based hepatocyte chip could be a useful tool in drug discovery research, including drug metabolism and toxicity studies

A novel transgenic chimaeric mouse system for the rapid functional evaluation of genes encoding secreted proteins

A major challenge of the post-genomic era is the functional characterization of anonymous open reading frames (ORFs) identified by the Human Genome Project. In this context, there is a strong requirement for the development of technologies that enhance our ability to analyze gene functions at the level of the whole organism. Here, we describe a rapid and efficient procedure to generate transgenic chimaeric mice that continuously secrete a foreign protein into the systemic circulation. The transgene units were inserted into the genomic site adjacent to the endogenous immunoglobulin (Ig) κ locus by homologous recombination, using a modified mouse embryonic stem (ES) cell line that exhibits a high frequency of homologous recombination at the Igκ region. The resultant ES clones were injected into embryos derived from a B-cell-deficient host strain, thus producing chimaerism-independent, B-cell-specific transgene expression. This feature of the system eliminates the time-consuming breeding typically implemented in standard transgenic strategies and allows for evaluating the effect of ectopic transgene expression directly in the resulting chimaeric mice. To demonstrate the utility of this system we showed high-level protein expression in the sera and severe phenotypes in human EPO (hEPO) and murine thrombopoietin (mTPO) transgenic chimaeras

異教科で協働できる教員を育成するための実践的研究（1） : 教科教育学専攻の共通科目の始動を通じて

本研究は，平成28 年度より始まった「教科教育学専攻」における新しい共通科目（「教科教育学研究方法論」，「教科教育学融合プロジェクト」，「教科教育学の実践的展開」，「教科教育学の実践的検証」）が始動する際に得られた知見を分析・考察し報告するもので，その全容は平成29 年３月に公開予定のホームページで公表される。本報告書は，その研究の要旨を，(1)　経緯について，(2)　各教科について，(3)　実践からの考察，(4)　理論からの考察，(5)　学生の振り返りからの考察の五点から述べる

Phylogenetic groups and cephalosporin resistance genes of Escherichia coli from diseased food-producing animals in Japan

A total of 318 Escherichia coli isolates obtained from different food-producing animals affected with colibacillosis between 2001 and 2006 were subjected to phylogenetic analysis: 72 bovine isolates, 89 poultry isolates and 157 porcine isolates. Overall, the phylogenetic group A was predominant in isolates from cattle (36/72, 50%) and pigs (101/157, 64.3%) whereas groups A (44/89, 49.4%) and D (40/89, 44.9%) were predominant in isolates from poultry. In addition, group B2 was not found among diseased food-producing animals except for a poultry isolate. Thus, the phylogenetic group distribution of E. coli from diseased animals was different by animal species. Among the 318 isolates, cefazolin resistance (minimum inhibitory concentrations: ≥32 μg/ml) was found in six bovine isolates, 29 poultry isolates and three porcine isolates. Of them, 11 isolates (nine from poultry and two from cattle) produced extended spectrum β-lactamase (ESBL). The two bovine isolates produced blaCTX-M-2, while the nine poultry isolates produced blaCTX-M-25 (4), blaSHV-2 (3), blaCTX-M-15 (1) and blaCTX-M-2 (1). Thus, our results showed that several types of ESBL were identified and three types of β-lactamase (SHV-2, CTX-M-25 and CTX-M-15) were observed for the first time in E. coli from diseased animals in Japan