MICROCOMPUTER BASED CONTROL SYSTEM FOR LEFT VENTRICULAR ASSIST PUMP

During the left ventricular bypass, it is important to keep the arterial and atrial pressures at a physiological level to maintain the circulation and at the same time to rest the failing heart (recovery of the failing heart). We have developed a microcomputer based control system for the left ventricular assist pump (LVAP). The control system regulates the arterial and atrial pressures at a physiological level by adjusting the cardiac output of the LVAP. The superior feature of the control system is that it has an indirect measuring system. The arterial and atrial pressures are observed from the careful analysis of pressure in the LVAP air chamber. The assist air pressure shows that the air pressure at the specific momentary points when a diaphragm begins to move reflects the pressure in proportion to the arterial or atrial pressure. The specific momentary points are monitored by an optical diaphragm position sensor when a diaphragm begins to move at a systolic or diastolic period of LVAP, and the pressures at those points are measured by means of a drive air pressure transducer. A microcomputer obtains the indirectly measured arterial and atrial pressures through the A/D converters. The control system regulates the cardiac output of LVAP by adjusting the driving conditions (driving pressure, vacuum pressure, ejection duration, and driving rate) according to the indirectly monitored parameters. The control system consists of an optical diaphragm position sensor, pulse motor driven pressure regulators, a drive air pressure transducer, and a microcomputer. As a result of in vitro experiments, the control system regulated the arterial and atrial pressures smoothly at a desired level

A medaka model of cancer allowing direct observation of transplanted tumor cells in vivo at a cellular-level resolution

The recent success with small fish as an animal model of cancer with the aid of fluorescence technique has attracted cancer modelers\u27 attention because it would be possible to directly visualize tumor cells in vivo in real time. Here, we report a medaka model capable of allowing the observation of various cell behaviors of transplanted tumor cells, such as cell proliferation and metastasis, which were visualized easily in vivo. We established medaka melanoma (MM) cells stably expressing GFP and transplanted them into nonirradiated and irradiated medaka. The tumor cells were grown at the injection sites in medaka, and the spatiotemporal changes were visualized under a fluorescence stereoscopic microscope at a cellular-level resolution, and even at a single-cell level. Tumor dormancy and metastasis were also observed. Interestingly, in irradiated medaka, accelerated tumor growth and metastasis of the transplanted tumor cells were directly visualized. Our medaka model provides an opportunity to visualize in vivo tumor cells "as seen in a culture dish" and would be useful for in vivo tumor cell biology

Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model.

Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S. pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S. pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S. pneumoniae in the BALF and the concentration of S. pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia

Synthesis of Aryl <i>C</i>‑Glycosides via Iron-Catalyzed Cross Coupling of Halosugars: Stereoselective Anomeric Arylation of Glycosyl Radicals

We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl <i>C</i>-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron­(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The chemoselective nature of the reaction allows the use of synthetically versatile acetyl-protected glycosyl donors and the incorporation of various functional groups on the aryl moieties, producing a diverse array of aryl <i>C</i>-glycosides, including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and a prevailing diabetes drug. The cross-coupling reaction proceeds via generation and stereoselective trapping of glycosyl radical intermediates, representing a rare example of highly stereoselective carbon–carbon bond formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-<i>O</i>-acetyl-2-<i>O</i>-allyl-α-d-glucopyranosyl bromide (<b>8</b>) and 6-bromo-1-hexene (<b>10</b>) confirm the generation and intermediacy of the corresponding glycosyl radicals. Density functional theory (DFT) calculations reveal that the observed anomeric diastereoselectivity is attributable to the relative stability of the conformers of glycosyl radical intermediates. The present cross-coupling reaction demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon–carbon bond formation in the synthesis of bioactive compounds of certain structural complexity

Synthesis of Aryl <i>C</i>‑Glycosides via Iron-Catalyzed Cross Coupling of Halosugars: Stereoselective Anomeric Arylation of Glycosyl Radicals

We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl <i>C</i>-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron­(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The chemoselective nature of the reaction allows the use of synthetically versatile acetyl-protected glycosyl donors and the incorporation of various functional groups on the aryl moieties, producing a diverse array of aryl <i>C</i>-glycosides, including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and a prevailing diabetes drug. The cross-coupling reaction proceeds via generation and stereoselective trapping of glycosyl radical intermediates, representing a rare example of highly stereoselective carbon–carbon bond formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-<i>O</i>-acetyl-2-<i>O</i>-allyl-α-d-glucopyranosyl bromide (<b>8</b>) and 6-bromo-1-hexene (<b>10</b>) confirm the generation and intermediacy of the corresponding glycosyl radicals. Density functional theory (DFT) calculations reveal that the observed anomeric diastereoselectivity is attributable to the relative stability of the conformers of glycosyl radical intermediates. The present cross-coupling reaction demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon–carbon bond formation in the synthesis of bioactive compounds of certain structural complexity

Synthesis of Aryl <i>C</i>‑Glycosides via Iron-Catalyzed Cross Coupling of Halosugars: Stereoselective Anomeric Arylation of Glycosyl Radicals

We have developed a novel diastereoselective iron-catalyzed cross-coupling reaction of various glycosyl halides with aryl metal reagents for the efficient synthesis of aryl <i>C</i>-glycosides, which are of significant pharmaceutical interest due to their biological activities and resistance toward metabolic degradation. A variety of aryl, heteroaryl, and vinyl metal reagents can be cross-coupled with glycosyl halides in high yields in the presence of a well-defined iron complex, composed of iron­(II) chloride and a bulky bisphosphine ligand, TMS-SciOPP. The chemoselective nature of the reaction allows the use of synthetically versatile acetyl-protected glycosyl donors and the incorporation of various functional groups on the aryl moieties, producing a diverse array of aryl <i>C</i>-glycosides, including Canagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), and a prevailing diabetes drug. The cross-coupling reaction proceeds via generation and stereoselective trapping of glycosyl radical intermediates, representing a rare example of highly stereoselective carbon–carbon bond formation based on iron catalysis. Radical probe experiments using 3,4,6-tri-<i>O</i>-acetyl-2-<i>O</i>-allyl-α-d-glucopyranosyl bromide (<b>8</b>) and 6-bromo-1-hexene (<b>10</b>) confirm the generation and intermediacy of the corresponding glycosyl radicals. Density functional theory (DFT) calculations reveal that the observed anomeric diastereoselectivity is attributable to the relative stability of the conformers of glycosyl radical intermediates. The present cross-coupling reaction demonstrates the potential of iron-catalyzed stereo- and chemoselective carbon–carbon bond formation in the synthesis of bioactive compounds of certain structural complexity