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Biomedical subjects

Akira Kamiya

Publications and source records attributed to Akira Kamiya.

30 records · Page 2Linked to original sources

Differential regulation of urokinase-type plasminogen activator expression by fluid shear stress in human coronary artery endothelial cells.

Atherosclerotic plaques preferentially localize at arterial regions exposed to turbulent low-shear flow. Urokinase-type plasminogen activator (uPA) plays a role in vascular remodeling by facilitating smooth muscle cell migration and proliferation in addition to the proteolysis of extracellular matrix, and the expression of uPA is elevated in atherosclerotic lesions. In this study, we analyzed the effects of laminar and turbulent shear stress on uPA expression in cultured human coronary artery endothelial cells. The application of laminar shear stress (1.5 or 15 dyn/cm2) significantly decreased the amount of uPA mRNA as well as the secretion of uPA protein. In contrast, turbulent shear stress (average intensity, 1.5 dyn/cm2) markedly increased uPA gene expression and protein secretion. Laminar shear stress downregulated uPA gene expression transcriptionally and posttranscriptionally; laminar shear stress activated transcription factor GATA6, which binds to a GATA consensus element located between -692 and -687 bp in the uPA promoter, thereby inhibiting uPA gene transcription. Laminar shear stress also accelerated the degradation of uPA mRNA; the half-life of uPA mRNA decreased to about half of the static control's half-life. Although turbulent shear stress had no effect on the transcription of uPA, it significantly increased uPA mRNA stability; the half-life of uPA mRNA increased by about two times the static control's half-life. Our results suggest that endothelial uPA expression is flow sensitive and differentially regulated by laminar and turbulent shear stress in vitro. We speculate that this effect may contribute to the local nature of atherosclerosis.

Arteries↗

[The role of pharmacists for promotion of cancer chemotherapy in outpatients].

To promote cancer chemotherapy among outpatients, a special room for cancer chemotherapy (outpatient drip infusion room) was established in Yamaguchi University Hospital in April 2002. Since then, pharmacists have played a central role in all aspects, including decisions on the flow rate for prescriptions/injections, protocol checking, preparation of injections, aseptic preparation of anticancer agents, provision of information to patients, and financial impact analysis. In this study, we analyzed the current status of these activities and conducted a questionnaire survey regarding the involvement of pharmacists in chemotherapy at the outpatient clinic among patients and physicians. Pharmacists contributed to the administration of anticancer agents, including protocol checking and aseptic preparation, and no malpractice incident has occurred since the outpatient drip infusion room was established. According to responses from patients, 28 of 29 patients reported that they underwent treatment without anxiety. According to responses from physicians, 15 of 18 physicians considered the involvement of pharmacists beneficial. In addition, the amount claimed for health insurance as of March 2003 was 500000 yen, which was about 5-fold that before the establishment of the outpatient drip infusion room. These results suggest that pharmacists contribute to the promotion of cancer chemotherapy in outpatients with respect to the safety of medical practice, patient services, and hospital management. Therefore participation in cancer chemotherapy at the outpatient clinic may become a primary activity of pharmacists.

Antineoplastic Agents↗

In vitro effects of combinations of antipseudomonal agents against seven strains of multidrug-resistant Pseudomonas aeruginosa.

OBJECTIVES: The aim of this study was to evaluate the combined effects of antibiotic combinations by agar incorporation inhibitory tests and by time-kill tests on seven geographically and epidemiologically distinct isolates of multidrug-resistant Pseudomonas aeruginosa. All seven strains were resistant to piperacillin, meropenem, ceftazidime, cefoperazone-sulbactam, aztreonam, amikacin and ciprofloxacin. METHODS: Strains were distinguished by pulsed-field gel electrophoresis after DNA extraction and restriction with SpeI. MICs of the seven antibiotics listed above were determined by agar dilution. The effect of combinations of these agents was determined by agar incorporation tests and by time-kill studies. RESULTS: Among the two-drug combinations, the combination aztreonam and amikacin was the most effective, inhibiting proliferation in five of the seven strains. Among the three-drug combinations, the combinations of piperacillin, ceftazidime and amikacin, and that of ceftazidime, aztreonam and amikacin were the most effective, inhibiting proliferation in all seven strains. In the killing tests, the three-drug combination of ceftazidime, aztreonam and amikacin was the most effective. This three-drug combination had bacteriostatic effects on all seven strains 2, 4, 6 and 24 h after drug addition, synergic effects on 2-3 strains and bactericidal effects on 1-2 strains after 4, 6 and 24 h. CONCLUSIONS: The three-drug combination of ceftazidime, aztreonam and amikacin may be effective against P. aeruginosa resistant to all commonly used antipseudomonal drugs, and deserves further study.

Anti-Bacterial Agents↗

Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress.

Endothelial progenitor cells (EPCs), circulating in peripheral blood, migrate toward target tissue, differentiate, and contribute to the formation of new vessels. In this study, we report that shear stress generated by blood flow or tissue fluid flow can accelerate the proliferation, differentiation, and capillary-like tube formation of EPCs. When EPCs cultured from human peripheral blood were subjected to laminar shear stress, the cells elongated and oriented their long axes in the direction of flow. The cell density of the EPCs exposed to shear stress was higher, and a larger percentage of these cells were in the G2-M phase of the cell cycle, compared with EPCs cultured under static conditions. Shear stress markedly increased the EPC expression of two vascular endothelial growth factor receptors, kinase insert domain-containing receptor and fms-like tyrosine kinase-1, and an intercellular adhesion molecule, vascular endothelial-cadherin, at both the protein and mRNA levels. Assays for tube formation in the collagen gels showed that the shear-stressed EPCs formed tubelike structures and developed an extensive tubular network significantly faster than the static controls. These findings suggest that EPCs are sensitive to shear stress and that their vasculogenic activities may be modulated by shear stress.

Antigens, CD↗

Endogenously released ATP mediates shear stress-induced Ca2+ influx into pulmonary artery endothelial cells.

The mechanisms by which flow-imposed shear stress elevates intracellular Ca2+ in cultured endothelial cells (ECs) are not fully understood. Here we report finding that endogenously released ATP contributes to shear stress-induced Ca2+ responses. Application of flow of Hanks' balanced solution to human pulmonary artery ECs (HPAECs) elicited shear stress-dependent increases in Ca2+ concentrations. Chelation of extracellular Ca2+ with EGTA completely abolished the Ca2+ responses, whereas the phospholipase C inhibitor U-73122 or the Ca2+-ATPase inhibitor thapsigargin had no effect, which thereby indicates that the response was due to the influx of extracellular Ca2+. The Ca2+ influx was significantly suppressed by apyrase, which degrades ATP, or antisense oligonucleotide targeted to P2X4 purinoceptors. A luciferase luminometric assay showed that shear stress induced dose-dependent release of ATP. When the ATP release was inhibited by the ATP synthase inhibitors angiostatin or oligomycin, the Ca2+ influx was markedly suppressed but was restored by removal of these inhibitors or addition of extracellular ATP. These results suggest that shear stress stimulates HPAECs to release ATP, which activates Ca2+ influx via P2X4 receptors.

Adenosine Triphosphate↗

Microbial viability in preparations packaged for single use.

We evaluated microbial viability in preparations packaged for single use only which mandate that residual solution be discarded such as albumin and globulin preparations as blood products, preparations containing albumin (such as urokinase and interferon), fat emulsions, and a preparation containing fat emulsions (propofol). In most preparations, Serratia marcescens and Burkholderia cepacia proliferated rapidly at 30 degrees C. However, in globulin preparations containing 1-2.25% glycine to prevent protein degradation (Gamma-Venin P, Venilon-I, Globulin Injection, and Ahlbulin), no growth of S. marcescens and B. cepacia was detected over 24 h at 30 degrees C. For globulin preparations containing 1-2.25% glycine, the injunction to "Discard residual solution after the package has been used" in the package inserts can be revised to "It is possible to use residual solution within 24 h after the package has been used with storage in a cool place."

Bacteria↗

Efficacy of disinfectants and hot water against biofilm cells of Burkholderia cepacia.

The effects of various disinfectants and hot water on planktonic cells and biofilm cells of Burkholderia cepacia were investigated. The survival rate of viable B. cepacia cells in suspension decreased to 0.001% or lower within 15 s of exposure to 0.5% benzalkonium chloride, within 30 s of exposure to 0.5% alkyldiaminoethyl glycine, or within 1 min of exposure to 0.1% alkyldiaminoethyl glycine, and decreased to about 0.1% with 60 min of exposure to 0.1% benzalkonium chloride or 0.5% chlorhexidine gluconate, but did not decrease to 1% or less with 60 min of exposure to 0.1% chlorhexidine gluconate. There were no effects of 0.1% and 0.2% chlorhexidine gluconate and 0.1% benzalkonium chloride against biofilm cells of B. cepacia, and 0.5% chlorhexidine gluconate, 0.5% benzalkonium chloride and 0.1% alkyldiaminoethyl glycine were barely effective against biofilm cells even after 60-min exposure. On the other hand, both planktonic cells and biofilm cells of B. cepacia were eradicated within 15 s by sodium hypochlorite, povidone-iodine, 80% v/v ethanol, and hot water at 65 degrees C or higher.

Biofilms↗

[Establishment and evaluation of a system for preventing mis-administration of powder using bar codes printed on drug envelopes].

Even if drugs are accurately dispensed, it is difficult to ensure their safety in the absence of an error-free medication system when or after drugs are given to patients. In particular, most powders are white and are impossible to distinguish based on appearance after they are placed in powder packages. In this study, we newly developed a system in which prescription order information is bar-coded on drug envelopes, and read when powder is folded, facilitating efficient and accurate printing of the patient's name and drug name on powder packages. Seventy-one (86%) of 83 nurses surveyed indicated that the system was useful for resolving high-risk problems they had experienced: "when powder was taken from the envelope, the contents were unknown", and "the powder was administered to another patient."

Drug Labeling↗

Assessment of and intervention for the misuse of aldehyde disinfectants in Japan.

A survey of 145 Japanese hospitals revealed the use of 4 inappropriate aldehyde disinfection methods in 5.5% to 16.8%. Following education, there was discontinuation of 3 of these practices in 26 of 28 affected centers, but only 4 of 18 affected centers stopped the use of formaldehyde vapor cabinets. There is a need to inform hospitals about inappropriate disinfection methods that pose chemical risks to patients and staff.

Disinfectants↗

In vitro susceptibility of four serotypes of enterohaemorrhagic Escherichia coli to antimicrobial agents.

We evaluated the in vitro susceptibility of four serotypes of enterohaemorrhagic Escherichia coli (E. coli 026, E. coli O111, E. coli O157, and E. coli O165) with diverse DNA patterns to antimicrobial agents. The minimum inhibitory concentrations (MIC) determined in a total of 83 strains using Mueller-Hinton agar under aerobic and anaerobic conditions were 0.015-0.12 microg/ml for ciprofloxacin, 0.06-1 microg/ml for norfloxacin, 2-64 microg/ml for fosfomycin without glucose-6-phosphate (G-6-P), 0.25-32 microg/ml for fosfomycin with G-6-P, 2- > or = 256 microg/ml for kanamycin, 0.125-2 microg/ml for cefoperazone, and 0.06-1 microg/ml for ceftazidime. The MIC of ciprofloxacin, norfloxacin, cefoperazone, and ceftazidime were low in all strains examined.

Anti-Bacterial Agents↗

[A checking system for injectable anticancer drugs using each patient's own data and its evaluation].

A checking system was developed for risk management of injectable anticancer drug use. Because the dosage and administration of injectable anticancer drugs vary with each patient, checking the prescription and aseptic i.v. admixing can be markedly complicated and time-consuming for pharmacists. The system we investigated in this study provided real-time checking of dosage, drip infusion rate, dosing periods, and dosing-free periods. The prescription parameters for this check included height, weight, body surface area, the medical history of each patient, the patient's ICD10 code' and disease indication from the package insert. Moreover, when preparing for aseptic i.v. admixing, the liquid volume after the anticancer drug has been mixed with other injectable drugs is calculated automatically. The time limits for stability after mixing and clinical laboratory test results are listed on the Work Sheet. As a result, 24 medication errors were prevented in the first 6 months of use of this system. These consisted of over- and under-doses, excessive dosing periods, insufficient dosing-free periods' etc. The time required for preparation of aseptic i.v. admixing decreased by 73% after introducing this system. Because clinical laboratory test results were referenced beforehand, patients to whom the drug should not be administered were recognized in advance. Thus 13 such cases were identified before i.v. admixing. Therefore this system may be useful in terms of rational anticancer drug use and risk management.

Antineoplastic Agents↗

Calcium-ion incorporation into titanium surfaces accompanied by electrochemical apatite-deposition.

The depths of calcium-ion incorporation into a commercially pure titanium and an experimental beta-type titanium alloy were determined using Auger electron spectroscopy. After the electrochemical deposition of apatite, new compositional gradients appeared in the profiles in which the Ca and P concentrations gradually decreased as a function of the depth up to 6-8 nm. The relative concentration of Ca in the outermost layer was higher than that of P. On the other hand, after the soaking in a simulated body fluid, the relative concentration of P was higher than that of Ca in the outermost layer. These results suggested that Ca ions were well incorporated into the outermost oxide layer of titanium accompanied by the electrochemical apatite-deposition on its surface.

Apatites↗