Biomedical subjects

Ryo Matsushita

Publications and source records attributed to Ryo Matsushita.

7 recordsLinked to original sources

PubMed2004

In vitro detection of mdr1 mRNA in murine leukemia cells with 111In-labeled oligonucleotide.

PURPOSE: The feasibility of intracellular mdr1 mRNA expression detection with radiolabeled antisense oligonucleotide (ODN) was investigated in the murine leukemia cell line, P388/S, and its subclonal, adriamycin-resistant cell line, P388/R. METHODS: The expression level of mdr1 mRNA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Existence of the multidrug resistance (MDR) phenomenon was assessed via cellular uptake of 99mTc-sestamibi (MIBI), a known substrate for P-glycoprotein. A 15-mer phosphorothioate antisense ODN complementary to the sequences located at -1 to 14 of mdr1 mRNA and its corresponding sense ODN were conjugated with the cyclic anhydride of diethylene triamine penta-acetic acid (cDTPA) via an amino group linked to the terminal phosphate at the 5' end at pH 8-9. The DTPA-ODN complexes at concentrations of 0.1-17.4 microM were reacted with 111InCl3 at pH 5 for 1 h. The hybridization affinity of labeled ODN was evaluated with size-exclusion high-performance liquid chromatography following incubation with the complementary sequence. Cellular uptake of labeled ODN was examined in vitro. Furthermore, enhancing effects of synthetic lipid carriers (Transfast) on transmembrane delivery of ODN were assessed. RESULTS: P388/R cells displayed intense mdr1 mRNA expression in comparison with P388/S cells. 99mTc-MIBI uptake in P388/S cells was higher than that in P388/R cells. Specific radioactivity up to 1,634 MBq/nmol was achieved via elevation of added radioactivity relative to ODN molar amount. The hybridization affinity of antisense 111In-ODN was preserved at approximately 85% irrespective of specific activity. Cellular uptake of antisense 111In-ODN did not differ from that of sense 111In-ODN in either P388/S cells or P388/R cells. However, lipid carrier incorporation significantly increased transmembrane delivery of 111In-ODN; moreover, specific uptake of antisense 111In-ODN was demonstrated in P388/R cells. CONCLUSION: Radiolabeling of ODN at high specific radioactivity and specific uptake of antisense 111In-ODN in drug-resistant cells may facilitate future gene imaging of mdr1 mRNA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

A comparative study of laboratory parameters and symptoms effected by Toki-shakuyaku-san and an iron preparation in rats with iron-deficiency anemia.

In order to more closely examine the effect of Toki-shakuyaku-san and an iron preparation in vivo in an animal experiment, we prepared anemic rats, divided them into 4 groups, i.e., an untreated group, a Toki-shakuyaku-san group, an iron-preparation group and a Toki-shakuyaku-san+iron-preparation group, and assessed the results of laboratory parameters, hematology, and general symptoms of anemia. The results showed trends toward improvement in indices of anemia, i.e., erythrocyte (RBC) count, hemoglobin (Hb), hematocrit (Ht) and serum iron (Fe), and improvement of anemic symptoms in the 3 treated groups. Examination of erythrocyte morphology showed that erythrocyte destruction had occurred only slightly in the 3 treated groups. The organ weight measurements showed an increase in the weight of the heart and spleen in the untreated group, but tended to be closer to normal in the 3 treated groups. The number and wet weight of the feces in the untreated group were markedly lower than normal, but increased in the Toki-shakuyaku-san group. In the iron-preparation group, the hemorrhage of stomach and pigmentation of the tail which seem to be a side effect of iron were observed, but was not seen in the Toki-shakuyaku-san group. The results animal experiment more closely examined the results of clinical study, and we concluded that by using Toki-shakuyaku-san and the iron preparation in combination, it is possible to lessen the adverse reactions such as gastrointestinal symptoms, and that more ameliorative effect on the anemic state can be expected.

Anemia, Iron-Deficiency↗

PubMed2003

A comparative study of the usefulness of toki-shakuyaku-san and an oral iron preparation in the treatment of hypochromic anemia in cases of uterine myoma.

We prospectively studied and compared the usefulness of Kampo medicine (Sino-Japanese traditional herbal medicine) "Toki-shakuyaku-san" and an oral iron preparation in the treatment of hypochromic anemia associated with uterine myoma. The study subjects consisted of 25 patients who were diagnosed as having hypochromic mild to moderate anemia associated with menorrhagia attributable to uterine myoma. They were divided into the Toki-shakuyaku-san group (n = 10) and the oral iron group (n = 15). We monitored the blood counts, subjective symptoms, and occurrence of side effects after oral administration of either preparation for 4 and 8 weeks in these subjects. In regard to the blood counts and improvements of the laboratory parameters of anemia, while marked improvement was observed in the oral iron group, no significant improvement was noted in the Toki-shakuyaku-san group. On the other hand, in terms of improvement of the signs and symptoms of anemia, such as facial pallor, spoon-shaped nails and dizziness, the latter group also showed significant improvement. In addition in the Toki-shakuyaku-san group, resolution of symptoms such as hypermenorrhea, dysmenorrhea, feeling cold, dizziness, headache and shoulder stiffness was also noted. While side effects were encountered in 80.0% of patients in the oral iron group, no significant side effects were observed in the Toki-shakuyaku-san group. From these findings, it is considered that Toki-shakuyaku-san may be useful for resolving the symptoms of mild or moderate anemia associated with uterine myoma.

Administration, Oral↗

PubMed2003

[Objective evaluation of clinical pharmacy lectures and experience in a master program using visual analog scale method].

We conducted an investigation to determine whether the visual analogue scale (VAS) method could be utilized in evaluating the lectures and pharmacy experience of the Division of Pharmacy and Health Sciences, Graduate School of Natural Science and Technology, Kanazawa University. Graduate students who had finished the 1-year pharmacy experience at the Kanazawa University Hospital were asked to make a self-evaluation of the understanding/attainment of lectures and experience in the course. Since the experience was carried out as a one-student-to-one-pharmacist system, the preceptors (pharmacists) were also asked to evaluate their corresponding students. When evaluating the necessity of the lectures, students tended to feel that the medical science- or pharmacotherapy-related subjects were important and those of social sciences were less important. These results suggest the need to review the contents of the lectures to enhance the interests of the students in the latter. By comparing the extent of understanding of each lecture before and after pharmacy experience, it was found that students had a better understanding of the lectures through their experience. In most results from the answers in pharmacy experience, students also scored themselves higher than their preceptors. Therefore comparisons of evaluation may provide more objective results in pharmacy experience. It was demonstrated that utilization of the VAS method and comparing the data are very useful in evaluating not only students' understanding/attainment but also the importance and usefulness of lectures and pharmacy experience in an objective way.

Adult↗

PubMed2002

Causative agent of vascular pain among photodegradation products of dacarbazine.

The photodegradation products of the anticancer drug, dacarbazine, cause adverse reactions including local venous pain when injected intravenously. In this study, we attempted to identify which of these products is responsible. We synthesized or purchased five photodegradation products of dacarbazine (dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate and 2-azahypoxanthine) and examined the pain reaction induced by their intraperitoneal administration in mice using an abdominal stretching or constriction assay. Only Diazo-IC clearly induced pain reaction in mice in a dose-dependent manner, the other products caused no pain reaction. The threshold concentration for pain reaction in mice was estimated to be about 0.1 mg mL-1. While diclofenac sodium significantly reduced acetic-acid-induced pain reaction in mice, it did not influence those induced by Diazo-IC. This result suggests that the mechanism of Diazo-IC-induced pain is different from that of acetic-acid-induced inflammatory pain. Dacarbazine itself produced marked relaxation of rat thoracic aorta strips in a concentration-dependent manner, but there was no difference between the activity of dacarbazine and its photo-exposed solution, so constriction or relaxation of blood vessels is unlikely to be a factor in the pain reaction. In conclusion, Diazo-IC generated by photodegradation of dacarbazine solution causes the side-effect of venous pain. Dacarbazine solution that has turned pink should not be used, because Diazo-IC is an intermediate in the formation of the reddish product, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo)imidazolium-5-olate. Drip infusion preparations of dacarbazine should be shielded from light.

Abdomen↗

PubMed2002

Evaluation of predictability for vancomycin dosage regimens by the Bayesian method with Japanese population pharmacokinetic parameters.

The predictability of serum vancomycin (VCM) concentrations by means of the Bayesian method was evaluated to establish whether the method can be used to select safe and effective VCM treatment regimens for individual patients. Serum VCM concentrations at the trough and 2 h after the end of infusion (peak) were measured. Pharmacokinetic parameters were calculated for VCM dosage regimens based on a two-compartment model with the Bayesian method, using the Japanese population pharmacokinetic parameters estimated by Yasuhara et al. (1998). The predictive performance for serum VCM concentrations and the dosage regimens were analyzed using two points of serum VCM concentration in 41 patients whose serum creatinine and age were in the ranges of 0.4-4.6 mg/dl and 24-92 years, respectively. Although the predicted values for trough and peak VCM concentrations were slightly lower than measured VCM concentrations, the predictive performance was generally good. There were no differences among the groups classified by serum creatinine or age. An examination of predicted data that differed markedly from the measured serum VCM concentrations indicated that a larger difference in volume of distribution at the steady state (Vdss) calculated from serum VCM concentrations at the beginning and revision of dosage regimens resulted in a poorer correlation of predicted values and measured values. This finding indicates that therapeutic drug monitoring should be conducted frequently, and the dosage regimen revised accordingly, in the case of patients who may have a change of Vdss of VCM, for example, due to a complication such as heart failure or edema.

Adult↗

PubMed2002

[The effects of the revision of medical repayment standards on pharmaceutical counseling services and revenue at pediatrics of Kanazawa University Hospital].

This paper analyzes the effects of the revision of medical repayment standards in April 2000 on pharmaceutical care and economics. The total number of sessions of counseling that can be claimed in 1 month has apparently improved at the Pediatrics Department of Kanazawa University Hospital. On the other hand, actual repayment for said services has not necessarily risen accordingly. This was shown by adopting new calculation modalities for actual claims before revision. We believe that this discrepancy occurs because the charge for each service has decreased from 480 points to 350 points, while maximum number of effective claims per month has risen from twice to four times.

Child↗