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YAKUGAKU ZASSHI, 126(4),265-272, 2006
We established adrenal medullary cell lines from transgenic mice expressing an oncogene, the temperature-sensitive simian virus 40 large T-antigen, under the control of the tyrosine hydroxylase promoter. A clonal cell line, named tsAM5D, conditionally grew at a permissive temperature of 33°C and exhibited the dopaminergic chromaffin cell phenotype as exemplified by the expression pattern of mRNA for catecholamine synthesizing-enzymes and secretory vesicle-associated proteins. tsAM5D cells proliferated at the permissive temperature in response to glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF) and ciliary neurotrophic factor (CNTF). At a nonpermissive temperature of 39°C, GDNF and CNTF acted synergistically to differentiate tsAM5D cells into neuron-like cells. In addition, tsAM5D cells caused to differentiate by GDNF plus CNTF at 39°C became dependent solely on nerve growth factor for their survival and showed markedly enhanced neurite outgrowth. In the presence of GDNF plus CNTF, the morphological change induced by the temperature shift was associated with up-regulated expression of neuronal marker genes including microtubule-associated protein 2, neuron-specific enolase, neurofilament, and growth-associated protein-43, indicating that the cells underwent neuronal differentiation. Thus, we demonstrated that tsAM5D cells could proliferate at permissive 33°C, and also had the capacity to terminally differentiate into neuron-like cells in response to GDNF plus CNTF when the oncogene was inactivated by shifting the temperature to nonpermissive 39°C. These results suggest that tsAM5D cells should be a good tool to allow a detailed study of mechanisms regulating neuronal differentiation.
Key words--adrenal chromaffin cells; temperature-sensitive SV40 T-antigen; immortalization; tsAM5D cells; neurotrophic factor; neuronal differentiation
YAKUGAKU ZASSHI, 126(4),273-282, 2006
Pharmacists are now facing a problem of developing measures for dispensing mistakes, because there recently is increasing social awareness on medical accidents and a tendency to increase medical accidents in pharmacies due to popularizing separation of dispensing and prescribing functions. In this study, questionnaire survey was conducted to investigate pharmacist's views on human error measures and the relationship between mistakes and the preventive measures. To clarify relationship between human error measures and preventive measures for avoiding mistakes, questionnaire result was analyzed based on structural equation modeling (SEM). Questionnaire survey was sent to community pharmacies in Hokkaido. The result was analyzed by SEM. The recovery rate of the questionnaire was 71.0%. Human error measures were classified into “The measures against deficient knowledge and insufficient experiences”. “Attention problem measures” and “The measures against a cognitive error”. While attention problem was strongly related to the cognitive error, there was no relationship between “Attention problem measures” and “The measures against a cognitive error”. Moreover, it were clarified that to develop human error measures for deficient knowledge and insufficient experiences was effective for the preventive against the mismatch of the cognitive mechanism and the intentional mistake and for bridging the gap between knowledge and experiences. This study showed that SEM was effective for adopting efficient preventive measures for medical accident and analyzing risk management in pharmacies. Applying these results to the medical accident preventive measures contribute to improvement of the risk management.
Key words--dispensing mistakes; human error measures; structural equation modeling (SEM)
YAKUGAKU ZASSHI, 126(4),283-287, 2006
A method is proposed to detect the abnormal situations of people's health in case of the unexpected outbreak of a disease by monitoring the daily variations in the prescriptions at a pharmacy. The abnormal situations are defined as the situations which are not included in the majority (99.9%) of the normal situations. An epidemic probably caused by infectious micro-organisms in a terrorist attack is taken as an example. The drugs for the typical symptoms are monitored: influenza anti-viral agent and common cold drug. This paper demonstrates that the border between the normal and abnormal situations corresponds to the detection limit which is a fundamental concept in analytical chemistry.
Key words--pharmacy; FUMI theory; terrorism; detection limit; spectral analysis
YAKUGAKU ZASSHI, 126(4),289-295, 2006
The purpose of this study is to clarify the presence of so much insoluble microparticles in the injections and to confirm the usefulness of the final filter for its removal. The test drugs used were Doyle® 1 g vial, Cefotax® 1 g vial, Minomycin® 100 mg vial, Omegacin® 0.3 g vial, Maxipime® 1 g vial, Rocephin® 1 g vial, Isovorin® 25 mg vial, Diamox® 500 mg vial and Fungizone® 50 mg vial. 1) An appropriate volume of physiological saline was poured into the test drug vial from the 500 ml physiological saline bag. 2) The dissolution of the preparation was checked. 3) That test drug solution was returned into the same 500 ml physiological saline bag. 4) 5 ml of test drug solution was extracted from the inside of the 500 ml physiological saline bag. 5) The number of insoluble microparticles in the each test drug solution at pre- and post-filtrations were counted by using a particle counter for the solution. Two results were shown as follows (microparticle size: 5 μm or greater), (a) Doyle® 1 g (ASPC): The number of insoluble microparticles in pre- and post-filtrations of a Doyle® 1 g vial were 250 ± 45 and 0/5 ml, respectively (microparticle size: ≦ 5 μm 1662/5 ml, 5~10 μm: 238/5 ml, >10 μm: 11/5 ml). (b) Diamox® 500 mg (acetazolamide): The number of insoluble microparticles in pre- and post-filtrations of Diamox® were 158 ± 53 and 0.3 ± 0.47/5 ml, respectively (microparticle size:≦ 5 μm 4030/5 ml, 5-10 μm: 144/5 ml, >10 μm: 14/5 ml). The presence of great numbers of insoluble microparticles in several injection preparations was clarified. Although the all test drugs used cleared the criteria of the number of insoluble microparticles of the Japanese Pharmacopoeia, it was suggested to be not suitable that great numbers of insoluble microparticles were administrated in the body fluid of patients, because a possibility to occlude capillaries and/or to injure the tissues by them was been thought. But we could remove them nearly completely by passing the solutions of drugs through an infusion filter. Otherwise, in this examination, we found that so much insoluble microparticles derived from the disposable syringe (10 ml) were used for dissolving freeze-dried preparations routinely (microparticle size:≦ 5 μm 329/5 ml, 5-10 μm: 125/5 ml, >10 μm: 39/5 ml). These results suggest that incorporation of a final filter in the IV line is extremely necessary not only for the prevention of bacterial infections, but also for elimination of insoluble microparticles.
Key words--microparticles; removal; filter; freeze-dried preparation; contamination
YAKUGAKU ZASSHI, 126(4),297-300, 2006
Chondroitin sulfate is widely distributed in animal tissues and possibly plays an important role in different types of metabolic reactions as well as protecting joints, the internal wall of blood vessels, skin, bone, etc. In cartilage, glycosaminoglycans have a protective function; in particular, chondroitin sulfate stabilizes fibrous and cellular elements of the connective tissue and, at the same time, lubricates and protects the membranes in joints. Recently, chondroitin sulfate has been used as a nutraceutical for the treatment of joint diseases such as osteoarthritis, although acidic and large molecules such as chondroitin sulfate might not be able to be absorbed through digestive apparatus such as the intestine. In this study, we investigated the effects of orally administered chondrosine derived from shark chondroitin sulfate on the uptake of inorganic 35S sulfate into rat cartilage and found that chondrosine stimulates the incorporation of 35S sulfate into cartilage compared with intact chondroitin sulfate.
Key words--chondrosine; 35S sulfate; uptake; rat cartilage
YAKUGAKU ZASSHI, 126(4),301-305, 2006
The effects of essential oil extracted from Nigella sativa (L.) seeds and its main components on human neutrophil elastase (HNE) activity were investigated. Essential oil was extracted from N. sativa (L.) seeds using hydrodistillation. The yield was equal to 0.4%. Inhibition of HNE activity by essential oil was found to be dose dependent. The highest inhibitory concentration (HIC) of essential oil which caused total inhibition of HNE activity was 5.8 mg/ml. Microassays carried out to evaluate the inhibitory effect of major components of essential oil on HNE activity revealed that carvacrol (5-isopropyl-2-methylphenol) showed marked HNE inhibitory activity with a very low IC50 value (12 μM). Based on these results, the inhibitory effects of essential oil on HNE activity are due to the presence of bioactive molecules, mainly carvacrol this compound is an inhibitor of HNE and could be considered as a natural antielastase agent and possible candidate for phytotherapy in the treatment of injuries that appear in some pathologic cases such as chronic obstructive pulmonary disease and emphysema.
Key words--Nigella sativa; essential oil; elastase; chronic obstructive pulmonary disease; emphysema
YAKUGAKU ZASSHI, 126(4),307-309, 2006
Aqueous solubility is often a limiting factor in any concentration-dependent process and n-octanol/water partition coefficient, usually expressed as log P, is equilibrium between surrogate of nonaqueous biophases and water phase. The aqueous solubility of seven liquid monoterpenes: (±)-β-citronellol, (±)-linalool, linalyl acetate, (−)-α-pinene, (−)-β-pinene, eucalyptol and terpinen-4-ol were experimentally determined at 293 K. The obtained aqueous solubility data correlate well with log P values calculated by ACD/Log P software.
Key words--aqueous solubility; log P; monoterpenes; terpenes
YAKUGAKU ZASSHI, 126(4),311-314, 2006
This paper puts forward a method for determining the infection order of influenza between adults and children from the daily variations in the amount of influenza anti-viral agents treated at a pharmacy. The time series of Tamiflu Capsule for adults and Tamiflu Dry Syrup for children are compared by means of the cross-correlation function. The results from pharmacies located in Tokyo and Kanagawa show that the influenza infection period of adults is earlier than that of children, indicating the infection order: first adults and second children. However, a pharmacy in Saitama yields no clear result.
Key words--correlation; pharmacy; influenza; spectral analysis
YAKUGAKU ZASSHI, 126(4),315-319, 2006
Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that can be easily taken. The MC tablets were made by the wet granule compression method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was used as a model drug. The binders were evaluated in terms of formability of the granules and tablets, their strength, disintegration of the tablets, and their effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules at a fairly low concetration, but more MT was needed to obtain the strong granules. The tablets could be formed only when using MT at 120% (w/w) of the MC amount. The tablet displayed good hardness and rapid disintegration. The adsorption potential was not affected by CMC-Na, and slightly prevented by MT. However, the adsorption ability of MC was lowered more with the increase in HPC. The granules and tablets exhibited similar adsorption potentials, which were a little lower than that of MC suspended in MT aqueous solution. Similar adsorption characteristics were also observed in a real drug, acetaminophen. It is suggested that the MC tablets prepared by the wet granule compression using MT as a binder should be useful as a compact dosage form of MC.
Key words--medicinal carbon; tablet; wet granule compression; maltitol; adsorption potential