Search PubMed⌕ Search

Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 307 records · Page 17Linked to original sources
PubMed1992

Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-beta-cyclodextrin and penetration enhancers.

The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-beta-cyclodextrin (CME-beta-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-beta-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-beta-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.

Administration, Cutaneous↗
PubMed1992

[Bacteriological study of traveller's diarrhoea. 4) Isolation of enteropathogenic bacteria from patients with traveller's diarrhoea at Osaka Airport Quarantine Station during 1984-1991].

During the last 8 years (1984 to 1991), 16,639,233 overseas travellers were quarantined at Osaka Airport Quarantine Station and 38,326 travellers reported that they were (or had been) suffering from diarrhoea. Bacteriological examination of stools from 12,573 persons revealed the following results. 1) Various enteropathogenic bacteria were isolated from 3,669 cases (29.2%) examined. The predominant species of bacteria isolated were as follows: Salmonella, 1049 cases; Plesiomonas shigelloides, 1030 cases; Vibrio parahaemolyticus, 789 cases; Shigella, 607 cases; enterotoxigenic Escherichia coli, 422 cases; Vibrio cholerae non-O1, 212 cases. 2) There were no apparent seasonal variations in the isolation rate of these pathogens. 3) The suspected regions for infection with these pathogens were as follows: a) Salmonella, Enterotoxigenic E. coli and Plesiomonas, mainly South-East and South-West Asia. b) Shigella, South-West Asia, especially India (59.8%). c) V. parahaemolyticus and V. fluvialis, mainly South-East and East Asia. d) V. cholerae non-O1, V. mimicus, almost restricted to Asia, mainly South-East Asia. 4) 22 strains of V. cholerae O1 were isolated and 19 were Ogawa, E1 Tor. Of these strains, 13 were cholera toxin-producing strains and 9 were non-toxigenic strains. 5) Several pathogens (mixed infection) were isolated simultaneously from 670 cases. 6) The 1247 Salmonella strains were identified into 98 serovars. 7) Of 624 Shigella strains isolated, 57.9% were S. sonnei, 29.2% were S. flexneri, 8.6% were S. boydii, 4.3% were S. dysenteriae. 8) The most predominant serovar of V. parahaemolyticus was O4:K8. Of 1,247 strains isolated, 9.8% were not producing thermostable direct hemolysin (TDH). 9) 570 (91.3%) of 624 Shigella strains and 409 (32.8%) of 1,247 Salmonella strains isolated were resistant to any one of the drugs tested (SM. CP. TC. KM. ABPC. NA. OFLX). The resistance rate and the number of multiple drug-resistance strains increased year by year. 10) Enterotoxigenic E. coli was isolated from 422 cases (10.7%) of 3,939 cases. Cases with enterotoxigenic E. coli strains producing ST (heat-stable), LT (heat-labile) or both ST and LT were 53.8%, 24.2% and 14.2% respectively. The others were cases with mixed types of enterotoxin production.

Asia, Southeastern↗
PubMed1992

[The first cholera case diagnosed early in the clinical laboratory by DNA probe method].

An alkaline-phosphatase-labelled synthetic oligonucleotide probe was applied to detect the structural gene of cholera enterotoxin (ctx). This DNA probe has a complementary base sequence to 30 base of the CT-A subunit. This method was, for the first time, applied to diagnosis of a diarrheal patient. The probe detected ctx rapidly and simply as compared with reversed passive latex agglutination (RPLA) and Beads-ELISA. The cfu minimal dose for detection with the probe was about 10(6-7)/ml. This method can be easily performed in any clinical laboratory because the procedure is safe, simple and rapid (it can be completed within about 3 hours).

Adult↗
PubMed1992

Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101).

A new compound, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101) was synthesized, and its skin penetration enhancing activity was examined by using 14C-indomethacin as a penetrant. A solution of HPE-101 and indomethacin was applied to a cloth pad affixed onto an adhesive tape to give a HPE-101 patch, and the patch was applied to hairless mouse skin. The amount of percutaneously absorbed indomethacin was determined by measuring the radioactivity excreted in urine for 24 h after application. 1) Azone and decylmethyl sulfoxide, enhanced markedly the percutaneous absorption of indomethacin when the propylene glycol-ethanol (9:1 v/v) mixture was used as the solvent. 2) Among various penetration enhancers dissolved in the indomethacin solutions and applied to screen for penetration enhancing activity, HPE-101 was found to be the most prominent. 3) Solvents containing more than 3% (w/w) of HPE-101 produced a plateau level of the penetration enhancing activity. 4) Daily application of 1% (w/w) solutions of HPE-101 or Azone increased the daily excretion of indomethacin significantly above the level excreted on the previous day. However, repeated daily application beyond 3 d gave a steady state excretion of indomethacin. 5) The mouse skin was pretreated with 3% (w/w) solutions of HPE-101 or Azone for 24 h on the 1st day, and the indomethacin solution was applied for 24 h on the 3rd day and 7th day to examine the recovery of skin barrier function. Enhanced excretion of indomethacin was still noted on the 3rd day, but enhancement was not observed on the 7th day.

Animals↗
PubMed1992

Laser diffraction estimation of particle size distribution of slightly water-soluble drugs coexisting with additives: application to solid dosage forms.

A simple and quantitative evaluation method for particle size distribution (fx(r)) of slightly water-soluble drugs dispersed in an aqueous medium together with other water-insoluble additives was developed using a laser diffraction method. The particle size distribution function of the powder mixture, (f(r)), was assumed as f(r) = phi x.fx(r) + phi a.fa(r), where phi is the volume fraction of each component dispersed in a measurement medium and fa(r) is the distribution function of another water-insoluble additive "a". In order to calculate fx(r) from f(r), it is necessary to know the density of drug and additive in the measurement medium, d(x) and d(a), but this is difficult to determine since particles usually swell in the medium. Thus, a method was developed to use their relative value, delta a (= da/dx). As a practical application, oxolinic acids (OA) of three sizes (OA-S (about 2 microns), OA-M (about 7 microns) and OA-L (about 24 microns)) were used as model drugs. delta a values were determined for various additives using the mixture of OA-S and each additive. Then, using delta as, fx(r) of OA-M or OA-L in the mixture containing OA-M or OA-L and additives was calculated from the f(r) experimentally determined for the mixture. They agreed well with their original distributions. The method was applied to some dosage forms, and the results obtained had good correlation with those from turbidity, wet sieving or dissolution test.

Algorithms↗
PubMed1992

Enhancement of bioavailability of dopamine via nasal route in beagle dogs.

Dopamine (DA), which is ineffective by oral administration due to first pass metabolism and is usually injected, was administered to dogs via rectal, dermal, buccal and nasal routes. The nasal route had the highest bioavailability and best avoided first pass metabolism. The effects of the addition of hydroxypropyl cellulose (HPC), sodium deoxycholate, POE (6) hydrogenated caster oil (HCO-60) and Azone on the nasal absorption increased bioavailability from 11.7% (control) to about 20%, 35%, 25% and 68%, respectively. Further, with a combination of 2% HPC and 5% Azone, bioavailability was increased to almost the same level as with i.v. administration. At the same time, plasma concentrations were maintained at a high level for more than 7 h. The increase in bioavailability is presumed to be caused by an enhancement in absorption and prolongation of the time DA is retained in the nasal cavity due to Azone and HPC, respectively.

Administration, Intranasal↗
PubMed1992

Design and preparation of pulsatile release tablet as a new oral drug delivery system.

To achieve time-controlled or site specific delivery of a drug in the gastrointestinal tract, an orally applicable pulsatile drug release system with the dry-coated tablet form was developed. The system consisted of a less water permeable outer shell and a swellable core tablet; from such a system, the drug was expected to be rapidly released after a certain period of time on the basis of time-controlled disintegration mechanism. Various model disks of outer shell, consisting of hydrogenated castor oil and polyethyleneglycol 6000, were tested for their water penetration rate. The experimental results showed that water penetration proceeded obeying the boundary retreating mechanism, so that the lag time of the system could be controlled by changing either the thickness or the composition of the outer shell. The swelling force of various commercially available disintegrants was quantitatively compared, and it was found that carboxymethylcellulose calcium was the preferable disintegrant to be used for the core tablet. On the basis of the results of a series of fundamental studies, various pulsatile release tablets of isoniazide with different lag times were designed. In the in vitro dissolution test, typical pulsatile release was achieved for all the tablets prepared, and a good correlation was found between the observed lag time and the estimated lag time calculated from an empirical equation deduced from the thickness and polyethyleneglycol 6000 content of the outer shell.

Administration, Oral↗
PubMed1992

Absorption of diltiazem in beagle dog from pulsatile release tablet.

An orally applicable pulsatile drug delivery system in dry-coated tablet form was prepared using diltiazem hydrochloride as the model drug, and a polyvinyl chloride-hydrogenated castor oil-polyethyleneglycol mixture as the outer shell of the tablet. In vitro drug release from the prepared tablet exhibited a typical pulsatile pattern with a 7 h lag phase (non-drug release period). This dosage form was orally administered to three beagle dogs under non-fasting and fasting conditions, and the plasma concentration level of diltiazem was determined according to time after administration. The result of the in vivo study in non-fasting dogs suggested that the drug could be released in the gastrointestinal tract as in the in vitro test. However, under the fasting condition, a large difference in the plasma concentration profile was found, suggesting that the disintegration time of the tablet tended to be influenced by the feeding condition of subject.

Administration, Oral↗
PubMed1992

Characterization of the triphenyltin-induced increase in intracellular Ca2+ of mouse thymocytes: comparison with the action of A23187.

The properties of triphenyltin (TPT) in increasing intracellular Ca2+ ([Ca2+]i) of thymocytes was studied, in comparison with those of A23187, by the use of fluorescent dyes to monitor membrane potential and [Ca2+]i. Both 1 microM TPT and 30 nM A23187 increased the [Ca2+]i associated with the hyperpolarization mediated by Ca(2+)-dependent K+ conductance. The time course for the TPT-induced increase in the [Ca2+]i was much slower than that of A23187. When the external Ca2+ ([Ca2+]o) was removed, TPT produced a slight, but persistent, increase in the [Ca2+]i while A23187 caused only a transient increase in the [Ca2+]i. Reintroduction of Ca2+ to the external solution produced an increase in [Ca2+]i in both cases. Therefore, these results suggested that the increase in the [Ca2+]i of thymocytes induced by TPT and A23187 was dependent on the presence of [Ca2+]o and an intracellular Ca store. The potency of TPT in increasing the [Ca2+]i was greater than those of diphenyltin and monophenyltin, suggesting an involvement of the lipophilic property of organotins in increasing [Ca2+]i. The TPT-induced increase in the [Ca2+]i may be partly responsible for the toxicity of TPT on organs and/or organ systems.

Animals↗
PubMed1992

Flow cytometric estimation of the effect of Ginkgo biloba extract on the content of hydrogen peroxide in dissociated mammalian brain neurons.

The effect of Ginkgo biloba extract (GBE) on the content of hydrogen peroxide was estimated in cerebellar neurons dissociated from rats, by means of a flow-cytometer and 2',7'-dichlorofluorescein (DCF) diacetate, a fluorescent dye for intracellular hydrogen peroxide. The GBE started to reduce the DCF fluorescence of the neuron at 0.1 microgram/ml to 0.3 microgram/ml. Further increases in the GBE concentration (up to 3 micrograms/ml) produced a dose-dependent decrease in the DCF fluorescence, suggesting that GBE reduces the content of hydrogen peroxide or suppresses the reactive oxygen species (ROS) formation of cerebellar neurons. The present technique may be useful for preliminary evaluations of agents affecting the ROS formation in mammalian brain neurons.

Animals↗
PubMed1992

Translation of rat ovarian mRNA to two 20 alpha-hydroxysteroid dehydrogenase isozymes in Xenopus oocytes.

20 alpha-Hydroxysteroid dehydrogenase (20 alpha-HSD) in rat luteal tissue catalyzes the conversion of progesterone into a biologically inactive steroid, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) and depletes the output of progesterone into the circulation. An increase in 20 alpha-HSD activity in luteal tissue is therefore a prerequisite for the regression of functional corpora lutea in rats. We have reported that ovarian 20 alpha-HSD is composed of two isoforms (HSD1 and HSD2). In this study, among batches of ovaries collected randomly during the estrous cycle, we selected two batches (batches A and B): the cytosol preparation from batch A contained both HSD1 and HSD2 activities, whereas that from batch B contained only HSD1 activity. From these 2 batches, we extracted mRNA, and each mRNA preparation was subjected to translation in Xenopus oocytes. The translation products of batch A exhibited both HSD1 and HSD2 activities, and those of batch B only HSD1 activity in accordance with the enzymatic activities observed in the respective cytosolic preparations. The results are compatible with the presence of two distinct mRNAs coding HSD1 and HSD2, and if so their transcription will be regulated separately according to the functional state of the ovary.

20-Hydroxysteroid Dehydrogenases↗
PubMed1992

Expression of activities of two 20 alpha-hydroxysteroid dehydrogenase isozymes in rat corpora lutea.

The rat ovary contains two isozymes of 20 alpha-hydroxysteroid dehydrogenase (HSD-1 and HSD-2). In this study, the expression of activity of each isozyme was investigated in ovaries that contained a single generation of corpora lutea during pseudopregnancy. This condition was induced by cervical stimulation in rats that had been rendered anovulatory by housing them in a continuously lit environment. The total activity of cytosolic 20 alpha-HSD was lower in the ovaries of these pseudopregnant rats than in ovaries containing multiple generations of corpora lutea. In normal pseudopregnancy, HSD-1 activity was low on days 5 and 9 and increased markedly on day 15, whereas HSD-2 was lower than HSD-1 and did not vary throughout pseudopregnancy. However, on days 5 and 9 of continuous-light pseudopregnancy, low activity of HSD-1 only was detected; by day 15, HSD-1 activity had increased sixfold and HSD-2 activity could be detected. Immunohistochemical methods using a specific antibody recognizing both HSD-1 and HSD-2 revealed that the number of 20 alpha-HSD-positive luteal cells increased by day 15. Thus, the increase in total enzyme activity and appearance of HSD-2 activity observed at late pseudopregnancy was accompanied by an increase in the number of 20 alpha-HSD-positive luteal cells.

20-Hydroxysteroid Dehydrogenases↗
PubMed1992

Peritoneal cytology in endometrial carcinoma.

Peritoneal cytology is accepted as part of the evaluation for patients undergoing laparotomy for a suspected or proven gynecologic malignancy. The study subjects were 83 patients with endometrial carcinoma. We investigated the significance of peritoneal cytology in endometrial carcinoma. Cytological positive results were observed in 11 (23%) of the 48 T1 cases, 9 (50%) of the 18 T2 cases and 4 (50%) of the 8 T3 cases. Cytological positive rates by histological differentiations were 14 (28%) for 50 G1 cases, 4 (36%) for 11 G2 cases and 6 (46%) for 13 G3 cases. Cytological positive results were found in 11 (28%) of 39 cases of less than 1/3 of intramuscular infiltration and 13 (37%) of 35 cases of 1/3 or more infiltration. Five (56%) of 9 metastasis cases and 17 (29%) of 59 nonmetastasis cases were found positive cytologically. An analysis of the data indicated that the influence of positive peritoneal cytology on recurrence superceded that of other known risk factors, such as grade, myometrial invasion, extrauterine disease, and lymph node metastasis. The patients with normal cytological findings at laparotomy tend to have a significantly (p less than 0.01) better prognosis than similar patients with abnormal cytological findings.

Adenocarcinoma↗
PubMed1992

Absorption, distribution and excretion of zenarestat, a new aldose reductase inhibitor, in rats and dogs.

1. The absorption, distribution and excretion of zenarestat have been studied in male rats and dogs after i.v. and oral administration of 14C-zenarestat. 2. The bioavailability of zenarestat was 93% in rats and 65% in dogs. A major proportion of the plasma 14C in rats and dogs was due to unchanged drug. The terminal elimination half-life of zenarestat in plasma was 6 h in rats and dogs. 3. Except for organs associated with absorption and elimination, tissue 14C levels were lower than plasma levels in rats. The distribution to, and elimination from sciatic nerve were slower than those of other tissues. 4. Most of the 14C from 14C-zenarestat administered orally and i.v. to rats and dogs was excreted in the faeces. After i.v. dosing to bile duct-cannulated rats, 96% of the radioactive dose was excreted in the bile.

Absorption↗
PubMed1992

Detection of human papillomavirus DNA in the normal cervices of Japanese women by the dot-blot (Vira Pap) method.

Exfoliated cervical cells obtained from 9 patients with cervical intraepithelial neoplasia (CIN) I and II, 11 with CIN III, 22 with cervical carcinoma, and 599 with cytologically normal cervices (including 63 pregnant women) were evaluated for the presence of human papillomavirus (HPV) by the dot-blot (Vira Pap) method. HPV infection was detected in 33.3% of the CIN I and II cases, in 54.5% of the CIN III cases, in 68.2% of invasive cervical carcinoma cases, and in 4.2% of the normal group. The rate of detectable HPV infection increased in exfoliated cervical cells during pregnancy. These results suggested that a few Japanese women with cytologically normal cervices were infected with HPV.

Adolescent↗
PubMed1992

[Effect of chemotherapy on the prognosis of ovarian cancer].

Through the collaboration of 22 institutions nationwide, a total of 1,185 cases of ovarian cancer treated between January, 1980 and December, 1987, were investigated as to their prognosis from the aspect of the chemotherapeutic effect. (1) An excellent effect of the remission-induction chemotherapy was observed in a group receiving combination therapy with CDDP as the main ingredient. In particular a significant effect was seen in stages III and IV. In addition, the effect on the remaining tumors by diameter also showed a significant difference in cases of tumors of not less than 2 cm in diameter. (2) As to the effect on histological types, a comparison in stage III showed a favourable effect on endometroid, serous and mucinous adenocarcinomas, while no effect was observed in clear cell adenocarcinoma. (3) The effect of the remission induction chemotherapy did not always give rise to an improvement in the long-term prognosis of ovarian cancer, and the establishment of a therapeutic method aimed at the prevention of recurrence was desired. (4) To improve the long-term prognosis, intermittent (or cyclic) chemotherapy with CDDP as the main ingredient was found to be very effective, but maintenance chemotherapy with orally administered of 5-Fluorouracil or Tegaful was not effective. (5) The effect of the conventional immunotherapy was not observed at all.

Adenocarcinoma↗
PubMed1992

[The relation of physical and mental stress to magnesium deficiency in patients with variant angina].

In this study we assessed the role of psychological factor in the etiology of coronary vasospasm using the Cornell Medical Index (CMI), focusing attention on the relationship between stress and serum magnesium (Mg). The study subjects consisted of 25 patients with variant angina (VA), 32 with old myocardial infarction without vasospasm (OMI), and 34 healthy men (controls). On a neurosis-discriminative diagram of CMI, areas I and II were considered as normal and areas III and IV were considered to be a neurotic disorder. The stress test included exercise and a quiz. Exercise test was performed in 8 patients with VA, 6 with OMI, and 5 controls, and a quiz was given to 4 patients with VA. Plasma catecholamines [noradrenaline (NA), adrenaline (Ad), dopamine], aldosterone, adrenocorticotropic hormone (ACTH) and serum electrolytes (Mg, Ca, Na, K, Cl) were measured before and after exposures to stress. The following results were obtained: 1) Of the patients with VA, 40.0% were categorized as area III or IV, compared to 18.7% of the patients with OMI, and 2.9% of the control subjects. 2) Among patients with VA, 64.0% exhibited anxiety states compatible with a psychological disorder. 3) NA and Ad were increased after exercise stress. 4) Serum Mg and Ca were also increased after exposure to exercise stress in all groups, and the degrees of these changes were correlated to the exercise intensity. The %delta Mg/%delta NA ratio, a parameter of the effect of catecholamine on the serum Mg, was greater in patients with VA than in those with OMI and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗