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Biomedical subjects

Y Sawada

Publications and source records attributed to Y Sawada.

At least 163 records · Page 9Linked to original sources
PubMed1998

Hydration and occlusive treatment of a sutured wound.

To evaluate the effects of surgical tape application to an incised wound after suture removal, a test using Micropore and Blenderm tape (3M, St. Paul, MN) was carried out. Eighteen patients with a sutured wound following surgery in the groin and extremities were divided into two groups. Each group was treated in one of the following ways for a period of 3 months: with Micropore, Blenderm, or with no treatment at all. After 3 months the plaster was removed and no further treatment was rendered. Evaluation of the scar was carried out for 6 to 9 months after surgery and the two areas were compared in each patient. In 13 groin wounds, better cosmetic results were achieved in the areas treated with Blenderm compared with the areas treated with Micropore or no treatment, although the difference was not significant. Better results were also observed on areas treated with Blenderm in 5 patients with scars on the extremities. The areas treated with Blenderm were less red and less hypertrophic than the areas treated with Micropore.

Abdomen↗
PubMed1998

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayama's method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Animals↗
PubMed1998

The new-concept full-face-type helmet with removable cheek pads.

BACKGROUND: The American College of Surgeons proposed a method of removing helmets. But the problem with full-face-type helmets is that their shape makes them difficult to remove. METHODS: A dummy doll was fixed to a smooth bed surface in the supine position, and a full-face-type helmet with a hook attached to the vertex was placed on the doll's head. A spring balance was attached to the hook, traction was applied to the helmet through the spring balance, and the maximum tension needed to completely remove the helmet was measured. RESULTS: A tension of 13.2 +/- 1.8 kg was found. But when cheek pads were removed, the tension required to remove the helmet was 1.7 +/- 0.2 kg. CONCLUSION: We devised a full-face-type helmet that uses removable cheek pads so that helmet removal can be performed safely by removing only the cheek pads in the event of an accident.

Cervical Vertebrae↗
PubMed1998

Nonsurgical correction of congenital auricular deformities in children older than early neonates.

It has been reported that nonsurgical correction of auricular deformities is not effective except in early neonates. We have succeeded in nonsurgical correction using thermoplastic splints for congenital auricular deformities on 50 ears of 45 patients without severe hypoplasia in children older than 1 year. Details of the types of ears we attempted to treat were 26 cryptotias, 5 lop ears, 5 Stahl's ears, 3 prominent ears, 3 shell ears, and 8 other miscellaneous conditions. The patients were between 1 and 14 years of age with an average age of 3.6 years. Our results were categorized as follows: excellent (the auricle was delicately corrected into a desirable form and satisfied the patient), improved (the auricle was corrected into a rough form that did not attain to a desirable shape and an irregular form still remained; however, its improvement satisfied the patient), recurrent (the auricle was initially corrected but the deformity recurred), not improved (the auricle was not corrected to the desired form and the result did not satisfy the patient), and gave up (the patient gave up before treatment could be completed). In our results, the average period of splint application was 2.1 months. In 27 of the 50 cases, the treated ears were excellent. Eleven ear cases showed improvement. Six cases showed recurrence. Three cases did not improve. Three patients gave up treatment. It is suggested that nonsurgical auricular correction is possible in almost all children, even if they are not early neonates, when corrections are made continuously and gradually.

Adolescent↗
PubMed1998

Reconstruction of defects involving the upper one-third of the auricle.

We describe here a reconstructive technique for the repair of defects involving the upper one-third of the auricle using a combination of several flaps. For a defect of the preauricular surface only, a chondrocutaneous flap from the concha and a postauricular subcutaneous pedicle flap were used. For a full-thickness defect, the reconstruction was made by using the chondrocutaneous flap, the postauricular subcutaneous pedicle flap, and a postauricular skin flap. The final skin defect was collected in the postauricular region and was directly sutured or covered by skin grafting. Seven patients were treated by this procedure. Although the tip of the postauricular skin flap fell into partial necrosis in one patient, all of the other flaps were well healed without vascular stasis. All of the reconstructed auricles had good three-dimensional forms with satisfactory color and texture to match. There was neither constriction of the ear nor deformation owing to scar contracture.

Aged↗
PubMed1998

Reconstruction of congenital stenosis of external auditory canal with a postauricular chondrocutaneous flap.

We describe here a new surgical technique for treatment of congenital stenosis of the external auditory canal using a postauricular chondrocutaneous flap. Our technique prevents recurring stenosis by cartilage support and provides a sufficient extension of the canal. The chondrocutaneous flap is safely elevated, easily reaches the canal, and has ample blood supply. It is beneficial for its self-cleaning function that the remnant canal, which contains cerumen glands, is used as part of the reconstructed canal. Six patients with congenital stenosis of the external auditory canal were treated by our procedure. In these patients, three patients were treated by a postauricular approach and the others were treated by an endaural approach. All patients had very satisfactory results.

Child↗
PubMed1998

Efflux transport of tolbutamide across the blood-brain barrier.

In an attempt to determine the reason for the low brain distribution of tolbutamide, we have demonstrated the transport of tolbutamide from the brain to the blood via a non-P-glycoprotein efflux transport system which is inhibited by sulphonamides. We evaluated the directional transport of tolbutamide across the blood-brain barrier by means of an in-vivo brain-tissue distribution study and experiments on in-vitro transcellular transport and uptake in cultured mouse-brain capillary endothelial cells (MBEC4). The brain-to-unbound-plasma concentration ratio of [14C]tolbutamide increased in the presence of high concentrations of unlabelled tolbutamide or sulphonamide at steady-state in-vivo. The brain-to-blood concentration ratios of [14C]tolbutamide were very low compared with that of [3H]propranolol obtained by in-vivo integration plot analysis. From the in-vitro transcellular transport study using a monolayer of MBEC4 cells, we found that the abluminal-to-luminal flux of [14C]tolbutamide was higher than the reverse flux. Both luminal-to-abluminal and abluminal-to-luminal transport of tolbutamide were saturable. The maximum transport rate (Jmax), the half-saturation concentration (Kt), and the first-order rate constant (kd) were 65.9 +/- 29 pmol min(-1) (mg protein)(-1), 7.54 +/- 4.4 microM, and 4.89 +/- 0.34 microL min(-1) (mg protein)(-1), respectively, for luminal-to-abluminal transport, and 128 +/- 66 pmol min(-1) (mg protein)(-1), 5.59 +/- 4.2 microM, and 4.43 +/- 0.86 microL min(-1) (mg protein)(-1) , respectively, for abluminal-to-luminal transport. At therapeutic plasma concentrations of tolbutamide (1-16.9 microM), the efflux rate would be faster than the influx rate. The estimated net efflux was consistent with the very low in-vivo brain distribution of tolbutamide. The efflux process observed in MBEC4 cells was inhibited by sulphonamides such as sulphaphenazole, sulphamethoxazole and sulpha-dimethoxine whereas the steady-state uptake of [14C]tolbutamide was not affected by either cyclosporin or verapamil, specific inhibitors of P-glycoprotein. These findings suggest that tolbutamide is partly transported from the brain via the non-P-glycoprotein-efflux transport system, which is inhibited by sulphonamides.

Animals↗
PubMed1998

P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier.

The mechanism for the accumulation of itraconazole (ITZ) in its elimination from the brain was studied in rats and mice. The concentration of ITZ in liver tissue declined in parallel with the plasma ITZ concentration until 24 h after intravenous injection of the drug (half-life, 5 h); however, the ITZ in brain tissue rapidly disappeared (half-life, 0.4 h). The time profiles of the brain/plasma ITZ concentration ratio (Kp value) showed a marked overshooting, and the Kp value increased with increasing dose; these phenomena were not observed in the liver tissue. This finding indicates the occurrence of a nonlinear efflux of ITZ from the brain to the blood. Moreover, based on a pharmacokinetic model which hypothesized processes for both nonlinear and linear effluxes of ITZ from the brain to the blood, we found that the efflux rate constant in the saturable process was approximately sevenfold larger than that in the nonsaturable process. The Kp value for the brain tissue was significantly increased in the presence of ketoconazole or verapamil. The brain Kp value for mdr1a knockout mice was also significantly increased compared with that of control mice. Moreover, the uptake of vincristine or vinblastine, both of which are substrates of the P glycoprotein (P-gp), into mouse brain capillary endothelial cells was also significantly increased by ITZ or verapamil. In conclusion, P-gp in the brain capillary endothelial cells participates in a process of active efflux of ITZ from the brain to the blood at the blood-brain barrier, and ITZ can be an inhibitor of various substrates of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells.

We investigated the effect of components in grapefruit juice (GFJ) on the transport of vinblastine, a substrate of P-glycoprotein (P-gp), across Caco-2 cells. The apical to basolateral flux of [3H]vinblastine was increased in the presence of GFJ extracts. The steady-state uptake of [3H]vinblastine from the apical side was significantly increased in the presence of GFJ in a dose-dependent manner within the range of 2.5 to 50% (v/v) of GFJ. Although naringin and naringenin reduced apical efflux of [3H]vinblastine at the concentration present in GFJ and increased steady-state uptake from the apical side to 124 and 240%, respectively, the observed effect of naringin was not enough to account for the effect of GFJ and naringenin is not naturally present in GFJ. To investigate the effective components in GFJ, we examined the inhibitory effect of several organic solvent extracts of GFJ on the transport of [3H]vinblastine in Caco-2 cells. Organic solvent extracts of GFJ enhanced the apical to basolateral transcellular transport and inhibited the apical efflux. The permeability coefficient of apical to basolateral transport of [3H]vinblastine increased in the order of the ethyl acetate>diethyl ether>methylene chloride extracts of GFJ. Since the extracted amount of naringenin by ethyl acetate was less than that with the other organic solvents, the primary inhibitor in GFJ is suggested to be different from this flavonoid. The present study demonstrated the existence of inhibitory components in GFJ for the P-gp function in Caco-2 cells, which are distinct from known components such as naringin or naringenin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I).

A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.

5-alpha Reductase Inhibitors↗
PubMed1998

[Therapeutic effects of beclomethasone dipropionate enemas on colon damage of inflammatory bowel disease model rats].

The effects of beclomethasone dipropionate (BDP) enemas on ulcerative colitis were investigated by administrating BDP enemas to Fischer male rats with an inflammatory bowel disease induced by 2,4,6-trinitrobenzensulfonic acid (TNB). After administration of a TNB ethanol solution to rats, diarrhea and melena were found in all rats, and the wet tissue weights of the colons in the rats increased by erosion and thickness of epithelial mucous membranes with edema. BDP enemas were administered to the rats one time a day at a dose of 20 or 50 micrograms of BDP for 4 or 11 days from the day 3 after TNB treatment, respectively. After dosing of BDP, the rate of rats developing diarrhea and melena decreased more with time in comparison with that of BDP-free rats, and the symptoms of all rats developing the diseases were improved on the day 4 after administration of a dose of 50 micrograms of BDP. A dose dependent recovery in the wet tissue weights and scores of damages, and the myeloperoxidase (MPO) activity in the tissue were found at the early days (until the day 4). However, their measurements on the day 11 at each dose of BDP were not different from those of control rats significantly, as the damages in the colons of the control rats were recovered naturally with time. In conclusion, the clinical usefulness of BDP enemas was supported by elucidating the dose dependent effect of BDP at the early days in the model rats with an inflammatory bowel disease induced by TNB.

Animals↗
PubMed1998

Surgical treatment of discrete subaortic stenosis in an adult.

We report on an adult patient with discrete-type subaortic stenosis. A 48-year-old man who had progressed asymptomatically since childhood despite heart murmur was transferred to our hospital. The patient was diagnosed as having severe aortic stenosis with a pressure gradient of 100 mmHg across the aortic valve, associated with a grade II aortic regurgitation. A conventional aortic valve replacement was scheduled. During surgery, the aortic valve was found to be tricuspid but incompetent as a result of shrinking and thickening of the left coronary cusp. A circumferential fibromuscular ridge was observed under the cusps, which corresponded to Kelly's type II discrete subaortic stenosis. Because of the small subaortic area and deformity of the cusp, we performed aortic valve replacement after excision of all cusps and the fibromuscular ridge. Early corrective surgery is recommended for discrete subaortic stenosis to prevention regurgitation progression.

Aortic Valve Stenosis↗
PubMed1998

Pharmacokinetic and pharmacodynamic study of a new nonsteroidal 5 alpha-reductase inhibitor, 4-[3-[3-[Bis(4-isobutylphenyl)methylamino]benzoyl]-1H-indol-1-yl]-butyr ic acid, in rats.

The pharmacokinetic and pharmacodynamic behaviors of 4-[3-[3-[Bis(4-isobutylphenyl) methylamino] benzoyl]-1H-indol-1-yl]-butyric acid (FK143), a new nonsteroidal steroid 5 alpha-reductase inhibitor, in the ventral prostate were investigated after i.v. administration to rats. The relationship between blood concentrations at 24 hr and doses was linear in the range of 0.1 to 20 mg/kg. However, the levels of FK143 in the prostate were saturated over the dose of over 5 mg/kg. The dissociation constant (Kd) and maximum amount of binding substances (Bmax), calculated according to nonlinear kinetic analysis including a specific binding pool, was 0.0553 +/- 0.0117 microgram/ml (92 nM, estimated value +/- S.D.) and 0.908 +/- 0.092 microgram/g tissue, respectively. A combined pharmacokinetic/pharmacodynamic (PK/PD) model was constructed using change in dihydrotestosterone (DHT) levels in the prostate after i.v. administration of FK143 as an index for its pharmacological effect and blood concentration as an input function. The apparent reaction rate constant of drug and enzyme (K) was 39.7 +/- 25.1 g tissue/microgram/hr (estimated value +/- S.D.), the apparent turn-over rate constant of enzyme (k) was 0.140 +/- 0.107 hr-1, the elimination rate constant of DHT (kel, DHT) was 1.13 +/- 0.94 hr-1 and the fraction of FK143-insensitive DHT synthesis (F) was 0.461 +/- 0.037. The PK/PD analysis suggested that the duration of the effect of FK143 was related to its accumulation in the binding pool of the prostate. After i.v. administration of FK143 in the range of 0.1 to 20 mg/kg, the DHT levels in the prostate decreased to about 40% of control value, after which despite the rapid decline of blood FK143 concentration, slowly recovered according to the elimination rate of FK143 in the prostate. Moreover, the PK/PD profiles of FK143 after repeated i.v. administration were predictable by using the PK/PD parameters obtained after single administration of FK143.

5-alpha Reductase Inhibitors↗
PubMed1998

Quantitative prediction of the interaction of midazolam and histamine H2 receptor antagonists in rats.

To quantitatively evaluate drug-drug interactions involving metabolic processes in the liver, we attempted to predict the increasing ratio of the plasma concentration of midazolam (MDZ) in the presence of cimetidine (CIM) or nizatidine (NZD) in rats. Under steady-state conditions for the plasma concentration of CIM or NZD, MDZ was administered through the portal vein. The AUC of MDZ in the presence of CIM was 2.5-fold higher than that in the absence of CIM. There was no effect of NZD on the AUC of MDZ. The liver/plasma concentration ratios for CIM and NZD were 4.0 and 2.7, respectively. The estimated liver unbound concentration (CH,f)/plasma unbound concentration (Cp,f) ratios for CIM and NZD were 1.9 and 2.4, respectively, suggesting concentrative hepatic accumulation of both drugs. The oxidative metabolism of MDZ in rat liver microsomes was competitively inhibited by CIM or NZD, and the Ki values of CIM and NZD were 110 and 2600 microM, respectively. Based on these data obtained in vivo and in vitro, the increasing ratios for MDZ in the presence of CIM or NZD were predicted using the equations Rp = 1 + Cp,f/Ki and RH = 1 + CH,f/Ki. The observed increasing ratios in the presence of CIM were very close to RH, compared with Rp. However, Cp, f and CH,f were much less than Ki and there was no difference between Rp and RH in the presence of NZD. Consequently, Cp,f and CH, f were greater than or equal to Ki and Cp,f was not equal to CH,f, as in the presence of CIM, and it was indicated that CH,f was more suitable for quantitatively predicting the drug-drug interactions than was Cp,f.

Animals↗