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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 613 records · Page 34Linked to original sources
PubMed1992

Preparation and evaluation of Eudragit gels. III: Rectal gel preparations for sustained release of pentoxifylline.

A novel method was established for the preparation of Eudragit S, Eudragit L, and Eudispert high-viscosity (hv) hydrogel and xerogel preparations containing a medicinal component such as pentoxifylline (an agent that improves cerebral microcirculation). A significant correlation was found between the in vitro mean dissolution time and the in vivo mean residence time of pentoxifylline after rectal administration of these preparations in rabbits. Staying properties of the hydrogel and xerogel preparations in the lower part of the rectum were compared with those of polyethylene glycol 2000 and Witepsol S-55 suppositories in rats, with water-insoluble dye. Eudispert hv hydrogel and xerogel preparations have excellent staying properties in the rectum. The efficacy of Eudispert hv xerogel preparations may be reduced by first passage through the liver after oral administration.

Acrylic Resins↗
PubMed1992

Preparation and evaluation of Eudragit gels. IV: Rectal gel preparations for sustained release and avoidance of first-pass metabolism of propentofylline.

Formulations of a high-viscosity acrylic resin gel (Eudispert hv) containing propentofylline, a new cerebral microcirculation-improving agent, were prepared and tested for avoidance of the first-pass metabolism of propentofylline through the liver and for sustained release of propentofylline. The absolute bioavailability of propentofylline after oral administration was only 4% in rabbits. The relative bioavailabilities of propentofylline from polyethylene glycol (M(r), 2000) and Witepsol H-15 suppositories were approximately 8- and 16-fold, respectively, compared with oral administration. Furthermore, the absolute bioavailability of propentofylline from Eudispert hv hydrogel and xerogel preparations was approximately 100%. The results indicate that, in principle, drug loss caused by first-pass metabolism may be avoided completely by placing Eudispert hv hydrogel and xerogel formulations in the lower part of the rectum for long periods.

Acrylic Resins↗
PubMed1992

Efficacy of PGI2 analog in preventing ischemia reperfusion damage of liver grafts from living donors.

In living-related transplantation, warm ischemia/reperfusion damage (IRD) of liver grafts is inevitable during harvesting. In this study, we investigated the effects of prostacyclin (PGI2) on IRD of liver grafts in the rat liver transplant model. Donor rats underwent 30-min warm ischemia of part of the liver (right lateral and medial lobes). After 10 min of reflow, the ischemic partial livers were flushed with Ringer's lactate and immediately transplanted into untreated recipients. Donor animals were divided into two groups: group I received vehicle, and group II received PGI2 analog OP-41483 (OP, 500 ng/kg per min, i. v.) during the donor operation. One-week survival was studied and cellular adenine nucleotide levels of donor livers were assayed by high-performance liquid chromatography (HPLC). Donor treatment with PGI2 analog group II significantly improved 1-week survival (86%), in comparison with the controls group I (25%). The levels of total adenine nucleotides (TAN, micromol/g dry wt) of the grafts just before implantation were well maintained by PGI2 treatment (12.22), as compared with the controls (10.36). In summary, PGI2 treatment of the donor maintained high energy metabolism of the liver graft after IRD and improved the survival of recipients after transplantation. Our study suggested that PGI2 treatment of donors improves viability in liver grafts from living donors thus and increases graft availability for transplantation.

Adenosine Diphosphate↗
PubMed1992

Predictive value of liver tissue flow in assessment of the viability of liver grafts after extended preservation in pigs.

The crucial damage in cold storage of liver allografts is to the hepatic sinusoidal lining (microcirculation). Using different solutions, we studied whether determinations of graft tissue flow were valuable in estimating the viability of liver grafts. Twenty-three pairs of female pigs underwent orthotopic liver transplantation and were assigned to five groups according to the cold preservation time or solutions used: in group I the liver grafts were stored in Euro-Collins solution (EC) for 4 h (n = 3), in group II the grafts were stored in EC for 12 h (n = 5), in group III the donor was pretreated with azathioprine (AZA), 1 mg/kg per day, orally (p.o.) for 3 days before harvesting and the graft was implanted after 12 h cold storage with EC (n = 6), in group IV the graft was stored in modified University of Wisconsin solution (mUW) for 4 h (n = 3), and in group V the graft was stored in mUW for 24 h (n = 6). Liver tissue blood flow (LTBF) was measured, using a laser doppler device, at 60 min after recirculation of the graft. In the case of EC preservation, LTBF (ml/100 g of liver tissue per min) correlated well with 4-day survival: 21.2 +/- 3.0 ml/100 g of tissue per min mean +/- SD, in group I (3/3, 100%); 10.0 +/- 2.8 ml/100 g of tissue per min in group II (0/5, 0%); and 19.1 +/- 3.4 ml/100 g of tissue per min in group III (5/6, 83.3%) (P < 0.05, group II vs I and III). All grafts with LTBF of more than 15 ml/100 g tissue per min functioned well. However, changes in microcirculation of the mUW-stored livers did not correlate with early function of the graft: 23.0 +/- 2.3 ml/100 g of tissue per min in group IV (4-day survival; 3 of 3, 100%) and 23.5 +/- 9.1 ml/100 g of tissue per min in group V (0 of 6, 0%). This was accompanied by graft dehydration during storage and an increased number of erythrocytes in the hepatic sinusoids post-recirculation. We concluded that assessment of liver tissue flow by LDF was very helpful and easy to apply in predicting liver graft failure in the case of preservation with Euro-Collins solution. However, LTBF should be carefully evaluated as a marker of liver graft viability when the liver graft is preserved with mUW.

Animals↗
PubMed1992

FK 506 ameliorates normothermic liver ischemia in rats by suppressing production of tumor necrosis factor.

In recent years, there has been growing evidence that tumor necrosis factor-alpha (TNF) plays an important role in the development of hepatic injury after ischemia-reperfusion. We have previously demonstrated that the immunosuppressants, cyclosporine, azathioprine and FK506 (FK), have a protective effect on warm ischemic injury of the rat liver. In the present study, we attempted to elucidate the mechanism for the beneficial effect of FK on liver ischemia, with special reference to the suppression of TNF production. After 60 min and 90 min of warm liver ischemia, the survival rates were significantly improved by FK pretherapy. This was associated with amelioration of hepatic injury, as assessed by histological examinations and determinations of serum AST and lipid peroxide levels in the liver. After 60 min of liver ischemia, TNF was measurable during the reperfusion period in the sera of the control animals, peaking of 6 h after reperfusion (123 +/- 15.8 pg/ml, mean SEM). In contrast, pretreatment with FK significantly suppressed the elevation of serum TNF levels at the same time point (75.8 +/- 13.1 pg/ml, P < 0.05). The present data showed that liver ischemia-reperfusion resulted in TNF production, and that FK could protect the liver from reperfusion injury by suppressing this production of TNF.

Animals↗
PubMed1992

Monoclonal antibody against ependymoma-derived cell line.

Mouse myeloma cells were fused with spleen cells from mice that had been immunized with a human ependymoma derived cell line, KMS II. Hybridomas producing monoclonal antibodies (MAbs) were screened and cloned. Specificity of the antibody was determined by enzyme-linked immunosorbent assay (ELISA) and/or indirect immunofluorescence assay. One of the MAbs, designated Ep-C4 (subclass = IgG1), reacted with two cell lines derived from ependymoma but did not react with 17 cell lines derived from other types of brain tumor nor with 4 neuroblastoma cell lines or 19 cell lines derived from carcinoma, hematopoietic tumors and amnion. Indirect immunofluorescence and immuno-electron microscopy studies revealed that the antigen recognized by MAb Ep-C4 was located on cell surface membrane. The membrane antigen of KMS II cells, immunoprecipitated by MAb Ep-C4, was a protein of 81,000 dalton. The reactivity of MAb Ep-C4 was further examined using immunofluorescence and/or immunoperoxidase methods and frozen sections and short-term cultures of various types of brain tumors. No cross-reactivity with normal adult or fetal brain tissues was detected by absorption assay and immunoperoxidase staining. Our results suggest that the antigen defined by MAb Ep-C4 is specific for ependymoma cells, and different from the antigens of glioma cells or other neuroectodermal-derived cells previously described.

Adult↗
PubMed1992

A clinical study of postoperative infections following open-heart surgery: occurrence and microbiological findings in 782 cases.

A total 782 consecutive patients underwent open-heart surgery with CPB between January, 1979 and December, 1988, at the Yamagata University Hospital. We assessed the incidence of postoperative infections in relation to age, the duration of surgery and antibiotic prophylaxis, and examined the causative organisms, after which the types of infecting flora were compared between the 1st period, from 1979 to 1983 and the 2nd period, from 1984 to 1988. Postoperative infection occurred in 104 of the 782 patients (13.3 per cent); in the form of a wound infection in 41 (5.2 per cent), pneumonia in 33 (4.2 per cent), urinary tract infection in 9 (1.2 per cent), prosthetic valve endocarditis in 6 (0.8 per cent), and other infections in 15 (1.9 per cent). Patients aged under 12 months or over 60 years showed a higher incidence of infection, being 17.4 per cent and 19.2 per cent, respectively. Patients who underwent an operation of over 8 hours duration also had a significantly higher incidence compared to those whose operation time was less than 4 hours, being 32.9 per cent and 6.3 per cent, respectively (p less than 0.0001). There was no significant difference in the incidence of postoperative infection between patients given or not given preoperative prophylaxis. A total 123 species of organisms were isolated from the 104 patients, 52.8 per cent being gram-negative bacteria (GNB), and 43.9 per cent gram-positive bacteria (GPB), and a remarkable increase in the incidence of GPB was seen in the 2nd period compared to the 1st period from 31.7 per cent to 50.0 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

A cross-sectional study on the brainstem auditory evoked potential among workers exposed to carbon disulfide.

In order to clarify the chronic effect of carbon disulfide (CS2) on the central nervous system (CNS), the brainstem auditory evoked potential (BAEP) was measured in spinning workers exposed to CS2 in a viscose rayon manufacturing factory and unexposed workers in Japan. Workers exposed to CS2 were divided into three groups according to length of exposure: current spinning workers with an exposure duration of more than 240 months (L group, n = 34), current spinning workers with an exposure duration of 24-84 months (S group, n = 25), and former spinning workers with an exposure duration of more than 120 months (R group, n = 16). Unexposed controls were selected from workers in a nylon filament factory using the same criteria (N group; n = 40). BAEP records were analyzed based on the latencies of three main components (I, III, V) and interpeak latencies (I-III IPL, III-V IPL, I-V IPL). Latencies of component V, III-V IPL, and I-V IPL in the L group were significantly greater (P < 0.01, P < 0.05, P < 0.05, respectively). The significantly, higher III-V IPL in the L group suggested that in humans, chronic exposure to CS2 involves the auditory ascending tract in the brainstem. Recovery from this neurotoxic effect is apparently possible, as the BAEP parameters in the R group were not significantly higher than those of the N group despite the long previous CS2 exposure of the R group.

Adult↗
PubMed1992

Changes in auditory brainstem response in rats chronically exposed to carbon disulfide.

The chronic effect of carbon disulfide (CS2) on the central nervous system (CNS) was studied by examining auditory brainstem responses (ABRs) in female rats (Jcl Wistar) exposed to 200 ppm or 800 ppm CS2 by inhalation, 6 h a day, 5 days a week, for 15 weeks. Two modes of ABRs evoked by clicks at 61 and 96 dB sound pressure levels (61 dB-ABR and 96 dB-ABR) were recorded during the exposure and for 6 weeks afterwards. Three main components (I, III and V) of ABRs were analyzed from the latencies and differences between latencies of them (interpeak latencies, IPL I-III, IPL III-V and IPL I-V). The latencies of the three components and IPLs of 96 dB-ABR in rats group exposed to 800 ppm of CS2 were significantly delayed during the exposure period. The delay of latency of component V and IPL III-V and I-V tended to increase with exposure time. At 61 dB-ABR, the changes in the latency of component V, IPL III-V and I-V resembled those at 96 dB-ABR. For the rats group exposed to 200 ppm CS2, the latency of component I, IPL III-V and I-V at 96 dB-ABR were delayed significantly but transiently during the exposure period. For both groups, recovery from the latencies of the three components and IPLs of ABR was observed by the end of the recovery period. The delayed latencies of ABR observed in rats exposed to 800 ppm CS2 suggested a conduction dysfunction in the brainstem due to CS2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prophylactic effect of bestatin on the onset of invasive mole--clinical and fundamental studies.

This study was performed to determine whether bestatin (Ubenimex) has clinical prophylactic effects on the onset of invasive mole and a direct inhibitory effect on the growth of hydatidiform molar cells. A total of 49 patients with hydatidiform mole treated at Nagoya University Hospital from 1984 to 1990 were randomly divided into two groups, a bestatin administered-group and a bestatin non-administered group. Patients in the bestatin group were given 30 mg of bestatin orally and daily for three months just after their molar deliveries. There was no significant difference in age, gravidity, parity and gestational weeks between the two groups. There was also no significant difference in the duration of human chorionic gonadotropin (hCG) negative conversion in patients without invasive mole between the two groups. However, the incidence of invasive mole in the bestatin group (2/25, 8%) was significantly lower than that of the non-bestatin group (7/24, 29.2%). Nevertheless, there was no significant difference between the two groups in such immunological parameters as PHA skin test, PPD skin test, PHA stimulation index (PHA-SI), white blood cell (WBC) count lymphocytes % per WBC, OKT 3% per lymphocytes, OKT 4% per lymphocytes, OKT4/OKT8 and Leu 11% per lymphocytes. In vitro studies were performed with primary cultured hydatidiform moles. The result was that bestatin inhibited the secretion of hCG and 3H-thymidine uptake of hydatidiform molar cells. Thus, a possibility was suggested that bestatin directly inhibits the growth of hydatidiform molar cells and prevents the onset of invasive mole.

Adolescent↗
PubMed1992

Collaborative study using the preincubation Salmonella typhimurium mutation assay for airborne particulate matter in Japan. A trial to minimize interlaboratory variation.

A collaborative study has been performed over a period of 3 years to develop a suitable method for monitoring the mutagenicity of airborne particulate matter. The study was organized with 8 laboratories and performed in the following steps: (1) selection of a suitable technique for each process involved in the mutagenicity monitoring, (2) developing a tentative protocol by combining systematically the selected techniques, (3) evaluation of the protocol by intra- and inter-laboratory studies, (4) modification of the protocol according to the evaluation, and (5) evaluation of the modified protocol by conducting an interlaboratory study. We found a suitable method for mutagenicity monitoring of particles in the atmosphere. Airborne particles were sampled with a high-volume sampler, the samples were stored at -80 degrees C, extracted by sonication using dichloromethane, solvent-exchanged, and assayed by the preincubation method using Salmonella typhimurium TA98 and TA100. The observed mutagenic activity was normalized with that of an internal standard. Round robin tests revealed that the method resulted in excellent reproducibility. The coefficient of variation for mutagenic activities of airborne particulate samples collected in various districts of Japan were in the range of 14.7 +/- 6.6% to 19.6 +/- 4.0% for strains TA98 and TA100 with and without metabolic activation. We also found that the plate incorporation method was equivalent to the preincubation method for airborne particulate extracts.

Air Pollutants↗
PubMed1992

Hypothyroidism impairs colonic motility and function. An experimental study in the rat.

Hypothyroidism (HT) may be associated with either megacolon or severe constipation that mimics Hirschsprung's disease. The exact nature of this relationship is unclear. This report evaluates colonic motility in experimental HT. HT was produced by a total thyroidectomy in 20 male Sprague-Dawley rats (200-300 g). Ten of the HT rats were given thyroxin (30 micrograms/kg/day i.p. for 4 weeks) for a replacement study (RS). Ten sham operated rats (SH) and 50 unoperated rats (UN) were studied as controls. HT was documented at 4 weeks following total thyroidectomy by measuring serum T3, T4 uptake, and TSH. At four to 6 weeks the animals were evaluated for several studies concerning colonic motility. Normal weight gain was significantly impaired under HT. In addition, daily stool volume as well as the number of fecal pellets were significantly reduced in HT. A barium enema showed a dilated colon in HT with an increase of recto-colonic ratio. Anal canal pressure was relatively low in HT. HT rats had a decreased frequency of rhythmic colonic activity (cycle/min) (HT: 10.22 +/- 2.16 vs. UN: 18.09 +/- 4.79, SH: 15.88 +/- 3.92, p less than 0.001). RS rats showed a recovery of rhythmic frequency (15.56 +/- 4.46, p less than 0.001). A positive recto-anal reflex was seen in all UN and SH rats, but only 40% in HT and 80% in RS. The effect of isoproterenol on anal canal pressure was significantly less in HT. Colonic transit at 4 hours was considerably slower in HT (HT: 29.0 +/- 21.0% vs. US: 60.4 +/- 18.3%, SH: 58.7 +/- 14.8%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of elemental diet following ileo-endorectal pull-through in rats.

Total colectomy, mucosal proctectomy and ileo-endorectal pull-through (IEP) have been carried out mostly in dogs, because of high mortality after IEP in rats. This report evaluates the effects of elemental diet on bodily metabolism and survival following IEP in the rat. Survival at 4 weeks was 100% in the sham operated group used as controls, 80% in IEP group given laboratory food + 10% Vivonex ten (group 2), 30% in IEP group given food + 1/2 saline (group 3), and only 10% in IEP group given food + water (group 1). The serum Na, Cl, HCO3 were significantly lower from day 3-7 to day 28 in the group 1. On the contrary, both serum K and osmolality were extremely elevated in the group 1. The total protein level also increased gradually in the group 1 due to extracellular fluid loss. Groups 2 and 3 maintained bodily metabolism related to water and electrolytes well. Our data support the suggestion that severe water and electrolytes imbalance may occur following total colectomy. A supplementary elemental diet prevents water and electrolyte depletion and improves survival following total colectomy and IEP in the rat.

Anastomosis, Surgical↗
PubMed1992

The in-vitro activity of RP 59500 against gram-positive cocci.

RP 59500 was more potent than erythromycin, josamycin, amoxycillin and ciprofloxacin, and as potent as vancomycin, against staphylococci and enterococci. Against streptococci, the activity of RP 59500 was very similar to that of amoxycillin, but was superior to that of erythromycin, josamycin, vancomycin or ciprofloxacin. Compared with the other antimicrobial agents tested, RP 59500 was the most active against erythromycin-resistant Gram-positive cocci.

Amoxicillin↗
PubMed1992

Effectiveness of prednisolone/aspirin therapy for recurrent aborters with antiphospholipid antibody.

Seventeen women with recurrent fetal loss associated with anti-phospholipid antibody were treated by prednisolone and low-dose aspirin (PSL/ASP) therapy from the early gestational period. The success rate of pregnancy in the treated patients was significantly higher than that in 12 untreated patients of similar background, including age, number of previous fetal losses and anti-cardiolipin titre (76.5 versus 8.3%, P less than 0.01). The degree of fetal growth retardation evident in previous pregnancies was also improved by the therapy, suggesting that PSL/ASP itself has a beneficial effect against placental damage. These clinical improvements were accompanied by a reduction in anti-phospholipid antibody titre, especially that of anti-phosphatidylserine antibody (anti-PS), to within the normal range within 8 weeks after PSL/ASP administration in most of the treated patients. There was no reduction of antibody titre in the untreated patients during pregnancy. It was concluded that PSL/ASP therapy, when started in the early gestational period (prior to 8 weeks gestation), was effective for the achievement of successful pregnancy and the prevention of fetal growth retardation and that the anti-PS titre was a good clinical marker for evaluating the effect of PSL/ASP therapy.

Abortion, Habitual↗
PubMed1992

Retinoblastoma gene product Rb accumulates during myogenic differentiation and is deinduced by the expression of SV40 large T antigen.

The cell growth suppression activity of the retinoblastoma gene (RB) product Rb is considered to be regulated by phosphorylation, whereas no positive correlation has been demonstrated between the activity and the amount of Rb protein in numbers of cell types examined. Both the RB mRNA and the protein were dramatically induced during terminal differentiation of the mouse skeletal muscle cell line C2 and its transfectant C2SVTts11, which stably harbors the SV40 T antigen gene linked to an inducible promoter. They were gradually deinduced when the terminally differentiated C2SVTs11 myotubes reentered the cell cycle through the induction of the large T antigen. Thus, the accumulation of Rb protein is likely to be required for growth arrest during differentiation of at least these myogenic cells, which have low basal levels of the protein.

Animals↗
PubMed1992

Separate isolation of Clostridium difficile spores and vegetative cells from the feces of newborn infants.

A modified taurocholate-cefoxitin-cycloserine-fructose agar medium, pH 5.5, on which vegetative cells alone could grow, was newly devised for separate isolation of Clostridium difficile vegetative cells and spores from feces. The ratio of C. difficile-positive feces from healthy newborn infants younger than 10 days of the age was 30.8%, and 93.3% of feces from healthy infants older than 20 days were positive for C. difficile. C. difficile spores alone were detected in twenty-one samples (75%) of C. difficile-positive Twenty-eight specimens. Only 10.7% (3/28) C. difficile vegetative cells alone were detected. C. difficile spores alone were detected in one of nine healthy adults. These collective results offer potential explanations for high frequent isolations of C. difficile from newborn infants without occurrence of pseudomembranous colitis.

Bottle Feeding↗