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Biomedical subjects

K Hirabayashi

Publications and source records attributed to K Hirabayashi.

At least 127 records · Page 7Linked to original sources

[Pharmacokinetics of cis-diammine (glycolato) platinum (254-S), a new platinum antitumor agent, following an intravenous and intraperitoneal infusion bioactive platinum concentration profile].

The pharmacokinetics of cis-diammine (glycolato) platinum (254-S) was investigated in cancer patients following intravenous and intraperitoneal infusion. The serum concentrations of total and unbound 254-S were determined by bioassay and chemical assay as platinum. Platinum detected by bioassay was thought to be active and unchanged 254-S. Almost all of platinum in plasma were found to be active and unbound to protein because of no differences in the concentrations determined by bioassay and chemical assay and in plasma and plasma filtrate. In abdominal ascites, platinum concentrations determined by bioassay corresponded with those determined by chemical assay, suggesting that 254-S was stable in abdominal ascites. The Cmax and AUC of active 254-S in plasma determined by bioassay following an intraperitoneal infusion were about 60% and 60-80% of those following an intravenous infusion, respectively. These results showed that 254-S was well absorbed into systemic circulation from abdominal ascites as an active form. It is concluded that antitumor effect may be obtained following an intraperitoneal infusion of 254-S as well as for the reduction of abdominal ascites.

Aged↗

Uterine perforation during second-trimester abortion by cervical dilation and instrumental extraction: a review of 15 cases.

Review of the records of 15 women who had uterine perforations at the time of second-trimester abortion by dilation and evacuation showed that unexpected pain (but not excessive bleeding) was the most prominent sign. All patients required laparotomy, but in no case was laparotomy necessary as an emergency procedure. Laparoscopy was not helpful. Two-thirds had bowel injuries and two required hysterectomy. Errors in estimating gestational duration, inadequate cervical dilation, and failure to use sonography characterized these complicated cases.

Abortion, Induced↗

[Malignant lymphoma with Adams-Stokes syndrome as the first manifestation].

A case of malignant lymphoma with Adams-Stokes attack which was the first manifestation was reported. A 56-year-old female admitted our institute because of unconsciousness attack. After implantation of pacemaker she had high fever and abdominal mass. Ga scintigraphy revealed many accumulation on the hepatic hilus and the heart. Abdominal Computed Tomography and echography revealed abnormal mass in the hepatic hilus. The biopsy of this abnormal mass was performed. The histological examination of this specimen showed diffuse middle sized type malignant lymphoma.

Adams-Stokes Syndrome↗

Tumor necrosis factor enhances replication of human immunodeficiency virus (HIV) in vitro.

The effect of tumor necrosis factor (TNF) on the replication of human immunodeficiency virus type 1 (HIV-1) was investigated in several T4 lymphocyte cell lines. TNF markedly enhanced the cytopathogenicity of HIV-1, virion-associated reverse transcriptase (RT) activity in the cell culture supernatant, and viral antigen expression in MOLT-4 cells as early as 3 days after HIV-1 infection. A slight increase in RT activity was also observed in the supernatant of H9 cell cultures exposed to TNF. However, TNF did not increase either RT activity in MT-4 cell supernatants or viral antigen expression in HUT-78 cells. Thus, TNF is able to stimulate the replication of HIV-1 in de novo infected T4 cells although not all T4 cells seem to be sensitive to this stimulatory effect.

Antigens, Viral↗

In vitro activity of mannan sulfate, a novel sulfated polysaccharide, against human immunodeficiency virus type 1 and other enveloped viruses.

Mannan sulfate, a novel sulfated polysaccharide, was prepared and investigated for its activity against human immunodeficiency virus type 1 (HIV-1) in vitro. Mannan sulfate completely inhibited HIV-1-induced cell destruction and viral antigen expression in HIV-1-infected Molt-4 (clone 8) cells at a concentration of 4 micrograms/ml. The 50% antiviral effective doses obtained with mannan sulfate in Molt-4 (clone 8) cells and in MT-4 cells were 1.5 and 9.3 micrograms/ml, respectively. No toxicity for Molt-4 (clone 8) cells or MT-4 cells was observed at a concentration of 4,000 and 2,500 micrograms/ml, respectively. Mannan sulfate was also inhibitory to other enveloped viruses, i.e. herpes simplex virus types 1 and 2, vaccinia virus and vesicular stomatitis virus. These results suggest that mannan sulfate may be useful for the chemotherapy of various viral infections, including those causing and associated with AIDS.

HIV-1↗

Controlled study of different sclerosing agents for coagulation of canine gut arteries.

Excellent clinical results have been reported with sclerotherapy for control of nonvariceal gastrointestinal hemorrhage. However, there are few controlled or comparative data on different sclerosing agents for treatment of lesions with active arterial bleeding or nonbleeding visible vessels. In a controlled, randomized study of canine small bowel arteries our purposes were (a) to evaluate the efficacy for arterial coagulation of six sclerosing agents compared with normal saline control, (b) to compare the resultant tissue injury of agents, and (c) to elucidate the possible mechanisms of arterial coagulation and tissue injury of the agents. The agents evaluated were (a) 98% ethanol, (b) TES, a mixture with final concentration of 1% tetradecyl sulfate, 32% ethanol, and 0.3 normal saline, (c) 1% polidocanol (Ethoxysclerol), (d) 1:10,000 epinephrine, (e) 7.2% hypertonic saline, (f) 3.6% hypertonic saline, and (g) 0.9% saline (normal saline control). Agents were injected from the mucosal side of the small bowel into and around the pentrating serosal arteries in the subserosal space. Ethanol and TES were the most effective agents for arterial coagulation. Polidocanol was less effective than ethanol and TES. However, it was the only other agent that induced significant arterial coagulation. Alcohol and TES also caused significant injury in surrounding tissue. The degree of this injury was dependent on the total volume injected. Epinephrine induced significant mucosal damage without significant serosal injury or arterial coagulation. The coagulation and tissue injury effects of hypertonic saline injections were not significantly different from normal saline control.

Animals↗

Inhibitory effect of a lichen polysaccharide sulfate, GE-3-S, on the replication of human immunodeficiency virus (HIV) in vitro.

A sulfate (GE-3-S) prepared by chlorosulfonic acid treatment of GE-3, a partially acetylated beta(1----6) glucan of the lichen Umbilicaria esculenta, inhibited the cytopathic effect of human immunodeficiency virus (HIV) and suppressed the HIV-antigen expression in Molt-4 (clone 8) cells. GE-3-S also suppressed the giant cell formation of HIV-infected Molt-4 cells, and inhibited HIV-induced plaque formation by 50% at the dose of 19.5 micrograms/ml and completely at 250 micrograms/ml in MT4 cells. GE-3-S had no direct effect on the reverse transcriptase of HIV.

Antiviral Agents↗

Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models.

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.

Animals↗

Enhanced percutaneous penetration of flufenamic acid using lipid disperse systems containing glycosylceramides.

The usefulness of lipid disperse systems, containing soybean phosphatidylcholine (PC) and glycosylceramide (GC) as lipid components, to enhance the percutaneous penetration of flufenamic acid (FA) through rat abdominal skin was examined by both in vitro permeation and in vivo absorption studies. The penetration of FA from a simple buffer suspension (pH 3.0) containing no lipid component was poor, but was markedly enhanced when FA was incorporated in PC-dispersions. However, this enhancing effect disappeared when the PC concentration in the preparation exceeded 40 mumol/ml. Enhanced penetration of FA from PC-dispersions could also be recognized when 30% propylene glycol or 30% glycerol was used as the dispersing medium instead of the aqueous buffer solution. Addition of GC to the PC-dispersions brought further enhancement of FA penetration through the skin. The maximal effect was observed when FA was incorporated in a 10%-GC system, and the cumulative amount of FA penetrating through the skin in 24 h from this system was approximately 6-fold larger than that from the simple buffer suspension. Enhanced absorption of FA from lipid disperse systems was also confirmed by in vivo application of these preparations.

Animals↗

[The effect of the elastase on aminonucleoside nephrosis].

In this paper, we studied the effect of elastase on aminonucleoside (AN) nephrosis which is considered a model of focal glomerular sclerosis (FGS). Elastase is an enzyme which disintegrates elastin, discovered by Balo, and used in the treatment of arteriosclerosis and hyperlipidemia. It has also been known to improve metabolism of acid mucopolysaccharides, so, this study focused on metabolic improvement. Three groups of male Sprague-Dawley rats were studied and observed at regular intervals; 30, 60, 90 days. The ANE group (AN + elastase) was administered one shot of AN (10 mg/100 g B.W.) during the test interval, while elastase (5 mg/kg B.W.) was injected 5 days/week for the entire test interval. The AN group was administered one shot of AN only. The third group was a control (C). The following results were observed: (1) Focal segmental hyalinosis and sclerosis (FSHS); ANE group was weaker than AN group. (2) Other significant qualifying glomerular changes (vacuolar change and hyaline droplets of the epithelial cells, adhesion, and foam cells); ANE group was weaker than AN group. (3) Anion loss in GBM was shown by a lack of colloidal iron staining under light microscopy, and by a lack of PEI particles under electron microscopy; there was significantly less anion loss with ANE group, than with AN group. The findings suggest that elastase has an affect on the metabolism of acid mucopolysaccharide and collagen in sclerotic lesion, and may restrain the progress of amino-nucleoside nephrosis.

Animals↗

[Pathomorphological studies on arterial cushion. 2. Aminonucleoside nephrotic rat].

The present study is an attempt to solve the problem of pathogenesis of focal glomerular sclerosis (FGS), especially in juxtamedullary cortex, we were investigated by measurement of luminal diameters of afferent arterioles (Aff), efferent arterioles (Eff) of numerous glomeruli, arterial cushion (AC), afferent arterioles (AC-aff) at a region of branching arteries from the interlobular arteries, using scanning electron micrographs of methyl methacrylate casts of intrarenal arteries of aminonucleoside nephrotic rats. As regards luminal diameters, Eff were nearly equal Aff in minor glomerular abnormalities (Minor). Nevertheless Eff of glomeruli with segmental sclerosis (FSHS) were smaller than Aff (t-test). AC with FSHS were smaller than ones of Minor, statistically (t-test). The results of these examination, the cushion may be important factor for the regulation of blood flow in sclerotic glomeruli.

Animals↗

Study of anionic sites on the mesangium in aminonucleoside nephrosis.

In recent years, various reports have appeared concerning anionic sites in glomerular lesions. However, no detailed results for anionic sites in the mesangium have been reported. The authors therefore prepared nephrotic rats by the administration of puromycin aminonucleoside (PA) and investigated the anionic sites in various mesangial regions, using polyethyleneimine (PEI) as a cationic probe. In the mesangium of the control group as well as the experimental groups, PEI particles were most numerous in the subendothelial regions, followed by the central region and paramesangial region, in that order. In the group treated with PA, the numbers of PEI particles in each mesangial region decreased as compared with those in the control group. Among the three mesangial regions considered, this decrease was most pronounced in the paramesangial region. In the group which received elastase, no significant decrease in numbers of PEI particles was observed in subgroups I and II, indicating maintenance of the anionic sites. The results obtained suggested that regional investigations of the mesangial matrix may be of considerable significance for elucidating the etiologic factors in glomerular sclerosis, and that negative charge impairment in the mesangial matrix plays an important role in the development of glomerular sclerotic lesions.

Animals↗

[Intraperitoneal chemotherapy].

A fact that the Second International Conference of Intracavitary Chemotherapy was held at Sandiego in 1988 clearly suggests that the intraperitoneal chemotherapy attracts again the attention as a new administration route aimed at complete cure and useful modality against refractory intraabdominal cancer. Basic problems (peritoneal circulation, importance of peritoneal clearance, conditions required for ip infusion and penetration depth from the tumor surface) are described. As to ip infusion of CDDP, pharmacokinetic characteristics (iv vs ip), the difference of ultrafiltrable Pt. value (chemical assay vs biological assay) and clinical notes are reviewed. Several clinical trials now on going (CDDP-STS combination, CDDP-STS-Angiotensin II, CHPP and IPCP) are introduced. Finally the future direction of intraperitoneal chemotherapy is discussed.

Abdominal Neoplasms↗