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Biomedical subjects

M Shirai

Publications and source records attributed to M Shirai.

At least 253 records · Page 14Linked to original sources
PubMed1988

The organ distribution of [3H]endotoxin following partial hepatectomy.

3H-labeled endotoxin was intravenously injected into Wistar rats 24 hours following 70% hepatectomy and also into the normal rats. They were sacrificed 12 hours, 24 hours or 5 days after the injection. Microscopical autoradiography was performed on the rats' organs. The distribution of endotoxin in the organs was investigated by quantitatively measuring their radioactivity. Endotoxin was taken up mainly by Kupffer cells of the liver in all the groups. Endotoxin was observed also in macrophages of the spleen and the lung in all the groups. The amount of endotoxin per 1 g organ weight of the hepatectomized rat was significantly smaller in the liver, and significantly larger in the spleen, lung and blood (per 1 ml) than that of the control groups early after hepatectomy. These differences of the organ accumulation of endotoxin between groups diminished 5 days later. Deficient tolerance of the liver to endotoxin at the peak phase of regeneration following partial hepatectomy was suggested.

Animals↗
PubMed1988

Fate of 3H-labeled endotoxin in partially hepatectomised rats.

Organ distribution of endotoxin was compared in normal and previously hepatectomised rats after administration of endotoxin lipopolysaccharide labeled at the galactose moiety. Most of the radioactivity was found in the liver in both cases, but total recovery was much higher in the organs of normal rats. In the liver, the amount of endotoxin per total organ and per 1 g organ weight was significantly reduced in the hepatectomised rats as compared with the intact controls. In normal rats, the radioactivity decreased 12 to 24 hours in the liver, but in the hepatectomised rats, no significant change was observed during this period. The total radioactivity in the lungs, spleen and blood (1 ml), as well as that per unit weight bases, was significantly higher in the hepatectomised rat than in normal rats. These results and autoradiographical studies suggest that endotoxin clearance activity of Kupffer cells in the liver is decreased by partial hepatectomy of the rats at the peak phase of regeneration, and that remaining endotoxin flow out of the liver is disposed mainly by the macrophages in the spleen.

Animals↗
PubMed1987

A study on the mechanism of acute hepatic necrosis following partial resection of the liver.

Endotoxin was injected intravenously into rats 48 hours after 70% hepatectomy. The remaining hepatic tissue demonstrated marked hemorrhagic necrosis in high frequency. However, hepatic lesions were slight in other groups such as the group in which heparin was administered simultaneously with injection of endotoxin 48 hours after 70% hepatectomy and the group in which endotoxin was injected 10 days after 70% hepatectomy. Defining of this marked necrosis to be a univisceral Shwartzman reaction in the liver may be justified from (i) conformity of experimental manipulations to those employed in the Shwartzman reaction, (ii) macroscopical as well as histological evidence, (iii) formation of microthrombi in hepatic lesions, (iv) inhibition of occurrence of the reaction by heparin, and (v) absence of any remarkable change in other organs. We concluded that the hepatic regenerative state might correspond theoretically to a state of preparedness for the Shwartzman reaction.

Animals↗
PubMed1987

A light and scanning electron microscopic study of hepatic veno-occlusive disease.

Hepatic veno-occlusive disease, which was observed in a patient with hepatic coma, was examined by scanning electron microscopy (SEM), and correlated with its histology. Postmortem examination disclosed microscopic occlusion of the centrilobular and sublobular veins in the liver. These veins were occluded, partially or completely, by intimal and medial thickening of their walls due to proliferation of collagen and reticulin fibers. In addition to venous obliteration, which had not been demonstrated by other techniques, frequent occlusion of the sinusoidal opening into the central veins was observed by SEM. The size and distribution of the openings were irregular in comparison with those in normal controls. There was no evidence of fibrin thrombus formation in the veins. This case exemplified the usefulness of the application of SEM to autopsy material.

Aged↗
PubMed1987

Nonuniform effects of histamine on small pulmonary vessels in cats.

In in vivo cat lung, using an X-ray TV system, we analyzed responses in internal diameter (ID), flow velocity, and volume flow of arteries and veins (100-500 microns ID) to histamine (8-15 micrograms/kg iv) under three conditions. With histamine alone, three types of ID response (constriction, dilatation, and no change) occurred in parallel-arranged arteries. Relative frequency and magnitude of constriction were maximum in arteries of 300-400 micron ID, whereas those of dilatation were maximum in arteries of 100-200 micron ID. In veins, relatively uniform constriction occurred. Under H2-blockade, histamine caused greater constriction than that with histamine alone in arteries and veins of 300-500 micron ID. Under beta-blockade, with histamine, ID of all vessels decreased significantly below the ID sizes under the above two conditions, and no dilatation occurred. In two parallel arteries that showed opposite ID changes to histamine, flow velocity increased, but volume flow decreased in a constricted artery while it increased in a dilated one. Those data indicated that, with histamine, qualitatively and quantitatively nonuniform ID response was induced in both parallel- and series-arranged small pulmonary arteries and, in turn, produced heterogeneous flow distribution. Factors to cause the nonuniformity may be partly explained by difference in density of H2- and beta-receptors in vascular walls.

Adrenergic beta-Antagonists↗
PubMed1987

Effects of prostaglandin F2 alpha and prostacyclin on pulmonary microcirculation in the cat.

In pulmonary microcirculation, using a new X-ray television system, we measured the effects of prostaglandin F2 alpha (PGF2 alpha) and prostacyclin on the internal diameter (ID), flow velocity, volume flow, and transit times of a contrast medium in small arteries (Ta) and veins (Tv) in anesthetized cats. The ID of the arteries and veins ranged from 100 to 500 micron. PGF2 alpha, 0.3, 1, and 3 micrograms/kg, predominantly decreased ID on the arterial side in a dose-dependent manner but increased flow velocity 27-62%. Consequently, volume flow was kept relatively constant. With PGF2 alpha, Ta and Tv were decreased 18-41% and 4-15%, respectively. Prostacyclin, 2 and 4 micrograms/kg, uniformly dilated the ID of small arteries 9-16% but did not change small veins. With prostacyclin, flow velocity was unchanged or decreased, whereas volume flow was increased significantly, 27-32%. No significant changes of Ta and Tv were observed in response to prostacyclin. When both prostaglandins, PGF2 alpha and prostacyclin, were administered, they canceled each other with respect to the ID of small pulmonary arteries. Prostacyclin also prevented the PGF2 alpha-induced vasoconstriction of the pulmonary venous microcirculation.

Animals↗
PubMed1987

Vagally and acetylcholine-mediated constriction in small pulmonary vessels of rabbits.

Using a new X-ray TV system, we analyzed effects of vagal nerve stimulation (VNS; 1-30 Hz) and intravenous injection of acetylcholine (Ach; 0.3-0.9 microgram) on the internal diameter (ID; 100-1,500 microns) of small pulmonary arteries and veins in anesthetized rabbits. In selective segments of the arteries, ID decreased abruptly and maximally by 50-70% in a specific stimulus frequency to the vagal nerve and a dose of ACh. The vasoconstrictor sites were distributed near the branching points of the arteries, particularly those downstream, and their numbers increased with an increase in the stimulus frequencies and ACh doses. The relative frequencies of occurrences were 15.3% with VNS (30 Hz) and 5.3% with ACh (0.9 microgram). In nonselective segments with VNS, ID decreased frequency dependently by 0, 4, 12, and 26% at 1, 4, 15, and 30 Hz, respectively, and with ACh, decreased dose dependently by 21 and 35% with 0.3 and 0.9 microgram, respectively. The vasoconstriction in response to VNS and ACh was attenuated by atropine, enhanced by eserine, and not affected by phentolamine. That vasoconstriction to VNS was abolished by hexamethonium. No selective constriction was found in veins and the ID was decreased uniformly by 1-2% with VNS and ACh.

Acetylcholine↗
PubMed1987

Effect of metabolic acidosis on pulmonary microcirculation in the cat.

Using a new X-ray TV system, we studied the effects of metabolic acidosis, produced by intravenous injection of lactic acid, on internal diameter (ID; 100-500 micron), flow velocity, and volume flow in pulmonary microcirculation of anesthetized cats. We found that metabolic acidosis decreased the ID of arteries by 21%, whereas it increased flow velocity by 28% but not volume flow.

Acidosis, Lactic↗
PubMed1987

Effects of human recombinant interleukin 2 in patients with chronic hepatitis B: a preliminary report.

Five patients with HBe antigen-positive chronic active hepatitis were treated with recombinant interleukin 2 (r-IL2) for 3 to 4 wk. r-IL2 inhibited HBV replication during therapy as judged by decrease of serum DNA polymerase activity. Two of five patients lost HBeAg from serum. Furthermore, characteristic increases of serum aminotransferase were observed during r-IL2 therapy. This rise might have been mediated by enhanced immune responses to hepatitis B virus and increased rate of lysis of the infected hepatocytes. No consistent changes in immune markers such as OKT4 positive cells or OKT8 positive cells were demonstrated during or after the therapy. The activities of natural killer cells gradually increased during therapy, although they tended to decrease within 1 wk after the start of r-IL2 injections. In two responders who lost HBeAg from serum, the natural killer activity was high before the therapy, compared with nonresponders. Furthermore, the percentage of OKT4-positive cells in the responders was increased within 1 to 2 wk after starting r-IL2 injections. These findings suggest that the responders might be immunologically different from the nonresponders. Recombinant-IL2 therapy over short periods did not result in complete clearance of hepatitis B virus. Further studies with high doses of r-IL2 given over longer periods are warranted.

Adult↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). I. Absorption, distribution, metabolism and excretion in rats].

Absorption, distribution, metabolism and excretion of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, after a single administration were studied in rats. After intramuscular administration of HAPA-B at a dose level between 6.25 and 100 mg/kg, the drug was rapidly absorbed to reach the peak in 0.10 to 0.21 hour (Tmax). The maximum drug concentration in the plasma (Cmax) and the size of the area under the plasma concentration-time curve (AUC) depended on dose levels. The HAPA-B disappeared rapidly from the plasma after intramuscular and intravenous administrations with biological half-lives (T1/2) from 0.41 to 0.47 hour with intramuscular administration and from 0.23 to 0.35 hour with intravenous administration. Peak time after intramuscular, intraperitoneal and subcutaneous administration of HAPA-B at a dose of 25 mg/kg were 0.18, 0.24 and 0.37 hour, respectively. Maximum drug concentrations in plasma were 64.15, 53.71 and 40.39 micrograms/ml and biological half-lives of the drug were 0.47, 0.73 and 0.87 hour, respectively. The HAPA-B was distributed rapidly into tissues, especially at a high level into kidney after intramuscular or intravenous administration of 25 mg/kg. Concentrations in lung and heart were next to that in kidney, but were not higher than plasma concentrations. The drug was excreted mainly into the urine after intramuscular and intravenous administration within 24 hours and approximately 79 to 90% of the administered amount was excreted. Meanwhile, the excretion of HAPA-B into the bile was 0.1% or less during the first 24 hours after intramuscular and intravenous administration. Bioautograms of thin layer chromatographs of 0 approximately 6 hours urine samples after intramuscular administration showed single bands with the identical Rf value to the standard HAPA-B. No difference between male and female was observed in the fate of the administered HAPA-B through intramuscularly. The shape of the plasma concentration curve and the urinary excretion after intramuscular administration of HAPA-B at the dose of 25 mg/kg was similar to those of amikacin (AMK) and gentamicin. Tissue concentrations after intramuscular and intravenous administration of HAPA-B were also similar to AMK.

Aminoglycosides↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). II. Accumulation of HAPA-B after multiple administration in rats].

The accumulation of isepamicin sulfate (HAPA-B) in tissues and plasma was studied upon multiple intramuscular and intravenous administrations of 25 mg/kg of HAPA-B daily for 8 or 15 days to male rats. Shapes of plasma concentration curves in multiple intramuscular and intravenous administrations were very similar to that in a single administration. Drug concentrations in kidney at 24 hours after 8- and 15-multiple administrations through both routes were 3 to 4 and 4 to 5 times as high as that after a single administration. The concentration in kidney increased by multiple administrations for 8 days, but did not increase so highly there after till the 15-multiple administrations. On the other hand, the elimination of HAPA-B from kidney after multiple administrations was similar to that after a single administration. The accumulation of HAPA-B upon multiple administration was also observed in lung, heart, spleen and liver, but peak concentrations of the drug in these tissues were lower than that in kidney.

Aminoglycosides↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). III. Intramuscular, intravenous and drip intravenous administration of HAPA-B in rabbits].

Absorption, distribution, metabolism and excretion of isepamicin sulfate (HAPA-B) were studied following intramuscular, intravenous and drip intravenous administration at doses of 6.25, 25 and 100 mg/kg to rabbits. Plasma concentrations of HAPA-B following intramuscular, intravenous and drip intravenous administration depended on dose levels. Biological half-lives (T1/2), body clearance (Clt) and areas under plasma concentration-time curves (AUC) for different routes of administration were similar in all 3 routes. A theoretical curve for drug concentrations vs. time was obtained using pharmacokinetic parameters calculated from drug concentrations in plasma following a 45-minute drip intravenous administration. From the curve, it was estimated that 60 to 90 minutes would be required to achieve a similar maximum drug concentration in plasma by drip intravenous administration to that obtained by intramuscular administration. Thus, drug concentration patterns obtained following intramuscular administration could be duplicated in drip intravenous administration by regulating the length of time for infusion. The concentration of HAPA-B in tissues obtained following a 15-minute drip intravenous administration reached maximum after 15 minutes at a level higher than that achieved by intramuscular administration, but an hour later, concentrations in tissues including the kidney decreased to similar levels obtained following intramuscular administration and patterns of concentration decrease for drip intravenous administration and intramuscular administration were quite similar to each other thereafter. The drug was rapidly excreted into the urine following any of the 3 routes, and urinary recoveries in 24 hours were 75 approximately 92% of dose amounts for all dose levels tested. Bioautograms on thin-layer chromatographs of 0 approximately 6 hours urine samples obtained following an intramuscular administration of the drug showed a single biologically active bands with similar Rf values to HAPA-B itself. No active metabolite of the drug was detected in the urine.

Aminoglycosides↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). IV. Intramuscular, intravenous and drip intravenous administration of HAPA-B in dogs].

The plasma concentration and urinary excretion of isepamicin sulfate (HAPA-B) were studied following intramuscular, intravenous and drip intravenous administrations of 6.25, 25 and 100 mg/kg in dogs. Maximum plasma concentrations (Cmax) of HAPA-B after intramuscular, intravenous and drip intravenous administration depended on dosage levels. Biological half-lives (T1/2) and areas under plasma concentration-time curves (AUC) for the three different routes of administration were similar to each other. The peak plasma concentration of HAPA-B achieved with intramuscular administration was similar to that with a 1-hour drip intravenous administration at a dose level of 6.25 or 25 mg/kg. On the other hand, at a dose level of 100 mg/kg, the Cmax following intramuscular administration was similar to that following 2-hour drip intravenous administration. It was, therefore, presumed that the plasma concentration curves which are similar to that of intramuscular administration can be obtained by regulating the infusion time. The observed Cmax value for drip intravenous administration was a little higher than the theoretical Cmax value for drip intravenous administration calculated from parameters for intramuscular administration. Simulation curves obtained for extended infusion times agreed more closely with observed curves than curves simulated for shorter infusion periods. These investigations showed that plasma concentration curves for any dosage levels can be estimated from parameters calculated from experimental data obtained using intramuscular or drip intravenous administration. HAPA-B was rapidly excreted into the urine after administration through any of these 3 routes and 71 approximately 89% of the dose was excreted into the unrine in 24 hours at all dosage levels. Bioautograms of thin-layer chromatographs of the 0 approximately 6 hours urine after intramuscular administration showed single bands with a similar Rf value to that of the standard HAPA-B. No significant differences in plasma concentration and urinary excretion between HAPA-B and amikacin were observed upon intramuscular or intravenous administration of 25 mg/kg.

Aminoglycosides↗
PubMed1987

[Studies on the metabolic fate of isepamicin sulfate (HAPA-B). V. Plasma concentrations of HAPA-B in dogs after multiple administrations].

Plasma concentrations after a single or multiple intramuscular administrations of isepamicin sulfate (HAPA-B) at dose levels of 6.25, 25 and 100 mg/kg to male and female dogs were measured by microbiological assay, and were also compared with those of amikacin at dose levels of 25 and 100 mg/kg. Shapes of plasma concentration curves after multiple administrations of HAPA-B were very similar to those after single administrations at all dosage levels tested. On the other hand, the shape of plasma concentration curve after multiple administration of amikacin at 100 mg/kg was markedly different from that after a single administration.

Amikacin↗