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T Suwa

Publications and source records attributed to T Suwa.

At least 109 records · Page 6Linked to original sources
PubMed1991

Determination of gallopamil in human plasma by selected ion monitoring.

A gas chromatographic mass spectrometric procedure using selected ion monitoring is described for the quantification of gallopamil in human plasma. Gas chromatographic separation of gallopamil from phenolic metabolite isomers is made possible by treatment with ethyl chloroformate. The detection limit for the quantitation by the present method is 0.09 ng/ml of plasma. The method has sufficient sensitivity to permit pharmacokinetic studies with human subjects following the oral administration of gallopamil hydrochloride.

Gallopamil↗
PubMed1991

Kinetic studies on the appearance of antigens of Chlamydia psittaci during its developmental cycle.

The kinetics of the antigen production of Chlamydia psittaci strains Izawa-1 and Pigeon-1041 (P-1041) was examined every 6 hr after infection up to 48 hr, by the indirect immunofluorescent antibody technique using monoclonal antibodies (MAbs). All three genus-specific antigenic determinants on lipopolysaccharide (LPS) appeared during the whole growth cycle. Antigenic determinants on proteins were, on the other hand, detected at various time periods from the early to the late stages of infection. However, a cross-reactive antigenic determinant on protein recognized by a MAb 3E9 was also detected during the whole growth cycle, similar to that on LPS. The time of appearance of common antigenic determinants on proteins of Izawa-1 and P-1041 was examined using cross-reactive MAbs, and it varied depending on heterologous and homologous MAbs. From the relationship between the detection of antigenic determinants and the morphological changes of chlamydial particles revealed by electron microscopy during the growth cycle, the antigenic determinants on proteins of Chlamydia psittaci were divided into two groups; one was specific to the elementary body and the other was coexisting in both the elementary body and the reticulate body.

Animals↗
PubMed1991

The disposition of loxistatin and metabolites in normal and dystrophic hamsters.

1. The absorption, distribution and excretion of loxistatin were studied in normal and dystrophic hamsters. 2. After oral administration of 14C-loxistatin to normal hamsters, the plasma level of radioactivity reached a maximum at 0.5 h and declined with an elimination half-life of 2.3 h. The ratios of metabolites M-1 and M-4, which are pharmacologically active, to the total radioactivity in the plasma were 63% and 25% at 0.5 h after dosing, respectively. 3. After oral administration to hamsters, excretion of radioactivity in urine, faeces and expired air during 120 h were 64%, 28% and 6% of the dose, respectively. 4. The highest radioactivity was observed in kidney followed by liver. From the microautoradiographic study, radioactivity was found to be located in the cardiac and skeletal muscle fibre cells, which are target organs of the drug, in both dystrophic and normal hamsters.

Animals↗
PubMed1990

An epoxysuccinic acid derivative(loxistatin)-induced hepatic injury in rats and hamsters.

Loxistatin is a possible therapeutic agent of muscular dystrophy. A single oral administration of loxistatin to male rats caused focal necrosis of the liver with inflammatory cell infiltration. The severity of the lesions was dose-dependent up to 200 mg/kg and also manifest by an increase in serum alanine aminotransferase and aspartate aminotransferase activities. Hepatic glutathione (GSH) levels decreased with a maximum 20% depletion within 5 hr after the oral administration of loxistatin. Pretreatment with diethyl maleate did not potentiate the loxistatin-induced hepatic injury. On the other hand, the hepatoprotective effect of cysteamine was observed when cysteamine was administered 24 hr before loxistatin dosing, but the effect was not observed when the antidote was administered concomitantly with loxistatin. Pretreatment of rats with phenobarbital or trans-stilbene oxide provided partial protection against the hepatotoxic effect of loxistatin. Pretreatment with SKF-525A resulted in increased hepatic injury, while pretreatment with piperonyl butoxide, cimetidine, or 3-methylcholanthrene had no effect on hepatic damage by loxistatin. Five hours after [14C]loxistatin administration to rats, the covalent binding of the radioactivity to proteins was greatest in the liver, followed by the kidney, then muscle and blood to a lesser extent. [14C]Loxistatin acid, the pharmacologically active form of loxistatin, irreversibly bound to rat liver microsomal proteins; more binding occurred when the NADPH-generating system was omitted and when the microsomes were boiled first. GSH did not alter the extent of irreversible binding, whereas N-ethylmaleimide decreased the binding of [14C]loxistatin acid to rat liver microsomal proteins by 75%. Unlike the rat, administration of loxistatin to hamsters caused neither hepatic injury nor hepatic GSH depletion even at a high dose (500 mg/kg). Both the distribution and covalent binding of radioactivity in the hamster liver were one-third of those in rats following [14C]loxistatin dosing. These results suggest that loxistatin causes species-specific hepatotoxicity and that, at least in part, some of the toxic effects of loxistatin are mediated by the nonenzymatic covalent binding of loxistatin acid to thiol residues on cellular macromolecules.

Alanine Transaminase↗
PubMed1990

Uptake of clarithromycin by rat lung cells.

To evaluate the affinity of clarithromycin (6-O-methylerythromycin A) for lung tissue, the in-vivo and in-vitro uptake of [14C]clarithromycin and [14C]erythromycin by rat lung cells was compared, and the characteristics of the uptake mechanism were investigated. After the administration into the external jugular vein of rats, clarithromycin was found in much higher concentrations in the lung tissue than erythromycin. In isolated lung cells, clarithromycin was also found in greater concentrations than erythromycin. The amount of clarithromycin was ten times that of erythromycin after 5 min incubation. This uptake profile was quite different from that observed in isolated liver cells. Uptake by lung cells for both antibiotics was shown to be an active process, as revealed by the need for cell viability, a suitable environmental temperature and ATP. Clarithromycin uptake proved to be dependent in part upon mitochondrial oxidative respiration. Kinetic analysis indicated that clarithromycin transport was saturable, with a relatively high binding affinity and velocity of uptake. Clarithromycin transport was significantly inhibited by 6-O-methylerythromycin analogues, but was not influenced by other analogues, including erythromycin. Competitive inhibition of clarithromycin uptake was demonstrated by 6,11,12.4"-tetra-O-methylerythromycin, one of the mutual inhibitors. These findings may suggest that clarithromycin utilizes a carrier-mediated transport system in the lung cells, which is common to 6-O-methylerythromycins. This difference of uptake mechanism between both antibiotics may account in part for the greater clarithromycin uptake by the lung cells.

Animals↗
PubMed1990

Further study of mucosal repair by sofalcone in experimental gastritis.

The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis.

Animals↗
PubMed1990

Autobacteriographic studies of clarithromycin and erythromycin in mice.

The antimicrobial activity of clarithromycin was compared with that of erythromycin in experimentally infected mice by whole-body autobacteriography. In mice with systemic staphylococcal infections, the number of vital microbes in the body was relatively low in the early period after oral administration of erythromycin, but increased thereafter to the levels found in nonmedicated control mice. On the other hand, with clarithromycin treatment, a significantly smaller number of microbes was evident throughout the body. The microbes were scarcely seen in the parenchyma of any organs during the examination period. This potent antimicrobial activity of clarithromycin compared with that of erythromycin was further demonstrated in mice with respiratory infections. On the other hand, to examine the distribution properties of both antibiotics in the whole body, an autoradiographic study was carried out with [N-methyl-14C]clarithromycin and [N-methyl-14C]erythromycin. Both labeled antibiotics were distributed widely throughout the body after oral administration in both uninfected control mice and mice with systemic infections. However, the radioactivity was more marked and persistent for [14C]clarithromycin than it was for [14C]erythromycin, particularly in the lungs. The observations described above indicate the superior in vivo antimicrobial activity of clarithromycin compared with that of erythromycin and suggest that the superiority of clarithromycin is largely attributed to its favorable distribution properties. The advantages of whole-body autobacteriography, coupled with whole-body autoradiography, are discussed.

Administration, Oral↗
PubMed1990

Effects of easily chewable diet and unilateral extraction of upper molars on the masseter muscle in developing mice.

The effects of easily chewable diets and unilateral extraction of upper molars on the masseter muscle were studied in developing mice. A liquid diet requiring no mastication suppressed the development of the masseter muscles more than a fine-grained diet, and extraction of unilateral upper molars also caused inhibition of muscle development. Moreover, both unilateral extraction of upper molars and a liquid diet had an additive effect on the suppression of the postnatal development of the masseter muscle, and bilateral suppression of the development of the masseter muscle was induced following unilateral extraction of upper molars. These findings suggest that the sensory input from the sensory endings in the periodontal ligament may also play an important role in the postnatal development of the masseter muscle and that there may be some crossing pathways to convey the sensory input coming from the side of the extracted upper molars to the contralateral motor neurons via the interneuronal circuits.

Animals↗
PubMed1990

Pathology of experimental chlamydiosis in chicks.

Twelve one-day-old chicks were experimentally inoculated with Chlamydia psittaci derived from turkeys. Acute chlamydial septicemic lesions were induced by the inoculation into the air sac and trachea. No lesions were produced by the esophageal injection. Clinically, the affected chicks showed emaciation and mouth breathing, and were inactive while some birds died. Grossly, they had hepatomegaly, splenomegaly and airsacculitis. Histopathologically, fibrinopurulent airsacculitis, pneumonia and bronchitis, multiple fibrinous serositis in the hepatic and splenic capsules, peri- and epicardium, and mesenterium, focal endoarteritis in the aortae, activation of reticuloendothelial cells in the spleen, and hepatic necrosis were noted. Immunohistochemically, chlamydial antigen granules were present in the cytoplasm of epithelial cells of the respiratory system, hepatocytes, macrophages in the air sac, lung, serous membrane, liver, spleen, aortae, reticuloendothelial cells in the spleen, and mesothelial cells in various organs or tissues. Chlamydial multiplication in the cells of the organs or tissues involved was preceded to form the lesions.

Air Sacs↗
PubMed1990

Metabolic fate of loxistatin in rat.

1. The urinary and plasma metabolites of 14C-loxistatin, a new thiol protease inhibitor, were studied after oral administration to rats. 2. The major metabolites in urine were identified as loxistatin acid (M-1), a pharmacologically active form, and its hydroxy metabolites (M-4a and M-4b). These metabolites were also shown to be the major metabolites in plasma. 3. The inhibitory activity of the synthetic metabolite, M-4b, on papain was almost the same as that of loxistatin acid.

Administration, Oral↗
PubMed1989

Comparative pharmacokinetics of clarithromycin (TE-031), a new macrolide antibiotic, and erythromycin in rats.

Clarithromycin (TE-031) is a newly synthesized macrolide with high stability in acidic conditions. In the present study, the pharmacokinetics of [N-methyl-14C]clarithromycin were compared with those of [N-methyl-14C]erythromycin in rats by radioassay and bioassay. Both radioactivity and bioactivity of [14C]clarithromycin in plasma and tissues were found to be significantly higher than those of [14C]erythromycin at the same oral dose of 20 mg/kg (body weight). Among the tissues, the peak level of [14C]clarithromycin in the lung was especially high. Levels of radioactivity and bioactivity amounted to 15 and 73 times the corresponding levels of [14C]erythromycin. In the urine, bioactivity recovered after administration of [14C]clarithromycin was sevenfold higher than that for [14C]erythromycin. This accounted for about 60 and 20% of the total radioactivity in the urine for [14C]clarithromycin and [14C]erythromycin, respectively. An examination of metabolites in the urine for [14C]clarithromycin revealed appreciable amounts of bioactive unchanged clarithromycin. These results indicate that clarithromycin has pharmacokinetic properties superior to those of erythromycin. The desirable properties of clarithromycin include high levels in plasma resulting from its high stability in gastric acid; a high tissue affinity, especially to the lung; and favorable urinary excretion.

Administration, Oral↗
PubMed1989

Prolonged degeneration of muscle spindles in the masseter muscle after treatment of developing mice with the local anesthetic lidocaine hydrochloride.

The effect of lidocaine-HCl on muscle spindles in the masseter muscle of developing mice was investigated. Repeated injections of mice with anesthetic in the short term decreased the diameters of primary endings, intrafusal muscle fibers and outer capsules in the equatorial regions of muscle spindles, and caused a drop in the succinic dehydrogenase activity in intrafusal muscle fibers of the muscle spindles. In addition, the diameters did not recover to the control value even after about 10 weeks following cessation of anesthetic treatment. Thus, the present results suggest that repeated use of lidocaine-HCl in developing animals may cause dysfunction of the skeletal muscles.

Animals↗
PubMed1989

Immunocytochemical component of endocrine cells in pancreatic islets of horses.

The endocrine cell components in the pancreatic islets of the following 4 pancreatic regions of the horse were investigated by immunohistochemical methods: lobus pancreatis sinister (left lobe); lobus pancreatis dexter (right lobe); and 2 regions of Corpus pancreatis (body), the duodenal lobe which lies along the cranial duodenal flexure and descending duodenum, and the intermediate lobe which is situated around the portal vein. The islets in the left and intermediate lobes contained a central mass of glucagon cells surrounded by insulin cells, a few somatostatin cells and sporadic pancreatic polypeptide (PP) cells. On the other hand, the islets in the duodenal lobe were small in size compared with the other 3 regions, and were predominant in insulin and pancreatic polypeptide (PP) cells, but almost lacked in glucagon cells. These findings suggested that the duodenal lobe was derived from the ventral pancreatic primordium, and the left and intermediate lobes were originated from the dorsal pancreatic primordium. In the right lobe, the composition and distribution of the islet cells were almost the same as those in the left and intermediate lobes, but there were several lobules containing numerous PP cells as seen in the duodenal lobe.

Animals↗
PubMed1989

Effects of prevention of coprophagy on pregnant mice--is coprophagy beneficial on a balanced diet?

The effects of prevention of coprophagy on reproductive performance were examined in ICR mice. Females were treated with restrainers in order to prevent them from ingesting their feces from day 1 through day 17 of pregnancy. The restrained animals fed a commercial diet did not show any clear adverse effects. In contrast, restrained dams fed a purified diet deficient in vitamin B12 exhibited stillbirths (14%) and abortions (7%). Restrained dams fed a diet lacking in vitamin B12 and folic acid also experienced frequent abortions (27%). In addition, six out of 14 restrained dams (43%) aborted when fed a vitamin B complex-deficient diet. Sham-restrained animals, fed the vitamin B complex deficient-diet, but able to ingest their feces trapped by smaller-mesh floors, escaped these adverse effects. Sham-restrained animals fed the commercial diet, however, showed only a slight improvement in their reproductive performance. In conclusion, coprophagy has nutritional significance as long as the diet is lacking at least B vitamins, especially vitamin B12 and folic acid, whereas it almost entirely loses its nutritional significance when the mouse has access to a balanced diet such as the one made available to the laboratory mice in the present study.

Animal Feed↗
PubMed1989

[Case of the maxillofacial defect patient. Prosthetic treatment after reconstruction of the palate and face using deltopectral flap].

The patient, a 72-year-old edentulous man, had an extensive maxillofacial defect caused by treatment of the maxillary cartinoma. As his left maxillary and zygomatic bone, a portion of the soft palate, orbital cavity contents and soft tissues of the cheek had been excised, his face was ugly, and his speech and eating were extremely poor. For this patient, first of all, plastic surgeons reconstructed the cheek and palate using deltopectral flap. Secondly, dentists prepared a facial prosthesis and a set of complete dentures. Four months after prosthetic treatment, plastic surgeons corrected the left corner of the mouth using temporal muscle flap and fascia lata, and strengthened infraorbial region of deltopectral flap by grafting the left 5th rib. Lastly, dentists remade the facial prosthesis. As a result, the patient had great improvement in his face, speech and eating. Periodic examination of the surgical site can be practiced through the remaining facial defect. The advantages of the surgical reconstruction in this case were as follows. (1) As reconstruction of the cheek narrowed a facial defect, it was easy to improve patient's appearance by a small facial prosthesis. (2) The closure of the palate was effective to improve hypernasal speech, to prevent fluid leakage into the nasal cavity and to improve the retention and stability of the upper complete denture.

Aged↗
PubMed1989

Identification of glutathione conjugate formed from loxistatin in rats.

1. The metabolic fate of loxistatin, ethyl-(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methyl- butylcarbamoyl)butylcarbamoyl]-2-oxiranecarboxylate, was studied in rats. 2. Following oral administration of 14C-loxistatin the major part of radioactivity was eliminated via the bile into the faeces. 3. The major metabolites in bile were isolated and identified as glutathione and cysteine conjugates of loxistatin acid, by chromatography, proton n.m.r. spectroscopy and mass spectrometry and comparison with those of the authentic reference compounds. 4. Formation of the glutathuone conjugate was also demonstrated in vitro by incubation of 14C-loxistatin acid with rat liver cytosol and glutathione.

Administration, Oral↗