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Biomedical subjects

S Sakuragi

Publications and source records attributed to S Sakuragi.

At least 73 records · Page 4Linked to original sources
PubMed1977

[Metabolic fate of carteolol hydrochloride (OPC-1085), a new beta-adrenergic blocking agent. (6) Pharmacokinetics of carteolol in the rat, dog, rabbit and man].

The kinetics (absorption, distribution and excretion) of carteolol were investigated after oral and intravenous administration to man, rats, Beagle dogs and rabbits. The half-life of carteolol in plasma was 1.22 approximately 1.45 hr in rats, 1.73 approximately 2.08 hr in dogs and 1.42 approximately 1.43 hr in rabbits, and was independent of the route of administration. The absorption rate constants, obtained from log(C1-C) approximately time plot, after oral administration were 1.89 hr-1 in rats, 1.04 hr-1 in dogs and 1.54 hr-1 in rabbits. There were no differences between tablet and film coated tablet in the pharmacokinetic parameters of carteolol in man after oral 30 mg (tablet or film coated tablet) administration [half life (t1/2)=4.50 hr (tablet), 4.30 hr (film coated tablet), elimination rate constant (k2) equals 0.154 hr-1 (tablet), 0.161 hr-1 (film coated tablet)]. The elimination rate constant, obtained from Sigma-minus plot after 2, 5 and 10 mg oral administration, was 0.137 approximately 0.160 hr-1.

Administration, Oral↗
PubMed1977

Metabolic fate of carteolol hydrochloride, (OPC-1085) VIII, a new beta-adrenergic blocking agent. Pharmacokinetic studies of carteolol in man.

The pharmacokinetics of 5-(3-tert.-butylamino-2-hydroxy)-propoxy-3,4-dihydrocarbostyril hydrochloride (carteolol hydrochloride, OPC-1085) have been investigated in man following single or repetitive oral administration. The plasma half-lives. The plasma half-lives of carteolol at single doses of 10, 15 and 30 mg were 5.4, 5.5 and 5.0 h, respectively. The amounts of carteolol excreted into urine within 24 h at the same dose levels accounted for 64, 70 and 76% of the respective doses. The half-lives obtained by the Sigmaminus method were 5.6, 5.6 and 5.4 h, respectively, being essentially consistent with the aforementioned plasma half-lives of carteolol after administration at 15 mg daily for 7 successive days were determined to be 5.54 h on the 1st day and 6.91 h on the 7th day, displaying the increase in half-life value with the repetitive dosing. While, the predicted value determined using the experimental value on the 1st day agreed with the experimental value on the 7th day. Furthermore, the amounts of carteolol excreted in the urine were not significantly different between the 1st and 7th days. The 7-day repetitive administration with carteolol brought about the steady state of plasma levels. It was concluded from these results that carteolol has little ability to accumulate in man.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Suppression of experimental autoimmune uveoretinitis by dietary calorie restriction.

To investigate the inhibitory effect of dietary calorie restriction on experimental autoimmune uveoretinitis (EAU) in rats, and its mechanism. Lewis rats were maintained on a 50% calorie-restricted diet for 2 months or 6 months. The control group was maintained on a 90% ad libitum intake for the same length of time. Experimental autoimmune uveoretinitis was elicited in both groups by immunization with an inter-photoreceptor retinoid-binding protein or its peptide. Rats in both groups were examined clinically, histopathologically, and immunologically. The severity of EAU was milder in the restricted diet group than in the control group. In EAU rats, production of interferon-gamma (IFN-gamma) in eyes and of IFN-gamma and tumor necrosis factor-alpha in draining lymph node cells was significantly lower in the restricted diet group than in the control group. Our results indicate that a calorie-restricted diet suppresses the development of EAU. The suppressed Th1-dependent immunological response is one of the reasons for the mildness of EAU in the calorie-restricted diet group of rats.

Animals↗
PubMedDate not supplied

Fas expression and apoptosis in rats with experimental autoimmune uveoretinitis.

PURPOSE: To evaluate Fas expression on CD4 and CD8 T cells in each organ at each stage of experimental autoimmune uveoretinitis (EAU) and apoptotic cells within EAU eyes. METHODS: Rats were immunized with the uveitopathogenic peptide derived from interphotoreceptor retinoid-binding protein. Flow cytometry was performed in ocular cells, draining lymph nodes cells and splenic cells of EAU rats to investigate Fas expression by CD4 and CD8 lymphocytes. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining of apoptotic nuclei was performed on sections of EAU eyes. RESULTS: Fas expression by both ocular and splenic CD4 and CD8 lymphocytes was significantly higher than in lymph nodes at each stage. In EAU eyes, there was a relatively large population of lymphocytes with Fas expression (19.6-25.6% of CD4 and 33.2-53.4% of CD8). Apoptotic cells were more prominent in the EAU eyes with established disease than in those with early or resolving disease. CONCLUSIONS: These results suggest that the relatively large population of lymphocytes with Fas expression in EAU eyes reflects the activation of lymphocytes in these eyes, and that the increase in apoptotic inflammatory cells at the peak of established disease may participate in the spontaneous disappearance of EAU.

Animals↗
PubMedDate not supplied

Uveitopathogenic site of the gamma-subunit of cyclic guanosine monophosphate phosphodiesterase in Lewis rats.

PURPOSE: The gamma-subunit of cyclic guanosine monophosphate phosphodiesterase (PDEgamma) plays an important role in the phototransduction process of rod photoreceptors. A previous report indicated that experimental autoimmune uveoretinitis (EAU) could be induced in Lewis rats by immunization with PDEgamma. In this study, we identified the uveitopathogenic site of PDEgamma synthetic peptides and identified pivotal amino acid residues using analogue peptides. METHODS: Several synthetic peptides derived from PDEgamma plus adjuvants were injected in Lewis rats. The induction of EAU was examined clinically and histologically. In addition, humoral and cellular immunity against peptides was investigated. RESULTS: The smallest uveitopathogenic peptide was identified as PDEgamma 64-76 (ITVICPWEAFNHL), which consists of 13 amino acid residues, and the core sequence was identified as PDEgamma 70-76 (WEAFNHL), which consists of 7 amino acid residues. The lowest dose of peptide to induce EAU was 0.03 nmol. The pivotal amino acid residues for eliciting EAU are at 70(W), 71(E), 73(F), and 75(H). CONCLUSION: Our findings demonstrated the presence of a potent uveitopathogenic site in PDEgamma whose potency in Lewis rats was comparable to that of interphotoreceptor retinoid-binding protein.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMedDate not supplied

Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis.

Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS) are reported. Their clinical signs at onset were similar to those of orbital cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma-associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be very poor. As far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. They died within 6 months after the first ophthalmological examination. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect HPS and should examine serum ferritin, which is a good marker of HPS. Early biopsy and consultation with a hematologist are very important.

Adolescent↗
PubMedDate not supplied

Lectin cytochemical analysis of lacrimal pleomorphic adenomas.

The activity of seven different types of biotinylated lectin were examined in normal and tumorous lacrimal gland tissue. In the normal lacrimal gland tissue, the glandular cells and the tubular epithelium were labeled by maclura pomifera agglutinin (MPA), soybean agglutinin (SBA), and bauhinia purpurea agglutinin (BPA). The myoepithelial cells were stained by griffonia simplicifolia agglutinin 1 (GS1). In the primary pleomorphic adenoma tissue, the epithelial components were labeled by MPA, ulex europaeus agglutinin, SBA, peanut agglutinin, and BPA. The mesenchymal components showed negative labeling. In contrast, the recurrent pleomorphic adenoma tissue showed a positive reaction in the mesenchymal components when GS1 and BPA were used. These results revealed differences in the glycoconjugate composition among normal and tumorous lacrimal gland tissues from patients with primary and recurrent pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMedDate not supplied

Lectin cytochemistry of the rabbit conjunctiva and lacrimal sac.

Four different types of lectin were applied to the rabbit conjunctiva and the lacrimal sac to examine the distribution of glycoconjugates. The conjunctival epithelium is comprised of goblet cells and nongoblet cells. The mucus granules of the goblet cells were stained with soybean agglutinin (SBA), and the cell body of the nongoblet cells was labeled with concanavalin A (Con A). The glycocalyx of the apical surfaces of the goblet cells and of the non-goblet cells was labeled with Maculura pomifera agglutinin. The lacrimal sac mucosa is comprised of superficial light and dark cells, and basal cells. The cell bodies of the light cells were stained with SBA. The glycocalyx of the apical surfaces of the light and dark cells was characteristically labeled with Con A. These results suggest that the composition of glycoconjugates is markedly different between the conjunctiva and the lacrimal sac, especially in the cell surface glycocalyx.

Animals↗