Biomedical subjects

S Hata

Publications and source records attributed to S Hata.

292 records · Page 17Linked to original sources

PubMedDate not supplied

The left ventriculographic pattern and serial electrocardiographic changes in hypertrophic cardiomyopathy patients with giant negative T waves.

The configuration of the left ventriculogram (LVG) was classified in 64 patients with hypertrophic cardiomyopathy (HCM) observed in ECG, and characteristics of the configuration and serial changes in SV1+RV5 and giant negative T (GNT) waves were studied. The LVG configuration was classified into the spade (15 patients), papillary-muscle hypertrophy (PMH; n = 23), oval (n = 24) and banana types (n = 2). The spade, PMH and oval types were observed for mean periods of 66, 90 and 91 months, respectively. Serial changes in ECG were as follows: GNT decreased from 16.7 +/- 3.3 to 13.3 +/- 5.1 mm in the spade type and decreased significantly from 16.9 +/- 5.9 to 9.8 +/- 6.9 mm in PMH but showed no changes in the oval type. SV1+RV5 decreased significantly from 69.0 +/- 14.9 to 58.2 +/- 14.7 mm in PMH but showed no significant changes in the spade or oval types. Thus GNT decreased progressively in many patients with the exception of a few with the oval type. From these findings, we consider that apical hypertrophy had been established at the time of the initial LVG and changed over time thereafter in the spade and PMH types but that hypertrophy was still in progress in some patients with the oval type.

Cardiac Catheterization↗

PubMedDate not supplied

A newborn rabbit model for total parenteral nutrition: effects of nutritional components on cholestasis.

A newborn rabbit model for total parenteral nutrition (TPN) was developed to examine the effects of nutritional components on cholestasis. Thirty-five newborn Japanese white rabbits were divided into five groups. Rabbits in group I received glucose-based TPN solution, Group II received lipid-based solution, group III received larger amounts of amino acids than group I, and group IV received larger amounts of nonprotein calories than groups I and II. Rabbits in group V were given mother's milk freely. After the duration of TPN for 7 days, blood samples and liver were obtained when rabbits were killed. In group IV, the serum level of T-Bil (1.44 +/- 0.68 mg/dliter) was significantly higher than those in other groups (group I: 0.28 +/- 0.04 mg/dl; group II: 0.49 +/- 0.12 mg/dl; group III: 0.21 +/- 0.04 mg/dl; group V: 0.28 +/- 0.07 mg/dl), and serum level of GOT (44.2 +/- 25.2 units) and total bile acid (20.6 +/- 8.9 nmol/ml) were significantly higher than those in groups I, II, and III (group I: 16.8 +/- 7.8 units and 6.7 +/- 3.3 nmol/ml, group II: 21.5 +/- 7.9 units and 12.5 +/- 6.4 nmol/ml, group III: 14.3 +/- 4.2 units and 8.4 +/- 5.0 nmol/ml, respectively). Furthermore, there was histological cholestasis characterized by bile plugs in bile ducts, and bile pigments in Kupffer cells and hepatocytes, whereas there were no, or scarce findings of cholestasis in the other groups. These results indicate that an excessive administration of nonprotein calories in TPN contributes to the occurrence of cholestasis. In addition this animal model may be useful in investigating the etiology of cholestasis.

Animals↗

PubMedDate not supplied

In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes.

The in vitro metabolism of dorzolamide, a potent carbonic anhydrase inhibitor, was investigated using liver microsomes from Sprague-Dawley rats. The liver microsomes metabolized dorzolamide to an N-deethylated form, whereas N-deethylation of dorzolamide was not detected in 10,000g supernatant from the small intestine, brain, heart, lung, kidney and spleen, or the cytosol fraction of liver. The dorzolamide N-deethylase activity was not detected without an NADPH-generating system and was inhibited by classical inhibitors for cytochrome P450, metyrapone and n-octylamine. Orphenadrine and diphenhydramine (specific inhibitors for CYP2B1/2), diethyldithiocarbamate, disulfiram and isoniazid (inhibitors for CYP2E1), troleandomycin (inhibitor for CYP3A), and testosterone inactivated dorzolamide N-deethylase activity. On the other hand, ajmalicine, a specific inhibitor for CYP2D1, did not inhibit the reaction. With phenobarbital-induced microsomes, 66%, 72%, 36%, and 53% of the 2 beta-, 6 beta-, 16 alpha-, and 16 beta-testosterone hydroxylase activities were inhibited by 5 mM dorzolamide, respectively, whereas the 2 alpha-hydroxylase activity was not inactivated. Antisera against rat CYP2B1, CYP2E1, and CYP3A2 suppressed dorzolamide N-deethylase activity by 52%, 43% and 46%, respectively, whereas only 18% and 15% of the activity were inhibited by anti-CYP1A1 and anti-CYP4A1 antibodies, respectively. Analysis of the N-deethylase reactions using Eadie-Scatchard plots showed high- and low-affinity components in rat liver microsomes. The high-affinity reaction was induced with phenobarbital and dexamethasone, but not with 3-methylcholanthrene. These results suggest that CYP2B, CYP2E1, and CYP3A subfamilies are involved in the dorzolamide N-deethylation in rat liver microsomes.

Animals↗

PubMedDate not supplied

Binding of dorzolamide and its metabolite, N-deethylated dorzolamide, to human erythrocytes in vitro.

Dorzolamide, previously known as MK-507, is a novel topical carbonic anhydrase (CA) inhibitor. The uptake and binding of dorzolamide and its N-deethylated metabolite to human erythrocytes were studied in vitro. Dorzolamide and N-deethylated dorzolamide were preferentially taken up by the erythrocytes, and the uptake of dorzolamide by erythrocytes was found to be much faster than that of N-deethylated dorzolamide. When 20 or 200 microM dorzolamide was incubated with human erythrocytes, 98% or 71% of the drug was taken up by the erythrocytes, respectively. Similarly, using 20 or 200 microM N-deethylated dorzolamide, 99.7% or 75% of the drug was taken up by the erythrocytes, respectively. These results indicate that human erythrocytes contain proteins that bind to dorzolamide and N-deethylated dorzolamide, and the binding of these proteins is saturable. The results of the in vitro binding study suggest that presence of at least three kinds of binding site for dorzolamide in human erythrocytes. One of the binding sites for dorzolamide was characterized by extremely high affinity (Kd = 0.0011 microM) and low capacity (Bmax = 16.1 microM), corresponding to CA-II. Another binding site was characterized by low affinity (Kd = 2.8 microM) and high capacity (Bmax = 117.1 microM), corresponding to CA-I. The third one was a nonspecific binding. The binding of N-deethylated dorzolamide to human CA-I and CA-II was competitively inhibited by dorzolamide, indicating that these compounds bind to the same binding site on CAs. In each other's presence, most of dorzolamide in erythrocytes binds to CA-II, whereas the N-deethylated metabolite mainly binds to CA-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗