Search PubMed⌕ Search

Biomedical subjects

J Sugihara

Publications and source records attributed to J Sugihara.

At least 55 records · Page 3Linked to original sources
PubMed1988

Lymphatic absorption of hypolipidemic compound, 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903).

The intestinal absorption process of 1-O-[p-(myristyloxy)-alpha-methylcinnamoyl] glycerol (LK-903), a new hypolipidemic compound, was studied in rats. When 3H-LK-903 or 3H-LKA [3H-p- (myristyloxy)-alpha-methyl cinnamic acid], labeled at the cinnamic acid moiety, or 14C-LK-903, labeled at the glycerol moiety, were administered orally to thoracic duct-cannulated rats at a dose of 0.233 mmol/kg, 31.1, 6.7 and 18.1% of the dose, respectively, appeared in the lymph within 24 h. In this case, radioactive compounds in the lymph lipids consisted of LKA (radioactivity was not detected in the fraction of LKA with 14C-LK-903), LK-903, diglyceride analogues and triglyceride analogues. The percentages of the triglyceride analogues were the highest, followed by the diglyceride analogues. On the other hand, when doubly labeled LK-903 (3H/14C = 1, corrected ratio) was administered orally, the values of 3H/14C for the monoglyceride, diglyceride and triglyceride analogues in the lymph were 1.2-1.5, 1.7-1.9 and 1.9-2.7, respectively. The lymphatic absorption of LK-903 was stimulated by the presence of lecithin but inhibited by a high dose of triolein. The results indicated that (1) LK-903 formed micelles in the intestine, (2) a large part of LK-903 was absorbed as such, (3) a part of LK-903 was hydrolyzed in the intestinal mucosa, and (4) a part of LKA formed by hydrolysis was again utilized to synthesize the higher glycerides and absorbed via the lymphatic absorption route for lipids.

Animals↗
PubMed1988

Studies on intestinal lymphatic absorption of drugs. I. Lymphatic absorption of alkyl ester derivatives and alpha-monoglyceride derivatives of drugs.

Several alkyl ester derivatives or alpha-monoglyceride derivatives of 3H-labeled compounds, i.e. trimetoquinol, TA-594, acetaminophen, naproxen and nicotinic acid, were synthesized and administered orally to rats cannulated in the thoracic duct. The radioactivity appearing in 24 h-lymph was measured and analyzed by thin-layer chromatography. Most of the alpha-monoglyceride derivatives were absorbed via the intestinal lymphatic system, while the alkyl esters were very poorly absorbed. After oral administration of alpha-monoglyceride derivatives of labeled naproxen and nicotinic acid, the radioactive compounds found in the lymph were mainly monoglyceride, diglyceride and triglyceride analogues, while in plasma the main radioactive compound was the parent drug. It was concluded that alpha-monoglyceride derivatives of drugs were absorbed via the lymphatic system and transported into blood, yielding the parent drug in blood.

Absorption↗
PubMed1988

Studies on intestinal lymphatic absorption of drugs. II. Glyceride prodrugs for improving lymphatic absorption of naproxen and nicotinic acid.

A series of alpha- and beta-monoglycerides and triglyceride derivatives of naproxen or nicotinic acid were synthesized and investigated in order to elucidate the molecular form of the derivative with properties that enhanced lymphatic absorption. The lymphatic absorption rate was increased by adjusting the length of an n-alkyl chain introduced between the alpha- or beta-position of glycerol and the drug residue. The alpha- and beta-monoglyceride derivatives (containing an n-alkyl chain) were approximately equal in lymphatic absorption rates, but differed markedly in the concentration of the di- and triglyceride analogues in the lymph lipids. The lymphatic absorption of triglyceride derivatives, drugs combined directly with beta-position of glycerol, was low in comparison with the monoglyceride derivatives. Compared with nicotinic acid, the alpha-monoglyceride derivative (n-alkyl chain length, Cn = 20) of nicotinic acid provided a higher AUC0-8 h value of free nicotinic acid and maintained a lower level of free fatty acids in blood.

Animals↗
PubMed1985

Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.

We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patient's erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

2,3-Diphosphoglycerate↗
PubMed1984

Studies on the metabolism of diltiazem in man.

The human urinary metabolites of diltiazem were analyzed by thin-layer chromatography (TLC) and gas chromatography-mass spectrometry. Diltiazem was metabolized by deacetylation, N-demethylation, O-demethylation and conjugation. Metabolite MA, N- monodemethyl -diltiazem, was identified as a new major metabolite in human urine, and four metabolites were identified as deacetyl-diltiazem (M1), deacetyl-N- monodemethyl -diltiazem (M2), deacetyl-O-demethyl-diltiazem (M4), deacetyl-N,O-demethyl-diltiazem (M6) which were known as rat urinary metabolites. Metabolite M2, M4 and M6 were converted in part to glucuronides and/or sulfates. Unchanged diltiazem and metabolite MA were determined in human plasma and urine by TLC-densitometry. Diltiazem and metabolite MA excreted in 24-h urine were 44.4 and 48.5% of the total unconjugated form, respectively. The mean plasma level of metabolite MA was approximately one-third of diltiazem level. On the basis of these findings, a probable metabolic pathway of diltiazem in man is presented.

Adult↗
PubMed1983

A new family with beta-thalassemia intermedia.

In a Japanese family several members in three generations had, on hemoglobin analysis, typical findings of heterozygous beta-thalassemia. However, hemoglobin concentrations, red cell morphology, splenic size and clinical histories indicated that the disorder was more severe than in the usual beta-thalassemia trait. From the previous and the present studies folic acid supplements appeared to be beneficial in ameliorating the anemia. The findings may provide an apparent pathophysiologic and genetic explanations for the more severe anemia and red-cell abnormalities present in a small proportion of families with beta-thalassemia trait.

Hemoglobins↗