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Biomedical subjects

J Azuma

Publications and source records attributed to J Azuma.

At least 127 records · Page 7Linked to original sources
PubMed1978

Yohimbine blockade of ionic channels in myocardial cells.

The effects of yohimbine, an alkaloid shown to have local anesthetic properties on nerve, were determined in isolated perfused chick embryonic (19--21-day-old) hearts. Effects on the fast Na+ channels were studied in hearts perfused with normal Ringer solution by using the maximal upstroke velocity (+Vmax) as an index of the inward current flowing during the rising phase of the normal action potential. Yohimbine (10(-5)--10(-4) M) depressed +Vmax and overshoot and prolonged the action potential. At 5 x 10(-4) M, yohimbine completely blocked the fast Na+ channels, since this dose abolished the action potential when Mn2+ (2 mM) was present to eliminate the slow Ca2+ current. Effects on the slow channels were studied in hearts in which the fast Na+ channels were voltage-inactivated by partial depolarization to about--40 mV with an elevated (25 mM) K+-Ringer solution or blocked by tetrodotoxin (TTX), resulting in loss of excitability. Isoproterenol (10(-6) M) restored excitability by inducing a slowly rising overshooting electrical response (the "slow response") that was accompanied by contractions. At low concentrations (10(-5)--10(-4) M), yohimbine enhanced the isoproterenol-induced slow response; yohimbine induced the slow response in the absence of isoproterenol, even in the presence of a beta-adrenergic blocker. In contrast, at high concentrations (10(-3) M), yohimbine markedly depressed or blocked the slow response. Consistent with this dual action, yohimbine exerted a small positive inotropic action at low doses in hearts perfused with normal Ringer solution and exerted a considerable negative inotropic action at high doses, causing complete blockade of the contractions within 20 min. Cultured reaggregated cells obtained from chick embryo (15--17 day-old) ventricles showed a similar response to yohimbine in that both the normal action potentials and the slow responses were abolished. It is concluded that yohimbine exerts a local anesthetic-like action on myocardial cells, since both fast and slow channels were blocked, but the fast channels were more sensitive to yohimbine.

Action Potentials↗
PubMed1978

Studies on pig serum lipoproteins. V. Optical properties of low density lipoproteins.

The circular dichroism (CD), optical rotatory dispersion (ORD), and fluorescence emission spectra of two subfractions of pig serum low density lipoproteins (LDL1 and LDL2) were compared. The contribution of the carbohydrate moiety to the CD and ORD spectra was estimated on the basis of data obtained from isolated glycopeptides and the constituent monosaccharides. The carbohydrate moiety had no effect on the conformation of the protein moieties of LDL1 and LDL2 (apoLDL1 and apoLDL2). However, the intensities of the observed extrema in the CD and ORD spectra of the glycopeptides were greater than those expected from the monosaccharide composition. This suggests the existence of secondary structure in the carbohydrate moiety. In contrast to the carbohydrate moiety, the contribution of the lipid moiety to the CD and ORD spectra could not be neglected. When the effect of the lipid moiety was subtrated from the CD and ORD spectra, the spectra due to apoLDL1 and apoLDL2 were quite similar. Delipidation in the presence of sodium dodecyl sulfate (SDS) induced an increase in the content of disordered structure and alpha-helix accompanied by a decrease in the beta-structure. In the presence of SDS, marked quenching occurred in the fluorescence emission spectra with a blue shift of the maximum emission wavelength from 332 to 326 nm. ApoLDL1 and apoLDL2 showed quite similar SDS-induced conformational transitions. The secondary structures of apoLDL1 and apoLDL2 in the native lipoproteins were stable to changes of pH and temperature. However, this stability was lost in the presence of SDS. These results suggest the importance of the lipid moiety in maintaining the native secondary structures of LDL1 and LDL2. From the overall similarity of the optical properties of apoLDL1 and apoLDL2, we conclude that the secondary structures of apoLDL1 and apoLDL2 are identical.

Animals↗
PubMed1978

Levels of the glutamic oxaloacetic transaminase of erythrocytes of pregnant women and of cord bloods of newborn infants.

The mean basal specific activity (S.A.) of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) for a group of 64 pregnant women was lower (p less than 0.001) than the value for the cord bloods of newborn infants, and lower (p less than 0.001) than the value for adults who had a top limit of S.A. of EGOT. In establishing the top limit of the S.A., it is important that the mean basal S.A. of the cord bloods from 49 newborn infants was identical to the mean basal S.A. of adults who had an adequate supplement of pyridoxine. There were no differences in the mean basal S.A.'s of the cord bloods between asymptomatic mothers and mothers who had anemia, edema, hypertension, proteinuria and glucosuria. An infant may be born with a top limit of S.A. which is non-deficient in pyridoxal 5'-phosphate, but a mother can have a low level of the transaminase, and which is deficient in the coenzyme.

Aspartate Aminotransferases↗
PubMed1977

Studies on pig serum lipoproteins. IV. Isolation and characterization of glycopeptides from pig serum low density lipoprotein.

Three glycopeptides were isolated from the pronase digest of the protein moiety of pig serum low density lipoprotein. The isolation procedure consisted of pronase digestion, gel filtration on Sephadex G-25 and G-50 columns, paper chromatography and DEAE-Sephadex A-50 column chromatography. Based on the carbohydrate analysis, the isolated glycopeptides were classified into two types. One type (GDI) consisted of mannose and N-acetylglucosamine residues in the molar ratio of 6:2 and had a molecular weight of about 2,300. The other type (GDII and GDIII) consisted of sialic acid, mannose, galactose, fucose, and N-acetylglucosamine residues in the molar ratio of 1:4:2:1:3 and 2:4:3:1:3, respectively. The molecular weights of GDII and GDIII were about 2,100 and 3,100, respectively. The results on the strong alkaline treatment of these glycopeptides suggested that all carbohydrate chains were linked to the peptide chains through N-acetylglucosaminyl-asparagine linkages. Of these glycopeptides and pig serum lipoproteins, only glycopeptide GDI and native LDL strongly interacted with concanavalin A.

Amino Acids↗
PubMed1977

A correlative study on the changes of cardiac dynamics and myocardial energy liberation in blood-let dogs.

Blood-letting of 450 to 1,000 ml with or without saline infusion was performed in dogs. In some dogs, right atrial pacing was carried out during blood-letting. Heart rate and isometric time-tension index were measured as the indicators of chronotropism and inotropism, respectively. After 60 min of blood-letting, dogs were sacrificed and mitochondria were isolated from the left ventricular myocardium. Mitochondrial respiration was measured polarographically and respiratory control index was calculated. As blood-letting advanced, the hearts revealed negative chronotropism with negative inotropism. Mitochondrial respiration was suppressed. When heart rate was forced to increase with atrial pacing, the hearts showed positive chronotropism with negative inotropism. Respiratory control index of mitochondria was deteriorated, showing uncoupling of oxidative phosphorylation. In consideration with our previous study on the ischemic heart, it is concluded that uncoupling of oxidative phosphorylation appeared in hypoxic myocardium when cardiac dynamics shifted to positive chronotropism with negative inotropism, though suppression of mitochondrial respiration was revealed when cardiac dynamics altered to negative chronotropism with negative inotropism.

Animals↗
PubMed1976

Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine.

Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine.

Adult↗
PubMed1976

Apparent deficiency of vitamin B6 in typical individuals who commonly serve as normal controls.

Individuals who typically serve as normal controls were found by the differential assay of the glutamic oxaloacetic transaminase in their erythrocytes to have a deficiency (P less than 0.001) of enzyme activity as well as a deficiency (P less than 0.001) of pyridoxal phosphate. Contrary to the understanding that the diet provides an adequate intake of vitamin B6, the dietary intake of vitamin B6 of these controls was inadequate.

Adult↗
PubMed1975

Studies on pig serum lipoproteins. I. Separation and properties of low-density lipoproteins.

The low-density lipoproteins in pig serum were separated into two subclasses (LDL1 and LDL2) by 2 to 7% pore size gradient gel electrophoresis. Preparative gel electrophoresis in 2 to 4% gradient gel made it possible to isolate these components as distinct entities. After delipidation by chromatography on Sepharose 4B in the presence of SDS, both apo-LDL1 and apo-LDL2 were found to have a molecular weight of 2.6X10(5). However, when these apoproteins were incubated in 10% sodium dodecyl sulfate, fragmentation occurred and the minimum fragment molecular weight was estimated to be 2.4X10(4). No essential difference was found in the amino acid compositions or fragmentation patterns of the apoproteins. However, the amounts of carbohydrates in the two apoproteins were different (7.09% in apo-LDL1 and 5.08% in apo-LDL2). The carbohydrate composition was 0.8% sialic acid, 2.38% N-acetyl-glucosamine, and 4.01% neutral sugars in apo-LDL1 and 0.5, 1.75, and 2.83% in apo-LDL2, respectively. In both apoproteins, mannose, galactose, and fucose were present in almost the same molar ratio of 4-5 : 2-3 : 1.

Amino Acids↗
PubMedDate not supplied

Protective effect of taurine against isoprenaline-induced myocardial damage.

The effect of the sulfur amino acid, taurine, was examined on histological and biochemical changes induced by a toxic dose of isoprenaline in chick hearts. Isoprenaline treatment (80 or 240 mg/kg id twice daily for 4 days) caused a dose-dependent increase in heart weight and decrease in myocardial ATP. Isoprenaline administration (240 mg/kg id twice daily) produced necrotic changes in hearts, such as eosinophilic degeneration, myolysis, interstitial oedema, fibrosis, and inflammatory cell infiltration. Substantial accumulation of calcium was also observed. Taurine content of the heart was not significantly decreased. Parenteral administration of taurine (200 mg/day for 7 days) partially protected against these necrotic changes induced by isoprenaline. It is suggested that the protective effect of taurine against isoprenaline-induced myocardial injury might be due in part to the prevention of the massive overloading with calcium which is thought to cause myocardial cell necrosis.

Adenosine Triphosphate↗
PubMedDate not supplied

Beneficial effect of coenzyme Q on myocardial slow action potentials in hearts subjected to decreased perfusion pressure-hypoxia-substrate-free perfusion.

Coenzyme Q, an important component of the electron transfer system in mitochondria, plays a central role in energy production aerobically. The effect of pretreatment with coenzyme Q10 (Co Q) on myocardial slow action potentials (APs) and accompanying contractions and on myocardial high energy phosphate content was studied in perfused hearts subjected to decreased perfusion pressure-hypoxia-substrate-free. Post-hatched chicks were treated i.p. with 10 mg/kg of Co Q daily for 5 days. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated by elevated K+ (25 mM) Tyrode solution. The Ca++-dependent slow APs were induced by elevating [Ca]o to 5.4 mM; hearts were paced at a rate of 40 per min. Hearts which had been pretreated with Co Q were protected against the deleterious effect of decreased perfusion pressure - hypoxia - substrate-free perfusion on mechanical performance accompanying the slow Ca++-Na+ APs. The slow APs in hearts pretreated with Co Q were also less affected than were non-treated hearts. However, the myocardial ATP and total adenine nucleotides were not affected by exogenous Co Q. It was suggested that exogenous Co Q could protect against the decline of cardiac contractions via improved availability of slow APs during decreased perfusion pressure - hypoxia - substrate-free, independently of the cellular high energy phosphate level.

Animals↗
PubMedDate not supplied

Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects.

OBJECTIVES: The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially available, were used in this study. METHODS: Sixteen healthy male Japanese subjects participated in this study and were divided into two groups for grapefruit juice and orange juice treatment. The study followed an open-labelled crossover design, comparing the effects of a single oral dose of 2 mg pranidipine taken together with 250 ml citrus juice or 250 ml water. Serum pharmacokinetics of pranidipine, adverse reactions, blood pressure, heart rate, 12-lead ECG, haematology, clinical chemistry and urinalysis were measured throughout the study. RESULTS: For grapefruit juice, mean Cmax and AUC0-24 h were significantly higher than those of water (P=0.0003 and 0.0005, respectively, ANOVA) with the ratios of log transformed values being 1.50 and 1.74, respectively. There were no differences in tmax and t1/2 between the juice and water treatments. A significant increase in heart rate (P=0.0240, ANOVA with repeated measurements) was observed in the juice treatment whereas there were no significant differences in systolic and diastolic blood pressure between the two treatments. For orange juice, a small decrease in mean Cmax was observed compared with water (P=0.0218, ANOVA) with the ratio being 0.86, but there was no significant difference in AUC0-24h between the two treatments. No marked differences were observed in tmax and t1/2. Oral pranidipine administration with orange juice did not affect heart rate, systolic and diastolic blood pressures or other parameters for safety evaluation. CONCLUSIONS: Oral co-administration with grapefruit juice and pranidipine was associated with increased bioavailability and changed the pharmacodynamics of pranidipine, particularly with regard to heart rate. Orange juice intake with pranidipine did not markedly affect the pharmacokinetics and no clinically significant changes were observed in the pharmacodynamics and safety evaluation.

Adult↗