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H Y Yu

Publications and source records attributed to H Y Yu.

At least 73 records · Page 4Linked to original sources
PubMed1991

Blood content in guinea-pig tissues: correction for the study of drug tissue distribution.

The blood content in different organs or tissues of guinea-pigs was determined by means of [125I]bovine serum albumin. The blood distribution expressed as percentage of total body blood for various organs or tissues ranged from 0.35 (adipose) to 17.5 (muscle)%. The blood content in tissue preparations expressed as the blood background correction factor, F (ml blood/g wet tissue) depended on the extent of bleeding during experiment; that factor can cause a considerable difference in the results of a tissue distribution study of a drug. Blood content was high in the lung (0.36 ml/g), heart, liver, kidney and spleen, but low in adipose and brain tissues (0.021 ml/g). The distribution of valproic acid in various tissues of guinea-pigs after intravenous injection was determined from the homogenates of isolated organs. The results showed that blood contamination can greatly alter the data of tissue distribution of a drug to as much as 25%. This study proposed a maximum (non-bled) and a minimum (extreme-bled) blood background correction factor for respective tissues of guinea-pigs, as well as equations for correcting the blood contamination in tissue during the drug distribution study. The results suggest that to obtain an exact analysis of drug concentrations in specific tissues, a correction for the blood of that specific tissue is necessary.

Animals↗
PubMed1991

Pharmacokinetics of valproic acid in guinea-pigs with biliary abnormality.

To explore whether biliary cannulation, biliary obstruction or gall bladder obstruction could alter the disposition of valproic acid, guinea-pigs were subjected to common bile duct cannulation or ligation, gall bladder-neck ligation or sham surgery as a control. They were then given an intravenous (i.v.) dose of sodium valproate (50 mg kg-1) and the pharmacokinetics of valproic acid in each group were compared. In the cannulated group, significant decreases (P less than 0.05) in the area under the elimination curve (AUC), the volume of distribution at steady-state (Vdss) and the mean residence time (MRT) were observed. Significant increases (P less than 0.05) in the elimination rate constant (kz) and total clearance (CLtot) of valproic acid were noted. In the biliary obstructed guinea-pigs, the Vdss was significantly decreased (P less than 0.05). In the gall bladder obstructed guinea-pigs, there was a secondary peak of valproate plasma concentration, and the kz was significantly decreased. The biliary excretion of unchanged and conjugated valproic acid was 2.0 +/- 0.7 (s.e.m.) and 19.7 +/- 3.6 (s.e.m.)% of dose, respectively, and was almost completely reabsorbed in the enterohepatic recycling. Urinary excretion of unchanged and conjugated valproic acid, as well as non-conjugate metabolic clearance of valproic acid, were not significantly different among the four groups. The results suggest that the pharmacokinetics of valproic acid in guinea-pigs are particularly sensitive to interruption of the enterohepatic cycle. Biliary obstruction may elevate plasma concentrations owing to the decreased Vdss of valproic acid. Gall bladder obstruction may cause fluctuation of valproate plasma concentrations. The data indicate that the apparent total clearance of valproic acid is significantly less than the intrinsic clearance owing to enterohepatic recycling.

Animals↗
PubMed1991

Effects of sodium valproate and 4en-valproic acid on isolated hepatocytes of guinea pigs.

The effects of valproic acid (VPA) (100 to 2,000 micrograms/ml) and its metabolite 4en-valproic acid (4enVPA) (2 to 2,000 micrograms/ml) on plasma membrane permeability of isolated hepatocytes of guinea pigs were studied. The ability of hepatocytes to exclude trypan blue was decreased significantly (p less than 0.05) by VPA at concentrations higher than 100 micrograms/ml. The leakage of intracellular enzymes, lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and gamma-glutamyl transpeptidase (GGT), were not significantly increased by VPA within therapeutic concentrations (100-200 micrograms/ml). However, GOT and GPT leakage were significantly increased (p less than 0.05) by VPA, 500 micrograms/ml, but tended to decrease with further increases in VPA concentration. The enzyme leakage or trypan blue exclusion was not significantly altered by 10 micrograms/ml 4enVPA unless phenytoin (PT) (20 micrograms/ml) or phenobarbital (PB) (20 micrograms/ml) was presented. Higher concentrations of 4enVPA significantly decreased the trypan blue exclusion as well as increased GOT and GPT leakage of hepatocytes. Under scanning electron microscopic examination some hepatocytes at therapeutic concentrations of VPA or 4enVPA showed blebs on the membrane. Higher drug concentrations caused serious membrane damage such as pits and pores. These results suggest that there may be at least two mechanisms for the hepatotoxic effect of VPA. One may occur at therapeutic concentrations of VPA, resulting in increases in membrane permeability and decreases in membrane tension of hepatocytes. The other mechanism may occur at high concentrations of VPA or 4enVPA, resulting in substantial damage to the hepatocyte membrane.

Animals↗
PubMed1990

[Immunosuppressive effect of cultured Cordyceps sinensis on cellular immune response].

The immunosuppressive effect of cultured Cordyceps sinensis (Bei Lin Capsule) was studied in vitro and in vivo. When the drug was added from 0.6 mg/ml to 5 mg/ml a significant dose-dependent inhibition effect was shown in the following immune reactions of mice (P less than 0.05-0.01): phagocytic function of peripheral blood leucocytes assayed by chemiluminescence; mitogenic response of spleen lymphocytes to Con A; mixed lymphocyte culture and LPS induced interleukin-1 release of macrophages. The survival rate of mice spleen lymphocytes cultured with Cordyceps sinensis 5 mg/ml in 37 degrees C 5% CO2 for 5 days was more than 80%. Cordyceps sinensis 4 g/kg daily significantly prolonged the mice skin allograft survival time (12.7 +/- 2.2 days v.s. 8.3 +/- 0.7 days in the control, P less than 0.01) and its immunosuppressive effect was close to that of Cyclosporin A 5 mg/kg daily on skin allograft.

Animals↗
PubMed1984

Clinical implications of serum protein binding in epileptic children during sodium valproate maintenance therapy.

Steady-state serum levels of total and unbound valproic acid as well as unbound fraction in epileptic children were studied in a clinical setting. Valproic acid binding parameters were analyzed and compared with in vitro findings. Daily dose of sodium valproate ranging from 29 to 73 mg/kg/day were administered per os. Considerable variation in total and unbound concentrations and unbound fractions within and between subjects was observed. In subjects evaluated in this study, serum level of total and unbound valproic acid ranged from 279 to 1,196 mumol/L and from 37 to 410 mumol/L, respectively. The unbound fraction ranged from 10.32 to 48.39%. In vivo binding parameters obtained from clinical material were as follows: association constant, Ka = 4.984 L/mmol; total binding sites, NP = 1.451 mmol/L, where P is the molar concentration of albumin; number of binding sites per molecule of albumin, N = 2.48. Using spiked sera, binding parameters of Ka = 8.032 L/mmol, NP = 1.262 mmol/L, and N = 1.86 were found in the in vitro study. The association constant obtained from in vivo and in vitro studies were not significantly different (p greater than 0.05) from each other. The unbound fraction of valproic acid was concentration dependent even within the therapeutic range. An equation for estimating unbound concentration (Cf') or unbound fraction (fp') from total concentration (Ct) of valproic acid is derived. The ratio of observed unbound fraction to the estimated unbound fraction (fp/fp') was used to evaluate the variation in valproate serum binding of that clinical sample. Nine samples from hospitalized patients whose medication and diet were closely supervised showed an fp/fp' ratio very close to 1 (mean +/- SD 1.04 +/- 0.24). It is suggested that a clinical sample showing a value of fp/fp' greater than 1.76 (mean + 3 SD) should be evaluated for the cause of the decrease in serum binding and for the associated pharmacokinetic alterations. Therefore, in clinical monitoring of valproate, determination of both total and unbound drug levels was preferable to determination of either one alone. Furthermore, an understanding of the unbound fraction of valproic acid would significantly contribute to the effective management of epileptic patients.

Adult↗
PubMed1982

Intracellular forms of simian virus 40 nucleoprotein complexes. IV. Micrococcal nuclease digestion.

The structures of DNAs present in various intracellular forms of simian virus 40 (SV40) nucleoprotein complexes were analyzed by micrococcal nuclease digestion. The results showed that the 70S SV40 chromatin was completely sensitive to nuclease digestion, whereas CsCl gradient-purified mature virion was completely resistant. Virion assembly intermediates with different degrees of virion maturation showed intermediate resistance, and three products were found: nucleosomal DNA fragments, representing the fraction of intermediates that were sensitive to nuclease; linear SV40 genome-sized DNA, representing the more mature intermediates that contained one or limited defects in the capsid shell; and supercoiled SV40, which was derived from mature virions. These digestion products, however, remained associated with capsid shells after nuclease digestion. These results were consistent with the model in which maturation of the SV40 virion is achieved through the organization of capsid proteins that accumulate around SV40 chromatin. Mild digestion of SV40 nucleoprotein complexes with micrococcal nuclease revealed the difference in nucleosome repeat length between SV40 chromatin and virion assembly intermediates. A novel DNA fragment of about 75 nucleotides was observed early in nuclease digestion.

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