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Biomedical subjects

M L Lai

Publications and source records attributed to M L Lai.

At least 55 records · Page 3Linked to original sources
PubMed1992

Comparison on bioequivalence of four phenytoin preparations in patients with multiple-dose treatment.

In previous pharmacokinetic studies on phenytoin, the authors found that a hybrid parameter, Vd/F, was much higher in Chinese subjects. It could be due to a lower bioavailability (F) of the tested phenytoin preparations and/or a higher volume of distribution (Vd) in Chinese. Therefore, the relative bioavailability of four phenytoin oral preparations, i.e. Dilantin (Taiwan), Dilantin (USA), Aleviatin (Taiwan), and Aleviatin (Japan), were compared in patients who regularly took Dilantin (Taiwan) with their phenytoin plasma level at steady state. Twenty-four-hour area under curve was measured by an HPLC method after substituting the daily dose with each 300-mg dose of the test preparation. The plasma level resulted from Dilantin (USA) was found significantly higher than that from Dilantin (Taiwan). Similarly, Aleviatin (Japan) gave a significantly higher plasma level than Aleviatin (Taiwan). The study in part explained the unexpected high Vd/F of phenytoin in previous studies.

Administration, Oral↗
PubMed1992

Effect of single- and multiple-dose carbamazepine on the pharmacokinetics of diphenylhydantoin.

A three-phase trial has been done in 11 volunteers. They were given 600 mg phenytoin (Dilantin capsules) in each phase after an overnight fast. In the first study, phenytoin was given alone. In the second phase 400 mg carbamazepine (CBZ) was given at the same time as the phenytoin, and in the third part, 200 mg CBZ t.d.s. was given for one week prior to the phenytoin. Blood samples were taken for 72 h in each phase. Plasma levels of phenytoin and CBZ were determined by HPLC, and plasma protein binding was determined by equilibrium dialysis. The unbound fraction of phenytoin was 0.082, 0.085, and 0.077 in the control, single-dose CBZ, multi-dose CBZ phases, respectively. Single and multiple doses of CBZ decreased the plasma level of phenytoin. The 72-h AUC of phenytoin was 276, 237, and 176 mg h.l-1 in the 3 phases, respectively, and the 72-h AUC of unbound phenytoin was 22.8, 20.5, 13.0 mg h.l-1. The AUC of phenytoin (unbound and total) after multiple doses of CBZ was significantly lower than in the other two phases. The apparent volume of distribution (Vz/f) was 89.9, 110.3, and 121.3 l in the 3 phases, respectively. Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered.

Adult↗
PubMed1991

Purification and characterization of a trypsin inhibitor from mouse seminal vesicle secretion.

A Kazal-type trypsin inhibitor in mouse seminal vesicle secretion was purified to homogeneity via a series of purification steps including ammonium sulfate fractionation, affinity chromatography on a trypsin Affi-Gel 10 column, and HPLC on a reverse phase C4 column. It was shown to be a weak basic protein with an isoelectric point of 8.7 and to contain no carbohydrate. The protein had a specific activity of 184 U/mg protein in the inhibitory effect on the trypsin digestion of N-benzoyl-Pro-Phe-Arg-p-nitroanilide. Analysis of the kinetic data for the trypsin digestion of N-benzoyl-Phe-Val-Arg 7-amido-4-methylcoumarin revealed that the protein was a competitive inhibitor with an inhibitory constant (Ki) of 0.15 nM. The molecular mass of the protein was determined to be 7 kDa by both gel chromatography and electrophoresis. Results of direct amino acid determinations indicated that this protein corresponded to the reading frame of MP12 cDNA identified from mouse prostate. We found that cleavage only at the reactive site of this protein (Arg19-Ile20) resulted in its denaturation.

Amino Acid Sequence↗
PubMed1991

Increased microsomal irreversible binding of phenytoin by valproic acid.

Phenytoin is known to be metabolized to form p-hydroxyphenyl-phenyl-hydantoin, possibly via the arene oxide intermediate. The reactive arene oxide may bind to macromolecules irreversibly and cause toxicity. In this study, valproic acid was found to increase the irreversible binding of phenytoin to rat liver microsomes at high concentrations. The effect was similar to that of TCPO and could be reversed by adding glutathione. Valproic acid may increase the hepatotoxicity of phenytoin.

Animals↗
PubMed1991

Metabolism of carbamazepine: evidence of autoinduction in Chinese.

To investigate the autoinduction of carbamazepine (CBZ) metabolism in Chinese, eleven healthy male volunteers joined in this study. There were two phases of drug administration with a wash-out interval of one month, 400 mg CBZ was taken orally in single-dose phase, and 200 mg three times per day were given for seven days in multiple-dose phase. Plasma samples were obtained in series of time after the last dose of drug in each phase. CBZ concentrations were determined by a high pressure liquid chromatography method. A non-linear regression program was applied in a personal computer to estimate the pharmacokinetic parameters. The average CBZ half-lives in single- and multiple-dose phases were 50.1 +/- 12.1 (mean +/- SD) hours and 26.1 +/- 4.2 hours and the clearances were 16.4 +/- 3.3 ml/kg/h and 45.3 +/- 23.4 ml/kg/h respectively, both with significant differences (p less than 0.005). There is evidence to support the presumption of autoinduction in Chinese.

Adult↗
PubMed1985

Steady-state serum levels of anticonvulsant drugs in Chinese epileptic patients living in Taiwan.

Steady-state serum concentrations of phenytoin and phenobarbital were obtained in 70 epileptic patients in Taiwan and evaluated with respect to age, sex, and body weight. As demonstrated, the steady-state serum level of phenytoin is not affected by the age and sex of the patients or by phenobarbital used as a comedication. Thus, the main contributing factor influencing the steady-state serum concentration of phenytoin is the drug dosage. Among Chinese epileptic patients, the saturation of phenytoin metabolism occurs at the dosage of 4 mg/kg/day.

Adolescent↗
PubMedDate not supplied

Calcitonin gene-related peptide in the human trigeminal sensory system at developmental and adult life stages: immunohistochemistry, neuronal morphometry and coexistence with substance P.

The distribution of calcitonin gene-related peptide (CGRP) has been examined by the indirect immunofluorescence technique in the Gasserian ganglion and spinal nucleus of the human trigeminal nerve. In the ganglion CGRP is present in almost 50% of primary sensory neurons, in varicose and non-varicose nerve fibres and in pericellular basket-like plexuses around non-immunoreactive ganglionic perikarya. Morphometric analysis reveals that the CGRP-positive neuronal population is heterogeneous in cell size. Observation of specimens from subjects at fetal, perinatal and adult life stages reveals that the percentage of CGRP-immunoreactive cells reaches a maximum at perinatal stages and then remains constant, declining only in old age. Pericellular basket-like nerve fibres are detectable only in fetal and pre-term and full-term newborn tissue. Coexistence between CGRP and substance P (SP) occurs, SP being present in about one quarter of the CGRP-immunoreactive neurons and CGRP being localized in a little more than half of the SP-immunoreactive neurons. However, perikarya, nerve fibres and pericellular fibres containing only one or other peptide are also present. Bundles of immunoreactive fibres and dot-like nerve terminals occur in the spinal tract and superficial and deep regions of the spinal trigeminal nucleus. A particularly dense plexus is present in the peripheral nuclear layers. Double immunostaining shows a similar regional distribution for SP. However, in inner substantia gelatinosa the density of CGRP-immunoreactive fibres is much higher than that of SP-immunoreactive ones. The results obtained add information to our knowledge of the organization of neurochemically identified neurons in the human trigeminal sensory system.

Adolescent↗
PubMedDate not supplied

Scanning electron microscopy of the interior of cells in Hürthle cell tumors.

Four cases of Hürthle cell tumor were examined by scanning electron microscopy after being macerated to remove all soluble components. By all morphological criteria, Hürthle cells are oncocytes with their usual augmented complement of mitochondria. The Hürthle cell mitochondria either are ovate with central stacks of cristae or elliptical or rod-like with cristae that often are finger-like. As in salivary gland oncocytes, the shelf-like cristae are anchored to the inner boundary membrane by tubular necks. In some Hürthle cells, all of the mitochondria exhibit reticulate cristae. A few mitochondria harbor a globular inclusion in their inner compartment. The Golgi apparatuses are relatively simple, consisting of imbricated saccules that are edged by small, bud-like structures. The rare lumina in the midst of clusters of Hürthle cells are lined by numerous microvilli. Thus, scanning electron microscopy of macerated Hürthle cell tumors has revealed a number of features, especially of their mitochondria, that have escaped detection by transmission electron microscopy.

Adenoma, Oxyphilic↗
PubMedDate not supplied

Expression of ATP7B in normal human liver.

ATP7B is a copper transporting P-type ATPase, also known as Wilson disease protein, which plays a key role in copper distribution inside cells. Recent experimental data in cell culture have shown that ATP7B putatively serves a dual function in hepatocytes: when localized to the Golgi apparatus, it has a biosynthetic role, delivering copper atoms to apoceruloplasmin; when the hepatocytes are under copper stress, ATP7B translocates to the biliary pole to transport excess copper out of the cell and into the bile canaliculus for subsequent excretion from the body via the bile. The above data on ATP7B localization have been mainly obtained in tumor cell systems in vitro. The aim of the present work was to assess the presence and localization of the Wilson disease protein in the human liver. We tested immunoreactivity for ATP7B in 10 human liver biopsies, in which no significant pathological lesion was found using a polyclonal antiserum specific for ATP7B. In the normal liver, immunoreactivity for ATP7B was observed in hepatocytes and in biliary cells. In the hepatocytes, immunoreactivity for ATP7B was observed close to the plasma membrane, both at the sinusoidal and at the biliary pole. In the biliary cells, ATP7B was localized close to the cell membrane, mainly concentrated at the basal pole of the cells. The data suggest that, in human liver, ATP7B is localized to the plasma membrane of both hepatocytes and biliary epithelial cells.

Adenosine Triphosphatases↗