Biomedical subjects

C M Chen

Publications and source records attributed to C M Chen.

At least 181 records · Page 10Linked to original sources

PubMed1995

The alpha-Ca2+/calmodulin kinase II: a bidirectional modulator of presynaptic plasticity.

The alpha-Ca2+/calmodulin kinase II (alpha CaMKII) is required for long-term potentiation in the CA1 region of the hippocampus. Here, we report that this kinase also has a crucial role in presynaptic plasticity. Paired-pulse facilitation is blunted in the CA1 region of mice heterozygous for a targeted mutation of alpha CaMKII, confirming that this kinase can promote neurotransmitter release. Unexpectedly, field and whole-cell recordings of posttetanic potentiation show that the synaptic responses of mutants are larger than those of controls, indicating that alpha CaMKII can also inhibit transmitter release immediately after tetanic stimulation. Thus, alpha CaMKII has the capacity either to potentiate or to depress excitatory synaptic transmission depending on the pattern of presynaptic activation.

Animals↗

PubMed1995

Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization.

A total of 100 women undergoing ovarian stimulation with gonadotrophin-releasing hormone agonist (GnRHa) and a human menopausal gonadotrophin (HMG) for in-vitro fertilization (IVF) participated in this randomized comparative study. Leuprolide acetate at a dose of 0.5 mg/day s.c. (n = 52, group I), or low-dose leuprolide acetate depot at a dose of 1.88 mg s.c. (n = 48, group II), was started on days 21-23 of the cycle. Stimulation with 225 IU/day HMG was started after pituitary desensitization had been achieved. The luteal phase was supported by human chorionic gonadotrophin (HCG) i.m. injection. There were no statistical differences in baseline oestradiol (24.5 +/- 4.8 versus 21.9 +/- 4.5 pg/ml) and follicle stimulating hormone (FSH) concentrations (3.9 +/- 1.9 versus 3.2 +/- 1.8 mIU/ml), and concentrations on the day of HCG administration of oestradiol (1657 +/- 245 versus 1512 +/- 165 pg/ml), luteinizing hormone (LH; 6.2 +/- 4.8 versus 5.6 +/- 4.3 mIU/ml) and FSH (10.6 +/- 2.8 versus 10.8 +/- 3.6 mIU/ml). There were also no statistical differences in the HMG dosage (26.8 +/- 1.8 versus 28.5 +/- 1.5), the number of oocytes retrieved (7.6 +/- 3.0 versus 8.1 +/- 4.3), the number of oocytes fertilized (5.3 +/- 2.1 versus 5.6 +/- 3.0) and the number of embryos transferred (3.5 +/- 1.3 versus 3.4 +/- 1.6). There was no evidence of a premature LH surge in either group, but two patients appeared to have a poor response in the leuprolide acetate group (group I). There were 11 pregnancies (21.2%) after the use of leuprolide acetate and 12 pregnancies (25.0%) in those given leuprolide acetate depot; no statistical difference existed between these two groups. Thus, a s.c. low-dose leuprolide acetate depot injection may offer a useful alternative for pituitary suppression in ovarian stimulation for IVF.

Adult↗

PubMed1995

Nucleotide sequence of the herpes simplex virus type 2 gene encoding the protease and capsid protein ICP35.

The complete nucleotide sequence of the gene encoding the protease and ICP35 capsid protein of herpes simplex virus (HSV) type 2 strain G has been determined. The gene consisits of a 1908 bp open reading frame capable of encoding 636 amino acids. Comparative nucleotide sequence analysis of the gene with published HSV-1 sequences revealed that the HSV-2 nucleic acid segment most likely encodes two distinct proteins. The first protein is the HSV-2 protease, which is required for the assembly of the herpes virus capsid. The second protein has been previously designated as ICP35 in HSV-1, and belongs to the family of herpesvirus capsid proteins.

Amino Acid Sequence↗

PubMed1995

Effect of body tilting on physiological functions in healthy term neonates.

The effect of body tilting on physiological functions was studied in 32 healthy, full-term neonates at 2 and 24 h of age. The neonates were placed in the supine position and the physiological functions were measured in the sequence of -30 degrees (head-down), 0 degree and 30 degrees (head-up) tilts. Arterial oxygen saturation and respiratory rate were comparable in the vaginal delivery and caesarean section groups. The baroreceptor responses were similar in the neonates delivered vaginally and by caesarean section. Mean heart rate increased on 30 degrees up tilting and the responses tended to be larger at 24 h compared with those at 2 h of age, but these differences were not significant. At 2 h of age, mean systolic and diastolic blood pressures decreased on 30 degrees up tilting. At 24 h of age, mean systolic and diastolic pressures decreased on up tilting (from -30 degrees to 0 degree) and the values were sustained on further up tilting (from -0 degree to 30 degrees). The present results indicate that baroreceptor reflexes are present from birth and the responses tend to be less developed at 2 h than those at 24 h of age.

Baroreflex↗

PubMed1995

Modulation of the trans-suppression activity of hepatitis C virus core protein by phosphorylation.

We previously demonstrated that the core protein of hepatitis C virus (HCV) can suppress gene expression and replication of hepatitis B virus (HBV) in a human hepatoma cell line (HuH-7). In this study, we have characterized the phosphorylation property of HCV core protein and examined the effect of phosphorylation on its suppressive activity of HBV. Our results indicated that both the full-length HCV core protein (22 kDa) and its processed or degraded forms (14 to 18 kDa) were phosphorylated in insect cells. As demonstrated by using the glutathione S-transferase fusion protein expression system and in vitro transcription and translation system, the phosphorylation of HCV core protein was carried out by protein kinase A (PKA) and protein kinase C (PKC) in vitro. In both kinase reactions, it was determined that the phosphorylated amino acid was a serine residue. The potential phosphorylated sites in core protein were identified as residues Ser-53 and Ser-116 for PKA and Ser-53 and Ser-99 for PKC. Comparison of the phosphorylation intensities of the wild type and Ser mutants suggested that Ser-99 and Ser-116 were the major phosphorylation sites for PKC and PKA, respectively. The phosphorylation of Ser-99 and Ser-116, but not Ser-53, in HCV core protein was essential for the suppressive activity of HCV core protein on HBV gene expression and replication in HuH-7 cells. Mutation of the former two serine residues to alanine or aspartate residues led to a drastic loss of the inhibitory effects of HCV core protein on HBV gene expression (both transcription and antigen production) and pregenomic RNA encapsidation, as well as the release of HBV virus particles. In contrast, the Ser-53 mutant conferred the same level of suppressive activity as the wild type did. This property is in accordance with the observation that Ser-99 and Ser-116 are the predominant phosphorylation sites in the HCV core construct. All serine mutants (including those with mutations in PKA, PKC, and both kinase recognition sites) of HCV core protein retained the ability to translocate into the nucleus. Furthermore, wild-type HCV core protein diminished its suppressive activity when cells were treated with PKA or PKC inhibitor. In conclusion, HCV core protein is a phospho-protein and in HuH-7 cells, its trans suppression of HBV gene expression and replication is positively regulated by PKA and PKC. The role of phosphorylation in the control of trans-suppressive activity cannot be reproduced by introducing an acidic residue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Exogenous surfactant function in very preterm lambs with and without fetal corticosteroid treatment.

We have asked whether the function of a bovine source surfactant frequently used clinically (Survanta) could be enhanced after exposure to the very preterm lung when the surfactant was subsequently tested in vivo in preterm surfactant-deficient rabbits. We also evaluated whether there would be effects resulting from fetal treatment with 0.5 mg/kg betamethasone given 48 h before delivery of lambs at 121 days gestational age. The fetal corticosteroid treatment significantly improved gas exchange, increased compliance, increased functional residual capacity, decreased vascular-to-alveolar protein leak, and increased static lung volumes. However, surfactant from both groups of lambs, recovered by alveolar wash and subsequently fractionated to recover the large-aggregate functional surfactant, was equivalent in function to the Survants given to the lambs when tested in preterm surfactant-deficient rabbits. Addition of plasma to Survanta resulted in high minimum surface tensions in vitro, and this inhibition could be prevented by supplementation of the Survanta with 5 or 10% sheep surfactant. No activation occurred with treatment of the very preterm lung, a result consistent with the lung being too immature to contribute components to the surfactant used for treatment. Fetal corticosteroid treatment had no effect on surfactant function at this gestational age.

Adrenal Cortex Hormones↗

PubMed1995

Gonadal dysfunction in mitochondrial encephalomyopathies.

To understand endocrine function and to determine which endocrine systems are likely to be affected, 6 patients with mitochondrial encephalomyopathies were studied. Three patients had myoclonus epilepsy and ragged-red fibers, and the other 3 patients had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Clinically, short stature (5/6), amenorrhea (2/3), impotency (3/3), and poor development of secondary sexual characteristics (4/6) were noted. The endocrinological studies including triiodothyronine, tetraiodothyronine, thyrotropin, adrenocorticotropin, cortisol, parathyroid hormone and blood sugar were normal. However, there were low serum concentrations of estradiol (2), and progesterone (2) in 3 female patients. Two patients (1 man and 1 woman) had growth hormone deficiency and 1 had low testosterone level. Hypothalamopituitary dysfunction was confirmed after a series of stimulation tests. We conclude that patients with mitochondrial encephalomyopathies are common to have gonadal dysfunction. Although target organ may play a role, hypothalamopituitary lesion may be responsible for this abnormality.

Adolescent↗

PubMed1995

Fetal corticosteroid and T4 treatment effects on lung function of surfactant-treated preterm lambs.

Three groups of sheep fetuses at 125 or 126 d gestational age randomly received a single ultrasound-guided intramuscular injection of saline, 0.5 mg/kg betamethasone, or 0.5 mg/kg betamethasone plus 50 micrograms/kg thyroxine (T4). Forty-eight hours later the fetuses were delivered, treated with a pulmonary surfactant preparation, and ventilated for 3 h. Corticosteroids alone and in combination with T4 increased FRC, compliance, and lung volumes, and decreased the protein leak into the airspace. Saturated phosphatidylcholine pool sizes recovered by alveolar washing were not changed after hormone treatment. To evaluate the function of surfactant recovered from the lambs in vivo, we treated preterm rabbits at 27 d gestational age with the large-aggregate surfactant from alveolar washes. Large-aggregate surfactants and the pulmonary surfactant preparation increased compliances and maximal lung volumes relative to those in untreated preterm rabbits. Large-aggregate surfactants improved compliance more than did the pulmonary surfactant preparation. We conclude that ultrasound-guided single fetal corticosteroid treatment followed by postnatal surfactant improved postnatal lung function in preterm lambs. Addition of T4 did not augment corticosteroid effects. The function of the exogenous surfactant was improved in premature lamb lungs independently of the fetal treatment modality.

Animals↗

PubMed1995

Surfactant protein-B supplementation improves in vivo function of a modified natural surfactant.

The effect of the addition of surfactant protein (SP)-B or SP-B plus SP-C (SP-BC) to a surfactant made from bovine lung (Survanta) was evaluated in 27-d-gestation preterm rabbits. The animals were treated with Survanta, Survanta + 2% SP-B, Survanta + 3% SP-BC, or sheep surfactant. They were then ventilated with 3 cm H2O positive end-expiratory pressure and tidal volumes of 8 mL/kg. Survanta + 2% SP-B was prepared by adding SP-B in water to Survanta or by adding SP-B in chloroform [SP-B(Chl)] to lipid-extracted Survanta. Dynamic compliances of the Survanta + 2% SP-B(Chl)- and Survanta + 3% SP-BC-treated rabbits were greater (p < 0.05) than those treated with Survanta or Survanta + 2% SP-B in water and were comparable to sheep surfactant. Postventilation pressure-volume curves for the groups treated with Survanta supplemented with SP-B had significantly larger retained volumes on deflation compared with those treated only with Survanta (p < 0.01). The effects of ventilation style on the responses were assessed by ventilating other groups of rabbits treated with Survanta, Survanta + 0.5% SP-B(Chl), Survanta + 2% SP-B(Chl), or sheep surfactant with tidal volumes of 10 mL/kg and 0 cm H2O positive end-expiratory pressure. SP-B (2%) augmented the in vivo function of Survanta without positive end-expiratory pressure, and 0.5% SP-B had no effect. Infasurf, a surfactant with more SP-B, was more effective than Survanta when tested in the preterm rabbits. SP-B is a critical factor for optimum immediate surfactant function.

Animals↗

PubMed1995

Early responses of trans-activating factors to growth hormone in preadipocytes: differential regulation of CCAAT enhancer-binding protein-beta (C/EBP beta) and C/EBP delta.

Using the 3T3-F442A preadipocyte line as a model of GH-dependent differentiation, early changes in the DNA-binding affinity of transcription factors in response to GH addition were investigated. Addition of 50 ng/ml human GH to cells in chemically defined medium led to a rapid increase in binding activity of activator protein 1 (AP-1) and CCAAT enhancer-binding protein (C/EBP), which was significant at 30 min and reached maximal induction by 2 h (3-fold for AP-1, 2.5-fold for C/EBP). Induction in AP-1 DNA binding correlates with a concomitant GH trans-activation of c-jun and c-fos genes described previously. Using specific antibodies in electrophoretic mobility shift assays and Western blots, it was shown that the increase in activity of C/EBP is the result of an increase in synthesis of two alternatively translated forms of C/EBP beta: 40-C/EBP beta and 23-C/EBP beta. This increase in protein was not accompanied by alteration in mRNA level and could be blocked by a Janus kinase 2 tyrosine kinase inhibitor and a C kinase inhibitor at concentrations shown to inhibit GH-dependent activation of microtubule-associated protein (MAP) kinases. Concomitant with the translationally activated increase in C/EBP beta, a GH-dependent increase was observed in C/EBP delta transcription. This was accompanied by an increase in mRNA for C/EBP delta, which was superinduced by cycloheximide and, unlike the increase in C/EBP beta protein, was not observed with insulin. Thus GH exerts its effects on C/EBP isoforms at two levels: transcriptional activation of C/EBP delta and translational activation of C/EBP beta. It is proposed that GH-dependent phosphorylation results in the efficient translation of 40-C/EBP beta and 23-C/EBP beta (the mouse homolog of the inhibitor liver-enriched inhibitory protein), and that together with the induction of C/EBP delta, these may be involved in initiating the adipocyte differentiation program.

3T3 Cells↗

PubMed1995

Evidence of transmission of hepatitis D virus to spouses from sequence analysis of the viral genome.

To study sexual transmission of hepatitis D virus (HDV), 52 spouses of 56 index patients were observed and HDV genomes from antibody to HDV (anti-HDV)-positive couples were sequenced. Of the spouses, 11 (21%) were serum HBsAg positive, 3 (27%) of whom were also anti-HDV positive. The HDV sequences between spouses were found to be nearly identical (98% to 98.8%) in the region analyzed (nt 911 to nt 1260). Only one couple showed an identity > 90% with the genotype I HDV strains. The HDV sequences of the remaining two couples showed > 95% identity with each other and > 91% homology with genotype II, but they shared only a 73.1% to 73.7% homology with those of the first couple. The regions corresponding to the autocatalytic cleavage sites, the junction between the middle and the carboxyl terminal one-third domains, and the middle domain of the open reading frame for delta antigen on the antigenomic HDV RNA were more conserved with < 19% divergence among the three couples. Interestingly, there was a 56% divergence in the region corresponding to the carboxyl end of the open reading frame for the large delta antigen on the antigenomic HDV RNA. In summary, this study provides a direct nucleotide evidence of a common source of HDV infection in each couple. Despite divergence in the viral nucleotide sequence, both genotypes I and II were found in Taiwan and were transmitted from patients with a history of prostitute contact to spouses through sexual contact.

Base Sequence↗

PubMed1995

Acquired immunodeficiency syndrome with CNS toxoplasmosis: a case report.

Central nervous system (CNS) toxoplasmosis is an important infectious complication of acquired immunodeficiency syndrome (AIDS) which appears to result from reactivation of a previously acquired infection and requires prolonged treatment. A 31-year-old male presented in a drowsy mental state and with an unstable gait. Computerized tomographic (CT) scan and magnetic resonance imaging (MRI) showed multiple nodular lesions in the cerebrum and cerebellum; the seropositivity for the human immunodeficiency virus (HIV-1) and high serum IgG toxoplasma titers were also demonstrated. A presumptive diagnosis of CNS toxoplasmosis was based on neurological signs and neuroradiological findings. This was confirmed by improvement in both clinical and neuroradiological pictures during treatment with pyrimethamine and clindamycin. Four months later, however the patient died of intracranial hemorrhage and massive upper GI bleeding.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Lupus in Chinese male: a retrospective study of 61 patients.

BACKGROUND: Systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, and is uncommon in men. In recent years, several large clinical series of male lupus patients have been reported. As no known data are available for lupus in males from Taiwan, a retrospective analysis of data from male lupus patients was done to determine whether these patients differed from other series of male or female SLE patients in the literature. METHODS: Sixty-one male lupus patients, diagnosed and followed in Tri-Service General Hospital, between 1983 and 1993, were studied and their data analyzed, retrospectively. RESULTS: The mean age of diagnosis was 30 +/- 17 (mean +/- SD, range: 13-81) years. The peak age of diagnosis was between 13 and 40 years. The mean duration of follow-up was 36 +/- 36 (range: 2-256) months. The 1-, 5- and 10-year survival rates were 84%, 76% and 75%, respectively. The frequency of clinical manifestations were renal disease, 75%; malar rash, 70%; arthritis, 60%; fever, 56%; photosensitivity, 48%; pleuritis, 39%; pericarditis, 31%; alopecia, 31%; mucosal ulcers, 29%; neuropsychiatric disease, 26%; discoid lupus, 21%; vasculitis, 15%; Raynaud's phenomenon, 10%; and lymphadenopathy, 2%. The frequency of abnormal laboratory findings were antinuclear antibodies (ANA), 95%; hypocomplementemia, 77%; antibodies to double-stranded DNA (anti-dsDNA), 57%; leukopenia, 44%; lupus erythematosus (LE) cells, 39%; anti-Ro, 39%; anti-Smith antibodies (anti-Sm), 19%; thrombocytopenia, 18%; rheumatoid factor, 17%; anti-ribonucleoprotein antibody (anti-RNP), 14%; autoimmune hemolytic anemia, 8%; false-positive venereal disease research laboratory test (VDRL), 6% and anti-La, 4%. CONCLUSIONS: In a review of the 61 ethnic Chinese male lupus patients, a higher frequency of renal disease, malar rash and photosensitivity, but a lower frequency of arthritis and lymphadenopathy, compared to previous reports of Caucasians. There were no significant immunological differences from other series of male lupus, except a lower frequency of anti-dsDNA. In general, poor prognosis was noted for male lupus patients here.

Adolescent↗

PubMed1995

X-linked agammaglobulinemia: a case report.

A 20-year-old male was admitted with fever and hemoptysis. Agammaglobulinemia was found, with bronchiectasis and sinusitis. Clinical and laboratory evidence included immunological examinations, bone marrow and small intestinal biopsies. Results suggested a diagnosis of X-linked agammaglobulinemia. After treatment with antibiotics and intravenous human immunoglobuline, the clinical symptoms demonstrated progressive improvement. The case is reported along with a review of the literature.

Adult↗

PubMed1994

Nuclear translocation and anchorage of the growth hormone receptor.

The extracellular domain of the rabbit growth hormone (GH) receptor has previously been shown to be associated with the nucleus. However, in this species the GH binding protein (BP) is derived by proteolytic cleavage of the full-length receptor, and thus distinction between the receptor and BP is difficult. The intracellular domain of the GH receptor is required for GH-stimulated function. Thus a direct nuclear function of GH would presumably require the receptor intracellular domain in the nucleus. We have therefore characterized the rat nuclear GH receptor and BP based on their distinct antigenic identity. We show, in vivo, that the full-length receptor is associated with the nucleus, including the respective subnuclear fractions (nucleoplasm, outer nuclear membranes, inner nuclear membranes, and chromatin). In vivo, the receptor is also subject to ligand-dependent nuclear translocation. Cellular transfection of rat GH receptor cDNA resulted in the appearance of nuclear binding sites for 125I-labeled human GH not present in the untransfected parental cell line (Chinese hamster ovary (CHO), buffalo rat liver). To determine which portion of the receptor was responsible for nuclear anchorage, we examined the binding of 125I-labeled human GH to whole nuclei isolated from CHO cells expressing the full-length receptor, a receptor in which 184 amino acids had been deleted from the carboxyl-terminal intracellular domain (CHO-454) and a receptor containing only 5 of 349 amino acids in the intracellular domain (CHO-294). Nuclear binding above the level of the untransfected parental cell line was detected only in CHO-638 and CHO-454 cells, suggesting that amino acids 294-454 of the receptor are necessary for nuclear anchorage. This observation was not due to membrane contamination, as the CHO-294 cells express a membrane-bound receptor that was not anchored in the nucleus. The full-length GH receptor in receptor cDNA-transfected cells is nucleocytoplasmic in the absence of ligand but is also subject to rapid ligand-dependent nuclear translocation. The presence of the intracellular domain of the GH receptor in the nucleus allows the possibility of a direct nuclear response to GH.

Amino Acid Sequence↗

PubMed1994

The role of the WSXWS equivalent motif in growth hormone receptor function.

Members of the cytokine receptor family have a consensus WSXWS sequence (WS motif) in the extracellular domain. With the interleukin-2, erythropoietin, and prolactin receptors, alteration of the WS sequence disrupts ligand binding and receptor signaling. The structural basis for these effects is unclear. To examine the role of the WS equivalent sequence (Y222GEFS226) in the function of the growth hormone receptor, each residue was mutated to alanine or to the WS consensus sequence. Although we used stable cell lines expressing all of these mutants, we show only three mutants, Y222A, G223A, and S226A, which display lower ligand affinity. Using conformation-specific monoclonal antibodies, we show that Y222A and S226A receptors have structural perturbations, which result in decreased signal transduction. This was shown by a decreased ability of growth hormone to stimulate protein synthesis and to transactivate the c-fos promoter with these mutants. The crystal structure of the ligand-occupied extracellular domain of growth hormone receptor indicates that Tyr222 and Ser226 have important interactions within the second beta-barrel domain, providing a structural basis for our results. The WS segment is not involved in sequence-specific accessory protein interaction, as mutation of residues Gly223, Glu224, and Phe225 does not alter receptor function.

Amino Acid Sequence↗

PubMed1994

Arsenate reductase of Staphylococcus aureus plasmid pI258.

Arsenate reductase encoded by Staphylococcus aureus arsenic-resistance plasmid pI258 was overproduced in Escherichia coli and purified. The purified enzyme reduced radioactive arsenate to arsenite when coupled to thioredoxin, thioredoxin reductase, and NADPH. NADPH oxidation coupled to arsenate reduction also required thioredoxin and thioredoxin reductase. Glutaredoxin and reduced glutathione did not stimulate arsenate reduction. NADPH oxidation showed Michaelis-Menten kinetics with a Km of 1 microM AsO4(3-) and an apparent Vmax of 200 nmol/min per mg of protein. At high substrate concentration (above 1 mM AsO4(3-), a secondary rise in the reaction rate was observed, with a Km of 2 mM and an apparent Vmax of 450 nmol/min per mg of protein. This secondary rise also occurred upon addition of phosphate or nitrate (which were not substrates for the enzyme). Arsenite (the product of the enzyme), tellurite, and antimonite [Sb(III)] were inhibitors. Selenate (but not selenite or sulfate) was a substrate for reductase-dependent NADPH oxidation, with an apparent Km of 13 mM SeO4(2-). Arsenate reductase was purified as a monomer of 14.5 kDa, consistent with the DNA sequence. Electrospray mass spectrometry showed two molecular masses of 14,810.5 and 14,436.0 Da, suggesting that 70% of the purified protein lacked the N-terminal three amino acids; HPLC coupled to electrospray mass spectroscopy of protease digest products confirmed this conclusion and verified the entire amino acid sequence.

Adenosine Triphosphatases↗

PubMed1994

Determination of higenamine in plasma and urine by high-performance liquid chromatography with electrochemical detection.

A method for the determination of higenamine in plasma and urine based on high-performance liquid chromatography (HPLC) with electrochemical detection was developed. The plasma or urine sample was treated by adsorption with acidic alumina and then higenamine was released by acid treatment. HPLC was performed on an ODS column with a mobile phase of acetonitrile-0.1% phosphoric acid (9:91) and an electrochemical detector at an oxidation potential of 0.75 V. The lower limits of the assay for higenamine in plasma and urine were 2.645 and 10.58 ng/ml, respectively. The recoveries of higenamine after alumina treatment in rabbit plasma and urine were ca. 77.5 and 84.4%, respectively. Intra- and inter-day precision and accuracy reported as coefficients of variation in plasma and urine were less than 7%. The application of the assay was demonstrated successfully by the determination of the concentration of higenamine in rabbit plasma and urine samples after doses of higenamine hydrochloride at 20 mg/kg intravenously and 50 mg/kg orally.

Administration, Oral↗