Perspective and overview of Chinese traditional medicine and contemporary pharmacology.
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Biomedical subjects
Publications and source records attributed to C F Chen.
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Porcine metallothionein III (MTIII) was isolated from brain tissue by the combination of gel filtration and anion-exchange chromatographies. The identity of MTIII was confirmed by comparing the chromatographic characteristics to other MT isoforms isolated from porcine liver. Porcine MTIII has a low molecular weight and a pl of 4.1. This protein contains both zinc and copper, and the zinc can be replaced by cadmium. Using reverse transcriptase-polymerase chain reaction, a 0.2 kb DNA fragment can be amplified from the porcine brain mRNA. This DNA fragment was demonstrated to contain MTIII coding region after cloning and sequencing. The revealed DNA sequence can be translated into 68 amino acids and shows a common structural characteristic of MTIII from other species. Northern blot analysis indicated that MTIII and mRNA is expressed in every specified region of the porcine brain examined here.
In this study, we used behavioral and biochemical methods to investigate the effects of Hemerocallis flava (Liliaceae) (abbreviated as HF) on motor activity and the concentration of monoamines in rats. The water fraction of the resuspended HF extract was most active in reducing the motility in rats. The water fraction of the HF extract enhanced the reduction of locomotor activity produced by alpha-methyl-p-tyrosine and 5-hydroxytryptophan, but it reduced the increase of locomotor activity produced by L-dopa plus benserazide and p-chlorophenylalanine. Furthermore, the water fraction of the HF extract significantly decreased the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in the brain stem. It also increased the concentration of vanilylmandelic acid in the cortex, homovanillic acid and 5-hydroxyindole-acetic acid in the brain stem. These results suggest that the reduction of locomotor activity produced by the water fraction of HF extract may be related to the decrease in the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in brain stem.
A simple high-performance liquid chromatographic method was developed to study the pharmacokinetics of osthole in rat plasma. After addition of an internal standard (paeonol), plasma was deproteinized by acetonitrile for sample clean-up. The drugs were separated on a reversed-phase column and detected by UV absorption at 323 nm. Acetonitrile-water-diethylamine (50:50:0.1, v/v/v) (pH 3.0, adjusted with orthophosphoric acid) was used as the mobile phase. It was applied to the pharmacokinetic study of osthole in rats after a dose of 10 mg kg-1 by intravenous administration. A biphasic phenomenon with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration-time curve.
The vasoreactivity of dehydroevodiamine (1), evodiamine (2), and rutaecarpine (3), quinazoline alkaloids isolated from Evodia rutaecarpa, to aorta smooth muscle demonstrated that they produce a vasodilatory effect on endothelium-intact rat aorta with equal potency. Compound 3 produced a full (100%) nitric oxide-dependent vasodilatation, whereas 2 and 1 produced a partially endothelium-dependent effect, 50% and 10%, respectively. At the same time, I and 2 may also act by other mechanisms, including probably an alpha1-adrenoceptor blocking action and a 5-HT antagonizing action, respectively.
A high-performance liquid chromatographic method has been developed for the determination of wogonin in the rat plasma. After addition of an internal standard (clomipramine), plasma was deproteinized by acetonitrile and centrifuged for sample clean-up. The supernatant was separated by a reversed-phase column chromatography, identified by a photodiode-array detector, and quantified by ultraviolet detection at a wavelength of 275 nm. Acetonitrile-water-diethylamine (50:50:0.1, v/v/v, pH 3.0 adjusted by orthophosphoric acid) was used as the mobile phase. The method was applied to the pharmacokinetic study of wogonin in rats after a dose of mg/kg by intravenous administration. A biphasic phenomenon with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration time profile.
The effects of the rhizome of Gastrodia elata Blume (Orchidaceae) (abbreviated as GE) and its active constituents on learning and memory by using the one-trial passive avoidance task were studied in rats. At the 1.0 g/kg dose administered for one week, the methanol extract of GE significantly prolonged the shortened step-through latency induced by scopolamine in the passive avoidance task. Furthermore, at the 50.0 mg/kg dose administered for one week, the ethyl acetate and n-butanol fractions of the methanol extract prolonged the shortened step-through latency induced by scopolamine in rats. Gastrodin, isolated from the n-butanol fraction of the methanol extract, and p-hydroxybenzyl alcohol, isolated from the ethyl acetate fraction of the methanol extract, also significantly prolonged the shortened step-through latency induced by scopolamine on the passive avoidance task. These results suggested that gastrodin and p-hydroxybenzyl alcohol may be the active constituents of GE.
We examined the mechanisms underlying the vasorelaxant effect of dehydroevodiamine (DeHE), one of the bioactive components of the Chinese herbal drug Evodia rutaecarpa that has been shown to produce vasorelaxant and hypotension. DeHE (10(-7)-10(-4) M) concentration-dependently relaxed isolated rat mesenteric arteries precontracted with phenylephrine (PE). This vasorelaxant potency was diminished by 15% by endothelial removal, L-NG-nitro arginine, or methylene blue (MB), but not indomethacin treatment, indicating that the vasorelaxant effect of DeHE was partially endothelium dependent and mediated by nitric oxide (NO) and the cyclic GMP pathway. In endothelium-denuded preparations, DeHE caused a rightward shift of the contractile concentration-response curve (CRC) to PE in a dose-dependent manner with a pA2 value of 6.15. Maximal response was unaffected. Receptor binding assay indicated that DeHE competed with alpha 1-adrenoceptor ligand prazosin with a Ki value of 3.57 microM. Potassium channel activity-attenuating conditions such as increased level of extracellular K+ (20 mM) and treatment with the antagonist tetraethylammonium (TEA) significantly inhibited DeHE's effect, suggesting a mode of action similar to that of a potassium channel activator. In addition, high concentrations of DeHE (3 x 10(-5) and 10(-4) M) relaxed high K+ (80 mM)-evoked contraction, indicating that DeHE might possess K+ channel blocking properties. Multiple-action mechanisms, including endothelium dependence, alpha 1-adrenoceptor blockade, K+ channel activation, and Ca2+ channel blockade were probably involved in the vasorelaxant effects of DeHE.
1. We have studied the role of kallikrein (KK) in the maintenance of renal function in chronic hypoxic rats (high altitude; HA), compared with control rats kept at sea level (SL). Hypoxia was induced by placing female Wistar rats (198-290 g) in an altitude chamber (5500 m) 15 h/day for 4 weeks. Experiments were also conducted to study the interaction of KK with renal nerve activity and endothelin (ET), two parameters previously shown to be altered in this model. 2. It was found that renal cortex tissue KK activity (TKA) was not significantly different in 10 SL and 10 HA rats. However, the urinary KK activity (UKA) was reduced nearly to half (from 35.2 +/- 4.6 to 18.5 +/- 1.7 pkat/min) in HA rats after 4 weeks of chronic hypoxia. 3. Acute renal denervated diuresis was accompanied by a significant increase in UKA (from 9 +/- 2 to 14 +/- 2 pkat/min in HA and denervated HA rats, respectively; P < 0.05) in HA rats. Intrarenal arterial pretreatment of aprotinin reduced the denervated diuresis. 4. Endothelin (600 ng/kg per h) reduced urine flow, sodium and potassium excretion in the ipsilateral kidney in another 10 SL and 10 HA rats. The extent of the drop of these parameters was significantly less in HA rats. Urinary KK activity was correlated significantly with the measured renal functional parameters (r ranging from 0.472 to 0.612) in SL rats, but was insignificant in HA rats (r ranging from 0.032 to 0.192). 5. We have demonstrated that chronic exposure to hypoxia decreases urinary KK excretion and that KK is involved in acute renal denervated diuresis generated in these animals. The present study suggests that KK plays a partial role in the maintenance of renal function in chronic hypoxic rats.
1. The effects of DL-tetrahydropalmatine (DL-THP) on cardio-vascular function and hypothalamic release of monoamines were assessed in rats under urethane anaesthesia. 2. Intravenous administration of DL-THP (1-10 mg/kg) produced hypotension, bradycardia, a decrease in hypothalamic serotonin and noradrenaline release and an increase in hypothalamic dopamine release in rats. 3. Intrahypothalamic administration of DOI (a serotonergic 5-HT2 receptor antagonist) or apomorphine (a dopamine D2-receptor agonist) produced the opposite effects and reversed DL-THP-induced hypotension and bradycardia. 4. The data suggest that DL-THP acts through the 5-HT2 and/or D2-receptor antagonism in the hypothalamus to induce hypotension and bradycardia in rats.
The pharmacokinetics of magnolol in rats was studied after 2, 5, or 10 mg/kg-1 intravenous bolus injection. Plasma concentration-time profiles of magnolol were fitted by a two-compartment open model. There were no significant differences in the elimination half-life, the total body clearance, steady-state volume of distribution, or mean residence time. The area under the plasma-time curve and area under the moment-time curve of magnolol appears to increase proportionally from a dose of 2 to 10 mg/kg-1. These results suggest that magnolol possess linear pharmacokinetics. Notwithstanding, brain concentration of magnolol showed no significant difference among various regions (cerebral cortex, olfactory bulb, hippocampus, striatum, cerebellum, brain stem and rest of brain) after 10 min of magnolol (5 mg/kg-1, i.v.) administration, the mean brain drug concentration was approximately fourfold that of magnolol in plasma.
A gene encoding a new heat shock protein that may function as a molecular chaperone for the retinoblastoma protein (Rb) was characterized. The cDNA fragment was isolated by using the yeast two-hybrid system and Rb as bait. The open reading frame of the longest cDNA codes for a protein with substantial sequence homology to members of the hsp90 family. Antibodies prepared against fusions between glutathione S-transferase and portions of this new heat shock protein specifically recognized a 75-kDa cellular protein, hereafter designated hsp75, which is expressed ubiquitously and located in the cytoplasm. A unique LxCxE motif in hsp75, but not in other hsp90 family members, appears to be important for binding to the simian virus 40 T-antigen-binding domain of hypophosphorylated Rb, since a single mutation changing the cysteine to methionine abolishes the binding. In mammalian cells, Rb formed complexes with hsp75 under two special physiological conditions: (i) during M phase, when the envelope that separates the nuclear and cytoplasmic compartments broke down, and (ii) after heat shock, when hsp75 moved from its normal cytoplasmic location into the nucleus. In vitro, hsp75 had a biochemical activity to refold denatured Rb into its native conformation. Taken together, these results suggest that Rb may be a physiological substrate for the hsp75 chaperone molecule. The discovery of a heat shock protein that chaperones Rb identifies a mechanism, in addition to phosphorylation, by which Rb is regulated in response to progression of the cell cycle and to external stimuli.
Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production on human mononuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 = 71.0 +/- 3.0 and 21.7 +/- 2.0 micrograms/ml, respectively), NK cell activity (IC50 = 25.0 +/- 2.5 and 12.9 +/- 5.8 micrograms/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 = 9.6 +/- 2.3 and 5.5 +/- 1.6 micrograms/ml, respectively). TNF-alpha production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (IC50 = 2.7 +/- 1.0 and 12.5 +/- 3.8 micrograms/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.
We have examined both the hypotensive effect and the mechanism of intracellular Ca++ regulation, underlying rutaecarpine (Rut)-induced vasodilatation. An i.v. bolus injection of Rut in anesthetized Sprague-Dawley rats produced a dose-dependent hypotensive effect. In isolated rat aorta rings, Rut (0.1-3 mu M) inhibited the phasic and tonic responses of norepinephrine- and phyenylephrine-induced contractions, respectively, mainly through an endothelium-dependent mechanism. However, the vasorelaxing effect of Rut (3 microM) persisted in denuded aorta, although to a much less extent than in intact tissue. As determined by the fura-2/AM (1-[2-(5-carboxyoxazol-2-yl)-6-aminobenzofuran-5-oxy]-2-(2'- amino-5'-methylphenoxy)-ethane-N,N,N,N-tetraacetic acid pentaacetoxymethyl ester) method, Rut (10 microM), in the presence of extracellular Ca++, suppressed the KCI-induced increment in the intracellular Ca++ concentration ([Ca++]i) of cultured vascular smooth muscle cells (VSMC). Rut (10 microM) also attenuated the norepinephrine-induced peak rise of [Ca++]i in VSMC placed in Ca++-free solution. On the other hand, Rut (1 and 10 microM) increased the level of [Ca++]i of cultured endothelial cells (EC) in the presence of extracellular Ca++. In conclusion, Rut acts on both VSMC and EC directly. In VSMC, it reduces [Ca++]i through the inhibition of Ca++ influx and Ca++ release from intracellular stores. In EC, Rut augments EC [Ca++]i by increasing Ca++ influx, possibly leading to nitric oxide release. The paradoxical regulation of Ca++ in both VSMC and EC acts simultaneously to cause vasorelaxation which could account, at least in part, for the hypotensive action. This is a most significant and a unique feature of this study.
BACKGROUND: The aim of this paper is to investigate the different factors influencing patients' choice of traditional Chinese medicine or modern western medicine, applying Andersen's health-service utilization model to analyze the basic demographic, enabling and need factors related to the choice of clinics by patients who use two-method treatment (i.e. both Chinese medicine and western medicine). METHODS: Systemic sampling was done and a structured questionnaire survey was carried out among patients from the outpatient departments of 13 teaching hospitals accepting reimbursement by Labor Medical Insurance in Taiwan. RESULTS: The total number of valid respondents was 549. Of them 181 (33%) were visiting western medicine clinics and 368 (67%) visiting Chinese medicine clinics. There were 279 (51%) males and 270 (49%) females, whose age distribution was in the range from 16 to 87 years old, with a mean of 42.7 years. Under univariate analysis, the significant variables (p < 0.05) related to visiting the two types of clinics were: applicability of medical insurance, bed rest from discomfort in recent years, the amount of discomfort from this disease episode, respiratory disease, circulatory disease, endocrine or metabolic disease, and sense organ and skin disorders. By logistic regression analysis, the significant variables (p < 0.05) related to visiting the two types of clinics were religion, bed rest during the past year, discomfort associated with the episode, respiratory disease, and endocrine or metabolic diseases. CONCLUSIONS: Patients with folk-religion beliefs or respiratory diseases favored Chinese medicine; patients with illness requiring bed rest in the past year, who experienced discomfort in this episode, or who suffered from endocrine or metabolic diseases were likely to visit western medicine clinics.
BACKGROUND: Endothelin-1 is known to exist in the nervous system. A notable increase of plasma endothelin-1 is associated with acute stroke. This study was designed to measure plasma endothelin-1 levels in Binswanger's disease and explore the relationship between endothelin-1 and this disorder. METHODS: Plasma levels of endothelin-1 were-examined by radioimmunoassay in 31 patients with Binswanger's disease and in three groups of control subjects. The ratio of the plasma concentration of endothelin-1 in the internal jugular vein to that in the antecubital vein was calculated as an indicator of endothelin-1 level in cerebral circulation. RESULTS: Endothelin-1 ratio devation was seen more often in patients with Binswanger's disease than in acute stroke patients. Endithelin-1 ratios were significantly negatively correlated with Hasegawa's Dementia Scale scores is subjects with Binswanger's disease. CONCLUSIONS: Abnormalities is vasoactive factors may make an important contribution to the pathophysiology of Binswanger's disease. Endothelin-1 might be involved in the pathogenesis of this illness.
Statistics of the structure of educational level and worked years of 140 occupied nurses, analysed by ABC curvegram, showed that the key training objects are class A (1 to 10 years at work) and class B nurses. Then the goal of nurses' training at work during 3 years for class A and B was made according to the difference of their classes and need of knowledge. In order to improve the effect of 3.3 style nurse training goal a method of two-direction teaching and assessing were applied, actual effect was achieved during a three-year conduction.
The BRCA1 gene product was identified as a 220-kilodalton nuclear phosphoprotein in normal cells, including breast ductal epithelial cells, and in 18 of 20 tumor cell lines derived from tissues other than breast and ovary. In 16 of 17 breast and ovarian cancer lines and 17 of 17 samples of cells obtained from malignant effusions, however, BRCA1 localized mainly in cytoplasm. Absence of BRCA1 or aberrant subcellular location was also observed to a variable extent in histological sections of many breast cancer biopsies. These findings suggest that BRCA1 abnormalities may be involved in the pathogenesis of many breast cancers, sporadic as well as familial.