Biomedical subjects

Z R Chen

Publications and source records attributed to Z R Chen.

At least 19 recordsLinked to original sources

PubMed1998

Nitric oxide synthesis in myocardium following burn injury in rats.

We investigated nitric oxide and cyclic GMP production in myocardium early after burn injury in rats. Nitric oxide synthase activity was measured in cytosol from the left ventricular wall of burned rats. Cytosol from control group animals was shown to contain mainly Ca2+-dependent nitric oxide synthase (cNOS) with a small amount of Ca2+-independent nitric oxide synthase (iNOS). Following burn injury, there was a marked increase in iNOS activity with a peak at 8 h post-burn, however, myocardial cNOS activity was found to decline. Parallel to iNOS induction there was a significant increase in myocardial nitric oxide and cyclic GMP production. All these changes were alleviated by treatment of the rats with dexamethasone. Since increases in cyclic GMP levels in the heart were associated with reduced myocardial contractility, it is possible that enhanced production of nitric oxide by a Ca2+-independent NO synthase accounts, at least in part, for the depression of myocardial contractility seen in burn animals and patients.

Animals↗

PubMed1995

Topical GM1 ganglioside to promote crushed rat sciatic nerve regeneration.

The effects of topical GM1 ganglioside on crushed rat sciatic nerve regeneration were studied in this presentation. Thirty-four rats, with 68 bilateral sciatic nerves, were divided into seven groups: one group of four rats for measurement of normal motor nerve conduction velocity (MNCV), three as controls, and another three in the GM1-treated groups. Sciatic nerves were exposed and crushed at a site 6 mm distal to the sciatic notch by the standard technique. In this manner, 3 mm wide crush injuries were created. Then 2.1 microliters of normal saline was injected into the crush site in the control groups and an equal volume of GM1 solution (containing 10 micrograms GM1) was injected into the GM1-treated groups. Electrophysiological, histological, and morphometric evaluations were carried out at 12, 28, and 56 days. A significantly higher muscle action potential (MAP) rate was found in the GM1-treated group (70%) vs. the controls (none) at 12 days (P < 0.005), and increased MNCV was found in the GM1-treated groups at both 28 and 56 days, especially at 56 days, when it was 39.59 +/- 9.23 m/sec vs. 31.42 +/- 4.07 m/sec in controls (P < 0.05). Morphometrically, there were more regenerated myelinated fibers (RMFs) at 12 days, and larger diameter of RMFs were observed at 12, 28, and 56 days in the GM1-treated groups.

Action Potentials↗

PubMed1994

Study of microvascular polyester prosthesis in rat carotid arteries.

The implantation of a microvascular polyester prosthesis (MPP) (internal diameter 1 mm, length 10 mm) in the carotid arteries was studied in 48 Sprague-Dawley rats. The left carotid artery was resected to 7 mm in length and replaced with MPP by means of sleeve anastomoses. Postoperatively the patency was monitored with Doppler ultrasound at 24 and 72 hr, and at 1, 2, 3, 4, 8, and 12 weeks and was confirmed either by direct inspection intraoperatively or by angiography at the time of removal. At each monitoring time, all the thrombosed and some selected patent grafts were removed and prepared for scanning electron microscopy (SEM) study. The early patency rate was 100% within 24 hr, and the cumulative long-term patency rate was 77.1% at 12 weeks. Rapid and complete endothelial lining (EL) restoration was demonstrated 3 weeks after operation, which provided a smooth and nonthrombogenic surface, and contributed to the long-term patency. Ten of the 11 failed grafts occurred within 3 weeks, that is, before EL, due to thrombosis. These observations indicate that MPP can be successfully used as arterial conduits in rats, and an enhanced patency rate may be expected with the use of anticoagulants or endothelial cell seeding for prevention of early thrombosis.

Animals↗

PubMed1994

Sites of inhibition of mitochondrial electron transport by D1, an organic solvent extractable component from burn eschar.

The inhibitory sites of component D1, isolated by extracting burn eschar with ethyl acetate, on rat liver mitochondrial respiratory chain was investigated. By using changes of the redox state of NADPH in various respiratory states, the effect of D1 on electron flow through the phosphorylation site 1 was studied. It was found that D1 did not interfere with electron transport through site 1, nor did it inhibit the activity of NADH:duroquinone reductase. The functional state of site 2 was tested directly by using duroquinol as an artificial electron donor and cytochrome c as electron acceptor. D1 inhibited the activity of this enzyme in a dose-dependent manner. The redox state of the electron carrier cytochrome b was not influenced by D1. However, a transient process of oxidation of cytochrome c1 was demonstrated, suggesting a brief inhibitory process in the reducing side of it. Two inhibitory sites in site 2 were found by studying the TMPD and DCIP bypasses. One was at the reducing side of cytochrome c1, and the other was at the reducing side of cytochrome b. Further studies are needed to find out the exact position and nature of these inhibitory sites.

Animals↗

PubMed1994

Dextromethorphan metabolism in rat: interstrain differences and the fate of individually administered oxidative metabolites.

1. Dextromethorphan undergoes O- and N-demethylation, with the resultant metabolites being further N- and O-demethylated respectively to 3-hydroxymorphinan. The polymorphically expressed O-demethylation reaction is catalysed by P4502D1 in the Sprague-Dawley (SD) rat. The Dark-Agouti (DA) rat lacks this enzyme. 2. The aims were: (1) to determine if there were strain differences also in the Hooded Wistar (HW) and Albino Wistar (AW) rats with respect to the four demethylation reactions after dextromethorphan 20 mg/kg intraperitoneally; (2) to investigate the inhibition of the demethylation reactions by quinine and quinidine (each 40 mg/kg i.p.) in the above strains; and (3) to investigate the fate of separately administered metabolites (5 mg/kg i.p.) of dextromethorphan in the SD strain. 3. The total recovery of dextromethorphan and metabolites in the four strains ranged from 38 to 64% of the dose. The O-demethylation ratios (expressed as the ratio of urinary total dextrorphan divided by dextromethorphan) in the AW and DA strains were similar but less than in the SD/HW strains; the N-demethylation ratios (expressed as the ratio of urinary total 3-hydroxymorphinan plus 3-methoxymorphinan divided by dextromethorphan) in the DA and SD strains were similar but greater than in the AW and HW strains. Quinine and quinidine significantly reduced the O-demethylation ratio in the SD and DA rat strains, and the N-demethylation ratio in the SD strain. 4. In the SD rat the major metabolic route was via O-demethylation to dextrorphan. The source of 3-hydroxymorphinan is primarily from N-demethylation of dextromethorphan to 3-methoxymorphinan and its subsequent O-demethylation to 3-hydroxymorphinan. The O-demethylation metabolic ratio for dextromethorphan should be calculated as the quotient of urinary total dextrorphan divided by dextromethorphan.

Animals↗

PubMed1994

[Effect of Salvia miltiorrhiza on lipid peroxidation antioxidant enzymes activity in patients with chronic cor pulmonale].

This paper studied the effect of Salvia miltiorrhiza (SM) on plasma lipid peroxidation (LPO), RBC superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activity in patients with chronic cor pulmonale. 30 patients were randomly divided into two treatment groups (routine and SM). The four parameters have been measured in 22 healthy subjects as control and patients of two treatment groups. The results showed: (1) Before treatment both treatment groups had significantly higher LPO and SOD and markedly lower GSH-Px and CAT level than that of healthy control (P < 0.001) respectively. (2) After treatment in routine group the four parameters have normalized, P < 0.05. (3) Routine treatment was compared with SM treatment, except SOD, the other three parameters were significantly different between two treatment groups (P < 0.001). The increased levels of GSH-Px and CAT and the decreased LPO were significantly greater in SM group than routine treatment (P < 0.001). The above-mentioned results indicated patients with cor pulmonale in acute exacerbation their lipid peroxide reaction was enhanced, the antioxidant enzymes lost their balance. SM could attenuate markedly lipid peroxide reaction, adjust the imbalance of the three antioxidant enzymes, enhance body's defence capability against damage of active oxygen free radical induced lipid peroxidation.

Adult↗

PubMed1993

[Arthroscopic microdiscectomy].

Forty six (42 cases) intervertebral discs were resected by the authors by means of arthroscopic microdiscectomy. Postoperative follow-up period was from 3 months to 6 months. According to MacNabis classification the result of treatment was excellent in 30 cases, which overs 71.4% of all patients. Failure of treatment occurred in 12 cases, this is mainly because of improper selection of cases. The authors expressed that this method is especially indicated in patients with simple disc protrusion.

Adult↗

PubMed1993

[Effect of thymic factor D on lipid peroxide, glutathione, and membrane fluidity in liver of aged rats].

The effects of thymic factor D (TFD) on aging were investigated in male Wistar rats at the age of 24 months. Thymic factor, polypeptides extracted from swine thymus, was given to aged rats in the dose of 2 mg.kg-1 sc every other day for 3 months. It was shown that TFU decreased the content of malondialdehyde (MDA) and lipofuscin in the liver of aged rats, accompanied by an increase of glutathione (GSH). Besides, the declined fluidity of hepatic mitochondrial and microsomal membranes in aged rats was recovered to the level of young adult rats by administration of TFD. It is suggested that TFD may possess beneficial effects on retarding the senile metabolic changes in hepatic cells.

Aging↗

PubMed1991

Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man.

Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (mumol.l-1.h) and CLR (ml.min-1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml.min-1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucuronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.

Acetaminophen↗

PubMed1991

Mu receptor binding of some commonly used opioids and their metabolites.

The binding affinity to the mu receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding (e.g. morphine-6-glucuronide Ki = 0.6 nM; morphine = 1.2 nM). Decreasing the length of the alkyl group at position 3 decreased the Ki values (morphine less than codeine less than ethylmorphine less than pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 (e.g. hydrocodone, Ki = 19.8 nM) had relatively weak receptor binding, whilst their O-demethylated metabolites (e.g. hydromorphone, Ki = 0.6 nM) had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

Animals↗

PubMed1991

Inhibition of mitochondrial respiratory function by an organic solvent extractable component from an extract of burn eschar.

Saline extracts of burn eschar (CEBE) and normal skin (CENS) caused inhibition to mitochondrial respiration and inner membrane function. Ethyl acetate extracts from CEBE (D1) and CENS (D'1) caused depression of the Respiratory Control Ratio, (RCR), an inhibition of respiration rate in state 3 and stimulation to state 4 respiration. Excellent linear correlations exist between the degree of inhibition to state 3, rate of stimulation to state 4 respiration and the logarithm of doses of D1 and D'1. The effective dose ranges (0.75-0.25 mg/ml for D1 and 4-1 mg/ml for D'1) differ by one order of magnitude. The activity of NADH dehydrogenase and succinate dehydrogenase of mitochondria after incubation with the highest toxic dose of D1 or D'1 remained normal. Dinitrophenol (DNP)-stimulated respiration was moderately inhibited by D1 and D'1. No change of oligomycin-sensitive ATPase activity was demonstrated. Exogenous malondialdehyde (MDA) did not show any inhibitory effect. Preliminary studies show that D1 contains a family of free fatty acids (FFA). Incubation of normal mitochondria with D1 increased the content of saturated FFA and a decrease of unsaturated FFA. The role of other peroxidative products is under investigation.

Adenosine Triphosphatases↗

PubMed1991

Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in the seven extensive metabolisers and 8 ml min-1 in the poor metaboliser; to norcodeine the values were 103 +/- 33 ml min-1 and 90 ml min-1; to codeine-6-glucuronide the values were 914 +/- 129 ml min-1 and 971 ml min-1; and intrinsic clearance was 1568 +/- 103 ml min-1 and 1450 ml min-1. These values were not significantly (P greater than 0.05) altered by chronic administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

PubMed1991

Polymorphic metabolism of opioid narcotic drugs: possible clinical implications.

The oxidative metabolism of many drugs is under genetic control. The enzyme responsible for this reaction for this group of drugs is cytochrome P-450IID6. Humans can be classified either as extensive metabolisers or, if lacking this enzyme, poor metabolisers. The incidence of poor metabolisers in caucasian subjects is 7-10%. The hepatic O-demethylation of codeine to morphine, quantitatively a minor metabolic process, represents this type of genetic polymorphism and has been studied in human pharmacokinetic studies, human urinary recovery studies, and in human and rat liver microsome experiments. Based on the current understanding that the analgesic effect of codeine is mediated primarily through morphine, one might anticipate that poor metabolisers would not obtain pain relief from codeine. The clinical significance of this polymorphism to the antidiarrhoeal and antitussive properties of codeine is not known. Others opioids (dihydrocodeine, hydrocodone, oxycodone, and thebaine) are structurally similar to codeine and their metabolism (O-demethylation at the 3 position) might also be under genetic control. Pharmacogenetics may play an important role in explaining the wide variability of the clinical response to many opioid drugs.

Alfentanil↗

PubMed1990

Morphine formation from codeine in rat brain: a possible mechanism of codeine analgesia.

The O-demethylation of codeine to morphine was demonstrated in rat brain homogenate. Maximal formation occurred at 10 minutes, with a Vmax of 5.93 +/- 0.16 nmol/g brain/h and Km of 37.82 +/- 4.99 microM. The formation was significantly (P less than 0.05) greater in the microvessel-rich brain fraction. Intraperitoneal injection of codeine in the rat resulted in brain concentrations of morphine which could not be solely attributed to transfer of morphine from the blood stream across the blood-brain barrier. Morphine formed in the brain after codeine administration may be an important mechanism for codeine-induced analgesia.

Analgesia↗

PubMed1990

Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man.

A simple, sensitive, and reproducible high-performance liquid chromatrography assay is described for the simultaneous determination of dextromethophan, dextrorphan, 3-hydroxymorphinan, and 3-methoxymorphinan in plasma and urine. A conventional solvent-solvent extraction procedure was used for the isolation of the analytes from plasma and urine samples. The compounds were separated on a cyano column (150 x 4.6 mm, 5-micron particle size) using a mobile phase of acetonitrile/triethylamine/distilled water (17:0.06:82.94, vol/vol), pH 3.0, and then were measured by fluorescence detection. Calibration curves in the range 2-200 ng/ml for plasma and 0.05-10 micrograms/ml for urine were linear and passed through the origin. The precision and accuracy were greater than 90% and the lowest detectable concentrations were 0.5 ng/ml for 3-hydroxymorphinan and 3-methoxymorphinan and 1 ng/ml for dextromethorphan and dextrophan in plasma. The utility of this method is demonstrated in a preliminary study of dextromethorphan metabolism and pharmacokinetics in man.

Chromatography, High Pressure Liquid↗

PubMed1990

[A clinicopathological and ultrastructural study on 147 cases of primary aldosteronism].

147 cases of primary aldosteronism was analysed, including 133 cases of adenoma (90%), 13 cases of cortical hyperplasia, and 1 case of carcinoma. The size of aldosteronoma was usually 1-2 cm in diameter. All the adenomas were well capsulated and the cut surface showed a homogeneous yellow color. The largest one in this group was 6 cm in diameter. The diameter of aldosteronoma was over 10 cm and the cut surface showed a brownish yellow color. Microscopically, the aldosteronoma was composed principally of clear cells arranged in a glomerular pattern, while the malignant one consisted of more granular cells with nuclear atypia and mitoses. Ultrastructure of the majority of tumor cells showed presence of numerous lipid vacuoles representing content of the steroid hormones. In those patients who had received spironolactone before operation, some eosinophilic concentric laminated spironolactone bodies could be obtained in the lipid vacuoles, which indicated that the steroid hormone had been blocked or destroyed. Additionally, the laminated cristae within the mitochondria in aldosteronoma looked closely similar to those of the normal cells in the zona glomerulosa, suggesting that these tumors are mainly derived from zona glomerulosa of the adrenals.

Adenoma↗

PubMed1989

Direct determination of codeine-6-glucuronide in plasma and urine using solid-phase extraction and high-performance liquid chromatography with fluorescence detection.

A sensitive and selective method was developed for the direct determination of codeine-6-glucuronide in plasma and urine using high-performance liquid chromatography (HPLC) with fluorescence detection. Codeine-6-glucuronide was synthesised and its purity estimated using acid and enzyme hydrolysis. The hydrolysis of codeine-6-glucuronide by beta-glucuronidase was incomplete and urine reduced the extent of hydrolysis. Codeine-6-glucuronide was recovered from plasma using a solid-phase extraction column and separated on a reversed-phase C18 HPLC column. The assay showed good reproducibility and accuracy (within 10%), and standard curves were linear between 32 and 1600 ng/ml in plasma and between 0.32 and 160 micrograms/ml in urine. The assay has been applied to the study of the pharmacokinetics and metabolism of codeine in patients.

Chromatography, High Pressure Liquid↗

PubMed1989

Simultaneous determination of codeine, norcodeine and morphine in biological fluids by high-performance liquid chromatography with fluorescence detection.

A novel high-performance liquid chromatographic method for the determination of codeine, norcodeine and morphine in plasma and urine has been developed. The compounds were separated on a cyano column (15 cm x 4.6 mm, 5 microns particle size) using a mobile phase of acetonitrile-triethylamine-distilled water (4:0.1:95.9, v/v) pH 3.1 and then determined by fluorescence detection. Calibration curves in the range 5-200 ng/ml for plasma and 0.1-10 micrograms/ml for urine were linear and passed through the origin. The imprecision and inaccuracy of the assay were less than 10% and the limits of detection were 2 ng/ml for all three compounds in human plasma.

Adult↗