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Biomedical subjects

J D Feng

Publications and source records attributed to J D Feng.

At least 19 recordsLinked to original sources
PubMed2006

A genome scan for quantitative trait loci associated with body weight at different developmental stages in chickens.

A genome scan to detect quantitative trait loci (QTL) affecting body weight in chickens was conducted on 238 F(2) chickens from a reciprocal cross of Silky Fowl and White Plymouth Rock using 125 microsatellite markers covering 23 autosomes and the Z chromosome. Two types of QTL were considered: static QTL (SQ) and developmental QTL (DQ). Static QTL affected the body weight from hatch to time t, and DQ affected the body weight from time t-1 to time t. Six SQ and nine DQ were detected. Of these QTL, four reached a genome-wide significance of 5% or better, with SQ1 and DQ1 being the most significant QTL. Static QTL1 was on chromosome 1 between GCT0006 and MCW0106 and explained 4.05-9.80% of the phenotypic variation in body weights from 3 to 12 weeks of age. At 9, 10 and 11 weeks, the genome-wide significance thresholds of SQ1 were <1%. Developmental QTL1 was located on chromosome 1 between MCW0168 and GCT0006, and explained 2.75% of the phenotypic variation for body weight from week 7 to 8 with a genome-wide significance level <1%. The results suggest that body weight from hatch to time t and developmental growth from time t-1 to time t may involve two different sets of genes or gene actions.

Animals↗
PubMed2001

Effect of administration route and length of exposure on pharmacokinetics and metabolism of diltiazem in dogs.

The objective of this study was to systematically determine the pharmacokinetics and metabolism of diltiazem (DTZ) after a single i.v. dose, and after single and multiple oral (p.o.) doses. Four mongrel dogs (3 M, 1 F), aged 1-3 years, body weight 19-25 kg, were each given a single 30 mg dose of DTZ as a solution by i.v injection, the same dose orally from an immediate release tablet (Cardizem, Aventis Pharma, Canada, QC), and also t.i.d. for 10 doses. A 3-4 week washout period was allowed between each treatment. Blood samples (4 ml each) were obtained after each treatment from each animal via a cephalic vein at 0 (just before dosing), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, and 12.0 h post dose. Urine samples were collected for 24 h. The plasma samples were immediately separated by centrifugation and stored at -20 degrees C until analysis. The results showed that the bioavailability after a single p.o. dose of DTZ was 26+/-24%. Following a single i.v. dose, DTZ declined bi-exponentially with a terminal half-life (t1/2) of 4.2+/-1.7 h. N-Monodesmethyl DTZ (M(A)), deacetyl DTZ (M1), and deacetyl N-monodesmethyl DTZ (M2) were the major metabolites. Contrary to the results observed in clinical studies, there were no increase of plasma concentrations of DTZ after repeated doses (accumulation factor R = 0.94+/-0.51). Plasma concentrations of M1 decreased following repeated oral doses, accompanying by an increase of plasma concentrations of M2, although these changes were not statistically significant (p >0.05). This study cautions the use of mongrel dogs for direct extrapolation to humans, particularly for chronic pharmacokinetics studies of DTZ.

Administration, Oral↗
PubMed2001

[Chemical constituents in volatile oil from fruits of Alpinia oxyphylla Miq].

OBJECTIVE: To study the chemical constituents in the volatile oil from fruits of Alpinia oxyphylla. METHOD: Using GC-MS to identify the constituents. RESULT AND CONCLUSION: Sixty-four compounds were identified on the basis of GC-MS, the main ones being p-cymene, valence, linalool, myrtenal, alpha-pinene, beta-pinene, furopelargone A and terpinen-4-ol. Three sesquiterpenes valencene, nootkanone and nootkanol have been isolated from the CHCl3 extract as check, of these 64 identified compounds linalyl oxide, valencene, bakkenolide A, furopelargone A and 3-hydroxycalamenene are reported for the first time.

4-Butyrolactone↗
PubMed2000

A simple high-performance liquid chromatography assay for simultaneous measurement of adenosine, guanosine, and the oxypurine metabolites in plasma.

To study the effect of pharmacologic agents on the biologic fate of adenosine, a reversed-phase high-performance liquid chromatography (HPLC) assay coupled with a solid-phase extraction (SPE) method was developed for simultaneous determination of plasma adenosine, hypoxanthine, xanthine, inosine, guanosine, and uric acid. The HPLC system consisted of a reversed phase C18 column, UV detector set at 254 nm, and a mobile phase composed of 0.01 M ammonium phosphate: methanol (9.5 : 0.5) vol/vol with the final pH adjusted to 3.9. The standard curves were linear between 0.1-2 microg/mL for all the analytes (except uric acid 50-400 microg/mL), with r2 > 0.99. The absolute recoveries were >60% and accuracy >85% in almost all cases. The limit of detection was <1 ng based on absolute injection of the analytes. The intraassay variations were <10% and interassay variations <15%. The presence of a wide range of medications in plasma samples did not interfere with the assay. The assay was applied successfully to measure plasma adenosine and the oxypurine metabolites in humans and rats. It was noted that plasma concentrations of adenosine and the oxypurine metabolites can vary considerably depending on the method of blood sample collection, and that species differences are apparent.

Adenosine↗
PubMed2000

[Genescan for STR analysis and genetic distribution in a population sample from Han, China].

Genetic distributions for nine STR loci and Amelogenin locus were determined in a Chinese Han population based on DNA sequencing. The databanks in Chinese Population were generated by using Genescan, genotype and genetic distribution analysis. Allele frequency distribution was determined for 10 loci, such as D3S1358, VWA, FGA, Amelogenin, THO1, TPOX, CSF1PO, D5S818, D13S317 and D7S820. The results show significant differences between ethnic groups (African-American, US-Caucasian and Chinese Han) in the pattern of distribution as well as in the related frequency of the most common alleles of their STR loci. The probabilities of identity values for the population described in this section are 2.79 x 10(-10) (U.S-Caucasian), 1.23 x 10(-10) (African-American) and 0.5 x 10(-10) (Chinese Han). The results show the probability of Paternity Exclusion (PPE) values of 0.9998 (Chinese Han), 0.9996 (African-American) and 0.9994 (U.S-Caucasian). These results suggested that the nine STR loci and the Amelogenin locus are very useful for human identification, such as analyzing forensis casework, establishing DNA databanks, processing paternity test, evaluation linkage genetics, studying gene natural resources and monitoring bone marrow transplants.

Asian People↗
PubMed2000

[STR polymorphisms in five Chinese ethnic groups(2)].

Population genetic studies were performed in Chinese Han, Hui, Mongolian, Tibetan and Uygur. Allele frequency distributions were analyzed for ten loci, i.e., D3S1358, VWA, CSF1PO, FGA, THO1, TPOX, D5S818, D13S317 and D7S820 by GeneScan. The results showed that there were 60 STR alleles and 149 genotypes in Han; 63 STR alleles and 144 genotypes in Hui; 69 STR alleles and 173 genotypes in Mongolian; 77 STR alleles and 168 genotypes in Tibetan; 70 STR alleles and 148 genotypes in Uygur. Significant differences were identified among ethnic groups (African-American, US-Caucasian and Chinese-Oriental), but similarity was found among the five Chinese populations, and immunogenomics and pharmacogenomics studied in this report. These findings indicated that the nine STR loci and amelogenin locus were very useful for individual identification in forensic science.

Alleles↗
PubMed1998

Pharmacokinetics and haemodynamic effect of deacetyl diltiazem (M1) in rabbits after a single intravenous administration.

Deacetyl diltiazem (M1) is a major metabolite of the widely used calcium antagonist diltiazem (DTZ). In order to study the pharmacokinetic and haemodynamic effects of this metabolite, M1 was administered as a single 5 mg kg-1 dose intravenously (i.v.) to New Zealand white rabbits (n = 5) via a marginal ear vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 8 h, and urine samples for 48 h post-dose. Plasma concentrations of M1 and its metabolites were determined by HPLC. The results showed that the only quantifiable basic metabolite in the plasma was deacetyl N-monodesmethyl DTZ (M2). The t1/2 and AUC of M1 and M2 were 2.1 +/- 0.5 and 3.0 +/- 1.1 h, and 1300 +/- 200 and 240 +/- 37 ng h mL-1, respectively. The Cl and Clr of M1 were 60 +/- 10 and 0.81 +/- 0.63 mL min-1 kg-1, respectively. M1 significantly decreased blood pressure (SBP and DBP) for up to 1 h post-dose (p < 0.05), but had no significant effect on the heart rate (P > 0.05). The Emax and EC50 as estimated by the inhibitory sigmoidal Emax model were 20 +/- 18% 620 +/- 310 ng mL-1, respectively for SBP; 20 +/- 8.3% and 420 +/- 160 ng mL-1 for DBP.

Animals↗
PubMed1998

Vernix caseosa peritonitis: report of two cases with antenatal onset.

Maternal peritonitis secondary to fetal vernix caseosa is considered an infrequent complication of cesarean section in which commonly spilled amniotic fluid is incompletely lavaged. Nine of the 10 reported cases have been diagnosed in the postpartum period after an uneventful cesarean section. Characteristically, vernix elicits granulomatous inflammation, occasionally with a mass lesion simulating bowel perforation and leading to colectomy. One case of antenatal leakage of amniotic fluid has been reported, also with granulomatous inflammation. We report two additional cases of antenatal leakage, both with acute inflammation lacking granulomatous features or mass lesions. The interval between amniotic fluid contamination and histopathologic evaluation is the basis for variations in the inflammatory pattern.

Adult↗
PubMed1998

Pharmacokinetics and hypotensive effect of diltiazem in rabbits: comparison of diltiazem with its major metabolites.

To assess the contribution of its metabolites to the antihypertensive effects of diltiazem, a previously established rabbit model has been used to compare the pharmacokinetics and haemodynamic effects of the drug with those of its major metabolites deacetyldiltiazem (M1) and deacetyl-N-monodemethyldiltiazem (M2). Diltiazem, M1 and M2 were administered separately to each animal (n = 5 or 6 per study group) as a single 5 mg kg(-1) intravenous dose. Blood samples, systolic and diastolic blood pressure (SBP and DBP) and heart rate were recorded for each rabbit up to 8 h, and urine samples were collected for 48 h post-dose. Plasma concentrations of diltiazem and its major metabolites were determined by HPLC. The results showed that systemic clearance (CL) and volume of distribution at steady state (Vdss) were smaller for diltiazem than for the metabolites. Diltiazem and the metabolites reduced both SBP and DBP, the effects of diltiazem being most potent. Their effects on heart rate were highly variable and not statistically different between treatment groups (P > 0.05). These results indicate that diltiazem is a more potent hypotensive agent than M1 or M2, possibly because of the higher plasma concentrations secondary to the smaller CL and Vdss of diltiazem compared with the metabolites. The effects of the metabolites might, however, be more sustained.

Animals↗
PubMed1998

Pharmacokinetics and haemodynamic effect of diltiazem in rats: effect of route of administration.

Diltiazem is a calcium antagonist widely used for the treatment of angina and hypertension. Previous studies in patients have shown that the haemodynamic effects of diltiazem are greater after parenteral rather than oral administration. The rat has been used as an animal model to determine the effect of the route of administration on the pharmacokinetic and haemodynamic effects of diltiazem. The results showed that plasma concentrations of diltiazem were more than 10 times higher after the intra-arterial dose. The plasma concentrations of the major metabolites were also higher after intra-arterial administration, although only for deacetyl diltiazem (M1) did the difference reach statistical significance (P < 0.05). The haemodynamic effects (on blood pressure and heart rate) of diltiazem were considerably greater after intra-arterial administration; this was attributed mainly to the much higher plasma concentrations of diltiazem. The hypotensive and chronotropic effects of diltiazem were similar; Emax and EC50 for diastolic blood pressure were 72+/-19% and 4.4+/-5.9 microg mL(-1); for heart rate they were 77+/-32% and 10.0+/-11.7 microg mL(-1), respectively. The haemodynamic effects of diltiazem are much greater after intra-arterial administration, mainly because of the much higher plasma concentrations of the drug. The contribution by the metabolites would be minimal after this route of administration.

Administration, Oral↗
PubMed1998

Pharmacokinetics and hypotensive effect of diltiazem in rabbits after a single intravenous administration: effect of phenobarbital.

Metabolism of the widely used calcium antagonist diltiazem (DTZ) is an important contributing factor to its therapeutic effects. In order to study the effects of CYP3A induction on the pharmacokinetics and haemodynamic effect of DTZ, it was administered as a single 5 mg/kg dose i.v. to two groups of New Zealand white rabbits (n = 6 in each group). Prior to the injection, one of the groups received phenobarbital 20 mg/kg s.c. two times a day for 3 days to ensure CYP3A induction, and the other received normal saline. A third group of animals (n = 6) received neither phenobarbital nor DTZ, and served as the control. Blood samples, systolic and diastolic blood pressure (SBP and DBP), and heart rate (HR) recordings were obtained from each rabbit up to 7 h, and urine samples for 48 h post-dose. Plasma concentrations of DTZ and its metabolites were determined by HPLC. The results showed that phenobarbital increased the Cl and Vdss of DTZ from 24 +/- 14 to 51 +/- 4.9 ml/min/kg and from 1.9 +/- 1.2 to 3.8 +/- 0.7 l/kg, respectively (p < 0.05). It also decreased the plasma concentrations of DTZ and all the measured metabolites in this study. Both phenobarbital and DTZ decreased SBP and DBP significantly without affecting the HR.

Animals↗
PubMed1997

Effect of diltiazem on plasma concentrations of oxypurines and uric acid.

To determine the clinical effect of diltiazem on the metabolism of adenosine, and its importance in ischemic heart disease, arterial plasma concentrations of the purine metabolites were determined in 21 healthy volunteers (10 female and 11 male) and 19 patients with effort angina (8 female and 11 male) before, during, and immediately after standard treadmill exercise tests conducted before and after they had taken 60 mg diltiazem (Cardizem; Hoechst Marion Roussel, Laval, QC, Canada) four times a day for 1 week. The results showed that the cardiac patients had significantly lower mean plasma concentrations of uric acid (46.82 +/- 25.51 versus 95.47 +/- 35.41 micrograms/ml, p 0.05), inosine (0.25 +/- 0.19 versus 0.84 +/- 0.17 microgram/ml, p < 0.05), and hypoxanthine (0.28 +/- 0.35 versus 0.50 +/- 0.27 microgram/ml, p < 0.05). Diltiazem decreased the mean resting plasma concentrations of uric acid in patients (uric acid 43.47 +/- 22.26 versus 46.82 +/- 25.51 micrograms/ml, p < 0.05) and healthy volunteers (uric acid 85.68 +/- 26.71 versus 95.47 +/- 35.41 micrograms/ml, p < 0.05). There was no statistically significant change in the plasma concentrations of the purine metabolites during exercise (p < 0.05). Female subjects had significantly lower plasma concentrations of uric acid than males (patients, 34.87 +/- 26.93 versus 55.78 +/- 21.25 micrograms/ml; healthy volunteers, 84.79 +/- 32.07 versus 104.22 +/- 37.05 micrograms/ml; p < 0.05 for both). Results of the study suggest that normal therapeutic doses of diltiazem may modulate the metabolism of adenosine and that some of the purine metabolites may be useful markers for specific types of ischemic heart disease.

Adenosine↗
PubMed1996

Steady-state plasma concentrations of diltiazem and its metabolites in patients and healthy volunteers.

Diltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina and hypertension. It is extensively metabolized in humans via N-demethylation, O-demethylation, deacetylation, and oxidative deamination, yielding a host of metabolites, some of which have potent pharmacological properties. After our initial identification of O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) as major metabolites of DTZ and our subsequent of identification of their chemical synthesis, an improved high-performance liquid chromatography assay was developed to determine the plasma concentrations of DTZ and seven of its major basic metabolites, including the previously unquantitated Mx and MB. The system consisted of a C18 analytical column protected by a C18 cartridge guard column and a variable wavelength ultraviolet detector set at 237 nm. The mobile phase was a mixture of methanol, 0.04 M ammonium acetate, and acetonitrile (38:36:26) containing 0.08% triethylamine, with final pH of the mobile phase adjusted to 7.5. The system was operated at room temperature isocratically at a flow rate of 1.2 ml/min. Using verapamil as an internal standard, DTZ and the basic metabolites in plasma were determined in young healthy volunteers (n = 21) and in patients with ischemic heart disease (n = 19) at steady state after repeated oral doses of 60 mg DTZ four times daily. Preliminary results show that steady-state plasma concentrations of DTZ and its metabolites were higher in the older patients than in young healthy subjects (p < 0.05).

Aged↗
PubMed1996

Effect of phenobarbital pretreatment on the pharmacokinetics and metabolism of diltiazem in rats.

In order to study the effect of cytochrome P-450 isozyme induction on the pharmacokinetics and metabolism of diltiazem (DTZ), male Sprague-Dawley rats weighing 300-600 g were randomly assigned to two groups. The enzyme induction group (n = 4) received phenobarbital 60 mg/kg i.p. once daily for 4 days, whereas the control group (n = 6) received normal saline for the same duration. Each rat then received a single oral dose of DTZ in solution (20 mg/kg). Blood samples (0.5 ml) were collected from each rat via an implanted polyethylene catheter (0.040" i.d.) in the right carotid artery at 0 (just before dosing), 0.25, 0.5, 1,2,3,4,6,8 and 10 h post-dose. Arterial plasma concentrations of DTZ and its metabolites M(A), M1, M2, M4 and M6 were determined by HPLC. Pharmacokinetics parameters were calculated using non-linear regression. The results showed that both mean Cmax and AUC of DTZ were lower (871.6 vs 79.8 ng/ml; 1171 vs 101.9 ng-h/ml), but the mean Cmax of the primary metabolites M1 and M(A) was higher after phenobarbital (M1 413.0 vs 648.9 ng/ml; M(A) 683.0 vs 814.8 ng/ml). The highest increase was seen in the mean Cmax and AUC of the secondary metabolite M2 (837.5 vs 2585.7 ng/ml; 3312.1 vs 13156.5 ng-h/ml). In contrast, plasma concentrations of the O-desmethylated metabolites M4 and M6 did not increase after phenobarbital. These results suggest that both deacetylation and N-demethylation of DTZ in rats are catalyzed by drug metabolizing enzymes inducible by phenobarbital.

Animals↗
PubMed1996

Presence of antibodies to heat stress proteins and its possible significance in workers exposed to high temperature and carbon monoxide.

Antibodies to the ubiquitous group of stress proteins known as heat shock proteins (Hsps) have been found to be associated with a number of diseases in humans. Hsps are known to be induced by certain xenobiotics, some of which are common in the working environment. The biological significance of the presence of such autoantibodies is presently unclear. In the present study, we used immunoblotting to investigate the presence of antibodies against the different stress proteins, Hsp27, Hsp60, Hsp71, Hsc (heat shock cognate) 73 and Hsp89 alpha and beta in groups of workers exposed to high temperature or carbon monoxide. These data were related to a detailed clinical evaluation and to various laboratory measurements including electrocardiogram (ECG), B echogram, white blood cell counts and typing, the activity of alanine aminotransferase (ALT), acid phosphatase (ACP) and alkaline phosphatase (ALP) and lymphocyte DNA damage. Antibodies to Hsp27 and Hsp71 were found more frequently in the high temperature and carbon monoxide-exposed groups than in controls (P < 0.05). The carbon monoxide-exposed group showed the highest incidence of anti-Hsp antibodies. Anti-Hsp60 antibodies were only detected in workers exposed to high temperature or carbon monoxide. The percentage of workers with abnormal ECG, B echogram changes and displaying hepatitis B antigen (HBsAg) was higher in the carbon monoxide group than in the control group (P < 0.05). There was a significant increase in the activity of ALT in the high temperature and carbon monoxide groups and in the activities of ACP and ALP in the carbon monoxide group (P < 0.05). The extent of DNA damage measured in lymphocytes was higher in workers from the high temperature and carbon monoxide-exposed groups. We suggest that the increased frequency of antibodies to Hsps is the result of these damages of the release of denatured Hsps and of a decrease in the phagocytic ability of macrophages in these workers. The data gathered in the present study show a statistical relation between the occurrence of antibodies against Hsps and the frequency of health problems in workers and suggest a potential role for the antibodies as useful biomarkers to assess whether workers are experiencing environmental stress.

Antibodies↗
PubMed1995

The combined effects of high temperature and carbon monoxide on heat stress response.

In this study, we have examined the effects of exposure to high temperature, carbon monoxide or a combination of both conditions in a model system, the rat and in industrial workers. In the rat liver, HSP70 mRNA and HSP70 synthesis were measured by dot hybridization and western blot. The results showed that after a heat stress HSP70 mRNA and its product, HSP70 increased significantly and there was a synergism in the combined effects of high temperature and carbon monoxide exposure on the induction of HSP70 mRNA and HSP70 synthesis. Heat played a major role in this induction. The presence of antibodies to human HSP27, HSP60, HSP70, HSC73, HSP89 alpha and beta in workers exposed to heat, carbon monoxide was also measured by western blot using purified HSPs as antigens. Plasma free amino acids were measured in the same group of workers. The incidence of antibodies to HSP27 and HSP70 was significantly higher in the workers working in an environment with extreme heat, and high carbon monoxide emission than in a control group. The carbon monoxide exposed group showed the highest incidence of antibodies to HSPs. Although our previous results indicated that workers had an insufficient protein intake, plasma free amino acids tended to increase, especially in methionine and tryptophan two kinds of amino acids which are absent from the main stress protein, HSP70. These results suggest that the major problems that these workers may face are how to facilitate the use of plasma free amino acids and reduce the inhibition of synthesis of normal proteins when they are exposed to occupational harmful factors. These results also add new information on the measurement of HSPs as a potential biomonitor to assess whether organisms are experiencing metabolic stress within their environment.

Adult↗
PubMed1990

[Effects of thyroxine and methimazolum on thermosensitive neurons in preoptic/anterior hypothalamic area in rats].

The effects of thyroxine (subcutaneous injection) and methimazolum (intubation feeding) on thermosensitive neurons (TSN) in the preoptic/anterior hypothalamic (PO/AH) area in rats were observed. The ratio of warm-sensitive neurons (WSN) to cold-sensitive neurons (CSN) was 1.86:1 and thermo-insensitive neurons (TIN) to thermosensitive neurons (TSN) 1:1.43 in the control group. The ratio of WSN to CSN decreased to 1.20:1 and the ratio of TIN to 1:2.36 in the thyroxine group, while the former increased to 2.40:1 and the latter decreased to 1:1.29 in the methimazolum group. There was significant difference among three groups, (X2 = 9.64, P less than 0.05). Thirty-two percent of neurons (11/34) showed higher firing rates (greater than 15Hz) in the control group, only 8% (3/37) in the thyroxine group and 9% (3/32) in the methimazolum group. In addition, the tolerance of TSN to warming stimulation was obviously lower in both pathological groups, as compared with the control group. The results suggest that a rise or fall of body temperature in rats with subcutaneous injecting thyroxine and intubation feeding methimazolum may be related to the changes of proportion and excitability of PO/AH neurons, and that the disturbance of thyroxine synthesis, release and metabolism may interfere temperature regulation at the level of hypothalamus.

Animals↗