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Biomedical subjects

Y D Zhang

Publications and source records attributed to Y D Zhang.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics of bendazac lysine in 10 Chinese young men.

AIM: To compare the pharmacokinetics of domestic and imported tablets of bendazao lysine (BL). METHODS: A single oral dose of 500 mg BL of this 2 kinds of tablets was given to 10 Chinese volunteers of Han nationality in a randomized crossover study. Plasma levels were determined with HPLC-UV method. Data were analyzed automatically by using a CAPP program on microcomputer. RESULTS: The plasma concentration-time curve was fitted to 2-compartment open model, and the major pharmacokinetic parameters of domestic and imported BL tablets were shown respectively as following: Cmax 66 +/- 16 and 65 +/- 8 mg.L-1; Tmax 0.98 +/- 0.22 and 0.98 +/- 0.21 h; T1/2 beta 6.2 +/- 1.8 and 6.2 +/- 1.7 h; AUC 335 +/- 47 and 337 +/- 58 mg.h.L-1. There was no significant difference between domestic and imported tablets. The bioavailability of the domestic vs that of the imported tablet was 99 +/- 12%. The unchanged BL in urine were about 5.4% and 5.6% respectively of the dosage in 24 h after a single oral dose. CONCLUSION: The two kinds of tablets had the same biological effects.

Adult↗

[Pharmacokinetic-pharmacodynamic modeling of metoprolol enantiomers in the dog].

The PK-PD model of (+)-Met and (-)-Met was studied in anesthetized dogs. The plasma drug concentration-time profiles were most adequately described by two compartment model. Significant differences of Vd/F, CLs/F and AUC between (+)-Met and (-)-Met were observed. The peak times of plasma (+)-Met and (-)-Met concentration in dogs were 24 +/- 5 and 30 +/- 5 min, respectively. But the peak times of drug inhibitory effects on Vmax, dp/dtmax, LVSP, SBP and HR were about 90-120 min, showing the hysteresis loops. When using the effect compartment model, the counterclockwise hysteresis collapsed and the relationships between the effects and concentration in effect compartment were fit by using Sigmoid-Emax model. The Ce50 values of inhibitory effects on Vmax, dp/dtmax and HR of (+)-Met were 250 +/- 80, 450 +/- 210, 520 +/- 210 micrograms.L-1 and those of (-)-Met were 70 +/- 30, 70 +/- 40 and 82 +/- 27 micrograms.L-1, respectively. Significant differences of Ce50 of (+)-Met and (-)-Met were found. The values of Ce50+/Ce50- were 3.7, 6.8 and 6.3, indicating that the inhibitory effects on Vmax, dp/dtmax and HR of (-)-Met were stronger than those of (+)-Met in dogs.

Adrenergic beta-Antagonists↗

Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds.

Inhibition of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) can cause excess mineralocorticoid effects and hypokalemia. Several substances causing hypokalemia (glycyrrhizic acid in licorice and gossypol) inhibit this enzyme. We tested other compounds for activity to inhibit 11 beta-OHSD in guinea pig kidney cortex microsomes with NADP as cofactor and cortisol as substrate. Furosemide was an inhibitor while bumetanide was not, indicating a mechanism for the increase K+ excretion caused by furosemide compared with bumetanide. Naringenin (found in grapefruit juice), ethacrynic acid, and chenodeoxycholic acid had inhibitor IC50 values similar to glycyrrhizic acid. We conclude that various compounds can inhibit this enzyme and may play a role in K+ metabolism and adrenocorticosteroid action.

11-beta-Hydroxysteroid Dehydrogenases↗

Flow dependence of metoprolol elimination in isolated perfused rat liver.

The effect of blood flow rates on hepatic elimination of metoprolol (Met) was studied in a recirculating isolated perfused rat liver system with a constant infusion of Met into the reservoir. This design ensures that, at a steady state, the elimination rate of Met is a constant. The results showed that at flow rates of 10, 20, and 30 ml.min-1, the concentrations of Met entering the liver (Cin) were 7.6, 5.0, and 3.4 micrograms.ml-1 and the concentrations leaving the liver (Cout) were 1.2, 2.0, and 2.7 micrograms.ml-1, while the logarithmic average concentrations in hepatocytes (C) were 3.4, 3.2, and 3.0 micrograms.ml-1, respectively. It is concluded that the hepatic elimination of Met is flow-dependent, which is in accordance with the 'parallel tube' model.

Animals↗

[Analysis of 110 cases of esophagogastrostomy by intraluminal elastic circular ligation with an absorbable supporting tube].

The result of 110 cases of esophagogastrostomy by intraluminal elastic circular ligation (IECL) with an absorbable supporting tube was reported. Postoperative X-ray observation of the tube showed that its supporting effect was satisfactory. The tube-drop time was 14.7 +/- 2.5 days and unaffected by the tube size or the site of anastomosis. The supporting tube could be safely absorbed or partially fragmented and expelled from the alimentary tract. Postoperative anastomotic leakage occurred in one case (0.91%) and the cause was analysed. The use of IECL, with the merits of saving time, anastomosing tightly and leaving no suture materials in the anastomotic site, can be expected to prevent the anastomotic leakage and may provide references for other gastrointestinal anastomosis.

Adult↗

Hepatitis C virus infection: its role in chronic liver diseases.

In order to find out the infectious rate of hepatitis C virus (HCV) among chronic liver diseases, we investigated antibodies against hepatitis C virus and HCVRNA by method of ELISA, RIBA and RT-PCR in 410 patients with chronic liver disease. The prevalence of HCV infection was found to be 4%. Whereas the positive rate of HBsAg and HBV-DNA of these cases was 69% and 58%, respectively. There is no statistical significance between HCV infectious rate of patients with positive and negative HBsAg. The relative low infectious rate of HCV infection among chronic hepatic diseases indicates that HBV infection plays a more important role in causing chronic hepatitis than that of HCV. Thus, special emphasis should be paid to the preventive and therapeutic measures against hepatitis B in China.

China↗

Effect of dose of metoprolol on its elimination by isolated perfused rat liver in vitro.

The effects of dose of metoprolol (Met) on hepatic elimination was studied in isolated rat liver perfused at a flow of 25 ml.min-1. The results showed that Met was eliminated by rat liver in accordance with one-compartment model. Linear kinetic eliminating processes (apparent first-order kinetics) were found in doses of Met 0.2, 0.5, 1.0, and 2.0 mg, T1/2 were 8.3, 8.8, 9.6, and 10.6 min and the clearance rate were 11.7, 11.8, 9.6, and 8.6 ml.min-1, respectively. Nonlinear eliminating processes were found in doses of Met 4, 8, and 12 mg. Vm and Km were 0.98, 1.05, and 0.94 microgram/min-1.ml-1 and 15.6, 16.9, and 14.6 micrograms.ml-1, respectively. It is concluded that hepatic Met elimination is independent on lower doses, but rested upon high doses.

Animals↗

Endoscopic variceal ligation. Experience in 78 patients.

Endoscopic variceal ligation (EVL) is a new alternative to sclerotherapy in the treatment of esophageal variceal hemorrhage, which results in strangulation, necrosis and scar formation of varices without systemic or local adverse effect. From May 1, 1991 through July 1, 1992, EVL was performed in 78 consecutive patients, in 35 of them it was performed during active massive bleeding, and active bleeding was controlled by the initial session in 31 patients. With repeated EVL treatment, 32 patients had their varices obliterated. The varices had reduced in size in other patients. No ligation-related complications were observed. This procedure is a safe, effective and rather simple method to treat esophageal varices, especially in patients with poor liver function and recurrent bleeding after devascularization or shunt surgery.

Adolescent↗

Hepatitis B virus DNA detected by PCR in sera and liver tissues of Chinese patients with chronic liver diseases.

To investigate the HBV infection and its replication in Chinese patients with chronic liver disease, polymerase chain reaction (PCR) was employed to detect hepatitis B virus DNA in sera of 410 patients with chronic liver disease and liver samples from 188 patients. The HBV DNA detectability in all serum samples was 58%. Among them 100% HBeAg-positive and 58% anti-HBe cases were HBV DNA detectable respectively. However, HBV DNA was also found in 23% HBsAg-negative/anti-HBc positive chronic cases. Furthermore, 30% anti-HBs positive chronic cases who had neutralizing antibody against HBV infection, continued to contain HBV DNA. Our findings indicate that HBV infection and its replication are dominant cause of chronic liver disease and some HBV variants may escape from the protective antibody to induce chronic liver disease, even anti-HBs antibody circulated.

Adolescent↗

[Effects of astragalus (ASI, SK) on experimental liver injury].

The saponins (ASI, SK) used in this study was extracted from the root of Astragalus membranaceous Bge and Astragalus sieversianus Pull. ASI and SK were found to protect liver from chemical injury induced by CCl4, D-galactosamine and acetaminophen in mice. The two saponins were shown to impede the elevation of SGPT level, decrease the MDA content and increase the GSH concentration in mouse liver. Obvious improvement of histological changes were also observed. The protective action of ASI and SK against the hepatotoxicity was also shown in experiments using primary cultured rat hepatocytes. The average value of GPT in the medium treated with different concentration of ASI and SK (0.00075-0.18 mmol/L) was lower than that in control. Analyzing through multiple linear correlation, we showed that the lowering of SGPT was negatively related to the increase of GSH, positively related to the decrease of MDA in mice given CCl4 or acetaminophen in combination with ASI or SK. These results indicate that the hepato-protective effects of ASI and SK may be due to their anti-oxidation activities, since the content of liver protein in mice given ASI or SK was more than that in the controls. Moreover, the level of hepatic microsomal cytochrome P-450 in all mice given the two saponins were significantly increased, the liver metabolism and immunoregulating action produced by ASI and SK may be also involved in their hepato-protective effects.

Acetaminophen↗

The morphology and distribution of photoreceptors in the retina of Bufo marinus.

The number, cell morphology and retinal distribution of rods and cones were determined in the retina of the toad, Bufo marinus. Adult animals were sacrificed, both eyes were removed and prepared for either tangential section across the outer segments of the photoreceptor layer, or transverse section across the whole retina. Cone densities increased from an average of 7000/mm2 in the peripheral to a maximum of 25,000/mm2 in the central retina. The high cone densities extended across the naso-temporal axis of the retina corresponding to the position of the visual streak in the ganglion cell layer. The total number of cones in the retina was estimated to be 1.1 million. Rod density of 21,000/mm2 in the central retina decreased to 17,000/mm2 at 1.5-4 mm eccentricity, and then increased to 29,000/mm2 in the peripheral retina. The total number of rods amounted to about 2 million. The mean of the cross-sectional area of rod outer segments was 11.2 +/- 1.5 microns 2 (mean +/- SD) in the highest and 17.9 +/- 4.7 microns 2 in the lowest density areas of the retina. The length of the rod outer segments extended from 28 microns in the ventral peripheral retina to a maximum of 89 microns in the dorsal retina, dorsal to the visual streak of the ganglion cell layer. The results of the present study showed a differential retinal distribution of photoreceptors, with a peak density in the retinal centre and a higher density along the naso-temporal axis of the eye. We conclude that the area of high photoreceptor density, matched by high neuron densities of the INL and GCL, corresponds to the site of acute vision of the Bufo retina.

Animals↗

[Drug evaluation of huperzine A in the treatment of senile memory disorders].

Huperzine A is an alkaloid which was first isolated from Huperzia serrata (Thumb) Trev by Zhejiang Academy of Medical Sciences and Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It exhibits a significant anticholinesterase activity and has been used on myasthenia gravis patients. The therapeutic effects were studied by random, match and double-blind method on 56 patients of multi-infarct dementia or senile dementia and 104 patients of senile and presenile simple memory disorders. The curative effects were evaluated by Wechsler memory scale. The im dose for multi-infarct dementia was 0.05 mg bid for 4 wk, whereas that for senile and presenile simple memory disorders was 0.03 mg bid for 2 wk. Saline was used on control group. The result showed that the curative effect of huperzine A was significant. Only a few patients felt slight dizziness and this did not affect the therapeutic effects.

Aged↗

Nonrandom chromosome changes in methylnitrosourea (MNU) induced mouse T-cell lymphomas.

Since nonrandom chromosome changes in neoplastic cells have proven to be good indicators of the site of gene alterations related to transformation, the authors examined the chromosomes of T-cell lymphomas induced in RF/J strain mice with methylnitrosourea (MNU). All treated mice developed thymic lymphomas within 10 weeks of injection. Chromosomes of the thymus cells were examined at intervals before and during lymphoma development, as well as after they were passaged in syngeneic and in nude mice for periods up to 424 days. In preparations made directly from the thymus cells nonrandom numerical and structural alterations were found that involved the X, 3, 15, 4, 8, 12, 14 and 17. (Chromosomes showing alterations are listed in decreasing order of the frequency of their occurrence). In cells passaged in nude mice the chromosomes similarly altered were the 10, X, 3, 12, 6, 1, 4, 19, 15, 18 and 14. In tumor cells passaged in syngeneic mice most of the same chromosomes were involved but the order was 15, 14, X, 1, 5, 6, 3, 11 and 12. The X, 15, 14, 3 and 12 were aberrant in both direct preparations and in those from passaged cells, suggesting that these chromosomes carry genes which, when altered, are particularly important in the multistep process of neoplastic transformation. Most of these chromosomes, or their homologs in other species, have been found to be involved frequently in several different cancers of mice and men, as for example the region on the mouse 15 carrying the Myc and Pvt-1 genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Etiology of acute exacerbation in patients with severe chronic active hepatitis by in situ HBVDNA hybridization technique.

To explore etiology of acute exacerbation in severe chronic active hepatitis, in situ HBVDNA hybridization was carried out combined with detection of HBV markers in the serum and the liver as well as intrahepatic HDAg in 15 cases. Four subgroups were identified based on the etiological evidence: 1) 9 cases were still undergoing HBV active replication or reactivation with cytoplasmic and membraneous HBcAg expression, often associated with the hepatic necrosis foci; 2) 3 cases showed HBsAg or/and HBVDNA positivity despite absence of HBcAg expression, the membranous and homogeneous HBsAg expression being closely related with hepatic necrosis; 3) 2 cases were HDAg positive; 4) the remaining case exhibited no HBV infection evidence. All findings suggested that HBV active replication or reactivation was the major cause of the exacerbation in severe chronic active hepatitis. In addition, HBV superinfection accounted for over 10% of cases with acute exacerbation. Hepatitis A or C may contribute to some episodes of exacerbation.

Acute Disease↗

Expression of androgen receptors and prostatic steroid-binding protein during development of the rat ventral prostate.

Prostatic steroid-binding protein (PSBP) mRNAs transcribed from the three genes C1, C2 and C3 were quantitated in neonatal rat ventral prostate by Northern blot analysis. Transcription was initiated at day 14 for C1 and C2 and day 10 for C3, and reached mature levels by day 21 for C1 and C2 and day 28 for C3. The changes of both cytoplasmic and nuclear prostatic androgen receptors in 10- to 150-day-old rats were investigated by radioligand assay and showed a fivefold transient increase between days 10 and 28. Thus there was a good correlation between the onset of PSBP gene expression and the transient increase in androgen receptors; increases in receptor concentration may be a prerequisite for changes in gene expression.

Androgen-Binding Protein↗

[New technique of esophagogastrostomy--improved intraluminal elastic circular ligation].

199 patients with carcinoma of the esophagus or gastric cardia treated by resection and intraluminal elastic circular ligation from January 1981 to July 1986 are reported. The management of these cases is divided into three periods for convenience in analysis: period of early practice 17 cases; period of technical and instrumental refinement 117 and period of standardization 65. No anastomotic leakage was found in 65 patients during the third period, indicating that the intraluminal elastic circular ligation is practical and advisable. In addition, this ligation, basing on successful animal experiments, is simpler and more rapid as compared with the manual method. Fundamental principles of this method are discussed. At present, the supporting tube needs further improvement.

Anastomosis, Surgical↗

Levels of fos, ets2, and myb proto-oncogene RNAs correlate with segregation of chromosome 11 of normal cells and with suppression of tumorigenicity in human cell hybrids.

The tumorigenicity in nude mice of human carcinoma-derived D98AH2 (D98) cells is suppressed when cell hybrids are made by fusing these cells with normal human diploid cells. Selection for hybrids that have segregated chromosomes results in the recovery of tumorigenic segregants. These segregants have all lost at least one copy of chromosome 11 of the diploid cell parent. Earlier we found that the parental D98 cells had detectable levels of mRNA specific for 13 of 21 proto-oncogenes examined. To determine if transregulation of proto-oncogenes by genes of the normal cell occurs in such hybrids, the steady-state levels of mRNA specific to 22 proto-oncogenes in the parental cells were compared with those of nontumorigenic D98 X human diploid hybrids as well as with those of their tumorigenic segregants and with the cells of the resulting tumors. The only chromosome consistently segregated in the latter was chromosome 11 of the diploid cell. fos and ets2 RNA levels and the amount of fos protein were consistently elevated in the segregants compared with amounts in the original hybrids. An unexpected finding was the inverse relationship for myb RNA that was barely detected in the parental D98 cells but was at least 10-fold elevated in hybrids that did not have segregated chromosomes compared with those that did. These patterns were evident in RNAs prepared from both subconfluent and confluent cell cultures. The findings suggest that genes of the normal cell parent can affect proto-oncogene expression. Whether the genes affecting fos, ets2, and myb RNA levels are on chromosome 11 and whether these alterations are causally related to the tumorigenic phenotype of the hybrid remain to be determined.

Animals↗