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Biomedical subjects

Y Zou

Publications and source records attributed to Y Zou.

215 records · Page 12Linked to original sources
PubMed1993

Quantitative analysis of the lipophilic doxorubicin analogue annamycin in plasma and tissue samples by reversed-phase chromatography.

A rapid and sensitive HPLC method was developed to detect and quantitate the lipophilic doxorubicin analogue annamycin (Ann) and its metabolites in biological samples. Reversed-phase chromatography coupled with fluorescence detection was used. The emission and excitation wavelengths of the fluorescent detector were set at 550 and 472 nm, respectively. The optimal mobile phase was acetonitrile:methanol:water at a 115:95:90 ratio (v/v/v). The lower limit of detection was 0.35 ng of Ann (7 ng/mL). The retention times of 4-demethoxyadriamycinone (Anone) and Ann were 2.6 and 4.3 min, respectively, and their resolution was 1.3. The precision of the determination of Ann and Anone were 0.5 +/- 0.3 and 0.8 +/- 0.7%, respectively. Ann dissolved in methanol was stable under the determination conditions. With chloroform, 60-90% of Ann was extracted from biological samples. Apart from Anone, two Ann metabolites (retention times 3.4 and 6.0 min) were detected in plasma and tissues from C57BL/6 mice bearing subcutaneous B16 tumors 6 h after intravenous administration of a 5-mg/kg suspension of Ann. No peaks were detected in blank tissues and plasma.

Animals↗
PubMed1993

Organ distribution and antitumor activity of free and liposomal doxorubicin injected into the hepatic artery.

The plasma levels, organ distribution, and in vivo antitumor activity of free and liposomal doxorubicin injected into the hepatic artery of rats bearing W256 liver tumors were studied. The administration of liposomal doxorubicin resulted in liver-tumor and liver-parenchyma doxorubicin areas under the curve (AUCs) that were 4.7- and 3.8-fold, respectively, those obtained after the administration of free doxorubicin. Spleen and plasma AUCs were also increased by 2.8 and 2.5 times, respectively, following administration of the liposomal form. In contrast, liposomal doxorubicin did not affect heart AUCs; peak doxorubicin levels in heart tissue were three times lower in animals treated with liposomal doxorubicin. Following treatment with the liposomal form, the cumulative urinary excretion of doxorubicin at 8 h was 38 times lower. In good correlation with these findings, liposomal doxorubicin (2.35 mg/kg on day 7) was more effective than free doxorubicin against liver W256 tumors as measured by tumor-growth inhibition at 5 days after treatment (16% for liposomal doxorubicin versus -53.7% for free doxorubicin, P < 0.05) and increased life span (ILS; 108% for liposomal doxorubicin versus 27% for free doxorubicin, P < 0.05). These results demonstrate that as compared with free doxorubicin, the administration of liposomal doxorubicin into the hepatic artery results in higher drug levels in the liver tumor and enhanced antitumor activity while maintaining the cardioprotective effect of the liposome carrier as suggested by the decreased peak drug levels measured in the heart tissue.

Animals↗
PubMed1993

Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles.

Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers. We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors. L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7. Mean particle size was 1.88 +/- 0.89 microns, and the entrapment efficiency was 93.08% +/- 2.96%. F-Ann was prepared as a suspension (particle size < or = 0.2 microns) in 10% DMSO. Drug levels were measured by fluorescence spectrometry after extraction with chloroform. The extraction ratio ranged between 60% and 90% for both drugs in most tissues. Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, sixfold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors. Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain. Heart AUCs were similar with all three drugs. Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX. The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system. The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated.

Animals↗
PubMed1992

Targeting liver tumors by administering liposomal doxorubicin into the hepatic artery.

The plasma levels, organ distribution, and in vivo anti-tumor activity of liposomal doxorubicin administered i.v. or i.a. (hepatic) in rats bearing W256 liver tumors were studied. I.a. administration of liposomal doxorubicin resulted in 4-fold and 1.3-fold higher liver tumor and liver parenchyma doxorubicin levels, respectively, than i.v. administration, thus suggesting a more preferential distribution of liposomal doxorubicin into the liver tumor with i.a. administration. By contrast, the heart, spleen, and plasma AUCs were decreased 3.8-, 3.2-, and 16-fold, respectively, after i.a. administration. Cumulative urinary excretion at 8 hr was also 14 times lower in animals that received liposomal doxorubicin i.a. In good correlation with these findings, i.a. administration markedly enhanced the anti-tumor effect of liposomal doxorubicin against liver W256 tumors as measured by tumor growth inhibition 5 days after treatment (-16% for i.a. administration vs. +89% for i.v. administration, p less than or equal to 0.05) and prolongation of survival (ILS: 108% for i.a. administration vs. 26% for i.v. administration, p less than or equal to 0.05). Our results show that i.a. administration of liposomal doxorubicin results in preferential distribution of the anti-tumor agent into the tumor tissue and increased anti-tumor activity, while increasing the cardioprotective effect of the liposome carrier by decreasing the plasma peak and heart-tissue levels of the drug.

Animals↗
PubMed1992

[High performance liquid chromatographic determination of hydroxyphenytoin in human urine].

A high-performance liquid chromatographic method for the determination of p-hydroxyphenytoin (p-HDPH) in human urine was reported. Following acid hydrolysis of urine sample at 90 degrees C for 1 h, an internal standard, nitrophenol, was added. The sample was extracted with n-hexane-ethyl acetate (50:50), and organic layer was evaporated. The residue was dissolved in methanol and chromatographed on an Ultrasphere-ODS column, using a mobile phase of phosphate buffer (0.03 mol/L, pH 6.0): methanol (65:35) at a flow rate of 0.8 ml/min. The eluent was monitored at 240 nm. The standard curve was linear within the range 5.0-200 micrograms/ml (r = 0.9998). Analytical recovery rates were 102.8 +/- 7.3% (p-HDPH 9.70 micrograms/ml, n = 5) and 104.9 +/- 6.4% (p-HDPH 54.70 micrograms/ml, n = 5). The cumulative recovery of p-HDPH in 0-12 h volunteers' urine samples accounted for 20% of the oral dose of 100 mg phenytoin sodium.

Chromatography, High Pressure Liquid↗
PubMed1991

EPR studies of spin-labeled bovine plasma amine oxidase: the nature of the substrate-binding site.

The carbonyl cofactor of bovine plasma amine oxidase (EC 1.4.3.6), recently shown to be 6-hydroxydopa (also known as topa), has been spin labeled to the extent of one label per enzyme dimer molecule, using 4-amino-2,2,6,6-tetramethylpiperidine-N-oxyl (4-amino-TEMPO) and 4-hydrazino-TEMPO followed by reduction with borohydride. By studying the EPR spectra of the labeled enzyme, it has been deduced that there is no magnetic interaction between the copper and the spin label, and that the spin label is at least 1.3 nm distant from the copper(II) ion in the resting enzyme. The bound label is strongly immobilized, is in a sterically constricted environment, and is not accessible to small anions. Removal of the copper does not alter the EPR spectrum of the label. The results are similar to results for porcine plasma amine oxidase, and show that the copper is not close to, and does not directly interact with, the topa-bound substrate.

Amine Oxidase (Copper-Containing)↗
PubMed1991

[Diagnostic value of pulsed Doppler ultrasonography in atherosclerosis of the carotid arteries. A report of 200 cases].

An analysis of ultrasound imaging characteristics and carotid bloodflow parameters in 200 cases of carotid atherosclerosis was made. A high-resolution dual-function ultrasound image displaying instrument was used. It was found that the pulsed Doppler ultrasonography was useful and accurate to help diagnose the presence of extracranial carotid atherosclerotic plaques with narrowing of the carotid arteries. The ratios of the calibres of the internal carotid arteries and the common carotid arteries (IC/CC) could be taken as one of the specific indicators in determining those arteries showing calibre stenosis greater than 50%. Authors suggested that the features of carotid atherosclerosis plaques as identified in the Doppler ultrasonography could be divided into 4 types: 1. coarse type;2. soft type;3. hard type; and 4. mixed type.

Adult↗
PubMed1990

[Effect of baoshen wan on serum lipid peroxide levels in nephritis treated based on the differentiation-syndromes].

This paper deals with the treatment of 22 cases of chronic nephritis with Baoshen Wan (protecting kidney pills) according to the differentiation of syndromes; the results showed that 3 cases had got perfect remission, 6 cases fundamental remission, and 10 cases partial remission; thus its effective rate reached to 86.4%. Before treatment, the mean value of serum LPO of the 22 patients was 4.44 +/- 0.099 (means +/- S means, mumol/L), which compare with the normal value (3.69 +/- 0.075), P less than 0.05. After treatment, the serum LPO level was lowered to 3.95 +/- 0.11, P less than 0.05. It suggested that Baoshen Wan could disperse the free radical and lower the serum LPO level in the patients with chronic nephritis.

Adult↗
PubMedDate not supplied

Induction of senescence-like phenotype and loss of paclitaxel sensitivity after wild-type p53 gene transfection of p53-null human non-small cell lung cancer H358 cells.

The p53 gene plays an important role in the regulation of cell-cycle progression and apoptosis. Recent studies have implicated p53 in determining cell fate, and shown that p53 status is associated with cellular sensitivity to anticancer agents. However, the role of p53 in paclitaxel-induced cytotoxicity remains unclear. Here we show that the induction of exogenous wild-type (wt) p53 genes in p53-null human NSCLC H358 cells via transient gene transfection with cationic liposome-wt p53 complexes resulted in a typical senescence-like phenotype. In short, cell growth was reduced, homeostasis occurred, cell morphology became enlarged and flat, the cell cycle was arrested at G1 phase, cyclin B1 and cdc2 expression was down-regulated, and DNA synthesis was suppressed. The sensitivity of wt p53-transfected cells (H358/p53) to paclitaxel was approximately 3-fold lower than that of H358 cells. Paclitaxel treatment gradually and significantly blocked cell-cycle progression at G2/M phase and increased the accumulation of cyclin B1 and cdc2 in H358 cells. In contrast, the same treatment slightly arrested the cell cycle at G2/M phase and slightly elevated cyclin B1 expression in H358/p53 cells. The rate of uptake and efflux of paclitaxel was not significantly different between H358 and H358/p53 cells, indicating that the reduction in cellular sensitivity caused by p53 transfection was not due to alterasion in intracellular drug concentration. Together, our findings suggest that the induction of exogenous wt p53 gene expression in cells lacking p53 function can trigger the senescence program and that loss of sensitivity to paclitaxel by p53-transfected cells may be associated, at least in part, with the induction of a senescence-like phenotype.

Biological Transport↗