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Biomedical subjects

M Zhu

Publications and source records attributed to M Zhu.

At least 145 records · Page 8Linked to original sources
PubMed1999

Identification of possible quantitative trait loci responsible for hyperglycaemia after 70% pancreatectomy using a spontaneously diabetogenic rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat exhibits sustained hyperglycaemia after partial pancreatectomy, while the normal control rat does not. This difference is thought to be genetically determined and to be caused by impairment of beta-cell regrowth, a possible event involved in the pathogenesis of NIDDM. Our investigation was designed to identify quantitative trait loci (QTL) responsible for post-pancreatectomy hyperglycaemia by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and Fischer-344 (F344) rats. We have identified three possible QTL on rat chromosomes (Chrs) 3, 14 and 19 that account for a total of approximately 75% of the genetic variance in the F2. For the QTL on Chr 14, the OLETF allele corresponds with increased glucose levels, as expected. Surprisingly, for the QTL on Chr 19, the F344 allele corresponds with increased glucose levels. The Chr 3 QTL exhibits heterosis, heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between the QTL on Chrs 14 and 19.

Animals↗
PubMed1999

Effects of taraxacum mongolicum on the bioavailability and disposition of ciprofloxacin in rats.

Taraxacum mongolicum (TM), also known as dandelion, is a herb widely used in the East for its antibacterial activity. The high mineral content of TM presents a potential problem for the absorption of quinolone antibiotics. This study was undertaken to discern the significance of a drug-drug interaction between TM and ciprofloxacin. Two groups of Sprague Dawley rats (220-250 g) were employed; one received a single oral dose of ciprofloxacin (20 mg/kg) with concomitant oral administration of an aqueous TM extract (2 g crude drug/kg) while the control group received oral ciprofloxacin (20 mg/kg) only. Ciprofloxacin in plasma and urine, collected over 6 and 24 h, respectively, was determined by HPLC. Noncompartment analysis was employed for pharmacokinetic parameter estimation. Results indicated that, as compared to control, maximum plasma concentration (Cmax) of ciprofloxacin was significantly lowered by 73% in rats receiving concurrent TM dosing. Oral TM also caused a 3-fold increase in both apparent drug distribution volume (Vd,lambdaz/F: 92. 0 vs 30.8 L/kg) and terminal elimination half-life (t1/2,lambdaz; 5. 71 vs 1.96 h). Partly due to the changes in drug distribution and elimination, relative bioavailability of ciprofloxacin, as assessed by AUC0-->infinity, remained similar for both dosing groups. These findings suggest the possibility of a multifactorial drug-drug interaction between TM and ciprofloxacin. Thus, the implications of concomitant dosing of the two agents should not be overlooked.

Animals↗
PubMed1999

Netilmicin pharmacokinetics in Hong Kong Chinese cancer patients.

OBJECTIVES: To study the pharmacokinetics of netilmicin in Chinese haematology-oncology patients and to determine the pharmacokinetic differences, if any, between this patient subpopulation of Chinese and Caucasians. METHODS: A prospective study was carried out in the adult oncology unit of a major hospital in Hong Kong. During a 6 week period in 1997, all patients commencing on netilmicin therapy were monitored; the patients' demographics, clinical status, netilmicin dose and regimen, and drug administration/blood sampling time were collected. Pharmacokinetic parameters were generated using the USC*PACK package based on specifics of the patients themselves and Caucasians matched for the same patients' parameters using the Bayesian alogrithms. RESULTS: A total of 22 patients were enrolled into the study. Twenty-nine sets of levels were drawn, but only 25 sets from 18 patients (86%) were interpretable. The predicted peak (7.47+/-1.46 microg ml-1 ) and trough levels (1.39+/-0.96 microg ml-1 ) generated by USC*PACK were found to be significantly higher than the levels observed (6.01+/-1.14 microg ml-1 and 0.93+/-0.71 microg ml-1, respectively). Netilmicin clearance, volume of distribution and rate of elimination were all significantly higher in this Chinese subpopulation than those predicted for matched Caucasians. Conclusion Alterations in the netilmicin pharmacokinetics observed in our study population might be related to the disease state and/or ethics of the study patient population. Direct application of Caucasian based population pharmacokinetic parameters to this subgroup of Chinese patients may not be appropriate and may result in underdose.

Adolescent↗
PubMed1999

Possible presence of enhancing antibodies in idiopathic thrombocytopenic purpura.

It is difficult to detect IgG anti-platelet autoantibodies in idiopathic thrombocytopenic purpura (ITP). Recently, it was reported that reactivity with glycoprotein IIb/IIIa was lost when IgG anti-GPIIb/IIIa antibodies from seven ITP patients were digested with pepsin to yield F(ab')2 fragments. These findings suggested that some IgG antiplatelet autoantibodies in ITP may be of low affinity and thus require the presence of 'enhancing' anti-IgG antibodies (i.e. rheumatoid factors, RFs) for detection. To test this hypothesis, we used a phage display technique to isolate five IgG RFs from an ITP patient (patient 1). Sequence analysis revealed that these RFs consisted of two clones, represented by GG3 and GG48. Both representative RFs bound specifically to IgG Fc fragments with apparent dissociation constants of 8.2 x 10(-8) M and 8.8 x 10(-7) M, respectively. Moreover, IgG RFs were subsequently found in a serum sample from patient 1. Combined, these results suggest that IgG RFs may occur in ITP, and may be required for the detection of some IgG anti-platelet autoantibodies and for the corresponding antibody-mediated platelet destruction in autoimmune ITP.

Amino Acid Sequence↗
PubMed1999

Receptor binding activities of Schefflera triterpenoids and oligosaccharides.

Roots and leaves of Schefflera bodinieri were studied for their activity in the central nervous system (CNS) by bioassay-guided isolation in conjunction with receptor binding assays. As demonstrated in preliminary screening, ethanol extracts of leaves and roots of S. bodinieri showed strong binding affinity to a number of CNS receptors. Chemical investigation of this plant species was then conducted and fourteen plant ingredients were obtained. In this study, nine of these isolated compounds were tested by fifteen receptor binding assays for their CNS activities. Results showed that three compounds, namely bodinone, bodinone glycoside and D-sorbitol, were able to selectively bind to muscarine receptors, a trisaccharide bound to Ca2+ channel and 5HT-2 receptors, stigmasterol 3-O-glucoside bound to 5HT-2 receptors, and bodirin A bound to dopamine-2 receptors with IC50 values at microM level. In the drug-interaction studies, bodinone, bodinone glycoside, bodirin A, bodinitin A and the trisaccharide were found to affect binding affinity of certain specific binding agents to the 5HT1C, 5HT2, opiate, beta-adrenergic and histamine 1 receptors. These observations suggest interactions between the plant ingredients and receptors as well as synergistic effect of various compounds at receptor level.

Animals↗
PubMed1999

Influence of Sanguisorba officinalis, a mineral-rich plant drug, on the pharmacokinetics of ciprofloxacin in the rat.

The significance of an interaction between ciprofloxacin and Sanguisorba officinalis L. (SO), a mineral-rich herbal medicine, was evaluated in this study. Male Sprague-Dawley rats (220-250 g) receiving ciprofloxacin dosages of 20 mg/kg po were concomitantly dosed with an aqueous extract of SO (equivalent to 2 g/kg crude drug). Blood and urine samples were collected over 6 and 24 h, respectively, for the quantitation of ciprofloxacin by HPLC. The presence of SO reduced significantly (P < 0.05) the maximum plasma concentration, the area under the concentration-time curve and the urinary recovery of ciprofloxacin, by 94%, 78% and 79%, respectively, compared with rats receiving only ciprofloxacin. The presence of SO also caused an eight-fold and two-fold increase in drug distribution (Vd, lambda(z)/F) and terminal elimination half-life (t1/2, lambda(z)) from 30.8 L/kg and 1.96 h, respectively. Therefore, should the use of both agents be required, sufficient time should be allowed to ensure the efficacy of ciprofloxacin.

Animals↗
PubMed1999

Angiotensin II decreases neuronal delayed rectifier potassium current: role of calcium/calmodulin-dependent protein kinase II.

Angiotensin II (Ang II) acts at specific receptors located on neurons in the hypothalamus and brain stem to elicit alterations in blood pressure, fluid intake, and hormone secretion. These actions of Ang II are mediated via Ang II type 1 (AT1) receptors and involve modulation of membrane ionic currents and neuronal activity. In previous studies we utilized neurons cultured from the hypothalamus and brain stem of newborn rats to investigate the AT1 receptor-mediated effects of Ang II on neuronal K+ currents. Our data indicate that Ang II decreases neuronal delayed rectifier (Kv) current, and that this effect is partially due to activation of protein kinase C (PKC), specifically PKCalpha. However, the data also indicated that another Ca2+-dependent mechanism was also involved in addition to PKC. Because Ca2+/calmodulin-dependent protein kinase II (CaM KII) is a known modulator of K+ currents in neurons, we investigated the role of this enzyme in the AT1 receptor-mediated reduction of neuronal Kv current by Ang II. The reduction of neuronal Kv current by Ang II was attenuated by selective inhibition of either calmodulin or CaM KII and was mimicked by intracellular application of activated (autothiophosphorylated) CaM KIIalpha. Concurrent inhibition of CaM KII and PKC completely abolished the reduction of neuronal Kv by Ang II. Consistent with these findings is the demonstration that Ang II increases CaM KII activity in neuronal cultures, as evidenced by increased levels of autophosphorylated CaM KIIalpha subunit. Last, single-cell reverse transcriptase (RT)-PCR analysis revealed the presence of AT1 receptor-, CaM KIIalpha-, and PKCalpha subunit mRNAs in neurons that responded to Ang II with a decrease in Kv current. The present data indicate that the AT1 receptor-mediated reduction of neuronal Kv current by Ang II involves a Ca2+/calmodulin/CaM KII pathway, in addition to the previously documented involvement of PKC.

Angiotensin II↗
PubMed1999

Green tea and its major components ameliorate immune dysfunction in mice bearing Lewis lung carcinoma and treated with the carcinogen NNK.

The protective effects of tea and/or its components on dysfunction of immune functions during tumor growth and carcinogenesis in mice were studied using two experimental models: C57/BL6J mice transplanted with Lewis lung carcinoma (LLC) and Kunming mice treated with a single dose of 4-(methylnitrosamino-)-1-(3-pyridyl)-1-butanone (NNK). In C57/BL6J mice bearing LLC, the weight of the thymus decreased, the proportion of CD4(+)-positive T lymphocytes and the ratio of CD4+ to CD8+ decreased, luminol-enhanced chemiluminescence of white blood cells in peripheral blood stimulated by zymosan increased, and plaque-forming cells (PFC) decreased. However, in LLC-bearing mice given green tea as drinking water, all immune functions were improved, along with inhibition of tumor growth. In Kunming mice treated with NNK, during the four weeks of observation, their immunologic indicators, such as phagocytosis of macrophages in the abdominal cavity, luminol-enhanced chemiluminescence of white blood cells, plaque-forming cells, and delayed-type hypersensitivity, increased or decreased to various extents compared with normal controls. However, these changes were significantly prevented in the mice given green tea, mixed tea, or tea polyphenol as drinking water. In conclusion, tea and its components ameliorated immune dysfunction in mice bearing LLC or treated with the carcinogen NNK.

Animals↗
PubMed1999

Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats.

We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.

Animals↗
PubMed1999

Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat.

The aim of this study was to investigate the possibility of a drug-drug interaction between ciprofloxacin and fennel (Foeniculum vulgare) in a rat model. Pharmacokinetic assessment of ciprofloxacin was performed in two groups of male Sprague-Dawley rats. One group (n = 5) received 20 mg kg(-1) antibiotic orally with concomitant oral dosing of the aqueous fennel extract (2 g herb kg(-1)) whereas the controls (n = 5) received 20 mg kg(-1) oral ciprofloxacin. Blood and urine samples were collected over 6 and 24 h, respectively, for quantitation of ciprofloxacin by HPLC. A non-compartmental model was employed for pharmacokinetic analysis. Major ingredients and metal cations in the fennel extract were determined. Compared with the control, maximum plasma concentration, area under the curve and urinary recovery of ciprofloxacin were significantly (P < 0.05) lower, by 83, 48 and 43%, respectively, in rats receiving concomitant dosing of the two agents. The relative bioavailability of ciprofloxacin, under the influence of fennel, was estimated to be 0.52. In addition, its apparent volume of distribution and terminal elimination half-life were significantly (P < 0.05) increased, from 30.8 +/- 11.1 (L kg(-1)) and 2.0 +/- 0.4 (h) to 143.8 +/- 31.6 (L kg(-1)) and 5.2 +/- 2.0 (h), respectively. Although none of the organic components of fennel seemed to cause this interaction, the total amount of ten metal cations measured was found to be 13 mg g(-1). Significant interaction between ciprofloxacin and fennel was observed in this study. Absorption, distribution and elimination of ciprofloxacin were all affected. These changes might be because of the formation of a more lipophilic ciprofloxacin chelate in the presence of relatively large amounts of metal cations. If, therefore, the two therapeutic agents are used concurrently, an adequate dosing interval is needed to ensure the efficacy of ciprofloxacin.

Administration, Oral↗
PubMed1999

Achieving an optimal outcome in the treatment of infections. The role of clinical pharmacokinetics and pharmacodynamics of antimicrobials.

Over the past few decades, the importance of applying pharmacokinetic principles to the design of drug regimens has been increasingly recognised by clinicians. From the perspective of antimicrobial chemotherapy, an improvement in clinical outcome and/or a reduction in toxicity are of primary interest. Before application of these pharmacokinetic theories can be effective, the interrelationships between antimicrobial, pathogen and host factors must be clearly defined. Information regarding the pharmacokinetics of the antimicrobial and the quantification of pathogen susceptibility is required. Even though susceptibility end-points such as minimum inhibitory concentration (MIC) and minimum bactericidal concentration are widely employed, they do not provide any information on dynamic changes of bacterial densities. In this regard, time-kill studies can provide more basic knowledge of the complex bacterial responses to the antimicrobial. Better prediction of these responses can be afforded by the use of mathematical models. More recently, various surrogate end-points employing a combination of suitable pharmacokinetic parameters and susceptibility data, for example the ratio of peak concentration to MIC, the area under the concentration-time curve above the MIC (AUC > MIC), the time above the MIC, or the area under the inhibitory curve (AUIC), have been suggested for better prediction of the activity of different classes of antimicrobials. To allow more extensive investigations of the contribution of pharmacokinetics to the pharmacodynamics of antimicrobials, various in vitro kinetic models have been developed. However, certain limitations exist, and it is necessary to avoid over-interpretation of the data generated by these models. Two important microbial dynamic responses, postantibiotic effect and resistance selection, must be further explored before the full impact of pharmacokinetics on antimicrobial chemotherapy can be depicted. The present paper aims at discussing all the relevant factors and provides some pertinent information on the use of pharmacokinetic-pharmacodynamic principles in antimicrobial therapy.

Animals↗
PubMed1999

Characterization of IgG monoclonal anti-cardiolipin/anti-beta2GP1 antibodies from two patients with antiphospholipid syndrome reveals three species of antibodies.

Antiphospholipid antibodies (aPL), including antibodies detected in anti-cardiolipin (aCL) enzyme-linked immunosorbent assays and in lupus anticoagulant (LA) tests, are strongly associated with recurrent thrombosis and recurrent fetal loss, i.e. the antiphospholipid syndrome (APS). Although recent studies suggest that most APS-associated aCL are directed against the phospholipid (PL)-binding plasma protein beta2-glycoprotein 1 (beta2GP1), the precise nature of aCL binding specificities remains controversial. To address the issue of aCL specificity we generated five new monoclonal IgG aCL from two patients with APS. Characterization of these five aCL, as well as two previously published IgG aCL, revealed three patterns of reactivity: (1) four antibodies reacted strongly with human beta2GP1-cardiolipin (CL) complexes and weakly with human beta2GP1 alone; (2) two antibodies recognized bovine beta2GP1, but not human beta2GP1; (3) one antibody reacted with complexes of human beta2GP1 and CL, but not with human beta2GP1 alone. Only one monoclonal displayed weak LA activity. These patient-derived IgG monoclonal antibodies, and additional ones to be generated, may help define varying species of antibodies detected in aCL assays and identify the specific antibodies that may be pathogenic.

Adolescent↗
PubMed1999

Pathoetiology and prevention of NIDDM lessons from the OLETF rat.

The OLETF rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the beta-cell proliferation per se is the primary pathogenetic event in this model rat. To clarify this matter, we used partially pancreatectomized rats as a model. Male rats of 6 weeks of age were allocated at random to two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into 4 subgroups by the date of sacrifice after surgery. Sustained hyperglycemia was evident in the Px OLETF rats after surgery. This was associated with insufficient proliferation of beta-cells, characterized by a decrease in beta-cell labeling with 5-bromo-2' deoxyuridine in proportion to a decrease in beta-cell mass and reduction in insulin content in the remnant pancreas. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing beta-cell proliferation. These findings suggest that OLETF rats have a poor capacity for proliferation of pancreatic beta-cells, and that this change may be the critical pathogenetic event prior to the onset of overt diabetes. OLETF rats following long-term caloric restriction and spontaneous exercise training show normal glucose tolerance accompanied by an increase in GIR as shown by a euglycemic clamp. Both exercise training and caloric restriction normalize the abnormalities in the pancreas such as marked hypertrophy of islets and hyperplasia of connective tissues in islets. It is particularly noteworthy that exercise training significantly elevated the beta-cell mass/body weight ratio. This evidence obtained from OLETF rats may be of value when the mechanism of diet and exercise effects on diabetic patients are considered.

Animals↗
PubMed1999

[Study of nylestriol effect on bone histomorphometric parameters in ovariectomized rats].

OBJECTIVE: To investigate the response of trabecular bone of ovariectomized (OVX) rats to nylestriol. METHODS: Thirty-three female Wistar rats were randomly divided into three groups, 11 rats in each: nylestriol-treated group (E), OVX and the control (C). The OVX rats were used as a model for osteoporosis. After being fed with nylestriol for 3 months, all rats were sacrificed. The effect of nylestriol on bone microarchitecture and dynamics were studied by bone histomorphometry. RESULTS: The data suggest that trabecular bone volume, mean trabecular width, density and cortical thickness were remarkably reduced in OVX group (P < 0.05) while tetracycline labeled surface, osteoid surface and bone turnover rate were increased in comparison with that in C group (P < 0.05). The bone turnover rate and trabecular bone volume were improved with the treatment of nylestriol for 3 months in the OVX rats(P < 0.05). CONCLUSIONS: Trabecular bone volume and bone turnover rate can be improved by 3 month administrations of nylestriol in osteoporotic rat models.

Animals↗
PubMed1999

[Evaluation of safety in Chinese women with amenorrhea following injection of depot-medroxyprogesterone for contraception].

OBJECTIVE: To determine whether serum estradiol (E2) level was low after Depot-medroxyprogesterone (DMPA) induced amenorrhea for contraception, thus to evaluate the safety of using DMPA. METHODS: Forty four Chinese women with amenorrhea after injecting DMPA were investigated, and the median period of amenorrhea was 18 months. Symptoms, pelvic examination, serum E2 and follicular stimulating hormone (FSH) levels, and vaginal cytology were examined. RESULTS: Women with amenorrhea had neither symptoms nor genital atrophy that similar to menopausal syndrome. The median level of serum E2 was 150.5 pmol/L (equal to the level of early follicular phase), and the median level of serum FSH was 14.0 IU/L. There were no correlation between E2 and FSH levels, and no correlation between amenorrhea period and E2 or FSH levels (P > 0.05) as well. No significant relationship between estrogen effects by vaginal cytology and the time period of amenorrhea was found. However, the estrogen effect was significantly correlated to the interval from last injection to vaginal smear tested. CONCLUSION: It could be concluded that though DMPA may induce amenorrhea, it will not lower serum E2 levels, and the inhibition of ovarian function is reversible.

Adult↗
PubMed1999

[Effects of synthetic peptides on ovarian cancer cells].

OBJECTIVE: To observe the effect of follicle-stimulating hormone(FSH) synthetic peptides(FSH binding Fragment), FSH and synthetic peptides on the proliferation of human epithelial ovarian cancer cell. METHODS: Human epithelial ovarian cancer cells lines SKOV3, OVCAR, AO and 3AO were incubated with FSH, FSH binding fragment, FSH and the binding fragment respectively. The cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) technique. RESULTS: The rate of proliferation in the cancer cell was increased apparently as increasing in the concentration of FSH and the rate of proliferation average value 28.0%, and was decreased apparently as increasing in the concentration of the synthetic peptides and the rate of inhibition average value 8.3%. When the cell was expressed in FSH, the proliferation was decreased apparently as increasing in the concentration of the peptides and the rate of inhibition average valve 3.1%. CONCLUSIONS: It is suggested that FSH binding fragment can inhibit the proliferation of ovarian cancer cell. The FSH binding fragment could be used as a binding part of anticancerous complex for ovarian cancer.

Dose-Response Relationship, Drug↗
PubMed1999

[A study on the cariogenic bacteria of plaque on abutment teeth of casting and wrought wire clasp removable partial dentures].

OBJECTIVE: The effect of clasp on the health of abutment teeth. METHODS: To analyse and compare the cariogenic bacteria plaque getting from the buccal cervical third of casting and wrought wire clasp teeth before and one week after wearing removable partial dentures. RESULTS: The average percentages of Streptococcus Mutans and Actinomyces Viscosus in total culturable bacteria rised significently in statistical analysis, but there was no significent difference of Lactobacilli. The average percentage of Actinomyces Viscosus increased less after wearing casting clasp RPD than that of wrought wire clasp. CONCLUSION: Clasps of RPD increased the risk of root caries of abutment teeth. However the influence of casting clasps was smaller than that of wrought wire clasps.

Bacteria↗