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H Zhou

Publications and source records attributed to H Zhou.

At least 181 records · Page 10Linked to original sources
PubMed2001

Tegaserod coadministration does not alter the pharmacokinetics of theophylline in healthy subjects.

Tegaserod (HTF 919), a selective 5-HT4 receptor partial agonist, is in development for the treatment of functional gastrointestinal motility disorders. Tegaserod has been found to inhibit cytochrome P-450 (CYP) 1A2, for which theophylline is a prototype substrate. This study was designed to assess the effect of tegaserod on the single-dose pharmacokinetic and safety profile of theophylline. Eighteen subjects were enrolled in a randomized, open-label, two-period crossover study. After an overnight fast, subjects were randomized to receive one of two treatments: (1) a single dose of controlled-release formulation of theophylline (Theo-Dur, 600 mg) on day 1 or (2) a single dose of tegaserod (6 mg) on day 1, concomitant administration of tegaserod (6 mg) and theophylline (600 mg) on the morning of day 2, followed by an additional dose of tegaserod (6 mg) 12 hours later. Four to 10 days later, the subjects received the alternative treatment regimen. The pharmacokinetic parameters of theophylline, including AUC, Cmax, and t(1/2lambda z), were similar for both treatment regimens, although the tmax of theophylline was statistically different between the treatments. Except for a decrease in partial metabolic formation clearance from theophylline to 1-methyluric acid, which is unlikely to be clinically relevant, there were no statistically significant differences in renal clearance of theophylline and partial metabolic formation clearances following the combined treatment compared with theophylline alone. The results of the current study indicate that no dose adjustment is required when drugs metabolized via CYP1A2 are coadministered with tegaserod.

Adolescent↗
PubMed2001

The effects of tegaserod (HTF 919) on the pharmacokinetics and pharmacodynamics of digoxin in healthy subjects.

Tegaserod (HTF 919) is a highly specific 5-HT4 receptor partial agonist that exhibits promotile activity throughout the gastrointestinal tract and is under development for the treatment of functional gastrointestinal motility disorders. The present study was designed to assess the effect of multiple doses of tegaserod on the single-dose pharmacokinetics and pharmacodynamics of digoxin, a commonly prescribed agent for congestive heart failure. The study was an open-label, randomized, two-period crossover design of 12 healthy subjects. One treatment included digoxin treatment alone; the other treatment included a combined digoxin and tegaserod treatment. On day 1 of the digoxin treatment period, subjects received a single 1 mg oral dose of digoxin. In the combined tegaserod/digoxin treatment period, subjects received a single oral dose of 1 mg digoxin after 3 days of tegaserod (6 mg bid). After coadministration of tegaserod, systemic exposure to digoxin was decreased; mean AUC decreased by 11.9% (p < 0.05) relative to digoxin alone. Cmax was decreased by about 15% (p < 0.05). The 0.5-hour difference in the median tmax between the two treatments was not statistically significant. Because the steady-state trough concentration of digoxin (C(SS,min)) correlates with pharmacological effects, C(SS,min) for digoxin alone and in combination with tegaserod was simulated based on both parametric compartmental modeling and nonparametric superpositioning approaches. The predicted arithmetic mean C(SS,min) for combination therapy is 86% to 89% of that following digoxin alone. Likewise, the predicted arithmetic mean steady-state peak concentration (C(SS,min)) and AUC at steady state during a dosing interval (AUC(SS,tau)) have a similar decrease. This extent of decrease in systemic exposure of digoxin at steady state is unlikely to be clinically relevant. Administration of tegaserod (6 mg bid) was well tolerated, both alone and in combination with a single dose of digoxin. There were no pharmacodynamic changes in ventricular rate and QT interval following coadministration of tegaserod with digoxin. The 1.5-hour and 2-hour postdose plasma concentrations of tegaserod on days 3 and 4 confirmed adequate exposure. In conclusion, dose adjustment for digoxin is unlikely to be needed when tegaserod is coadministered.

Adolescent↗
PubMed2001

Pharmacokinetics of intravenous itraconazole followed by itraconazole oral solution in patients with human immunodeficiency virus infection.

This randomized, open-label, comparative study assessed the pharmacokinetics and safety of intravenous and oral hydroxypropyl-beta-cyclodextrin (HP-beta-CD) solutions of itraconazole in patients with advanced human immunodeficiency virus (HIV) infection. All patients received 1-hour intravenous infusions of itraconazole 200 mg twice dailyfor 2 days, then once dailyfor 5 days. Patients were then randomized to receive itraconazole oral solution, 200 mg twice daily or 200 mg once daily, for a further 28 days. Itraconazole was solubilized by HP-beta-CD in both intravenous and oral solutions, so HP-beta-CD concentration in plasma was measured. Thirty-two patients were enrolled and analyzed (n = 32 for intravenous treatment, 32 completed; n = 16 for oral once daily, 15 completed; n = 16 for oral twice daily, 12 completed). Steady-state plasma concentrations of itraconazole and hydroxyitraconazole were reached by days 3 and 6, respectively. After intravenous dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were 906 ng/ml and 1,690 ng/ml, respectively. During oral dosing, mean trough plasma concentrations of itraconazole and hydroxyitraconazole were maintained or increased in the 200 mg twice-dailygroup but fell with the 200 mg once-daily oral dose. Itraconazole was generally well tolerated and had a favorable safetyprofile; minor changes in hematology variables were noted during the intravenous phase, and HP-beta-CD was cleared rapidly, mostly in urine. Twenty-eight patients (88%) experienced at least one adverse event; no adverse event was severe, and only seven were definitely related to itraconazole. In conclusion, itraconazole 200 mg given intravenously twice daily for 2 days, then once daily for 5 days, rapidly achieves amean steady-state trough concentration of itraconazole of over 250 ng/ml, which is associated with clinic outcome and is effectively maintained with itraconazole oral solution 200 mg twice daily in patients with advanced HIV infection.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Identification of differentially expressed genes in human papillomavirus type-16 infected oral cancer cells.

OBJECTIVE: The goal of this study was to determine the genes required for head and neck cancer development. STUDY DESIGN AND SETTING: Differential mRNA display analysis was performed using human papillomavirus Type-16 infected immortalized human oral keratinocytes (HOK-16B) and its benzo(a)pyrene-exposed tumorigenic derivative (HOK-16B-BaP-T). RESULTS: Twenty-one differentially expressed cDNA clones were identified between the 2 cell lines. Clone 4 with no known homology showed lower expression in tumorigenic cells compared with either normal or immortalized oral keratinocytes. Clone 6 expression was elevated in several head and neck cancer cells, in addition to Burkitt's lymphoma Raji harboring latent Epstein-Barr virus. CONCLUSION: These findings suggested that clone 6 may be involved in the oncogenic transformation whereas clone 4 may potentially function as a tumor suppressor gene. SIGNIFICANCE: Differential mRNA analysis using the in vitro oral carcinogenesis model may help to identify important genetic markers for the early detection and progression of head and neck cancer.

Blotting, Northern↗
PubMed2001

Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study.

We examined paired iliac crest bone biopsy specimens from patients with osteoporosis before and after treatment with daily injections of 400 U of recombinant, human parathyroid hormone 1-34 [PTH(1-34)]. Two groups of patients were studied. The first group was comprised of 8 men with an average age 49 years. They were treated with PTH for 18 months. The second group was comprised of 8 postmenopausal women with an average age 54 years. They were treated with PTH for 36 months. The women had been and were maintained on hormone replacement therapy for the duration of PTH treatment. Patients were supplemented to obtain an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D. The biopsy specimens were subjected to routine histomorphometric analysis and microcomputed tomography (CT). Cancellous bone area was maintained in both groups. Cortical width was maintained in men and significantly increased in women. There was no increase in cortical porosity. There was a significant increase in the width of bone packets on the inner aspect of the cortex in both men and women. This was accompanied by a significant decrease in eroded perimeter on this surface in both groups. Micro-CT confirmed the foregoing changes and, in addition, revealed an increase in connectivity density, a three dimensional (3D) measure of trabecular connectivity in the majority of patients. These findings indicate that daily PTH treatment exerts anabolic action on cortical bone in patients with osteoporosis and also can improve cancellous bone microarchitecture. The results provide a structural basis for the recent demonstration that PTH treatment reduces the incidence of osteoporosis-related fractures.

Bone Density↗
PubMed2001

Continuous parathyroid hormone and estrogen administration increases vertebral cancellous bone volume and cortical width in the estrogen-deficient rat.

Generally, it is believed that intermittent administration of parathyroid hormone (PTH) has an anabolic effect on the skeleton, whereas continuous administration is catabolic. However, there is evidence that continuous exposure to PTH may have an anabolic effect, for example, in patients with mild primary hyperparathyroidism (PHPT). The possibility of delivering PTH continuously may have important implications for the treatment of osteoporosis. Furthermore, estrogen treatment may be useful in the medical management of PHPT. Therefore, we examined the skeletal effects of continuous administration of PTH, with or without estrogen, in the estrogen-deficient rat with established osteopenia. Forty 7-month-old SD rats were divided into four ovariectomy (OVX) groups and one sham-operated group. Eight weeks post-OVX, three groups received subcutaneous implants of Alzet mini pumps loaded with PTH(1-34) (30 microg/kg per day), 17beta-estradiol (10 microg/kg per day) pellet, or both PTH and 17beta-estradiol separately for 4 weeks. OVX and sham control groups were given the mini pumps loaded with vehicle. Two doses of calcein (10 mg/kg) were given subcutaneously to all rats 2 days and 8 days before death. Histomorphometry was performed on cancellous and cortical bone of the fourth lumbar vertebra. At 3 months, post-OVX rats displayed bone loss with high bone turnover. Estrogen reversed OVX-mediated high turnover without restoring cancellous bone volume (BV/TV). PTH infusion further increased bone turnover and partially restored BV/TV. However, PTH infusion increased cortical porosity. Estrogen inhibited PTH-mediated cancellous bone resorption and substantially increased BV/TV above sham control. The combined treatment was associated with a significant increase in peritrabecular fibrosis and woven bone formation. The combined treatment of PTH infusion and estrogen replacement enhanced cortical width but estrogen did not prevent the PTH-induced cortical tunneling. We conclude that continuous administration of PTH and estrogen increases cortical porosity but has substantial beneficial effects on vertebral cancellous bone volume and cortical width in OVX rats.

Animals↗
PubMed2001

Polychlorinated biphenyl serum levels in pregnant subjects with diabetes.

OBJECTIVE: Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly everyone. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound, have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded. RESEARCH DESIGN AND METHODS: Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects. RESULTS: The adjusted mean serum level of PCBs among the subjects with diabetes was 30% higher than in the control subjects (P = 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear. CONCLUSIONS: The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment.

Adult↗
PubMed2001

Atypical mouse cerebellar development is caused by ectopic expression of the forkhead box transcription factor HNF-3beta.

To assess the role of hepatocyte nuclear factor-3beta (HNF-3beta) in hepatocyte-specific gene transcription, we reported the characterization of the liver phenotype with transgenic mice in which the -3-kb transthyretin (TTR) promoter functioned to increase HNF-3beta expression. During breeding of the TTR-HNF-3beta transgenic mice we noticed that they displayed severe ataxia. In this study, we describe the analysis of our transgenic cerebellar phenotype and demonstrate that ectopic expression of HNF-3beta disrupted cerebellar morphogenesis and caused reduction in cerebellar size. In postnatal cerebellum, the HNF-3beta transgene expression pattern is colocalized to glial fibrillary acidic protein-positive cerebellar astrocytes and Bergmann glial cells. As a result of protracted expression, the transgenic cerebella are impaired in terms of astrocyte dispersal and formation of Bergmann glial cell processes. This caused a disruption in neuronal cell migration to the cortical laminar layers and Purkinje dendritic arbor maturation, thus leading to diminished foliation. Differential hybridization of cDNA arrays was used to identify altered expression of cerebellar genes, which is consistent with the observed defect in transgenic cerebellar morphogenesis and size as well as glial maturation. These include diminished expression of the brain lipid-binding protein, which is required for glial morphological differentiation, and the basic helix-loop-helix NeuroD/Beta2 and homeodomain Engrailed-2 transcription factors, which are required for normal cerebellar morphogenesis and foliation. Undetectable levels of ataxia telangiectasia (ATM), which is required for proper development of the Purkinje dendritic arbor, were found in postnatal transgenic cerebella. Furthermore, the transgenic cerebella displayed levels of insulin-like growth factor binding protein-1 elevated to 22 times greater than those measured for wild-type cerebella, an elevation consistent with the reduction in transgenic cerebellar size.

Animals↗
PubMed2001

[The method of instantaneous pulse detection based on hybrid wavelet transform].

In this paper, we discuss the relation between matched filter and wavelet transform(WT), and point out that wavelet transform is just the matched filter with changeable detection template. According to this idea, the method of signal detection based on hybrid wavelet transform (HWT) is proposed. HWT in this paper means that in WT decomposition and reconstruction, we use two different mother wavelets. One is used as a changeable template for the pulses detection and the other is used for the characteristic enhancement of detected pulse. This method has been applied to the interference pulse detection in EEG signal. The experiment result shows that HWT has the good property for instantaneous signal detection.

Algorithms↗
PubMed2001

[Primary discussion on the imported materia medica].

The features, with respect to medical use, dosage form, manufacture technology and quality, of licensed imported materia medica and botanical preparation in market were discussed in this paper. The international market competition of Chinese Materia Medica was analyzed, and the countermeasure to resist the imported materia medica was also included.

Drugs, Chinese Herbal↗
PubMed2001

The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model.

The role of urokinase plasminogen activator (uPA) in osteosarcoma is poorly understood. We examined the importance of uPA, its receptor, uPAR, and its inhibitor, PAI-1, in our in vivo model of metastatic osteosarcoma. Rodent osteosarcoma cells (UMR 106-01) were inoculated into the tibia of athymic mice. Animals were sacrificed and autopsied at 4 days to 5 weeks after inoculation. Tibiae and lungs were excised, fixed, and examined histologically and by in situ hybridization. Osteosarcoma development was associated with tibial swelling and lameness, and radiographic changes included osteolysis and new bone formation. Lung metastases developed spontaneously. In the tibial tumors, uPAR mRNA was expressed early (4 days), whereas uPA and PAI-1 mRNA increased as the tumor invaded the surrounding tissue (3 weeks). There was also an increase in the mRNA expression of the osteoblast-related genes, alpha1(I) procollagen and osteopontin, but not matrix Gla protein. Lung metastases also expressed mRNA for the uPA system and the bone-related proteins. We have produced a model of metastatic osteosarcoma, which typifies the characteristics of the human tumor. Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and, in particular, indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma.

Animals↗
PubMed2001

[Progress in studies on the mechanism of substance addiction in central nervous system].

The mechanism of substance addiction in the central nervous system is the key point to solve the problem of drug addiction in clinical prophylaxis and treatment, but it has been obscure so far. Previous researches in this field suggested that the higher brain function of the learning and memory might be pivotal in understanding the mechanism of substance addiction. It is the intent of this review to integrate and analyze the substance addiction and the learning and memory in an attempt to shed light on the strategies to conduct further studies in this field.

Central Nervous System↗
PubMed2001

Correlation between the expression of cyclin A protein and p53 activity in oral squamous cell carcinomas.

Cyclins and wild-type p53 protein are prime cell cycle regulators and may be involved in tumorigenesis. Cyclin A is a late S cyclin and its abnormalities have been reported in several cancers, including oral squamous cell carcinomas. To explore whether aberrant G1/S in p53 mutant tumours leads to increased cyclin A protein in oral squamous cell carcinomas (OSCC), a total of 39 samples were evaluated for the expression of cyclin A and p53 protein by an immunohistochemical method using a labelled polymer assay. These samples comprised two hyperkeratotic and three oral premalignant lesions (two moderate and one severe dysplastic lesions), and 27 OSCC, together with seven healthy controls. The results demonstrated that the cyclin A protein was localized and highly expressed in the nuclei of the tumour cells. Although there was no correlation between cyclin A detection and the local lymph node involvement, a positive correlation was noted between the positivity of cyclin A and p53 protein (p <0.05). The results suggested that cyclin A may contribute to the progression of oral cancer and correlated to some degree with that of the p53 gene activity.

Carcinoma, Squamous Cell↗
PubMed2001

Phosphorylation and desensitization of the human thromboxane receptor-alpha by G protein-coupled receptor kinases.

The thromboxane A(2) receptor (TP), which mediates vasoconstriction, mitogenesis, and platelet aggregation, has been shown to undergo rapid agonist-induced desensitization. Two isoforms (alpha and beta) of TP have been recognized. The potential role of the G protein-coupled receptor kinases (GRKs) in the phosphorylation and desensitization of TP alpha was investigated. Human embryonic kidney (HEK) 293 cells stably transfected with the His-tagged TP alpha was used to study the phosphorylation and desensitization of the receptor. Rapid isolation of the (32)P-labeled receptor was achieved by Ni(2+)-nitrilotriacetic acid agarose after agonist stimulation of HEK293 cells prelabeled with (32)P(i). [1S-[1 alpha,2 alpha(Z),3 beta(1E,3S*),4 alpha]]-7-[3-[3-Hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid (I-BOP) induced receptor phosphorylation and Ca(2+) release in a time- and dose-dependent manner. Pretreatment of cells with I-BOP abolished subsequent induction of Ca(2+) release through a second dose of I-BOP. Transfection with expression plasmids encoding the cDNA of GRK5 or GRK6 augmented I-BOP-induced phosphorylation and inhibited I-BOP-stimulated Ca(2+) release. Both I-BOP-induced and GRK-mediated phosphorylation and phorbol ester-induced phosphorylation were blocked by the addition of 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide) (GF 109203X). This indicates that GF 109203X, a known protein kinase C (PKC) inhibitor, also inhibits GRKs. This finding was further supported by in vitro studies in which preparations of GRK5 and GRK6 were found to be inhibited by GF 109203X. These results suggest that GRK5 and GRK6 may phosphorylate the TP alpha in an agonist-dependent manner. Furthermore, the results obtained with PKC inhibitors in assessing the role of PKC in agonist-induced receptor phosphorylation should be interpreted with caution.

Amino Acid Sequence↗
PubMed2001

[Clinical and pathological study of autoimmune hepatopathy].

OBJECTIVE: To study the clinical and histologic characteristics of autoimmune hepatopathy, and to explore the diagnostic criteria and therapy. METHODS: Sixty-two patients with autoimmune hepatopathy were studied between 1996 and 1998 to compare primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) in the clinical symptoms, signs, laboratory findings and histologic features. RESULTS: PBC was 59.68% and AIH 40.32% in the autoimmune hepatopathy. The morbidity in middle and old aged female patients with autoimmune hepatopathy was 83.8%. The ratio of male and female was 1:10. Whereas, the ratio of male and female was 1:5 in AIH patients and average age was 35 years old. Seropositive autoimmune antibodies were detected in 53 serum sample (PBC 85.29%; AIH 78.95%). Positive rates of the mitochondrial antibody and subtype-M2 were 100% for PBC. IgM increasing was 80% in PBC (P<0.05) and 82.35% in AIH (P<0.025). Histologic features in PBC group consisted of cholangitis, destruction or proliferation of the bile duct and inflammation within the portal tract; while in AIH group inflammation, necrosis and fibrosis of periportal region, the aggregation of lymphocytes, mononuclear cells and plasma cells in the portal tract or periportal area were found. CONCLUSIONS: PBC and AIH are the most common two types in the patients with autoimmune hepatopathy. AIH-I is more often seen clinically. AMA-M2 is the special autoimmune antibody of PBC. The efficacy of prednisolone is better for AIH than PBC.

Adult↗
PubMed2001

[A study for optimal method of separating and cultivating embryonic rat cerebral neurons].

In order to improve the method of separating and cultivating the embryonic rat cerebral neurons in vitro, we compared different digestive enzymes, mechanical separating methods and two different mediums. It was found that highly purified and active embryonic rat cerebral neurons could be harvested by cultivating the neurons in the standard neurobasal medium with B-27 supplement, 10% horse serum, 10% fetal bovine serum and L-Glutamine after separated by digestion with the use of 0.05% trypsin and 0.05% collagenase II.

Animals↗