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Y L He

Publications and source records attributed to Y L He.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.

OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients. METHODS: This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.

Administration, Oral↗
PubMed2005

Gas slippage effect on microscale porous flow using the lattice Boltzmann method.

A lattice Boltzmann method is developed for gaseous slip flow at the pore scale in microscale porous geometries. Flow characteristics through various porous structures are studied for different Knudsen numbers and inlet to outlet pressure ratios. It is found that the gas permeability is larger than the absolute permeability of porous media due to the gas slippage effect. Furthermore, the rarefaction influence on the gas permeability is more evident for porous structures with low porosity. The Klinkenberg equation is confirmed for the simulated porous structures. However, the second-order term of the Knudsen number (Kn2) cannot be neglected for gaseous flow with relatively high Knudsen numbers. A model for predicting the pressure drop of the flow through microscale porous media is presented based on the Ergun equation and the Carman-Kozeny equation by taking into account the effects of gas rarefaction and compressibility.

Journal Article↗
PubMed2005

Thermal boundary condition for the thermal lattice Boltzmann equation.

A thermal boundary condition for a double-population thermal lattice Boltzmann equation (TLBE) is introduced and numerically demonstrated. The unknown distribution population at the boundary node is decomposed into its equilibrium part and nonequilibrium parts, and then the nonequilibrium part is approximated with a first-order extrapolation of the nonequilibrium part of the populations at the neighboring fluid nodes. Numerical tests with Dirichlet and Neumann boundary constraints show that the numerical results of the TLBE together with the present boundary schemes agree well with the analytical solutions and those of the finite-volume method.

Journal Article↗
PubMed2005

Vildagliptin, a dipeptidyl peptidase-IV inhibitor, improves model-assessed beta-cell function in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function. METHODS: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors. RESULTS: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo. CONCLUSION: Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.

Adamantane↗
PubMed2002

Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched parent.

A six-year-old boy was diagnosed with beta-thalassaemia major during infancy. Since then, he required monthly blood transfusion and irregular iron chelation therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His one-antigen-mismatched mother was chosen as a bone marrow donor. He was pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks prior to conditioning. The conditioning included total body irradiation (300 cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone. Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day 45. The patient developed complications including septicaemia, haemorrhagic cystitis, intracranial haemorrhage and heart failure. He subsequently recovered from the complications without sequelae. The patient remained transfusion-independent at a follow-up examination after 18 months. This case suggested that a mismatched family member may be considered as a bone marrow donor for beta-thalassaemia major. In places where conventional treatment is not feasible, for example, in China, this approach may be an alternative option. A more intensive immunosuppressive regimen and a higher marrow cell dose may be important for successful engraftment. High-dose anti-thymocyte globulin may also prevent severe GVHD.

Bone Marrow Purging↗
PubMed2001

Quantitative estimation of renal clearance of N-acetylprocainamide in rats with various experimental acute renal failure.

The dosage regimen of a drug eliminated predominantly through the kidney need to be adjusted for the patients with renal disease. The objective of the present study was to establish a quantitative approach to precisely predicting the renal clearances of basic drugs using N-1-methylnicotinamide (NMN). A variety of experimental acute renal failure (ARF) in rats were prepared and N-acetylprocainamide (NAPA) was used as a model drug. The renal clearances of NAPA were significantly decreased in rats with ARF, resulting in significantly increased plasma concentrations. Remarkable reduction in clearance ratios (CL(ratio)) was observed, indicating that the impairment in tubular and glomerular function did not proceed in a parallel manner. The renal clearance of NAPA (CL(rNAPA)) was better predicted from the renal clearance of NMN (CL(rNMN)) than from GFR. A mathematical equation was also constructed to estimate the CL(rNMN) from the NMN plasma concentration. Therefore, the renal clearance of basic drugs excreted predominantly from the kidney can be easily and more accurately estimated based on the concentrations of endogenous NMN to provide a precise dosage regimen for patients with renal failure.

Acecainide↗
PubMed2001

The effects of uterine and umbilical blood flows on the transfer of propofol across the human placenta during in vitro perfusion.

UNLABELLED: The safety of using propofol in parturients is controversial, and little information is available on the factors that influence the placental transfer of propofol. In this study, we investigated the effects of uterine and umbilical blood flows on the placental transfer of propofol by using the dually perfused human placental cotyledon. Placental transfer was evaluated on the basis of the placental clearances at various uterine and umbilical flow rates. The placental transfer of propofol was significantly facilitated by the increased uterine flow rates over the range from 7.5 to 25 mL/min. The placental clearances of propofol were also dependent on the umbilical flow rates over the range from 0.5 to 4.0 mL/min. In contrast, the placental transfer of antipyrine was flow dependent when the umbilical flow rate was <2.0 mL/min and became permeability limited when it was >2.0 mL/min. No differences in either maternal or fetal venous concentrations of propofol were observed as umbilical flow rates varied from 0.5 to 4.0 mL/min, suggesting that an equilibration across the placenta occurs at low flow rates. These results indicate that fetal uptake of propofol can be profoundly altered by the changes in both uterine and umbilical blood flows observed in various pathophysiologic conditions and that lipid solubility greatly influences placental transfer of drugs. IMPLICATIONS: Uterine and umbilical blood flows are determinant features in controlling the placental transfer of propofol, and, therefore, changes in these variables would significantly affect the extent of fetal exposure to propofol.

Adult↗
PubMed2000

Effects of protein binding on the placental transfer of propofol in the human dually perfused cotyledon in vitro.

The placental transfer of propofol was investigated using the in vitro dually perfused cotyledon model of the human placenta, and the effects of protein binding in the foetal perfusate were examined. Both maternal and foetal circulations were perfused in a single-pass mode and > 30 min of stabilization was allowed before adding propofol and antipyrine to the maternal perfusate. The placental clearances of propofol were significantly increased by the augmented albumin concentrations in the foetal perfusate (1.68 (SD 0.68), 3.08 (1.55), 4.79 (1.76), 5.75 (1.89) and 7.03 (1.46) ml h-1 g-1 at the albumin concentrations of 4.4, 11, 22, 33 and 44 g litre-1, respectively). Although the total propofol concentration in the foetal vein increased significantly with increasing albumin concentration, the concentration of free propofol remained unchanged. These results indicate that binding to foetal albumin is a determining feature in the control of the placental transfer of propofol, and that the pharmacological effects of propofol on the foetus can be expected to be fairly constant and predictable from the maternal propofol concentration.

Albumins↗
PubMed2000

Pulmonary disposition of propofol in surgical patients.

BACKGROUND: The lungs have been mentioned as a possible site contributing to the extrahepatic clearance of propofol. The objective of the present study was to clarify the pulmonary disposition of propofol directly in human lungs by investigating both the first-pass uptake and pulmonary extraction at pseudo-steady state. METHODS: Nine patients were enrolled in the first-pass uptake study. Propofol (5 mg) and indocyanine green (ICG; 15 mg) were simultaneously administered via a central venous catheter within 1 s, and sequential arterial blood samples were obtained from the radial artery at 1-s intervals up to 45 s. Eleven patients were included in the infusion study, and propofol was infused via the jugular vein at a rate of 50 microgram. kg-1. min-1. Blood samples were simultaneously collected from pulmonary and radial arteries up to 60 min. RESULTS: A pronounced difference in the dilution curves between propofol and ICG was observed, and 28.4 +/- 11.6% (mean +/- SD) of propofol was taken up during the single passage through the human lung. The mean pulmonary transit time of propofol (31.3 +/- 6.0 s) was significantly longer than that of ICG (22.4 +/- 2.7 s; P < 0.01), indicating that some of the propofol trapped by lungs returned to the circulation by back diffusion. In the constant infusion study, no significant differences were observed with the plasma concentrations of propofol between pulmonary and radial arteries except for that at 2 min. The area under the curve of pulmonary and radial arterial concentration curves to 60 min were 59.1 +/- 14.8 and 56.8 +/- 12.5 microg. ml-1. min-1, respectively. No significant difference was observed with the area under the curve, suggesting that metabolism was not involved in the pulmonary uptake in human lungs. CONCLUSIONS: Most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion. Metabolism was not involved in the pulmonary uptake in human lungs.

Anesthesia, General↗
PubMed1999

Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective Cesarean section.

BACKGROUND: The role of crystalloid preloading to prevent hypotension associated with spinal anesthesia in parturients during cesarean section has been challenged. Direct measurement of blood volume should provide insight regarding the volume-expanding effects. The aim of the current study was to clarify the effects of volume preload with either crystalloid or colloid solution on the changes in blood volume of parturients undergoing spinal anesthesia for cesarean section. METHODS: Thirty-six healthy parturients scheduled for elective cesarean section during spinal anesthesia were allocated randomly to one of three groups receiving 1.5 l lactated Ringer's solution (LR; n = 12), 0.5 l hydroxyethylstarch solution, 6% (0.5 l HES; n = 12), and 1.0 l hydroxyethylstarch solution, 6% (1.0 l HES; n = 12), respectively. Blood volume and cardiac output were measured before and after volume preloading with indocyanine green (ICG), and the indocyanine green blood concentrations were monitored by noninvasive pulse spectrophotometry. RESULTS: After volume preload, the blood volume significantly increased in all three groups (P < 0.01). The volume of infused solution remaining in the vascular space in the LR, 0.5-l HES, and 1.0-l HES groups were 0.43+/-0.20 l, 0.54+/-0.14 l, and 1.03+/-0.21 l, respectively, corresponding to 28% of lactated Ringer's solution and 100% of hydroxyethylstarch solution infused. Significant increases in cardiac output were observed in the 0.5-l and 1.0-l HES groups (P < 0.01). A significant correlation between the percentage increase in blood volume and that of cardiac output was observed by volume preloading (r2 = 0.838; P < 0.001). The incidence of hypotension was 75% for the LR group, 58% for the 0.5-l HES group, and 17% for the 1.0-l HES group, respectively. CONCLUSIONS: The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups, showing that greater volume expansion results in less hypotension. This result indicates that the augmentation of blood volume with preloading, regardless of the fluid used, must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension.

Adult↗
PubMed1998

Species differences in size discrimination in the paracellular pathway reflected by oral bioavailability of poly(ethylene glycol) and D-peptides.

Animal models are frequently used to aid prediction of intestinal absorption in humans. However, there is little comparative quantitative information on species differences in paracellular permeation, which is an important route for oral absorption of small to medium-sized hydrophilic drug molecules. This study addresses this issue by comparing the molecular mass (MM) dependency in oral bioavailability between rat and dog of poly(ethylene glycol) (PEG), a polydispersed model mixture commonly used to characterize paracellular absorption, and of a series of eight D-peptides (based on D-phenylalanine). Fasted rats and dogs received PEG (400/900) and the D-peptides (MM 236-406 Da), orally and intravenously, with total 24-48 h urine collection to estimate oral bioavailability. After HPLC separation, the individual PEG oligomers and D-peptides were determined using radiometric detection, for radiolabeled material, and LC-MS, for unlabeled (PEG) material. All compounds were predominantly excreted unchanged following intravenous administration. After oral administration, the predominant peak in the radiochromatogram was unchanged material, indicating stability of the compounds in the gastrointestinal tract. A clear molecular mass dependency in oral bioavailability was seen with both series, but with absorption much greater in dog than rat. Thus, for PEG in rat, bioavailability decreased sharply from 79 to around 2% with increasing MM between 282 and 591 Da, and then tapered to around 1. 5% up to 1295 Da. Whereas in dog, bioavailability remained around 100% for oligomers up to 600 Da and then decreased quite sharply with increasing MM, tending to plateau around 13% beyond 900 Da. Likewise, for the d-peptides in rat, bioavailability decreased from 30 to 1% with increasing MM between 236 and 406 Da, whereas in dog it was 100%, declining to 16% over the same molecular range. This species difference appears to be due to a larger pore size and greater frequency of pores in the paracellular pathway of dog compared to rat. Furthermore, on the basis of comparison with literature data for PEG and selected drugs, rat would appear to be a better predictor than dog of absorption of hydrophilic compounds in human.

Absorption↗
PubMed1998

Measurement of blood volume using indocyanine green measured with pulse-spectrophotometry: its reproducibility and reliability.

OBJECTIVE: To systematically investigate the reproducibility and reliability of a newly developed, less invasive approach of estimating blood volume (BV), using indocyanine green (ICG) measured with pulse-spectrophotometry. DESIGN: Prospective, clinical study. SETTING: Surgical unit at a university hospital. PATIENTS: Twenty-two patients undergoing general anesthesia for elective surgery and seven healthy volunteers. INTERVENTIONS: Catheters were inserted into the forearm veins of healthy volunteers for the administration of ICG and blood sampling for the measurement of hemoglobin concentration. MEASUREMENTS AND MAIN RESULTS: The distribution volumes of ICG in seven healthy volunteers were estimated repetitively following three or four consecutive intravenous administrations at 30-min intervals. A low intrasubject coefficient of variation of 3.94 +/- 2.03 (SEM) % and a reasonable intersubject coefficient of variation of 13.3 +/- 5.52% (in mL/kg) for the BV measurements were obtained. In addition, ICG was administered to 22 patients, first under general anesthesia by a bolus, and then by a bolus with a constant-rate infusion. The ICG blood concentration was noninvasively measured with pulse-spectrophotometry. The blood concentration time courses following both bolus and constant-rate infusion were well fitted by the one-compartment model, indicating that the distribution equilibrium of ICG is instantaneous. The distribution volumes estimated following bolus injection correlate closely with the distribution volume estimated based on constant-rate infusion administration (r2 = .90). CONCLUSIONS: The BV estimation with a bolus injection of ICG and pulse-spectrophotometry is reliable, as reflected by the reproducible BVs estimated in the same subject. The integrated pulse-spectrophotometry monitoring system offers a less invasive and useful tool for bedside estimation of BV.

Adolescent↗
PubMed1997

Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro.

PURPOSE: The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comparison of paracellular permeability in different epithelia is complicated by variations in junctional density and/or the absorptive surface area. METHODS: This study used a combination of morphometric analyses and in vitro absorption studies to define permeability characteristics in relation to the amount of paracellular pathway present in rat ileum, colon and the model epithelium, Caco-2. RESULTS: Mucosal to serosal amplification was higher in ileum (3.9) than colon (1.9) or Caco-2 (1). Tight junctional density (lp) of ileal crypts was approximately 3 fold greater (91 m/cm2) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34-37 m/cm2). However, when the relative contributions of the crypts and villi was taken into account there was no significant difference in the mean lp per mucosal area for the three epithelia studied. Using these data to correct for morphometric differences the permeabilities of a range of small hydrophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) was measured. Permeability of rat ileum and colon were virtually identical for all compounds studied. In contrast, Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the difference increasing markedly with molecular size. CONCLUSIONS: These studies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epithelial systems.

Animals↗
PubMed1996

Comparison of HT29-18-C1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption.

PURPOSE: To compare the permeability characteristics of HT29-18-C1 colonic epithelial cell line with Caco-2, an established model of intestinal drug transport. METHODS: Cell lines were grown as epithelial monolayers. Permeability was measured over a range of transepithelial electrical resistance (Rt) using a group of drug compounds. RESULTS: HT29-18-C1 develop Rt slowly when grown in culture, allowing permeability to be measured over a wide range (80-600 Omega x cm2). In contrast, Caco-2 monolayers rapidly develop Rt of approximately equal 300 Omega x cm2 and require Ca2+ -chelation to generate Rt equivalent to human intestine (60-120 Omega x cm2). Permeability of atenolol, ranitidine, cimetidine, hydrochlorothiazide and mannitol across HT29-18-C1 decreased 4-5 fold as Rt developed from 100-300 Omega x cm2 indicating they permeate via the paracellular route. In contrast, ondansetron showed no difference in permeability with changing Rt consistent with transcellular permeation. Permeability profiles across low Rt HT29-18C1 and pulse EGTA-treated Caco-2 monolayers were the same for all 5 paracellular drugs suggesting that transient Ca2+ removal does not alter selectivity of the tight junctions. Permeabilities of cimetidine, hydrochlorothiazide and atenolol across 100 Omega x cm2 HT29-18-C1 monolayers reflect more closely those reported for the human ileum in vivo than did mature Caco-2 monolayers. CONCLUSIONS: HT29-18-C1 monolayers can be used to study drug permeability at Rt values similar to human intestine without the need for Ca2+ chelation. As such, they offer a useful alternative to Caco-2 for modelling intestinal drug absorption.

Atenolol↗
PubMed1996

Oral absorption of D-oligopeptides in rats via the paracellular route.

PURPOSE: This study was undertaken to examine the structural determinants of oral bioavailability in the rat of a set of oligopeptides comprising D-amino acids, which were taken to be absorbed paracellularly based on a pronounced sensitivity of permeability to electrical resistance in Caco-2 cell monolayers. METHODS: The study series comprised eleven D-oligopeptides, designed not to be recognised by peptidases or transport proteins, and to have molecular weights between 222 and 406 daltons with different net electrical charges and composition of D-amino acids. All the peptides were [3H]-radiolabelled and analyzed by HPLC with radiometric detection. Bioavailability was estimated based on 24-hr urinary excretion of unchanged peptide after oral and intravenous administrations. RESULTS: As expected, the series proved metabolically stable. Bioavailability was independent of oral dose when varied by a factor of 10,000, suggesting passive absorption. Whereas bioavailability decreased sharply from 30% to 1% with increasing molecular weight, net charge showed little, if any, effect on bioavailability. CONCLUSIONS: This D-oligopeptide model series served as a useful probe for the structural requirements for paracellular absorption in vivo. A critical determinant of bioavailability is molecular size, expressed as molecular weight in this study; net charged appeared of much lesser importance.

Absorption↗
PubMed1995

Experimental study of corneal innervation in diabetic mellitus.

The morphology of corneal innervation was studied in rabbits with alloxan-induced diabetes. The experimental rabbits were killed after 6, 8, 10, 12 weeks. Corneal innervation was studied by histochemical techniques and transmission electron microscopy. The results revealed that in diabetic rabbits, from 6 weeks, the density of nerve-nets was markedly sparser, the fibers were thinner and the activity of nerves was lower than those of the control group. Ultrastructural changes showed swelling of axons, irregular distribution of fibril and degeneration of mitochondria of varying degree. With the progress of disease the above changes were becoming more marked gradually. It may be assumed that these changes are related to hyperglycemia.

Animals↗
PubMed1995

[Study of pharmacokinetics of liver targeting antimalarial agent neoglycoalbumin-primaquine conjugate (NGA-PQ) and primaquine phosphate in mouse].

A normal phase high-performance liquid chromatography process was used to separate and detect primaquine in blood and liver after a single intravenous dose of the hepatic targeting agent neoglycoalbumine-primaquine conjugate (NGA-PQ) and primaquine phosphate (PQP) in mice. 6-Methoxy-8-(4-amino-butyrylamino) quinoline synthesized and identified by us was used as an internal standard to be added to biologic samples obtained from mice at different times after given NGA-PQ or PQP. The mixture was extracted with ether after alkalinization in the PQP group. In the NGA-PQ group, the biological samples must be hydrolized by heating under nitrogen and acid condition in a domestic pressure cooker before extraction. The extracts were evaporated to dryness under nitrogen, then dissolved in the mobile phase (chloroform-methanol-amonium hydroxide = 86.8: 12.5: 0.7). The results showed that the hepatic PQ collecting ratio and the retention time of PQ in liver in the NGA-PQ group were higher and longer than those in the PQP group. The results also point out that NGA-PQ has liver targeting property.

Albumins↗