Primary prophylaxis with tacrolimus in kidney transplants in China.
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Adult↗
Biomedical subjects
Y L Cheng
Publications and source records attributed to Y L Cheng.
The pilH gene encodes an ABC transporter homologue required for type IV pilus biogenesis and social gliding motility in Myxococcus xanthus.
Type IV pilus genes have been shown to be required for social gliding motility in Myxococcus xanthus. We report the discovery of four additional pil genes: pilD, a homologue of type IV prepilin leader peptidases; and pilG, pilH and pilI, which have no known homologues in other type IV pilus systems. pilH encodes an ATP-binding cassette (ABC) transporter homologue, the first such homologue to be required for the biogenesis of any bacterial pilus type. pilG and pilI are co-transcribed with pilH and appear to be functionally related to pilH. Null mutants of pilG, pilH and pilI all lack social motility, are deficient in pilus production, have elevated sporulation efficiencies and display similar developmental abnormalities. In addition, all three mutations reduced the amount of PilA found in the supernatant after cells were sedimented from liquid culture. We suggest that the products of these three genes form a single ABC exporter complex, in which pilI is an integral membrane protein with membrane-spanning domains, and pilG is an accessory factor. The complex may participate in pilus assembly and/or the export of PilA pilin.
ATP-Binding Cassette Transporters↗
Determination of the solute removal index for urea by using a partial spent dialysate collection method.
In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.
Female↗
Preparation of a phosphorus-enriched hemodialysate using an 'acid concentrate' solution and a sodium bicarbonate powder.
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Bicarbonates↗
A semi-solid drug delivery system for epidermal growth factor in corneal epithelial wound healing.
PURPOSE: To examine the effects of EGF, delivered from a semi-solid drug delivery system, on corneal epithelial wound healing following anterior keratectomy wound creation in the eyes of New Zealand white rabbits. METHODS: A semi-solid drug delivery system based on a Carbopol gel was developed. Following creation of a 7.5 mm circular anterior keratectomy wound, 50 microL of either a placebo gel or an EGF-containing gel, was instilled in the inferior fornix. The gel remained in the eye for 8 hours, at which time it was removed. Anaesthesia was maintained for the entire 8-hour period. Wound healing was evaluated by quantitative morphometry. We evaluated 0.04, 0.1, 0.2, 0.4, and 1% EGF concentrations in the gel. Tear EGF concentrations and histology of the healing corneas were also examined. RESULTS: The enhancement factor (ratio of the healing rate with the EGF gel and control gel) was 1.13 +/- 0.12, 1.40 +/- 0.14, 1.29 +/- 0.12, 1.80 +/- 0.22, and 1.09 +/- 0.12 for the gels containing 0.04, 0.1, 0.2, 0.4, and 1% EGF by mass, respectively. The increases in the rate of wound healing were significant with the 0.1, 0.2 and 0.4% gel formulations. Histologically, the 0.4% gels resulted in cellular hyperplasia after 5 days of healing. Differences between the placebo gel-treated and EGF-containing gel-treated eyes were evaluated at both 2 and 5 days. The concentration of EGF in the tears during the treatment period was approximately constant for both the 1% and 0.04% gels. The average tear concentration during the instillation period was 2.87 +/- 0.36 micrograms/mL and 200.61 ng/mL +/- 116.10 for the 1% and 0.04% gels respectively. CONCLUSIONS: Treatment with EGF in a Carbopol gel carrier for a period of 8 hours results in significant wound healing enhancement (p < 0.05). The optimum EGF loading in the gel was determined to be 0.4%. A slow release gel may be an effective way to deliver EGF to the corneal surface.
Animals↗
Drug distribution in the vitreous humor of the human eye: the effects of intravitreal injection position and volume.
PURPOSE: The purpose of this study was to determine how the position and volume of an intravitreal injection affect the distribution and elimination of drug from the vitreous humor. METHODS: A mathematical model that had been developed and used previously to study drug distribution in the vitreous humor of the rabbit eye was modified to match the physiology of the human eye. Fluorescein and fluorescein glucuronide were used as the model compounds for these studies. Four extreme injection locations were considered: a central injection, an injection displaced towards the retina, an injection displaced towards the lens, and an injection displaced toward the hyaloid membrane. Injections containing an equal mass of drug dissolved in volumes of either 15 microL or 100 microL were compared. RESULTS: The location of an intravitreal injection was found to have a substantial effect on elimination and distribution in the vitreous. Peak concentrations at different vitreous locations varied by over three orders of magnitude, depending on the injection location. The mean concentration of drug remaining in the vitreous 24 hours after the intravitreal injection varied by up to a factor of 3.8, depending on the injection location. Changing the volume of the injection from 15 microL to 100 microL dampened the effects of the initial injection location; however, meant concentrations at 24 hours still varied by up to a factor of 2.5. CONCLUSIONS: Careful control of the conditions of an intravitreal injection could reduce treatment variability, improve bioavailability, and reduce the possibility of retinal toxicity.
Computer Simulation↗
Drug distribution in the vitreous humor of the human eye: the effects of aphakia and changes in retinal permeability and vitreous diffusivity.
The majority of eyes that receive drug therapy exhibit some form of pathophysiological degradation. Two common pathophysiological states are retinal inflammation, which results in breakdown of the blood-retinal barrier, and aphakia. The purpose of this study was to examine the effects of aphakia and changes in retinal permeability and vitreous diffusivity on drug distribution in the vitreous humor of the human eye. The study was performed using a finite element model that accurately accounts for the vitreous geometry and boundary conditions. Intravitreal injection is the most common method for treating posterior segment disorders; therefore, this administration method was simulated using the models. Elimination from aphakic and phakic eyes was compared for four extreme injection locations and for two retinal permeabilities. When the retinal permeability was fixed at 5.0 x 10(-5) cm/s, increasing the drug diffusivity through the vitreous from 5.4 to 10(-7) to 2.4 x 10(-5) cm2/s decreased the half-life of drug from 64 hours to 2.7 hours. When the drug diffusivity was fixed at 5.6 x 10(-6) cm2/s, increasing the retinal permeability of the drug from 1.0 x 10(-7) to 1.0 x 10(-4) cm/s decreased the half-life of drug from 44 to 7 hours. Therefore, drug diffusivity and retinal permeability are key factors that influence elimination from the vitreous, and must be considered, particularly if the blood retinal barrier has been compromised. Faster drug elimination was observed in aphakic eyes than in phakic eyes, especially for drugs with a low retinal permeability and injected close to the lens capsule. Injection position is also important if the drug is injected in close proximity to a primary elimination barrier.
Aphakia↗
A partial dialysate collection method.
This study validates Ing's partial dialysate collection method, which employs proportionate collection using a side tube capped with a small-gauge plastic needle. The urea nitrogen and creatinine levels of the small representative fraction of spent dialysate collected in the above fashion are undistinguishable from those obtained from the total spent dialysate. The estimated urea nitrogen removed during hemodialysis using this approach is similar to that using the total dialysate collection method; Ing's method is simple and useful in quantifying the dialysis dosage and in its assessment of the nutritional status of patients on hemodialysis.
Bicarbonates↗
Peptides modeled on the transmembrane region of the slow voltage-gated IsK potassium channel: structural characterization of peptide assemblies in the beta-strand conformation.
A 27-residue peptide, having a sequence corresponding to the transmembrane domain of the IsK protein with slow voltage-gated potassium channel activity, has been incorporated into synthetic saturated-chain phospholipid membranes. The peptide-lipid complexes have been characterized by attenuated-total-reflection Fourier-transform-infrared spectroscopy (ATR-FTIR), spin-label electron spin resonance (ESR) spectroscopy, 31P and 2H nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry, and low-angle X-ray diffraction. From FTIR spectroscopy, it is found that, when reconstituted into membranes by dialysis from 2-chloroethanol, the peptide has a predominantly beta-strand secondary structure in which the peptide backbone is oriented at an angle of approximately 56 degrees relative to the membrane normal in dry films of phosphatidylcholines. Hydration of the dry film in the gel phase does not appear to affect the orientation of the peptide backbone, and a relatively small change in orientation occurs when the bilayer undergoes the transition to the fluid phase. The ESR and NMR spectra from spin-labeled and 2H-labeled phospholipids, respectively, indicate that the incorporated peptide restricts the rotational motion of the lipids, without appreciably affecting the chain order, in a way similar to that found for integral membrane proteins. The characteristic two-component ESR spectra from spin-labeled lipids further indicate a selectivity in the interaction of anionic phospholipids with the peptide. The motional restriction of the chains of the spin-labeled phosphatidylcholine and the reduction in the enthalpy of the lipid chain-melting transition indicate that, on average, approximately two to three phospholipid molecules interact directly with each peptide monomer, which is consistent with a limited degree of aggregation of the beta-sheet structures. Both 31P NMR spectroscopy and X-ray diffraction indicate that the lipid-peptide complexes have a lamellar structure up to the highest peptide concentration studied (Rp = 0.2). The surface area occupied by lipid molecules (ca. 30 A2 per chain) in the peptide complexes, deduced from the lamellar repeat spacings at defined water content, is very similar to that in pure fluid lipid bilayers, consistent with the 2H NMR results. The additional membrane surface area contributed by the peptide is approximately 112 A2 per monomer. This large value for the peptide area in the fluid bilayer is consistent with the ATR studies of dry peptide/lipid films which suggest that the long axis of the beta-strand is strongly tilted with respect to the bilayer normal (56 degrees in the dry film).
1,2-Dipalmitoylphosphatidylcholine↗
Tear EGF concentration following corneal epithelial wound creation.
The effect of corneal epithelial wound creation on epidermal growth factor (EGF) concentration in tears was evaluated in order to better understand the effects of EGF on the wound healing process. The tears of New Zealand white rabbits were sampled by micropipette one day prior to wounding, immediately prior to the creation of a 7.5 mm diameter anterior keratectomy wound, immediately following wound creation, and at 1, 2, 3, 7, and 14 days following wounding. A volume of 50 microL was taken at each sampling time, and all tear samples were assayed for EGF by an enzyme linked immunosorbent assay (ELISA). The results demonstrated that the concentration of EGF in the tear layer rises dramatically immediately following wound creation. The basal measured EGF concentration was approximately 600 pg/mL; immediately following wound creation, this rose to approximately 1600 pg/mL. By 1 day following creation of the wound, the concentration of EGF in the tears had returned to the basal level. A second, marginally significant increase in the tear concentration was noted at 3 days post wounding. The EGF concentration in the tears were not significantly different at any other time. The measured dramatic rise in EGF concentration in the tears in response to the creation of a corneal epithelial wound provides further evidence of the importance of tear EGF in the wound healing process. The concentrations in all cases were on the order of ng/mL, suggesting that the intercellular concentrations in this range result in optimal cell stimulation.
Animals↗
Pharmacokinetic differences between ocular inserts and eyedrops.
Controlled release ocular inserts have been found to increase the amount of drug which is absorbed into the aqueous humour when compared to eyedrops. Systemic absorption following delivery using a controlled release insert has been found to be dependent on the release rate of the insert. The objective of this study was to determine if ocular inserts affect drug absorption into other ocular tissues such as the conjunctiva and iris-ciliary body. Ocular absorption studies were performed using albino rabbits and ethylene-vinyl acetate controlled release devices containing timolol maleate. A compartmental model previously developed to simulate ocular absorption following eyedrop administration was modified and used to simulate these experiments. The conjunctival absorption coefficient calculated by the model and the AUC of the conjunctiva per mumol of delivered drug were found to be 2.7 and 42 times higher, respectively, for the ocular insert as compared to eyedrop administration. The increased conjunctiva absorption was likely the result of reduced tear mixing, which caused a high local concentration of timolol between the insert and the conjunctiva. The AUC of the iris-ciliary body per mumol of delivered drug was found to be 24 times higher for the ocular inserts as compared to eyedrop administration. The AUC of the iris-ciliary body was found to be 1.4 times higher than the AUC of the aqueous humour for eyedrop administration, but 9 times greater for delivery via the ocular inserts. Thus, the increased absorption into the iris-ciliary body and aqueous humour observed for ocular inserts is partially the result of an increase in the amount of drug which enters these tissues via penetration across the conjunctiva and sclera.
Absorption↗
Effect of an pyruvate-based peritoneal dialysis solution on the pH of a residual peritoneal dialysis fluid.
An acidic (pH 5.2) pyruvate-based peritoneal dialysis solution or an equally acidic lactate-based counterpart was added to a residual fluid (i.e., peritoneal effluent) obtained from each of 6 continuous ambulatory peritoneal dialysis patients. It was found that the residual fluids were able to raise the pH of the resultant residual fluid/peritoneal dialysis solution mixture to a higher level in the case of the pyruvate-based solution than in the case of the lactate-based one.
Ascitic Fluid↗
Peritoneal catheter-related complications: a comparison between hemodialysis and intermittent peritoneal dialysis in the break-in period.
We prospectively monitored the clinical outcome of 89 curled, double-cuff peritoneal catheters (PC) implanted by surgeons over one year. Thirty-six cases (40%) were supported with hemodialysis (HD) (group A) and 53 cases (60%) were supported with weekly intermittent peritoneal dialysis (IPD) (small exchange volume with a cycler) (group B) for four weeks before commencing continuous ambulatory peritoneal dialysis (CAPD). PC-related complications between the two groups were compared. Ten cases failed to complete the six-month observation period (8 died, 1 received kidney transplant, and 1 defaulted follow-up),Total experience accumulated was 494 patient-months (195 patient-months in group A, 299 patient-months in group B). The incidence of pericatheter leakage (group A vs group B) was significantly higher in group B (0% vs 13%, p < 0.05). There were no significant differences in the incidence of other PC-related complications, removal of PC, and mortality rate in the two groups. The incidence of pericatheter leakage was significantly higher in diabetic patients (71% vs 22%, p < 0.05), and group B patients with leakage had a higher incidence of external cuff erosion 57% vs 7%, p < 0.005) and delay in CAPD training (71% vs 7%, p < 0.005). We conclude that both HD and IPD are equally safe renal replacement therapies in the break-in period, while patients supported with IPD had a higher incidence of pericatheter leakage, which was associated with other catheter-related morbidities including external cuff erosion and delay in CAPD training.
Adult↗
A compartmental model for the ocular pharmacokinetics of cyclosporine in rabbits.
Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a comprehensive pharmacokinetic model. Following a bolus dose into the anterior chamber, drug levels were measured in the aqueous humor, cornea, iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was rapidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and iris/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tissues could act as a reservoir for the drug. It was found that a compartmental model accurately described the experimental data. A single compartment was used for each of the tissues and fluids sampled, except for the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.
Animals↗
Contribution of hypervariable domains to the conformation of a broadly neutralizing glycoprotein 120 epitope.
Three of the five hypervariable domains (V1-V3) of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 have previously been shown to be dispensable for antigenic epitopes recognized by broadly neutralizing monoclonal antibodies. In this study, the influence of the V4 and V5 domains on an epitope recognized by a broadly neutralizing human monoclonal antibody, 1.5e, was investigated. In contrast with the V1, V2, and V3 domains of gp120, the V4 and V5 domains were found to be critical for binding to both CD4 and 1.5e. Our results suggest that V4 and V5 are in structurally less flexible regions of gp120 than V1, V2, and V3 and raises the question of whether variable domains V4 and V5 are also indispensable for other broadly neutralizing antibodies in the same class as 1.5e.
Antibodies, Monoclonal↗
A subconjunctival degradable implant for cyclosporine delivery in corneal transplant therapy.
The effect of local cyclosporine therapy upon corneal transplant survival was investigated. A high risk rabbit model with vascularized corneas was used to assess the efficacy of subconjunctivally implanted degradable devices for cyclosporine therapy. Animals were divided into four groups, receiving either no therapy, a placebo PLGA device, or drug containing devices implanted either at the time of transplantation or two weeks previous. The mean survival times of animals in the control and placebo groups were statistically equivalent (21 +/- 4 days vs 18 +/- 4 days). Devices containing CsA improved the survival time of grafts. Predosing the animals with CsA improved the survival time to 28 +/- 7 days, and CsA devices implanted at the time of transplantation increased the survival time to 35 +/- 7 days. The improvement in survival times was consistent with the in vitro drug release profiles. No systemic CsA was detected, suggesting that the effect may have been local. Histological assessment indicated that devices were well tolerated.
Animals↗
Identification of malaria-infected dried mosquitoes by biotinylated DNA probe.
Dot-blot hybridization with cloned genomic DNA labeled with photobiotin as a probe is used to detect Plasmodium falciparum sporozoites in dried mosquitoes. The assay is sensitive enough to detect 2 pg Plasmodium parasite DNA, or one infected mosquito in a pool of 40 insects using DNA extraction samples, or one infected mosquito in a pool of 25 insects without DNA extraction. A single mosquito squashed directly on a nitrocellulose filter for the determination of parasites provides a simple method for the detection of sporozoites. The mosquitoes triturated in reduction buffer were efficient for the screening of malaria infection of mosquitoes in a large number of samples. The species specificity, sensitivity, and ease of performance of this assay as well as the stability of the reagents may make it a useful epidemiological tool.
Animals↗
The 'first-use syndrome' revisited: a dialysis centre's perspective.
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Biocompatible Materials↗