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Biomedical subjects

F C Lam

Publications and source records attributed to F C Lam.

14 recordsLinked to original sources
PubMed2006

Influence of an anti-diabetic foot ulcer formula and its component herbs on tissue and systemic glucose homeostasis.

Complications of diabetes impose major public health burdens worldwide. The positive effect of a Radix Astragali-based herbal preparation on healing diabetic foot ulcers in patients has been reported. Formula 1 is also referred as the 'Herbal drink to strengthen muscle and control swelling'. This formula contains six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali, Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in different anti-diabetic formulae of Chinese medicine. The objective of the current study is to use an interdisciplinary approach to test the hypothesis that Formula 1 and its components influence tissue and systemic glucose homeostasis. In vitro and in vivo models have been established including: (1) glucose absorption into intestinal brush border membrane vesicles (BBMV); (2) gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic rat model. The results of in vitro studies indicated that all herbal extracts can modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis Chinensis extracts demonstrated potent effects on modifying glucose homeostasis in multiple tissues in vitro, they were further studied for their anti-diabetic activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not significantly improve oral glucose tolerance or basal glycaemia in diabetic rats. In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active in modifying tissue glucose homeostasis in vitro but these biological activities could not be associated with improved glycaemic control of diabetes in vivo.

3T3 Cells↗
PubMed2006

Traumatic wound dehiscence after penetrating keratoplasty-a cause for concern.

AIM: We report the incidence, causes, characteristics, and the outcome of traumatic corneal graft ruptures in a tertiary referral centre in the UK. METHOD: A retrospective analysis of all graft ruptures secondary to trauma that were treated at our centre between 1999 and 2005 was undertaken. Statistical analysis of possible prognostic factors was undertaken using the Fisher's test. RESULTS: Nineteen eyes in 18 patients sustained eye trauma resulting in graft rupture (median age of 53 years; range 27-82; 15 men and four women). Seventeen cases were accidental and two were from violence. The median time interval between grafting and rupture was 8.3 months (range 3 days to 15 years). The 6-year incidence was 3.8%. All graft ruptures occurred at the host-graft junction and ranged from 45 to 270 degrees . Iris prolapse/loss was noticed in 89% and lens loss in 53%. The most common posterior segment complication was vitreous loss (74%), followed by vitreous haemorrhage (32%) and retinal detachment (21%). Grafts with 180 degrees or more of dehiscence were more likely to fail (P<0.001), had more extensive posterior segment damage, and a poorer visual outcome. Grafts without sutures had a more extensive dehiscence (P<0.01). Final visual acuity was worse than 6/60 in 58%. CONCLUSIONS: The risk of traumatic corneal graft rupture is significant and is associated with a poor visual outcome. This fact needs to be clearly emphasised during preoperative counselling and protective measures encouraged.

Adolescent↗
PubMed2001

beta-Amyloid efflux mediated by p-glycoprotein.

A large body of evidence suggests that an increase in the brain beta-amyloid (Abeta) burden contributes to the etiology of Alzheimer's disease (AD). Much is now known about the intracellular processes regulating the production of Abeta, however, less is known regarding its secretion from cells. We now report that p-glycoprotein (p-gp), an ATP-binding cassette (ABC) transporter, is an Abeta efflux pump. Pharmacological blockade of p-gp rapidly decrease extracellular levels of Abeta secretion. In vitro binding studies showed that addition of synthetic human Abeta1-40 and Abeta1-42 peptides to hamster mdr1-enriched vesicles labeled with the fluorophore MIANS resulted in saturable quenching, suggesting that both peptides interact directly with the transporter. Finally, we were able to directly measure transport of Abeta peptides across the plasma membranes of p-gp enriched vesicles, and showed that this phenomenon was both ATP- and p-gp-dependent. Taken together, our study suggests a novel mechanism of Abeta detachment from cellular membranes, and represents an obvious route towards identification of such a mechanism in the brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Moment method for the estimation of mass transfer coefficients for physiological pharmacokinetic models.

In vitro and in vivo techniques have been utilized to estimate mass transfer coefficients for physiological pharmacokinetic models. No single method has been adopted for estimating this parameter, in part, due to the different model structures with which this parameter may be associated. A specific method has been derived to calculate mass transfer coefficients for non-eliminating membrane-limited tissue compartments. The present method is based on observed concentration-time data, and requires the calculation of the areas under the zero and first moment curves for plasma, and the first moment curve for the tissue. A Monte Carlo simulation technique was used to determine the percentage biases of the method based on a published model for streptozoticin and adriamycin. For the latter model, the method was compared to a non-linear regression parameter estimation technique.

Humans↗
PubMed1991

Relative bioavailability of oral sustained-release and regular-release oxprenolol tablets at steady-state.

The relative bioavailability of a test sustained-release (SR) oxprenolol tablet against an approved regular-release (RR) tablet has been investigated at steady-state. In a randomized two-way crossover study, one tablet of 160 mg SR oxprenolol once every 24 h and one tablet of 80 mg RR oxprenolol once every 12 h were given to 12 healthy volunteers for 5 days. Blood samples were collected from each subject just prior to each dose-administration on days 1 through 4, and at scheduled time points on day 5 and analysed for oxprenolol concentration using HPLC. The SR tablet resulted in 42 per cent reduction in mean peak drug levels (p = 0.0341) and a statistically non-significant 14 per cent increase in mean trough levels (p = 0.8357) than the RR tablet. However it required 160 per cent longer time to reach average steady-state concentrations (Css) on day 5 (1.38 h for SR versus 0.53 h for RR; p = 0.0205). The mean area under the plasma drug concentration-time curve at steady state (AUC96-120) with the SR tablet was approximately 18 per cent lower than that observed with the RR tablet, and the degree of fluctuation (DF) was reduced by 30 per cent (2.81 for SR versus 4.11 for RR; p = 0.0069). On average, a single dose of SR tablet and two doses of RR tablets maintained the drug levels above a constant Css of 204.6 ng ml-1 for 7.88 and 7.65 h, respectively (p = 0.3513).

Adult↗
PubMed1990

Application of regression analysis in the evaluation of tumor response following the administration of adriamycin either as a solution or via albumin microspheres to the rat.

Regression analysis has been applied to compare the tumor response following the administration of free and microsphere-loaded adriamycin to the rats. A nonmetastasizing sarcoma was induced in male A.S. inbred rats. When the sarcoma was in its fourth passage and 12 days old, four groups of animals received intratumoral injections of 2 or 8 mg/kg of adriamycin as a solution or via albumin microspheres. The animals in each group were monitored over a period of three weeks for changes in body weight and tumor size and their survival, and the results were statistically compared with the data obtained from an untreated group of animals (control). The use of regression analysis in conjunction with partial F-test revealed that the microsphere-delivered drug exhibited a meager but significantly greater response than the free drug. The implications of intratumoral administration of microsphere-loaded drug in the treatment of sarcomas is discussed.

Albumins↗
PubMed1989

Interaction of L-ascorbic acid on the disposition of lead in rats.

L-Ascorbic acid (As-Ac) has been investigated for its potential in the prophylaxis of lead poisoning. Using rats as the animal model, the pharmacokinetics of As-Ac was determined following a single intravenous dose (100 mg/kg) administered through a jugular vein. Plasma As-Ac levels were monitored using an enzyme assisted UV spectrophotometric method. The pharmacokinetic parameters of As-Ac obtained were used to establish a dosage regimen which could maintain its average plasma concentration of about 11 micrograms/ml at steady state in rats. The disposition of lead acetate (1 mg/kg) in rats was studied in the absence and presence of As-Ac at steady state. Lead concentrations were monitored in femur, kidney, liver and plasma over a 120 hr period using flameless atomic absorption spectrophotometry. In presence of As-Ac, femur, kidney and liver demonstrated 56, 22 and 41% respective reductions in their exposure towards lead. In addition, the half-life of lead in femur and plasma was found to be reduced by 27 and 51% respectively.

Animals↗
PubMed1988

Optimization of high-performance liquid chromatographic analysis for isoxazolyl penicillins using factorial design.

A 3 X 3 factorial design has been used to study the effects of pH and acetonitrile concentration of the eluents on the retention and resolution of cloxacillin, flucloxacillin and dicloxacillin on a C18 column. The logarithm of the capacity factors of these solutes have been found to vary linearly with the pH and quadratically with the acetonitrile content. The equations generated have been employed to predict experimental conditions necessary for an optimum separation. The chromatographic condition selected has been applied to the quantitation of flucloxacillin in human plasma using dicloxacillin as the interval standard. Sample preparation consists of protein precipitation and solid-phase extraction. The detection limit of the assay at 220 nm for flucloxacillin is in the region of 0.1 microgram/ml. This assay has been employed in a study of the relative bioavailability of two commercial flucloxacillin sodium capsules in ten healthy volunteers.

Adult↗
PubMed1988

Optimized synthesis of polyglutaraldehyde nanoparticles using central composite design.

A central composite design was applied to the optimization of the synthesis of polyglutaraldehyde nanoparticles (PGNP). The effects of monomer concentration, surfactant concentration, pH, oxygen level, and stirring rate on the particle size, polydispersity, surface carboxyl group concentration, and yield of PGNP were investigated. The optimal conditions for the synthesis of PGNP were found to be: 7% (w/v) glutaraldehyde, 2.5% (w/v) dextran, pH 12, 70% (v/v) oxygen, and a stirring rate of 1080 rpm. Under these conditions, the values of the dependent variables adequately resembled those predicted by the model. The usefulness of these particles in the targeted delivery of cytotoxic drugs is discussed.

Aldehydes↗
PubMed1987

Determination of pharmacokinetics of cocaine in sheep by liquid chromatography.

Cocaine was administered as 1-, 2-, and 4-mg/kg intravenous bolus doses to each of six sheep. Plasma samples were collected as a function of time and assayed for cocaine using reversed-phase ion-pair HPLC. The assay involved double extraction with ether and UV detection at 229 nm. Using 2 mL of plasma, levels of 1 ng/mL of cocaine can be measured. The concentration versus time data obtained for the plasma samples were analyzed by a "noncompartmental" method. The pharmacokinetic parameters of cocaine in sheep had mean values of 4.0 L/kg, 3.5 L/kg, and 0.29 L X min-1 X kg-1 for Vd, Vdss, and CL respectively. The clearance of cocaine in sheep was much higher than cardiac output. Pulmonary first-pass effect has been suggested as the possible explanation for the large clearance of cocaine in sheep.

Animals↗
PubMed1987

Area method for the estimation of partition coefficients for physiological pharmacokinetic models.

A new technique, the area method, is derived for the determination of partition coefficients for both blood-flow limited and membrane limited physiological pharmacokinetic models. This method was compared to a standard technique by Monte Carlo simulation. Partition coefficients were calculated for the blood-flow limited case for both eliminating and noneliminating organs. It was found that the area method compared favorably to a standard technique and was less prone to error. This may be attributed to the more subjective interpretation as to which data points are included in the terminal phase, since the standard method relies on the accurate determination of the terminal slope for the calculation of partition coefficients. Both methods are satisfactory for the calculation of partition coefficients with the area method being more accurate and precise.

Humans↗
PubMedDate not supplied

Factorial design based optimization of the formulation of albumin microspheres containing adriamycin.

The use of factorial design in the formulation of adriamycin-associated albumin microspheres, using the heat-stabilization technique, is illustrated. The effect of stabilization temperature, protein concentration and stabilization time on the entrapment and recovery of adriamycin in microspheres have been investigated using a 2 x 4 x 4 factorial design. The associated drug content in unwashed and four times washed microspheres was determined using HPLC. Maximum drug association and drug recovery were obtained from microspheres synthesised using 25 per cent w/v albumin solution and stabilized at 120 degrees C for 2.5 min. Under these conditions, the entrapped and total associated drug content of the microspheres was about 4 per cent and 12 per cent w/w respectively, and the drug recovery was about 75 per cent. The in vitro dissolution study carried out using dynamic dialysis revealed that the release of adriamycin from these particles follows a bi-phasic pattern. The results demonstrate that use of short stabilization time, low protein concentration and low stabilization temperature are required for the formulation of microspheres with high adriamycin content.

Albumins↗