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F H Hsu

Publications and source records attributed to F H Hsu.

10 recordsLinked to original sources

Separation method based on affinity reaction between magnetic and nonmagnetic particles for the analysis of particles and biomolecules.

A separation method is reported for particle and biochemical analysis based on affinity interactions between particle surfaces under magnetic field. In this method, magnetic particles with immunoglobulin G (IgG) or streptavidin on the surface are flowed through a separation channel to form a deposition matrix for selectively capturing nonmagnetic analytes with protein A or biotin on the surface due to specific antigen (Ag)--antibody (Ab) interactions. This separation method was demonstrated using model reactions of IgG--protein A and streptavidin-biotin on particle surface. The features of this new separation method are (1) the deposited Ag-Ab complex can be examined and further analyzed under the microscope, (2) a kinetic study of complex binding is possible, and (3) the predeposited matrix can be formed selectively and changed easily. The detection limits were about 10(-11) g. The running time was less than 10 min. The selectivities of studied particles were 94% higher than those of label-controlled particles. This method extends the applications of analytical magnetapheresis to nonmagnetic particles. Preliminary study shows that this separation method has a great potential to provide a simple, fast, and selective analysis for particles, blood cells, and immunoassay related applications.

Biotin↗

Order parameter of MgB(2): a fully gapped superconductor.

We have measured the low-temperature specific heat C(T) for polycrystalline MgB(2) prepared by high pressure synthesis. C(T) below 10 K vanishes exponentially, which unambiguously indicates a fully opened superconducting energy gap. However, this gap is found to be too small to account for T(c) of MgB(2). Together with the small specific heat jump Delta C/gamma(n)T(c) = 1.09, scenarios such as anisotropic s-wave or multicomponent order parameter are called for. The magnetic field dependence of gamma(H) is neither linear for a fully gapped s-wave superconductor nor H(1/2) for nodal order parameter. It seems that this intriguing behavior of gamma(H) is associated with the intrinsic electronic properties other than flux pinning.

Journal Article↗

Correlation of unbound plasma clearances of fifteen extensively metabolized drugs between humans and rats.

Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phenytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin, Biopharm. 13:477-491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW 0.657 +/- 0.0935. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.

Animals↗

The phenomenon and cause of the dose-dependent oral absorption of chlorothiazide in rats: extrapolation to human data based on the body surface area concept.

The reported incomplete and dose-dependent absorption of chlorothiazide in humans was demonstrated in six rats after five oral solutions at doses of 0.93, 2.55, 9.23, 25.6, and 70.2 mg/kg. Mean 48-hr urinary recoveries of intact drug were 57.3, 50.4, 36.7, 22.8, and 15.3%, respectively. A similar degree of dose dependency in absorption was found in rat, dog, and human when the doses were related to unit body surface area (BSA) but not on unit body weight, indicating similar interspecies absorptive capacity in terms of unit BSA. This finding may be partly rationalized by marked similarities in the reported solution transit time (2-3 hr) in the small intestine as well as in the calculated gross surface area of the small intestine per unit BSA (0.163 for rat and 0.132 for human). Contrary to the previous postulation of a specific absorption site, the drug was absorbed from different regions of the GI tract with apparent 1-hr absorption rates, studied by the in situ closed-loop method, in the following rank order: jejunum (34.6%) greater than duodenum (32.7%) greater than large intestine (20.1%) greater than ileum (18.0%) greater than stomach (12.4%). Different from the commonly assumed first-order absorption process, the intestinal loop absorption was concentration-dependent, suggesting a saturable mechanism. For example, the absorption rate at 0.008 mg/mL was higher than that at 0.2 mg/mL in ileal loops (61%, p less than 0.01) and jejunal loops (22%, p less than 0.1). In addition, the absorption rates at pH 6 and 7.4 were statistically identical, indicating a lack of ionization effect that is important in the passive absorption process. The solubility-limited absorption could probably be ruled out at doses below 2.55 mg/kg for rat and 125 mg for human in view of higher aqueous solubilities at 37 degrees C (e.g., 1.3 mg/mL at pH 7) found in the present study. Contrary to the previous hypothesis of low membrane permeability as a limiting factor for absorption, the "intrinsic" partition coefficient in 1-octanol/aqueous buffer was moderate, 0.6. Furthermore, the absorption in ileal and jejunal loops was enhanced by an apparent increase in mesenteric blood flow by caffeine. The existence of prolonged oral absorption in rats and humans is discussed.

Animals↗

Correlation of creatinine levels in saliva and plasma in normal subjects and renal patients.

Whole saliva and serum creatinine levels were evaluated in three normal subjects and 12 patients with chronic renal failure receiving regular hemodialysis treatments. Ratios of the serum vs. saliva creatinine levels ranging from 4.5 to 30.0 were found. Repeated studies also revealed marked intra-subject variations in these ratios. We conclude that the monitoring of whole saliva creatinine levels is only of limited value in accurately predicting serum or plasma creatinine levels, despite its appeal of simplicity, convenience and non-invasiveness. Its value in the qualitative monitoring of renal function may, however, be useful.

Adolescent↗

A new simple and rapid method to monitor the renal function based on pharmacokinetic consideration of endogeneous creatinine=.

Based on the linear single-compartment pharmacokinetic consideration of endogeneous creatinine a new equation is derived to estimate the true creatinine renal clearance and hence the renal function of a patient; By using this equation one can estimate clinically the creatinine renal clearance of a patient simply by measuring the creatinine serum levels at two different times without the necessity of urine collection. Almost a perfect prediction of the status of renal function in two anephric patients was demonstrated using this proposed methodmwith a sensitive assay technique for endogeneous creatinine, the proposed equation would enable on to monitor the creatinine clearance on an hourly basis= The method is especially valuable to monitor the rapidly changing (improving or deteriorating) renal function in all types of patients and also in certain groups of patients whose urine is difficult to ba accurately collected;

Acute Kidney Injury↗

Absorption of iothalamate after oral administration and absorption enhancement by amino acids in dogs and rats.

The oral absorption of iothalamate and the effect of amino acids on its absorption were studied in 6 dogs and 6 rats using a simple HPLC assay. The results showed that iothalamate was absorbed in dogs, averaging 9.9, 8.5, and 10.0 per cent following the administration of 40 and 100 mg kg-1 of iothalamic acid capsules and 50 mg kg-1 of sodium iothalamate solution, respectively. The absorption from the capsule was slower and more sustained than that from the solution. In rats, the absorption appeared to be dose-independent (averaging about 4.2 per cent) in the dose range of 20-800 mg kg-1. The low bioavailability obtained was mainly due to the high polarity of iothalamate molecules as suggested by the GI recovery and in vitro partition studies. Among several amino acids tested as possible ion-pair formers, only homoarginine hydrochloride increased the partition of iothalamate into chloroform layer. However, both homoarginine hydrochloride and arginine hydrochloride at the amino acid/iothalamate molar ratio of 25 were found to significantly enhance (about 70 per cent) the iothalamate absorption in dogs. The in situ rat small intestinal loop study indicated that the absorption-enhancing effect of arginine was sodium dependent. At the sodium chloride concentration of 0.09 M, no significant increase in the absorption was observed, while at the concentration of 0.3 M or higher, a marked increase (about twofold) was obtained in both upper and lower intestine. Thus, the mechanism of the amino acids in facilitating the iothalamate absorption may be more closely related to the active amino acid transport system rather than the possible increase in lipophilicity of the ion-pair formed. The potential use of such naturally occurring, relatively non-toxic amino acids for increasing the GI absorption of water-soluble weak acids or bases through ion-pair formation remains to be fully investigated.

Administration, Oral↗

Pharmacokinetics of creatinine in man and its implications in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency.

A single-compartment model is proposed to describe the pharmacokinetics of creatinine in man. Based on the information from the literature, it was estimated that the average biological half-life of creatinine in normal male adults between 20 to 39 years old is 3.85 hours. This half-life is prolonged in renal patients and becomes 77 hours when renal function decreases to 5 per cent of normal. Based on pharmacokinetic analysis, it was also shown that the time required to reach a new steady-state serum creatinine level after onset of renal failure is highly dependent upon the degree of renal insufficiency. For example, for the subjects analyzed in this paper, it was estimated that it will take 1.1, 2.5, 6.7, and 13.4 days to reach 95 per cent of the steady-state levels when the renal function drops to 50, 25, 10, and 5 per cent of the normal capacity. The model analysis also predicts that from a practical point of view the daily fluctuation in serum level in patients with better than 25 per cent of normal renal function is not very significant. On the other hand, the fluctuation in the early stage of severe renal failure is predicted to be very dramatic. The analysis also predicts that the serum level will decrease to a normal or near normal value within two days after improvement of renal function from moderately to severely impaired state. The data obtained from an anuric patient seems to support the validity of the pharmacokinetic approach used in this study. The implications of the above pharmacokinetic analyses for the monitoring of renal function and dosage regimen modifications in patients with renal insufficiency were discussed.

Creatinine↗