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Biomedical subjects

Z Shao

Publications and source records attributed to Z Shao.

177 records · Page 10Linked to original sources
PubMed1993

Differential effects of anionic, cationic, nonionic, and physiologic surfactants on the dissociation, alpha-chymotryptic degradation, and enteral absorption of insulin hexamers.

Various surfactants were investigated to compare their effects on insulin dissociation, alpha-chymotryptic degradation, and rat enteral absorption. With a circular dichroism technique, sodium dodecyl sulfate (SDS) at a 5 mM concentration was found to completely dissociate porcine-zinc insulin hexamers (0.5 mg/ml) into monomers. The catalytic activity of alpha-chymotrypsin (0.5 microM) was also abolished by 5 mM SDS. When insulin was injected into the distal jejunum/proximal ileum segment of the rat, 5 mM SDS greatly enhanced its pharmacological availability, from a negligible value to 2.8%. Being a cationic surfactant, hexadecyl trimethylammonium bromide (CTAB) also efficiently dissociated insulin hexamers at concentrations of 1-5 mM. However, extensive charge-charge interaction was observed below a CTAB concentration of 0.6 mM, leading to insulin precipitation at a molar CTAB:insulin ratio of 1:1 to 2:1. An alpha-chymotryptic degradation study also revealed near-complete dissociation of insulin hexamers at 1 mM CTAB. Above 1 mM, however, CTAB acted as an enzyme inhibitor, most likely by means of charge repulsion. Enteral absorption studies showed a much lower pharmacological availability, only 0.29%. Nonionic surfactants such as Tween 80 and polyoxyethylene 9 lauryl ether were ineffective in dissociating insulin hexamers. Tween 80, at 5 mM, neither significantly altered the alpha-chymotryptic degradation pattern nor enhanced the enteral absorption of insulin. The relative effectiveness of different species of bile salts on insulin hexamer dissociation appeared to be similar. Sodium glycocholate at a 30 mM concentration also significantly increased insulin pharmacological availability, to 2.3%. A morphological study did not reveal any significant alteration of the rat intestinal mucosal integrity after exposure to 5 mM SDS for 30 min.2+ transport.

Administration, Oral↗
PubMed1992

Atomic force microscopy of DNA molecules.

DNA-cytochrome c complexes adsorbed on carbon-coated mica surfaces were directly imaged by atomic force microscopy in air using commercially available cantilevers, with a routine resolution of 6 nm. Images of M13 phage DNA and M13-DNA polymerase complex are also shown.

Cytochrome c Group↗
PubMed1992

Scanning tunneling microscopy of an ionic crystal: ferritin core.

Ferritin molecules were imaged directly in air by scanning tunneling microscopy (STM). The lateral dimensions were close to the values determined by electron microscopy, and the vertical dimension was much reduced. Several clusters of partially naked ferritin cores displayed a hexagonal structure of lattice constant 4.9 +/- 0.5 A. It is thus shown that the STM can be used to image thin ionic crystals at high resolution.

Crystallography↗
PubMed1992

Nasal membrane and intracellular protein and enzyme release by bile salts and bile salt-fatty acid mixed micelles: correlation with facilitated drug transport.

The effects of four bile salts, one fusidate derivative, and one mixed micellar formulation of bile salt-fatty acid combination on the nasal mucosal protein and enzyme release have been investigated in rats using an in situ nasal perfusion technique. Deoxycholate (NaDC) was found to possess the maximum protein solubilizing activity, followed by taurodihydrofusidate (STDHF), cholate, glycocholate (NaGC), and taurocholate (NaTC) in a descending order. The difference in protein solubilization of NaDC and NaGC was further characterized by the release of 5'-nucleotidase (5'-ND), a membrane-bound enzyme, and lactate dehydrogenase (LDH), an intracellular enzyme, in the perfusate. While both NaDC and NaGC caused comparable 5'-ND release from nasal membrane, intracellular LDH release was significantly higher with NaDC. The greater protein and LDH solubilizing effects of NaDC corresponded well with its faster rate of disappearance from the nasal perfusate. Therefore, the dihydroxy bile salt NaDC tends to cause intracellular damage and cell lysis, whereas the trihydroxy bile salt NaGC appears to produce primarily mucosal membrane perturbations. Linoleic acid in the form of soluble mixed micelles with glycocholate caused a further increase in nasal protein release. However, the rate and extent of nasal membrane protein release by the mixed micelles composed of 15 mM glycocholate and 5 mM linoleic acid were significantly lower than those caused by either deoxyholate or STDHF at the same concentrations. Nasal absorption of acyclovir, a non-absorbable hydrophilic model antiviral agent, was found to be enhanced in the presence of conjugated trihydroxy bile salts and bile salt-fatty acid mixed micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1992

Acyclovir permeation enhancement across intestinal and nasal mucosae by bile salt-acylcarnitine mixed micelles.

The purpose of this study was to investigate the absorption enhancement of acyclovir, an antiviral agent, by means of bile salt-acylcarnitine mixed micelles. The specificity, site dependence, palmitoyl-DL-carnitine chloride (PCC) concentration dependence, and effects of absorption promoters on acyclovir absorption via the nasal cavity (N) and four different intestinal segments of the rat, i.e., duodenum (D), upper jejunum (UJ), combined lower jejunum and ileum (LJ), and colon (C) were evaluated. The present study employed the rat in situ nasal and intestinal perfusion techniques and utilized sodium glycocholate (NaGC), three acylcarnitines, and their mixed micelles as potential nasal and intestinal absorption promoters. Acylcarnitines used were DL-octanoylcarnitine chloride (OCC), palmitoyl-DL-carnitine chloride (PCC), and DL-stearoylcarnitine chloride (SCC). All acylcarnitines and NaGC by themselves produced negligible enhancement of acyclovir absorption in the rat intestine, while OCC and SCC were totally ineffective in the nasal cavity. However, the mixed micellar solutions of NaGC with PCC or SCC could significantly increase the mucosal membrane permeability of acyclovir in the colon and nasal cavity. On the other hand, NaGC-OCC mixed micelles slightly increased the absorption of acyclovir by both routes. When a mixed micellar solution of NaGC with PCC was used, the rank order of apparent acyclovir permeability (Papp; cm/sec), corrected for surface area of absorption, was N (10.54 +/- 0.62 x 10(-5)) > D (6.82 +/- 0.30 x 10(-5)) > LJ (2.90 +/- 0.08 x 10(-5)) > C (2.54 +/- 0.14 x 10(-5)) > UJ (2.30 +/- 0.22 x 10(-5)).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1992

Cyclodextrins as nasal absorption promoters of insulin: mechanistic evaluations.

The safety and effectiveness of cyclodextrins (CD) as nasal absorption promoters of peptide-like macromolecules have been investigated. The relative effectiveness of the cyclodextrins in enhancing insulin nasal absorption was found to be in the descending order of dimethyl-beta-cyclodextrin (DM beta CD) greater than alpha-cyclodextrin (alpha-CD) greater than beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP beta CD) greater than gamma-cyclodextrin (gamma-CD). A direct relationship linking absorption promotion to nasal membrane protein release is evident, which in turn correlates well with nasal membrane phospholipid release. The magnitude of the membrane damaging effects determined by the membrane protein or phospholipid release may provide an accurate, simple, and useful marker for predicting safety of the absorption enhancers. In order to estimate further the magnitude of damage and specificity of cyclodextrin derivatives in solubilizing nasal membrane components, the enzymatic activities of membrane-bound 5'-nucleotidase (5'-ND) and intracellular lactate dehydrogenase (LDH) in the perfusates were also measured. HP beta CD at a 5% concentration was found to result in only minimal removal of epithelial membrane proteins as evidenced by a slight increase in 5'-ND and total absence of LDH activity. On the other hand, 5% DM beta CD caused extensive removal of the membrane-bound 5'-ND. Moreover, intracellular LDH activity in the perfusate increased almost linearly with time. The cyclodextrins are also capable of dissociating insulin hexamers into smaller aggregates, and this dissociation depends on cyclodextrin structure and concentration. Enhancement of insulin diffusivity across nasal membrane through dissociation may provide an additional mechanism for cyclodextrin promotion of nasal insulin absorption.

5'-Nucleotidase↗
PubMed1992

Dissociation of insulin oligomers by bile salt micelles and its effect on alpha-chymotrypsin-mediated proteolytic degradation.

Bile salts have been found to be effective absorption promoters of insulin across mucosal barriers, i.e., nasal and gastrointestinal. One of the mechanisms proposed for absorption enhancement is the dissociation of insulin oligomers to monomers, rendering a higher insulin diffusivity. alpha-Chymotryptic degradation and circular dichroism studies were used to characterize such a transition. When zinc insulin (hexamers) and sodium insulin (dimers) were subjected to alpha-chymotryptic degradation, a 3.2-fold difference in the apparent first-order rate constants was observed (zinc insulin being slower than sodium insulin), representing the intrinsic difference in the concentration of total associated species in solution (three times). In the presence of a bile salt, sodium glycocholate (NaGC), the rate of degradation of both zinc and sodium insulin increased in an asymptotic manner. A maximum increase of 5.4-fold was observed for zinc insulin at a 30 mM NaGC concentration and a 2.1-fold increase was noted for sodium insulin at 10 mM NaGC, both values being close to the theoretical numbers of 6- and 2-fold as predicted by the complete dissociation of hexamers and dimers to monomers. The result indicates dissociation of insulin oligomers to monomers by bile salt micelles, probably by hydrophobic micellar incorporation of monomeric units. Circular dichroism studies also revealed progressive attenuation of molecular ellipticities at negative maxima of 276, 222, and 212 nm for zinc insulin solution in the presence of NaGC. Therefore, both alpha-chymotryptic degradation and circular dichroism studies have consistently demonstrated that the bile salts may be capable of dissociating insulin oligomers to monomers, a fact which may play an important role in enhancing insulin bioavailability.

Bile Acids and Salts↗
PubMed1991

Ca2(+)-surrogate action of Pb2+ on acetylcholine release from rat brain synaptosomes.

The effect of lead ions on the release of acetylcholine (ACh) was investigated in intact and digitonin-permeabilized rat cerebrocortical synaptosomes that had been prelabeled with [3H]choline. Release of ACh was inferred from the release of total 3H label or by determination of [3H]ACh. Application of 1 microM Pb2+ to intact synaptosomes in Ca2(+)-deficient medium induced 3H release, which was enhanced by K+ depolarization. This suggests that entry of Pb2+ into synaptosomes and Pb2(+)-induced ACh release can be augmented by activation of the voltage-gated Ca2+ channels in nerve terminals. The lead-induced release of [3H]ACh was blocked by treatment of synaptosomes with vesamicol, which prevents uptake of ACh into synaptic vesicles without affecting its synthesis in the synaptoplasm. This indicates that Pb2+ selectively activates the release of a vesicular fraction of the transmitter with little or no effect on the leakage of cytoplasmic ACh. Application of 1-50 nM (EC50 congruent to 4 nM) free Pb2+ to digitonin-permeabilized synaptosomes elicited release of 3H label that was comparable with the release induced by 0.2-5 microM (EC50 congruent to 0.5 microM) free Ca2+. This suggests that Pb2+ triggers transmitter exocytosis directly and that it is a some 100 times more effective activator of exocytosis than is the natural agonist Ca2+.

Acetylcholine↗
PubMedDate not supplied

Immobilization of glucose oxidase with the blend of regenerated silk fibroin and poly(vinyl alcohol) and its application to a 1,1'-dimethylferrocene-mediating glucose sensor.

The structure and properties of the blend of regenerated silk fibroin (RSF) and poly(vinyl alcohol) (PVA) were investigated. The two polymers in the blend are in the state of phase segregation. Infrared (IR) spectra indicate that the RSF in the blend maintains its intrinsic properties, thus, ethanol treatment can transfer silk I structure of RSF to silk II structure. The water absorption property and mechanical property of the blend are improved in comparison with those of RSF. The blend maintains the major merit of RSF, that is, it can immobilize glucose oxidase on the basis of the conformational transition from silk I structure to silk II structure. The properties of the immobilized enzyme are examined. Moreover, the second generation of glucose sensor based on the immobilized enzyme is fabricated and it has a variety of advantages including easy maintenance of enzyme, simplicity of construction, fast response time and high stability.

Biosensing Techniques↗
PubMedDate not supplied

Optimization of quantitative electron energy loss spectroscopy in the low loss region: phosphorus L-edge.

The purpose of this study was to optimize quantitative electron energy loss spectroscopy (EELS) of elements that have characteristic edges in the low energy loss region and are components of organic matrices. The optimum parameters for phosphorus L2,3-edge (at 135 eV) detection were determined by numerical analysis of computer-generated, Poisson-noisy spectra and by experimental measurements (at 80 keV) of films of the phosphoprotein, phosvitin. When the first, second and third valence electron/plasmon scatterings are included in the multiple least-squares (MLS) fit, the background subtraction of (first-difference) spectra is significantly more accurate than that obtained with the "inverse power law" method, even for a specimen thickness of only 0.25 lambda. Taking into account the effects of plural scattering, the optimal thickness for P quantitation is approximately 0.3 lambda. Signal-to-noise (S/N) ratio decreases rapidly with thickness, and at 1.0 lambda, it is only about 60% of the optimum S/N. The combined effects of the statistical uncertainty of measurements and of the systematic error due to gain variations of the parallel detector were evaluated, and the relative sensitivities of the no-difference (raw spectrum), first-difference and second-difference methods were compared. For channel-to-channel gain variations greater than 0.1% and up to 0.8%, the first-difference method results in the lowest uncertainty of P measurements. In the absence of gain variations, direct fitting provides the greatest sensitivity (least uncertainty), whereas at larger gain variations it may be necessary to use the second-difference method. The optimum energy shift for collecting a first-difference spectrum, approximately 15 eV, did not show any great variation between 5 and 25 eV, and is, in general, specimen dependent. Quantitation with EELS showed excellent correlation with simultaneous electron probe X-ray microanalysis, but, for the detection of P in a 0.25 lambda thick specimen, EELS was approximately five to six times more sensitive than X-ray. The minimal detectable P concentration, with 0.5 nA beam current for 100 s in a 0.25 lambda thick specimen, was 8.4 mmol/kg (0.01 at%) at the 99% confidence level, equivalent to 34 phosphorus atoms for a 15 nm probe. This value is close to the theoretical prediction of 7.5 mmol/kg, and can be improved only by further reducing the gain variation and directly fitting the non-difference spectrum. Appropriate reduction of the gain variations to less than 0.1% would result in a further, approximately two-fold, improvement in the parallel EELS detection system.(ABSTRACT TRUNCATED AT 400 WORDS)

Computer Simulation↗
PubMedDate not supplied

The effect of solvents on spider silk studied by mechanical testing and single-fibre Raman spectroscopy.

We used well-defined, fluorescence-free Raman spectra of single silk fibres to study silk ultrastructure. Major ampullate (MA) silk was reeled from the Araneus diadematus spider under controlled conditions. With a custom-built stress-strain gauge, we examined the mechanical properties of this silk both before and after supercontraction in a range of solvents. The solvents were found to modify the material properties considerably. We suggest that the solvents with their different polarities affect different regions of the silk's composite microstructure, in particular the conformation of the molecular chains.

Animals↗