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Biomedical subjects

Z Shao

Publications and source records attributed to Z Shao.

At least 163 records · Page 9Linked to original sources
PubMed1994

Tris(hydroxymethyl)aminomethane (C4H11NO3) induced a ripple phase in supported unilamellar phospholipid bilayers.

A commonly used buffer compound, tris(hydroxymethyl)aminomethane (C4H11NO3), was found to induce a ripple phase in supported unilamellar phospholipid bilayers at room temperature. The ripple structure showed various types of domains that could extend to several micrometers in length with many well-defined bendings of either 120 degrees or 60 degrees. Two different periodic ripples were found to coexist in 1,2-dipentadecanoyl-sn-glycero-3-phosphatidylcholine bilayers. Some intermediate states during the transition to the ripple phase were also observed.

Chemical Phenomena↗
PubMed1994

Molecular resolution atomic force microscopy of soluble proteins in solution.

We introduce a simple specimen preparatory method for atomic force microscopy of soluble proteins in aqueous solutions. It is demonstrated that the mica surface is suitable for direct adsorption of macromolecules that are sufficiently stable to withstand the disturbance of the probe for reproducible imaging at high resolution. It is also shown that the main problem impeding successful imaging is the excessive adsorption of macromolecules, as loosely bound macromolecules readily stick to the tip and produce various imaging artifacts.

Animals↗
PubMed1994

Structure and stability of pertussis toxin studied by in situ atomic force microscopy.

Pertussis toxin, both complete and the B-oligomer, were imaged by atomic force microscopy (AFM), using specimens prepared by simple surface adsorption on mica without further manipulation. The spatial arrangement of the subunits of the B-oligomer was clearly resolved, representing the first protein quaternary structure obtained by AFM in situ. The results suggest that the B-oligomer is a flat pentamer with the two large subunits located next to each other, and the catalytic A-subunit situated at the center above. We found that the B-pentamer was structurally stable for temperatures up to 60 degrees C and within the pH range of 4.5-9.5. It is also demonstrated that the AFM was capable of resolving features down to 0.5 nm on the B-oligomers, indicating its great potential for structural determination.

Hot Temperature↗
PubMed1994

Enhancement of intestinal insulin absorption by bile salt-fatty acid mixed micelles in dogs.

The pharmacokinetics and pharmacodynamics of porcine zinc insulin following intravenous (iv), intrajejunal, and ileocolonic delivery were evaluated in dogs. The concentration-time profile of plasma immunoreactive insulin following iv injection could be best described by a two-compartment model with a mean distribution half-life of 1.1 min and a mean elimination half-life of 5.6 min. Maximum hypoglycemia occurred at 15 min after injection. Intrajejunal administration of 10 units/kg insulin in phosphate-buffered saline resulted in minimal insulin absorption or hypoglycemia. Incorporation of mixed micelles containing 30 mM sodium glycocholate and 40 mM linoleic acid significantly improved enteral insulin absorption. When delivered with mixed micelles, the mean absolute bioavailability of insulin was 1.8%. To study the effect of intestinal site on insulin uptake, the same formulation was delivered to the ileocolonic region. The mean absolute bioavailability of insulin absorbed from this site was 0.6%. Delivery of insulin to both sites caused significant hypoglycemia in all dogs. Insulin combined with mixed micelles is enterally absorbed in dogs; however, the bioavailability is much lower than that observed in similar studies with rats.

Animals↗
PubMed1994

The physicochemical properties, plasma enzymatic hydrolysis, and nasal absorption of acyclovir and its 2'-ester prodrugs.

A series of 2'-(O-acyl) derivatives of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) was synthesized by acid anhydride esterification. Aqueous solubilities in isotonic phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer, and hydrolysis kinetics in rat plasma were determined. The ester prodrugs showed consistent increases in lipophilicity with corresponding decreases in aqueous solubility as a function of side-chain length. The bioconversion kinetics of the prodrugs appear to depend on both the apolar and the steric nature of the acyl substituents. When perfused through the rat nasal cavity using the in situ perfusion technique, acyclovir showed no measurable loss from the perfusate. Nasal uptake of acyclovir prodrugs, on the other hand, were moderately improved. Furthermore, the extent of nasal absorption appears to depend on the lipophilicity of the prodrugs in the descending order hexanoate > valerate > pivalate > butyrate. Simultaneous prodrug cleavage by nasal carboxylesterase was also noted in the case of hexanoate.

Absorption↗
PubMed1994

Bile salt-fatty acid mixed micelles as nasal absorption promoters. III. Effects on nasal transport and enzymatic degradation of acyclovir prodrugs.

The absorption enhancement and presystemic degradation kinetics of a homologous series of acyclovir 2'-ester prodrugs were investigated in rats using the in situ nasal perfusion technique in the presence of bile salt-fatty acid mixed micelles. In vitro incubation studies indicated that nasal perfusate containing a mixed micellar solution generated higher ester-cleaving activity than isotonic phosphate buffer washings. Inhibitor screening and substrate specificity studies demonstrated the enzyme to be most likely carboxylesterase rather than true cholinesterase. The extent of prodrug cleavage by the carboxylesterase appears to correlate well with the substrate lipophilicity for esters with linear acyl chains. On the other hand, branching of the acyl side chain significantly retards acyclovir prodrug breakdown. To estimate the nasal epithelial membrane and cytoplasmic damaging effect caused by sodium glycocholate (NaGC)-linoleic acid (15 mM:5 mM) mixed micelles, the release profiles of 5'-nucleotidase (5'-ND), lactate dehydrogenase (LDH), and carboxylesterase in the nasal perfusate were measured as a function of time. The results indicated that the activities of all three enzymes resulting from the mixed micellar solution appeared to be significantly higher than those caused by 15 mM NaGC alone. The apparent nasal absorption rate constants of acyclovir and its butyrate, valerate, pivalate, and hexanoate ester prodrugs in mixed micellar solutions containing an esterase inhibitor (1 mM phenylmethylsulfonyl fluoride) were individually calculated. Without an inhibitor, lengthening of the linear acyl side chain of the prodrug resulted in greatly accelerated degradation coupled with moderate absorption improvement. The solubilities and micellar binding constants of acyclovir prodrugs were also determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1994

Cyclodextrins as mucosal absorption promoters of insulin. II. Effects of beta-cyclodextrin derivatives on alpha-chymotryptic degradation and enteral absorption of insulin in rats.

The relative effectiveness of two beta-cyclodextrin derivatives, i.e., dimethyl-beta-cyclodextrin (DM beta CD) and hydroxypropyl-beta-cyclodextrin (HP beta CD), in enhancing enteral absorption of insulin was evaluated in the lower jejunal/upper ileal segments of the rat by means of an in situ closed loop method. The incorporation of 10% (w/v) DM beta CD to a 0.5 mg/ml porcine-zinc insulin solution dramatically increased insulin bioavailability from a negligible value (approximately 0.06%) to 5.63%, when administered enterally at a dose of 20 U/kg. However, addition of 10% (w/v) HP beta CD did not improve enteral insulin uptake significantly with a bioavailability of only 0.07%. Similarly, the pharmacodynamic relative efficacy values obtained after the enteral administration of 20 U/kg insulin, 20 U/kg insulin with 10% HP beta CD, and 20 U/kg insulin with 10% DM beta CD were 0.24%, 0.26%, and 1.75%, respectively. Biodegradation studies of 0.5 mg/ml insulin hexamers by 0.5 microM alpha-chymotrypsin revealed no inhibitory effect on the enzymatic activity by the two cyclodextrins. On the contrary, the apparent first-order rate constant increased significantly in the presence of 10% DM beta CD, suggesting insulin oligomer dissociation by DM beta CD. Histopathological examination of the rat intestine was performed to detect tissue damage following enteral administration of the beta-cyclodextrin derivatives. Light microscopic inspection indicated no observable tissue damage, thereby arguing direct membrane fluidization as the primary mechanism for enhanced insulin uptake. This study indicates the feasibility of using cyclodextrins as mucosal absorption promoters of proteins and peptide drugs.

Administration, Oral↗
PubMed1994

A high-sensitivity CCD system for parallel electron energy-loss spectroscopy (CCD for EELS).

A cooled frame transfer CCD camera system was developed and tested as a parallel detector in an electron energy-loss spectrometer mounted on a transmission electron microscope. The use of a shutterless camera with a frame transfer CCD collected virtually 100% of the photon signal with a reasonably fast acquisition time. The system detective quantum efficiency was over 90% under normal experimental conditions. Because of the low channel to channel gain variations in the CCD, the signal-to-noise ratio and the detection limit were substantially better than that obtained with a silicon intensified target (SIT) camera, and direct fitting to the standard data was feasible. Quantitation at the phosphorus L edge generated from a phosphoprotein, phosvitin, showed that, under identical experimental conditions, direct fitting of spectra obtained with this CCD system gave better sensitivity than that given by the SIT camera system. Because of its larger pixel charge well, the CCD system can also operate at a much higher beam current, resulting in a significant reduction in the time required for elemental mapping at a given sensitivity.

Image Processing, Computer-Assisted↗
PubMed1994

A physical map of the hyperthermophilic bacterium Aquifex pyrophilus chromosome.

A genomic map of the hyperthermophilic hydrogen-oxidizing bacterium Aquifex pyrophilus was established with NotI (GC/GGCCGC), SpeI (A/CTAGT), and XbaI (T/CTAGA). Linking clones and cross-hybridization of restriction fragments revealed a single circular chromosome of 1.6 Mbp. A single flagellin gene and six rRNA gene units were located on this map by Southern hybridization.

Biological Evolution↗
PubMed1994

[Further study on the essence of acupoint specialty in mice].

Trace element, Cr+3 or V+5 are injected into acupoint of mice for pretreatment and then pentobarbital sodium injected into the same points, it is found that the element Cr+3 may shorten time of onset sleeping and prolong time of maintenance sleeping of injecting pentobarbital sodium at "Zusanli" point, while the element V+5 may shorten time of onset sleeping and prolong time of maintenance sleeping of injecting pentobarbital sodium at "Neigran" point. It indicates different trace elements can produce different influence on acupoint drug effect entering "Zusanli" or "Neiguan" point. The results mentioned above suggest that the different responses of different acupoints to same drug may be related to the different ion structures or different semi-conductive properties of the different acupoints.

Acupuncture Points↗
PubMed1993

Sequencing and characterization of the sdaB gene from Escherichia coli K-12.

The sdaB gene which codes for the second L-serine deaminase (L-SD) of Escherichia coli K-12 has been sequenced and shown to be very similar to the sdaA gene which codes for the first L-serine deaminase. sdaB is transcribed in rich medium, particularly in the absence of glucose, and is under the control of catabolite activator protein. A mutation which established expression of the sdaB gene and synthesis of L-serine deaminase 2 in minimal medium has been demonstrated to result in a change in the ribosome-binding site of the sdaB gene.

Amino Acid Sequence↗
PubMed1993

New approach for atomic force microscopy of membrane proteins. The imaging of cholera toxin.

We demonstrate that supported synthetic phospholipid bilayers, which are stabilized by lateral cross-linking in both leaflets, can be used for specimen preparation for atomic force microscopy of purified membrane proteins with high stability and excellent reproducibility under water or low-salt buffer. A bilayer containing 1,2-dipentacosa-10,12-diynoyl-phosphatidylcholine and 20 mol % ganglioside (GM1) was transferred onto the surface of mica from a Langmuir trough. Cholera toxin, both the B-subunit and the complete molecular randomly bound to the gangliosides, were imaged by atomic force microscopy in solution with a resolution of better than 2 nm. The pentameric structure of the B-subunit oligomers was well resolved. This result indicates that, with this preparation procedure, other membrane proteins may be studied at intermediate to high resolution under physiologically relevant conditions without the need for crystallization.

Cholera Toxin↗
PubMed1993

The dynamics of aging and mortality in the People's Republic of China, 1957-1990.

The Strehler-Mildvan modification of the Gompertz relationship between aging and mortality predicts a negative linear relationship between the theoretical logarithm of the mortality rate at birth (log R0) and the exponential rate of increase (alpha) in the age-specific mortality rates under specified conditions. This prediction has been generally validated using mortality data from the United States with respect to general and many disease-specific age-specific mortality rates by the method of longitudinal Gompertzian analysis. Estimated age-specific mortality rates from the People's Republic of China for seven years from 1957 to 1990 were analyzed using the method of longitudinal Gompertzian analysis. The results in this population further validate the Strehler-Mildvan modification of the Gompertz relationship between aging and mortality.

Adolescent↗
PubMed1993

Effect of probe force on the resolution of atomic force microscopy of DNA.

Experimental results are presented to show that the adhesion force is the single most important limiting factor in high-resolution atomic force microscopy of DNA in air, prepared by the cytochrome-C-assisted spreading method. It is also shown that humidity plays a minor role in the control of probe force. Using a pure carbon film as the substrate to clean the AFM tip prior to imaging, it is demonstrated that 4-6 nm resolution on DNA can be routinely obtained by the atomic force microscope with commercial Si3N4 pyramid cantilevers. We also show that in organic solvents a resolution of up to 3 nm can be obtained under optimal conditions.

DNA, Bacterial↗
PubMed1993

Thickness determination of biological thin sections by multiple-least-squares fitting of the carbon K-edge in the electron energy-loss spectrum.

We show that the local thickness of biological thin sections can be measured by fitting the electron energy-loss spectrum of the plurally scattered carbon K-edge, and that such measurements are consistent with the results obtained by a conventional method based on the relationship t/lambda alpha ln(It/I0). The new method allows the simultaneous measurement and/or mapping of both local thickness and core-level excitations (e.g. Ca L-edge) in this energy range (280-400 eV) without requiring the measurement of the zero-loss and the valence/plasmon excitations.

Animals↗
PubMed1993

Chemical and alpha-chymotrypsin-mediated proteolytic degradation of insulin in bile salt-unsaturated fatty acid mixed micellar systems.

The proteolytic degradation of porcine zinc insulin by alpha-chymotrypsin was previously found to depend markedly on the state of insulin aggregation (Pharm. Res. 9:864-869, 1992). In this study, the effect of bile salt-unsaturated fatty acid mixed micelles on alpha-chymotryptic degradation of insulin was further characterized. The incorporation of linoleic acid has greatly accelerated insulin degradation with the apparent first order rate constant being linearly related to the concentration of linoleic acid. At a 10 mM linoleic acid concentration solubilized in 10 mM sodium glycocholate, the proteolytic degradation rate constant increased by 16 times, which could not be explained solely by the mechanism of insulin oligomer dissociation. Further, this effect is significantly reduced when the free carboxylic group of linoleic acid is methylated. The catalytic role of mixed micelles on chemical degradation of insulin was found to depend on the concentration of linoleic acid incorporated. When solubilized in the form of mixed micelles, linoleic acid chemically catalyzes peptide bond cleavage in a concentration-dependent manner.

Animals↗
PubMed1993

Pulmonary delivery of free and liposomal insulin.

The effects of oligomerization and liposomal entrapment on pulmonary insulin absorption were investigated in rats using an intratracheal instillation method. The results indicated that both dimeric and hexameric insulins can be rapidly absorbed into the systemic circulation, producing a significant hypoglycemic response. Intratracheal instillation of insulin in two different oligomerized states has not resulted in any significant difference in the duration of hypoglycemic effect. However, the initial hypoglycemic response (first 10 min) obtained from intratracheal administration of 25 IU/kg hexameric insulin appears to be slower than that from the 25 IU/kg dimeric insulin, thereby suggesting that hexameric insulin may have a lower permeability coefficient across alveolar epithelium than the dimeric insulin. Intratracheal administration of insulin liposomes (dipalmitoylphosphatidyl choline:cholesterol, 7:2) led to facilitated pulmonary uptake of insulin and enhanced the hypoglycemic effect. Nevertheless, similar insulin uptake and pharmacodynamic response were obtained from both the physical mixture of insulin and blank liposomes and liposomally entrapped insulin.

Animals↗