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1.
The objectives of this study were to evaluate the physical structure and the release mechanisms of theophylline microspheres
made of Eudragit S 100 polymer as an enteric polymer, combined with a nonerodible polymer, Eudragit RL 100. In the preparation
process, polymer combinations (1:1) were dissolved in an organic solvent mixture composed of acetone and methanol at a specific
ratio containing a theoretical drug loading of approximately 15%. Two microsphere formulations (LS1 and LS2) were prepared
at two different total polymer concentrations (10% in LS1 and 12.7% in LS2). Dissolution studies were carried out using US
Pharmacopeia Dissolution Apparatus II in an acidic medium for 8 h and in an acidic medium (2 h) followed by a slightly basic-buffered
medium for 10 h. Both LS1 and LS2 microsphere formulations produced particles that were spherical in shape and had very narrow
size distributions with one size fraction comprising 70–80% of the yield. Scanning electron microscopy and quantitative Fourier
transform infrared were used for microsphere physical structure evaluation. Except for the absence of drug crystals, photomicrographs
of both LS microspheres after dissolution in pH 1.2 and 7.2 buffer solutions were similar to those before dissolution. Dissolution
results indicated the ability of LS microspheres to minimize drug release during the acid stage. However, in the slightly
basic medium that followed the acidic stage, the drug release was sustained and controlled in its kinetics and data fitted
to Peppas equation indicated a case II transport suggesting that the drug release is mainly through swelling/erosion mechanism. 相似文献
2.
3.
The concept of the blood-aqueous barrier is largely based on the use of horseradish peroxidase (HRP). The present investigation
was designed to check its reliability as a macromolecular tracer, especially with regard to the transport of plasma proteins.
Rabbits were killed 5 min to 24 h after being intravenously injected with HRP. The tracer diffused rapidly, reaching the aqueous
humor of the eye in 3 min or less and was detected at high concentration in the narrow space between the outer epithelial
layer of the ciliary epithelium and the wall of the pervious capillaries in the stroma of the processes. HRP appeared to migrate
from the blood to the posterior chamber, permeating the tight junctions, viz., the anatomical basis of the blood-aqueous barrier.
It was detected at higher concentration at the anterior surface of the iris, at short time intervals; this was interpreted
as penetration of the tracer from the aqueous humor of the anterior chamber. The choroid was also labeled in continuation
with the reaction in the stroma of the pars plana of the ciliary body which, in turn, sometimes reached the iris root. Therefore,
the pervious blood vessels of the choroid could be a source of macromolecules for the iris root. HRP also induced the formation
of lysosomes in the ciliary epithelium. This can hardly be accepted as the way in which plasma proteins are physiologically
transported to the aqueous humor. However, the pathway of HRP migration over short time intervals seems to be in agreement
with previous research indicating that the entrance of serum albumin into the posterior chamber is the first step of its incorporation
into the aqueous humor.
Received: 7 June 1996 / Accepted: 15 January 1997 相似文献
4.
Rayna C. Bell Cinthia A. Brasileiro Célio F. B. Haddad Kelly R. Zamudio 《Journal of Biogeography》2012,39(9):1733-1742
Aim We investigated how Pleistocene refugia and recent (c. 12,000 years ago) sea level incursions shaped genetic differentiation in mainland and island populations of the Scinax perpusillus treefrog group. Location Brazilian Atlantic Forest, São Paulo state, south‐eastern Brazil. Methods Using mitochondrial and microsatellite loci, we examined population structure and genetic diversity in three species from the S. perpusillus group, sampled from three land‐bridge islands and five mainland populations, in order to understand the roles of Pleistocene forest fragmentation and sea level incursions on genetic differentiation. We calculated metrics of relatedness and genetic diversity to assess whether island populations exhibit signatures of genetic drift and isolation. Two of the three island populations in this study have previously been described as new species based on a combination of distinct morphological and behavioural characters, thus we used the molecular datasets to determine whether phenotypic change is consistent with genetic differentiation. Results Our analyses recovered three distinct lineages or demes composed of northern mainland São Paulo populations, southern mainland São Paulo populations, and one divergent island population. The two remaining island populations clustered with samples from adjacent mainland populations. Estimates of allelic richness were significantly lower, and estimates of relatedness were significantly higher, in island populations relative to their mainland counterparts. Main conclusions Fine‐scale genetic structure across mainland populations indicates the possible existence of local refugia within São Paulo state, underscoring the small geographic scale at which populations diverge in this species‐rich region of the Atlantic Coastal Forest. Variation in genetic signatures across the three islands indicates that the populations experienced different demographic processes after marine incursions fragmented the distribution of the S. perpusillus group. Genetic signatures of inbreeding and drift in some island populations indicate that small population sizes, coupled with strong ecological selection, may be important evolutionary forces driving speciation on land‐bridge islands. 相似文献
5.
Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O2 in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O2. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance. 相似文献
6.
C Haddad M Wilkinson L M Roeder J T Tildon J A Armour 《Canadian journal of physiology and pharmacology》1987,65(9):1928-1933
A new technique was developed to characterize the binding of a hydrophilic beta-adrenergic antagonist, [3H]CGP-12177, to 1-mm thick slices of canine cardiac tissue. This technique was used to quantify the density (Bmax) and the affinity (Kd) of these receptors in the right ventricular conus (RVC) and the left ventricle (LV) at day 1 to 6 weeks of age, and in the adult. Binding was found to be reversible, saturable, stereospecific, of high affinity, and thermolabile. There was an increase in the density of beta-adrenergic receptors between day 1 (Bmax = 2.2 +/- 0.3 fmol/mg tissue in RVC and 2.9 +/- 0.8 fmol/mg tissue in the LV) and 2 weeks of age postnatally, after which it remained constant until 6 weeks of age (Bmax = 7.5 +/- 0.4 and 6.8 +/- 0.9 fmol/mg tissue in RVC and LV, respectively); however, by 6 weeks of age it had not reached adult levels (10.3 +/- 1.0 fmol/mg tissue). The affinity of these receptors did not change between early neonatal life (Kd = 1.3 +/- 0.4 nM) and adulthood (Kd = 1.4 +/- 0.2 nM). The density of beta-adrenergic receptors in the RVC was similar to that in the LV. This new method of quantifying beta-adrenergic receptors in cardiac tissue is simple and fast, and requires minimal tissue handling. It proved to be useful in studying the development of cardiac beta-adrenergic receptors with age. 相似文献
7.
Jamal Bayad Nicole Sabolovic Denyse Bagrel Athanase Visvikis Maria Wellman Gerard Siest 《Cell biology and toxicology》1990,6(2):157-170
Eighteen IgGl monoclonal antibodies (blabs) have been produced against gamma-glutamyl transferase (GGT) from rat kidney. They were specific to the light subunit of the enzyme with affinity constants ranging from 0.3 to 7.5 108 M–1, while they did not react with GGT from other sources i.e. human and pig kidney, rat and guinea pig liver, suggesting species and organ specificity. Two of the blabs (N° 11 and 21) lost their immunoreactivities towards rat kidney GGT in the presence of N-acetyl-neuraminic acid, while immunoreactivities of the other blabs were unchanged. Furthermore, Mabs No 11 and 21 did not react with desialylated rat kidney GGT. These findings suggest that N-acetyl-neuraminic acid is involved in the epitopes recognized by these two Mabs.Abbreviations ELISA
enzyme linked immunosorbent assay
- GGT
gamma-glutamyltransferase
- Mab
monoclonal antibody
- SDS-PAGE
sodium dodecyl sulfate-polyacrylamide gel electrophoresis 相似文献
8.
M Jamal 《Journal of human stress》1985,11(2):60-68
This study examined Type A and Type B differences in job performance, psychosomatic complaints, and career progression among white-collar employees (N = 218) in a field setting. Significant differences were found between Type A's and Type B's in quality of performance, effort exerted at the job, and psychosomatic complaints. Employees' cultural background and sex moderated some of the relationships observed in the study. Implications of the findings for future research on the topic are discussed. 相似文献
9.
T. C. B. Stamp J. M. Round D. J. F. Rowe J. G. Haddad 《BMJ (Clinical research ed.)》1972,4(5831):9-12
Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0·001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 μg daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized. 相似文献
10.
Synthesis of RNA in neurons of the hypoglossal nerve nucleus after axonal section was studied by means of [5-3H]uridine administration and radioautographic counting techniques in mice. The results of the experiments were evaluated by counts of silver grains over the nucleoplasm and cytoplasm of the neurons. RNA synthesis was greater in neurons after axonal section, and this increase was evident from 12 hr after the operation. The greatest increases in the operated side were observed in the 1st, 2nd and 3rd days after operation. In the 7th and 14th days RNA synthesis was still greater in the hypoglossal nucleus of the sectioned nerve but the difference in the control nucleus was not so striking. In the 30th day synthesis of RNA in left and right hypoglossal nuclei was comparable. 相似文献