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Biomedical subjects

J Heller

Publications and source records attributed to J Heller.

At least 19 recordsLinked to original sources

Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device.

A novel, closed-loop drug delivery system was developed where the presence or absence of an external compound controls drug delivery from a bioerodible polymer. In the described delivery system, hydrocortisone was incorporated into a n-hexyl half-ester of a methyl vinyl ehter-maleic anhydride copolymer, and the polymer-drug mixture was fabricated into disks. These disks were then coated with a hydrogel containing immobilized urease. In a medium of constant pH and in the absence of external urea, the hydrocortisone release was that normally expected for that polymer at the given pH. With external urea, ammonium bicarbonate and ammonium hydroxide were generated within the hydrogel, which accelerated polymer erosion and drug release. The drug delivery rate increase was proportional to the amount of external urea and was reversible; that is, when external urea was removed, the drug release rate gradually returned to its original value.

Delayed-Action Preparations

Renal blood flow distribution at varying perfusion pressure in the alloperfused dog kidney.

Tissue blood flow (TBF), its percent distribution and glomerular blood flow (GBF) were measured using labelled microspheres 15 micrometer in diameter (M) and chicken red blood cells (CRBC) at perfusion pressures (PP) of 17.3, 12.8 and 8.0 kPa (130, 95 and 60 mm Hg) in isolated alloperfused dog kidneys. Renal blood flow (RBF) was never interrupted during the isolation. Experiments with M showed a marked inequality of the tissue blood flow in different parts of the renal cortex at a constant PP of 17.3 kPa. TBF was highest in the outermost quarter and lowest in the juxtamedullary one. Using CRBC, a homogeneous TBF was observed in the outer 3/4 of the renal cortex with a lower flow in the innermost quarter. With M, a typical percent "redistribution" of TBF and GBF into the inner cortical regions was indicated during PP reduction. With CRBC, this phenomenon was observed only at PP below the range of RBF autoregulation (8.0 kPa) and was much less conspicuous than with M. The smaller size and higher elasticity of CRBC as compared with M, may result in a more realistic reflection of cortical blood flow distribution. The GBF of outermost superficial glomeruli decreases, even with CRBC, with each PP reduction, the difference exhibiting only a 5% significance level. The lower limit of BF autoregulation in these glomeruli seems to be somewhat higher than that of total RBF autoregulation.

Animals

Autoregulation of superficial nephron function in the alloperfused dog kidney.

Isolated dog kidneys were each pump-perfused by another dog during 4 experimental periods at perfusion pressures (PP) of 21, 17, 13, and 8 kPa, resp. (i.e. 160, 130, 94, and 60 mm Hg). At the 3 highest PP values, the total kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were perfectly autoregulated while at the lowest value both values were significantly lowered. No significant difference was observed between the single nephron GFR (SNGFR) of periods 1 and 2; in period 3 (PP = 13 kPa) a lower value was observed (P less than 0.05). Free flow pressure in proximal convolution (FFP), stop-flow pressure (SFP), and peritubular capillary pressure (PCP) were not different in period 2 than in period 1, but were significantly lower in period 3 (P = 0.02--0.05). Effective filtration pressure (EFP) was the highest in period 1, decreasing significantly with decreasing PP. Filtration pressure equilibrium was observed in period 4 at PP 8 kPa. Total blood flow resistance (RT) fell with decreasing PP, the drop being due to a steep decline in afferent resistance (RA). Efferent resistance (RE) increased as PP decreased. Ultrafiltration coefficient (Kf) rose with declining PP both within and outside the autoregulatory range. The results indicate that the lower limit of autoregulation is higher in superficial nephrons than in the whole kidney.

Animals

The effect of renal arterial infusion of albumin and dextran on tubular fluid reabsorption in the dog.

Albumin or Dextran solutions of varying concentration were infused into the renal artery of hydropenic dogs. Their effect on urine flow, sodium excretion, creatinine and PAH clearance, single nephron GFR, fractional and absolute fluid reabsorption in the proximal convolution, reabsorptive t1/2, and hydrostatic pressures in the proximal tubules and adjacent capillaries was compared with a similar infusion of isotonic saline solution. Six, 9, 12, 18 and 25% albumin and 6% Dextran solution did not significantly change the measured parameters. Infusion of 9 and 12% Dextran solution elicited a decrease in water and sodium excretion as well as absolute and fractional proximal tubular fluid reabsorption to a 5% level of significance. Infusion of 18% Dextran was accompanied by a marked decrease in total and proximal reabsorption combined with a decline of GFR, PAH clearance, and hydrostatic pressures in tubules and peritubular capillaries. The results do not support the hypothesis of a direct action of oncotic pressure on tubular fluid reabsorption; the above described effects of Dextran seem to be accounted for by its other "pharmacological" effect.

Absorption

Autoregulation of renal blood flow in the rat.

Renal blood flow was measured in rats anaesthetized with pentobarbital sodium by employing the PAH clearance method and the 133Xe washout technique. Both methods were in good agreement. In 17 rats a 25% decrement of blood pressure was attained through haemorrhage: RBF measured by PAH clearance declined by 3%, according to 133Xe washout by 2.7%. In futher 21 rats an increase of blood pressure by an average of 26% was achieved by occlusion of the carotid arteries; RBF measured by PAH clearance declined by 3% according to 133Xe washout by 1.1%. RBF was therefore almost perfectly autoregulated during both experimental manoeuvres: glomerular filtration rate (inulin clearance) was autoregulated in a similar manner. Water and sodium excretion changed in proportion to changes of blood pressure.

Animals

Intracellular retinol-binding proteins from bovine pigment epithelial and photoreceptor cell fractions. Purification of high molecular weight lipoglycoproteins.

Cytosol retinol (vitamin A)-binding lipoglycoproteins were isolated from preparations of bovine retinal pigment epithelial cells and from rod photoreceptor outer segment fractions. The lipoglycoproteins had molecular weights of at least 1.5 X 10(6) as determined by gel filtration chromatography. The purified lipoglycoprotein which was obtained from pigment epithelial cells contains at least two kinds of polypeptide subunits (molecular weight about 35,000 and 150,000), while the rod outer segment cytosol lipoglycoprotein contains at least four kinds of polypeptide subunits (molecular weight about 50,000, 75,000, 120,000, and, 200,000). The pigment epithelial cytosol retinol-binding material contains about 30% (by weight) of lipid, while the material obtained from rod photoreceptor outer segment fractions contains about 65% (by weight) of lipid. Both lipoproteins contain predominantly cholesterol and phosphatidylcholine, while cholesterol esters, triglycerides, phosphatidylethanolamine, and phosphatidylserine are absent. The amino acid compositions of the delipidated proteins from pigment epithelial cells and rod outer segment fractions are similar. The neutral and amino sugars are co-valently linked to the polypeptide moiety of the molecule. The absorption and circular dichroism spectra of the lipoproteins obtained from pigment epithelial cells and rod outer segment fractions are different.

Amino Acids

Characterization of bovine plasma retinol-binding protein and evidence for lack of binding between it and other bovine plasma proteins.

Bovine retinol-retinol-binding protein (RBP) was isolated from serum as a free, uncomplexed protein under experimental conditions in which human, rabbit, and chicken retinol-RBP are present as tight complexes with prealbumin (thyroxine-binding protein). Purified bovine retinol-RBP formed tight complexes with purified human and chicken prealbumin in physiological ionic strength buffers as judged by gel filtration chromatography, hyperchromic effect on the absorption spectrum of retinol-RBP, and changes in the circular dichroism spectrum. Addition of purified human prealbumin to whole bovine serum shifted the elution position of the specific retinol-RBP fluorescence from a gel filtration column, indicating complex formation in the whole bovine serum. It was concluded from this series of experiments that bovine serum lacks a protein with the binding properties of prealbumin and that bovine retinol-RBP has the normal potential binding to human, chicken, and presumably other prealbumins. Bovine retinol-RBP has a molecular weight, amino acid composition, absorption, and fluorescence spectra which are indistinguishable from that of human retinol-RBP, although the magnitude of the optical rotatory strength of the induced circular dichroism signal at 330 nm was 50% larger in the bovine than in the human material (1.65 and 1.1 Debye-Bohr magnetons, respectively). About 12 liters of bovine and human urine were concentrated by pressure dialysis and a search was made for retinol-RBP using gel filtration and ion exchange chromatography. No retinol-RBP was found in either of these species. This suggested that if, indeed, bovine retinol-RBP is filtered through the kidney's glomeruli due to small molecular size (molecular weight 21,000), there are efficient mechanisms of tubular reabsorption.

Amino Acids