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Biomedical subjects

J Diez

Publications and source records attributed to J Diez.

At least 91 records · Page 5Linked to original sources

Stimulation of K+ fluxes by diuretic drugs in human red cells.

Two different families of diuretic drugs--(i) (aryloxy)acetic acid diuretics (ethacrynic acid, tienilic acid and (--)-indacrinone) and (ii) furopyridines [(+/-)-BN 50157 and (+/-)-cycletanide]--stimulate K+ movements across human red cell membranes. The kinetic properties of this effect (K+-specificity, saturability, optical isomerism, antagonism by structural analogues, etc.) strongly suggest that it is mediated by a K+-transport system with a specific binding site for some diuretic drugs. The stimulated K+ fluxes are resistant to ouabain, bumetanide and quinine, thus suggesting that they are not mediated by the Na+,K+-pump, Na+,K+-cotransport or by the Ca2+-dependent K+-permeability ('Gardos effect'). The replacement of Cl- by NO3- ions can either decrease, increase or have no effect on the stimulated K+ fluxes, depending on the diuretic drug. Although not conclusive, these observations suggest that the K+ fluxes are not mediated by stimulation of a chloride-dependent K+ carrier. The study of structural analogues showed that the intensity of the stimulation of K+ fluxes is strongly correlated with the magnitude of the natriuretic effect. Curiously, some antiallergic furopyridines are able to inhibit K+ fluxes.

Bumetanide↗

Intracerebroventricular infusion of sodium chloride-rich artificial cerebrospinal fluid in rats induces natriuresis and releases an inhibitor of prostaglandin synthesis.

Urinary sodium excretion in anaesthetized rats subjected to high-sodium artificial cerebrospinal fluid (CSF) infusion into the lateral brain ventricle, was significantly higher than in rats infused with normal-sodium CSF. Urinary immunoreactive 6-ketoprostaglandin F1 alpha, the stable derivative of prostacyclin, was significantly reduced in the high-sodium CSF group, as compared with the normal-sodium CSF group. When dog aortic endothelium was incubated in the presence of plasma, endothelial prostacyclin production was found to be inhibited by plasma from rats infused with high-sodium CSF compared with the effect of plasma from the rats infused with normal-sodium CSF. Our results indicate that intracerebroventricular infusion of high-sodium CSF induces a natriuretic response and is associated with the appearance of a humoral factor which blocks prostacyclin biosynthesis.

6-Ketoprostaglandin F1 alpha↗

Ion transport, prostaglandins, and essential hypertension.

Prostaglandins (including PGE1, PGE2 and PGI2) showed little or no effect on Na+ and K+ transport across human red cell membranes. Conversely, they were able to: i) inhibit Na+, K+ cotransport system, ii) stimulate Na+, K+-pump and iii) stimulate Na+, Ca2+ exchange in mouse macrophages. These effects which seem to be mediated by cyclic AMP, provoke a more rapid extrusion of a cell Na+ -load. This may counterbalance the abnormal cell Na+ regulation that appears to be associated with essential hypertension.

Animals↗

An analysis of the positive inotropic effect of AR-L 115 BS on isolated rat atria.

The effect of AR-L 115 BS on mechanical and electrical properties of isolated rat atria was investigated. AR-L 115 BS (10(-7) M -5 X 10(-4) M) produced a dose-dependent increase in rate, contractile force and df/dtmax and shortened the sinus node recovery time and the effective refractory period. The increase in contractile force occurred concomitantly with an increase in the height of the plateau of the atrial action potential. The positive inotropic effect produced by AR-L 115 BS depended on the external Ca concentration and was diminished in low Na solution. The drug also decreased the amplitude-interval relationship and post-extrasystolic potentiation. The positive inotropic effect of AR-L 115 BS was inhibited by verapamil and caffeine. These results suggest that in isolated rat atria the positive inotropic effect of AR-L 115 BS might be due to an increase in transmembrane Ca influx into atrial fibres as well as to an effect probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.

Animals↗

Inotropic and electrophysiological effects of PY 108-068 on isolated cardiac preparations.

The inotropic and electrophysiological effects of PY 108-068 (PY), a new Ca-antagonist agent, were studied on isolated atria and guinea-pig papillary muscles. On isolated atria PY produced a dose-dependent decrease in amplitude and rate of spontaneous contractions. This negative inotropic effect was more evident at fast stimulation rates. PY decreased the maximum inotropic and chronotropic responses to isoprenaline and caused a dose-response parallel shift of the Ca dose-response curve. On papillary muscles, PY produced a shortening in action potential duration without changes in the resting potential and the Vmax and amplitude of phase O. PY also produced a dose-dependent decrease in amplitude and Vmax and a shortening of the duration of the slow action potentials elicited by isoprenaline in K (27 mM)-depolarized papillary muscles. These results suggest that in isolated right atria and guinea-pig papillary muscles PY produced a selective inhibition of Ca Influx via the slow inward current.

Action Potentials↗

The effect of cyclic nucleotides and icosanoids on Na+ and K+ transport in human red cells.

Cyclic AMP inhibits the bumetanide-sensitive Na+,K+ cotransport system in human red cells. The cotransport inhibition is enhanced by addition of phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine to the incubation medium. The cyclic AMP concentration giving half-maximal cotransport inhibition showed a wide variation among different individuals (from 0.1 to 5 mM external cyclic AMP concentration). In contrast to cyclic AMP, cyclic GMP showed little effect on the cotransport system. The ouabain-sensitive Na+,K+ pump was almost unaffected by cyclic nucleotides. Prostacyclin was the only tested prostaglandin showing an effect on Na+ and K+ transport in human red cells. In some individuals, this icosanoid stimulated the Na+,K+ cotransport system. Leukotriene B4 stimulated K+ fluxes.

1-Methyl-3-isobutylxanthine↗

Molecular heterogeneity of ferredoxin:NADP+ oxidoreductase from the cyanobacterium Anabaena cylindrica.

The enzyme ferredoxin:NADP+ oxidoreductase (EC 1.18.1.2) from whole filaments of Anabaena cylindrica can be separated into four major fractions by chromatography on phosphocellulose; chromatography using ferredoxin-Sepharose 4B proved to be less satisfactory in separating the fractions. The purified fractions, designated 1, 2, 3 and 4, all showed diaphorase and ferredoxin-dependent cytochrome c reductase activity. The major fractions present were 2 and 3 which were each obtained in an electrophoretically homogeneous state (forms 2 and 3) and represented 30-37% and 30-42%, respectively, of the total enzyme activity. Each was a monomeric species with a molecular weight of approx. 33 000 as determined by gel filtration and sodium dodecyl (SDS)-polyacrylamide gel electrophoresis. Evidence for the presence of a 70 000 molecular weight dimer was also obtained. Forms 2 and 3 had isoelectric points of 5.75 and 6.0, respectively, had similar kinetic properties and were flavoproteins. Extracts of isolated heterocysts showed no form 2 or 3 activity but contained a single form which closely resembled one of the species present in fraction 4; fraction 1 may have been a purification artifact because it was not detected in crude extracts of the cyanobacterium.

Cyanobacteria↗

Membranous glomerulonephritis secondary to hydatid disease.

To study the association of hydatid disease of the liver with a nephrotic syndrome we processed renal biopsy tissue for light microscopy, immunofluorescence and electron microscopy studies. These procedures disclosed the typical features of a membranous nephropathy whereas indirect immunofluorescence revealed glomerular deposits of hydatid antigen. Rabbits, previously immunized with bovine hydatid fluid, provided the specific antiserum. Clearly, the pathogenicity of this parasitosis derives, in part, from its immunologic repercussions. In this regard, our results support an etiopathogenic role for hydatid antigen in an immune-mediated glomerulonephritis.

Aged↗

Studies on benzene mutagenesis. I. The micronucleus test.

The mutagenic action of benzene was studied by means of the micronucleus test performed on mice. A linear dose effect relationship was found for the percentage of micronucleated erythrocytes, against the benzene-dose logarithms. A significant dose effect correlation was found either after the standard 30-h experiments or after a prolonged 54-h one. A higher effect was found in the prolonged experiments, suggesting the induction of a delay in the cell cycle by benzene.

Animals↗

Purification and properties of assimilatory nitrate reductase [NAD(P)H] from Ankistrodesmus braunii.

Assimilatory nitrate reductase [NAD(P)H] (EC 1.6.6.2) from Ankistrodesmus braunii has been purified to homogeneity by a simple procedure that utilizes as the main step affinity chromatography on Blue-Sepharose. The best enzyme preparation has a specific activity of 61.25 units/mg protein. The enzyme has a sedimentation coefficient of 10.9 S by sucrose-density-gradient centrifugation, and a Stokes radius of 9.8 nm was estimated by gel filtration techniques. Its molecular weight is 460000, but only one single band of 58000 was detected after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The native enzyme seems thus to be composed of eight subunits. The nitrate reductase absorption spectrum shows wavelengths maxima at 280 and 416 nm and a broad shoulder at 450 nm. Reduced enzyme shows maxima at 424 (Soret), 527 (beta) and 557 (alpha) nm, and a bleaching at 450 nm. The reduced extracted heme chromophore, in pyridine and KOH, shows absorption bands at 414, 522 and 552 nm. These properties indicate the presence of a b-type cytochrome and flavin as prosthetic groups of A. braunii nitrate reductase. A minimum of four molecules of heme has been calculated per molecule of the enzyme complex. Redox titration of the enzyme shows a midpoint potential for the heme of -73 mV at pH 7.0. In the presence of p-hydroxymercuribenzoate, which inhibits the NAD(P)H-dependent activities of the complex, the enzyme-bound heme can be reduced with dithionite, but not with NAD(P)H.

Centrifugation, Density Gradient↗

Metabolism of the polyadenylate sequence of nuclear RNA and messenger RNA in mammalian cells.

The poly(A) sequences at the 3' end of mRNA and nuclear RNA molecules of mouse sarcoma and Chinese hamster cells are subject to an elongation process distinct from de novo synthesis. This process continues in cells treated with a high level of actinomycin D to block transcription. This results in the labeling of the steady-state poly(A) population in the cytoplasm and of unusually long poly(A) segments in the nucleus. In cells incubated with 3H-adenosine in the absence of drug treatment, cytoplasmic steady-state poly(A) segments with short labeled sequences at the 3' end can be detected by their heterogenous size distribution and by measurements of adenosine and AMP released by alkaline hydrolysis. These measurements indicate an average size of 8 residues for the labeled sequences. In the nucleus, a slow elongation of preexisting poly(A) chains can also be detected through measurements of AMP and adenosine. The cytoplasmic elongation process leads to turnover of the 3' end of the poly(A) sequence on mRNA, because of concomitant removal of AMP residues. It is apparently not linked to mRNA translation. The Chinese hamster and mouse sarcoma cells appear to differ markedly with respect to relative extents of poly(A) chain extension and de novo synthesis.

Adenine Nucleotides↗

Elongation of the polyadenylate segment of messenger RNA in the cytoplasm of mammalian cells.

Chinese hamster and mouse sarcoma 180 ascites cells, treated with high levels of actinomycin D, still carry out limited poly(A) synthesis. The residual activity, which consists of poly(A) chain extension in the cytoplasm as well as in the nucleus, is essentially insensitive to cordycepin. Nuclear polyadenylation proceeds linearly and involves the gradual extension of unusually long poly(A) sequences. Cytoplasmic poly(A) labeling is initially more rapid than in the nucleus, but levels off within 5-10 min. It consists of addition of seven to eight AMP residues to the poly(A) sequences in preexisting mRNA molecules. The levelling off can be accounted for by a rapid turnover of the extremity of the poly(A) chain in the mRNA. Cytoplasmic poly(A) chain extension can be detected in cells not subjected to the actinomycin treatment. The rate of this process is of the same order of magnitude as that of new poly(A) transfer from nucleus to cytoplasm. It could serve to control the length of the poly(A) sequence in mRNA.

Adenine Nucleotides↗

Effect of intrarenal adenosine on urinary excretion of prostaglandins and leukotrienes in the anesthesized dog.

Adenosine is a renal vasoconstrictor that plays an important role in mediating renal adaptive responses to decreases in renal perfusion pressure. It is known that adenosine acts on the metabolism of arachidonic acid, but the direct repercussions of adenosine in the production of renal prostaglandins and leukotrienes have not been studied. This study was undertaken to evaluate the effect of the intrarenal infusion of adenosine upon the urinary elimination of arachidonic acid derivatives. Samples of urine were collected with lysine acetylsalicylate and determination of prostaglandins (PGs) and leukotrienes (LTs) was performed by radioimmunoassay of samples previously separated by HPLC. The infusion of adenosine decreases the urinary excretion of 6-keto-PGF1 alpha and TxB2 significantly. There was no significant change in urinary excretion of PGE2 while LTB4 and LTC4 showed a tendency to increase. These results suggest that a fall in the synthesis of PGI2 along with an increase in LTC4, which is a constrictor of mesangial cells, could be responsible for the renal vasoconstriction phase of adenosine. Therefore, it was concluded that adenosine vasoconstriction is mediated through the inhibition of the cyclo-oxygenase pathway, diminishing the synthesis of PG vasodilators.

6-Ketoprostaglandin F1 alpha↗

Myocardial calcification following heart transplantation.

A case of dystrophic calcification of the myocardium in the transplanted heart of a 34-year-old man is presented. The calcification appeared immediately after transplantation with massive progression until the thirty-fifth day when the patient died. Pulmonary hypertension, cardiac surgery, administration of steroids and calcium chloride, in addition to transitory acute renal failure may be the multicausal factors that produced this myocardial calcification.

Adult↗

[Nephrologic aspects of amyloidosis].

Amyloidosis is a syndrome characterized by intercellular deposition of a predominantly proteic substance in any organ and tissue. The kidney is one of the most affected organs and very important in as much as its involvements might produce the initial manifestations of the syndrome and could be the one responsible to establish the prognosis in many cases. In this paper, the most relevant features of the different types of renal amyloidosis (glomerular, vascular and tubulo-interstitial), and one special type of amyloidosis in patients on chronic hemodialysis and likewise other interesting aspects in the evolution of amyloidosis of kidney transplanted patients were reviewed. Emphasis was placed on renal vascular amyloidosis and on amyloidosis among patients on hemodialysis as these might deserve special clinical and etiopathogenic considerations according to our own experience.

Amyloidosis↗