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J L Imbs

Publications and source records attributed to J L Imbs.

At least 199 records · Page 11Linked to original sources
PubMedDate not supplied

[Anti-angiogenesis effects of aldosterone antagonist diuretics].

Angiogenesis requires endothelial cell proliferation and their vascular rearrangement. A report of inhibiting effect of spironolactone on smooth muscle cell proliferation led us to study in vitro the effects of this drug on the endothelial cell proliferation and migration. Spironolactone (10 to 100 microM) and one of its active metabolite, canrenone (10 to 100 microM), are added to human umbilical vein endothelial cells (HUVEC). Their effect on cellular proliferation is evaluated by measuring the amount of the cellular nucleic acids using a fluorometric assay (CyQuant). Cell migration is measured using a multiwell chamber assay (Transwell). In further experiments, we investigated their effect on the capillary-like tube formation in vitro generated by HUVEC seeded in a three-dimensional biological gel (Matrigel). The VEGF (10 ng/mL) and the bFGF (10 ng/mL) were used as mitotic and cell differentiation factors. Effect on cell cycle distribution is investigated by flow cytometry analysis. Spironolactone inhibits HUVEC proliferation but canrenone does not have any significant effect. The growth promoters VEGF or bFGF do not modify inhibiting effect of spironolactone. Spironolactone (50 microM) and canrenone (50 microM) are without effect on cell migration. Capillary-like networks on Matrigel is not modified by spironolactone or canrenone. Spironolactone inhibits progression through S phase of the cell cycle. Spironolactone inhibits the proliferation of the endothelial cells in vitro but shows no effect on their migration and their rearrangement in capillary-like structures. These data should be confirmed in models of angiogenesis in vivo.

Canrenone↗
PubMedDate not supplied

[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats].

Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.05%) and control were implanted into the dorsal subcutaneous space of wistar rats. After 14 days of implantation, an invasion of the fibrin gel chamber by neovascularised buds had occurred through the holes. The number of vessels in the central field and in two or three peripheral fields covering the surface of the bud, were measured for each drug tested and compared to the control. In spironolactone treated chambers, the numbers of peripheral and central vessels were significantly reduced compared to control (p < 0.001). Canrenone, eplerenone and DMSO did not reduce the number of vessels (m +/- ESM, ANOVA followed by Newman-Keuls test). Spironolactone but not canrenone, nor eplerenone inhibited vessels formation in vivo. This antiangiogenic activity appeared to be not related to the antimineralocorticoid effect of spironolactone.

Amenorrhea↗
PubMedDate not supplied

[Clinical pharmacology of prostacyclin and stable analogs].

Prostacyclin (PGI2) has vasodilatory effects and a powerful platelet anti-aggregating action. Receptors which may be common to prostaglandin E1 have been described on the platelet membranes, the uterus and various human arterial segments. The platelet activity is linked to the activation of adenylate-cyclase, coupled with a G protein. The mechanisms of the vasorelaxant effect have still not been fully studied. PGI2 is synthesized and released in vessels by the endothelium and the smooth muscle cells, and is very unstable. Its short half-life probably restricts its role to local regulation of platelet activity and vasomotricity. The kinetics and pharmacological effects of prostaglandins have been studied during intravenous injections in healthy volunteers and patients. The synthesis of numerous stable analogues is designed to produce drugs which can be administered orally to treat arteriopathies. The side-effects linked with the vasodilatory effects restricts the use of maximally active dosage.

Epoprostenol↗
PubMedDate not supplied

[Iatrogenic fluorosis. 2 cases].

Two new cases of osteofluorosis are presented. They are attested by the existence of a bone X-ray densification, by histological lesions of hyperosteoidosis and a large increase in the fluorine content. One is a 61 year-old man who consumed 2.5 l a day of Vichy St-Yorre (a mineral water containing 8 mg of fluorine ions per litre) during 11 years; the other, an 86 year-old man who during 20 years took 500 mg of niflumic acid a day, a non-steroidal anti-inflammatory drug containing 3 fluorine atoms per molecule (i.e., 50 mg fluorine per 250 mg gellule). Both these hypertensive patients had severe renal insufficiency. These two observations serve as a reminder of the indispensable precautions to be observed when prescribing fluorine salts in the treatment of post-menopausal osteoporosis: at least the plasma creatinine level should be available in order to calculate the endogenous creatinine clearance and any possible supplementary intake of fluorine salts should be checked.

Aged↗
PubMedDate not supplied

Effects of SK&F 82526 and SK&F 83742 on the renal vascular dopamine receptor.

The renal vascular effects of benzazepine derivatives were studied on the isolated perfused rat kidney in the presence of phenoxybenzamine and sotalol after contraction of the vascular bed with prostaglandin F2 alpha. SK&F 82526 was a very potent dopaminomimetic drug (ED50 = 7.6 +/- 0.8 X 10(-9) M) on the renal vascular dopamine receptor. It displayed partial agonist activity (similar to SK&F 38393) and was devoid of alpha-adrenomimetic effects. SK&F 83742 was a potent dopaminolytic drug. It antagonized dopamine-induced relaxation of the renal vascular bed in a competitive way, with an apparent pA2 of 7.47 +/- 0.23.

Animals↗
PubMedDate not supplied

Binding of (3H)-piretanide to a specific receptor of renal medulla.

We had previously demonstrated that (3H)-piretanide binds to a receptor located on medullary membranes of canine kidney. Here we show that binding is specific for a particular group of loop diuretics. Sulfonamide diuretics of the benzoic acid family, other substituted sulfonamides, and phenoxy-acetic acid derivates displace (3H)-piretanide from its receptor. Loop diuretics that do not act at the luminal tubular membrane do not displace piretanide, nor do diuretics with a different site and mode of action (thiazides; inhibitors of the Na+/H+ antiporter (amiloride), of Na+K+ ATPase (ouabain), or of carbonic anhydrase (acetazolamide). We demonstrate that no interference occurs between the piretanide receptor and membrane bound receptors of several neurotransmitters.

Animals↗
PubMedDate not supplied

[Interaction between non-steroidal anti-inflammatory agents and lithium salts].

Since the first observation in 1978, it has been clearly established that the non-steroidal anti-inflammatory drugs (NSAIDs) interfere with the pharmacokinetics of lithium: by reducing urinary clearance of the metal, they can raise the plasma lithium level and thus lead to intoxication. Among the NSAIDs available in France, this interaction has been reported with phenylbutazone (Butazolidine, Carudol), diclofenac (Voltarène), indomethacin (Indocid) and its antalgic derivative clomethacin (Dupéran), ketoprofen (Profenid), mefenamic acid (Ponstyl), niflumic acid (Nifluril) and piroxicam (Feldène). This interaction does not occur with aspirin; this exception suggests that the inhibition of prostaglandins synthesis is not the mechanism responsible for the decrease in the urinary elimination of lithium linked with an increase in its tubular reabsorption. In practice, in view of the growing diffusion of NSAIDs, it is necessary to inform all patients under lithium treatment of the risk of interaction resulting from their use.

Animals↗