PubMed Health⌕ Search

Biomedical subjects

D Stephan

Publications and source records attributed to D Stephan.

80 records · Page 5Linked to original sources
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

[Angiogenesis and arteriogenesis are increased in the SHR at the pre-hypertensive stage].

OBJECTIVE: A microvascular rarefaction by angiogenic deficiency could promote the onset of hypertension in SHR, in young hypertensive patients and in normotensive descendants of hypertensive parents. We studied the angiogenic potency in prehypertensive SHR, in fibrin chambers implanted in rats, an in vivo model of angiogenesis. METHODS: Four-week pre-hypertensive SHR (n=9) and controls WKY (n=9) were implanted with fibrin gel chambers. The chamber is a cylinder (dia.: 13 mm; H: 5 mm) whose base is perforated with 10 holes of 0.8 mm. The chambers are filled with rat fibrin and implanted (n=4) into the rat dorsal subcutaneous space. After 14 days, vasculo-conjunctive buds have invaded the fibrin gel through the holes and the chambers are removed, fixed and coloured. The intact vascular buds were studied using optical microscopy. The number of vessels counted in central field corresponds to the vascular pedicle, the average number of vessels counted in 3 peripheral fields, represents the vascular branching. The number of arterialised vessels including at least 2 layers of SMC was counted in the central field of each bud. RESULTS: Both rat strains remained normotensive all along the experiment. In SHR fibrin chambers, the number of peripheral vessels (20 +/- 2.6 vs 9.5 +/- 3; p<0.0001) and the number of central arterialized vessels (7.5 +/- 2 vs 2.1 +/- 1.3; p<0.0001) was significantly higher compared to WKY. CONCLUSION: Angiogenesis and arteriogenesis are increased in pre-hypertensive SHR compared to WKY. These results plead against a microvascular rarefaction hypothesis in these genetically hypertensive rats.

Animals↗
PubMedDate not supplied

[Gene transfers of kallikrein, bradykinin receptor B2 and a mutated B2 receptor stimulate neoangiogenesis in peripheral ischemia].

In this work, we evaluated the angiogenic effect of the gene transfer of human tissue kallikrein (TK), bradykinin B2 receptor (B2R) and a mutated form (RB2m) in a rabbit peripheral model of ischaemia. We studied the effects of the transfection of each of these factors and the effects of their co-transfection. In New Zealand anesthetised rabbits we first induced an ischaemia of the left posterior leg by ligation-excision of the superficial femoral artery and its collaterals. Seven days later, we performed i.m. injections in the ischemic tight with transfection solutions containing either the control (pcDNA3 empty backbone) or the pcDNA3-TK, the pcDNA3-TK and the pcDNA3-B2R, the pcDNA3-TK and the pcDNA3-B2Rm. Twenty eight days later, the therapeutic effect was evaluated using ultrasonographic debitmetry of the common iliac artery, perfusion index (PI) = ischemic leg blood flow /non ischemic leg blood flow (%) and capillaries measurements i.e. capillary density: number of vessels/mm2 and the ratio of vessels/muscular fiber, in the adductors and gastrocnemian muscles. The PI was increased in each treated group vs control (32.61 +/- 5.2%), pcDNA3-TK: 59.72 +/- 2.33%; p = 0.001; pcDNA3-RB2: 55.25 +/- 2.29%; p = 0.008; pcDNA3-TK + pcDNA3-RB2: 84.77 +/- 3.15%; p < 0.001; pcDNA3-TK + pcDNA3-RB2m: 103.25 +/- 4.9%; p < 0.001. The capillary density and the vessel/muscular fiber ratio increased in a parallel with the hemodynamic in the ischemic adductors (pcDNA3-TK + pcDNA3-B2Rm > pcDNA3-TK + pcDNA3-RB2 > pcDNA3-TK = pcDNA3-B2R; p < 0.001). There was no angiogenic effect measurable neither in the non ischemic adductors (right) nor in the gastrocnemian muscles. In rabbit peripheral ischaemia, the cotransfection of TK and B2R increases the arterial flow in the treated leg and potentiates the neoangiogenesis. Cotransfection of the B2Rm cDNA enhanced the synergic effect of this therapeutic strategy.

Animals↗
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

[Aldosterone antagonists: new pharmacologic prospects].

The pharmacology of the mineralocorticoid receptor antagonist spironolactone and analogues is reviewed in the light of recent discoveries regarding the primary structure of corticosteroid receptors and the different isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase. The type 2 isoform of this enzyme functions in some tissues to keep the aldosterone receptor activation specific, i.e. it allows stimulation by aldosterone while eliminating glucocorticoids such as cortisol and corticosterone. The type 2 isoform has been shown in the colon, hypothalamus, kidney, placenta and salivary gland. New clinical uses of aldosterone antagonists may be derived from these developments. Most prominent in this respect appear to be myocardial fibrosis and specific forms of hypertension with altered mineralocorticoid receptor functioning and deficiencies in the protection system of the receptor against glucocorticoids.

Animals↗