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Biomedical subjects

D Stephan

Publications and source records attributed to D Stephan.

At least 73 records · Page 4Linked to original sources
PubMed1991

Effects of dopamine prodrugs and fenoldopam on glomerular hyperfiltration in streptozotocin-induced diabetes in rats.

The effects of dopamine (DA) prodrugs (L-dopa and gludopa) and of a D1-selective agonist (fenoldopam) on glomerular hyperfiltration were studied in the early stage of diabetes in rats. Wistar rats received one injection of streptozotocin (STZ) and were treated 1 week later with L-dopa (2 x 10 mg/kg/day, s.c.), gludopa (2 x 3 or 2 x 10 mg/kg/day, s.c.), or fenoldopam (2 x 0.3 or 2 x 1 mg/kg/day, s.c.). Their renal functions were compared with those of untreated diabetic and nondiabetic control rats. STZ injection led to hyperglycemia that was kept moderate (20-25 mmol/L) by daily insulin therapy (2-4 U of NPH insulin). Within 2 weeks, glomerular hyperfiltration (polyfructosan clearance) developed in diabetic rats (30% increase vs. nondiabetic control). A rise in renal plasma flow (PAH clearance) was sometimes observed. One week of treatment with either L-dopa, gludopa, or fenoldopam normalized the glomerular filtration rate and decreased filtration fraction. These corrections occurred despite similar metabolic disturbance and kidney hypertrophy. Gludopa was less well tolerated by diabetic rats than L-dopa. Results with L-dopa showed that the normalization of glomerular hyperfiltration was linked to DA synthesis and stimulation of D1 receptors, since it was reversed by carbidopa, a dopa decarboxylase inhibitor, and by SCH 23390, a D1-selective antagonist. These data show that DA prodrugs and a D1 agonist can suppress diabetic glomerular hyperfiltration in the very early course of the disease in rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

[Comparison of the efficacy and tolerability of sustained-release verapamil and captopril in mild to moderate essential arterial hypertension].

A randomised, double-blind, double-placebo trial compared the efficacy and safety/acceptability of sustained release verapamil and of captopril in two parallel groups of patients with mild to moderate hypertension. After a 2 week placebo period, 45 patients were randomised into 2 groups, the 1st group (n = 22) given sustained release verapamil (240 mg/24 h) as a single morning dose and the second (n = 23) captopril 25 (50 mg/24 h) as two daily divided doses. Treatment was given for 75 days, with the possibility of a combination of sustained release verapamil + captopril from day 45 onwards if diastolic blood pressure remained at 95 mmHg or more. After 45 days of treatment, the reduction in supine diastolic blood pressure did not differ significantly in the 2 groups (-10.4 mmHg in the sustained release verapamil group and -9.7 mmHg in the captopril), with 68.2 per cent responders to sustained release verapamil and 52.2 per cent in the captopril group. After 75 days of treatment, once again there was no significant difference in efficacy between the two groups: -14 mmHg for diastolic pressure and 80 per cent responders in patients treated with sustained release verapamil, -11.3 mmHg and 62.5 per cent responders in the captopril group. The percentage of responders was 58.3 per cent in the group treated with the combination of sustained release verapamil + captopril from day 45 onwards. The number of patients showing evidence of clinical or electrocardiographic adverse reactions was not significantly different: 20.7 per cent in the sustained release verapamil group and 34.8 per cent in the captopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Management of hypertensive patients in private practice].

In private practice mild or moderate arterial hypertension is controlled primarily to prevent the development of a severe, organ-damaging hypertensive disease. The general practitioner's approach to management proceeds in 3 steps. 1) He must decide to initiate a treatment after obtaining sufficient evidence that the hypertension is permanent and after starting to correct the associated risk factors. 2) He must select a single-drug initial treatment among the four families of antihypertensive medications, viz.: diuretics, beta-blockers, angiotensin-converting enzyme inhibitors and calcium antagonists. The selection is based on the information available concerning the benefit/risk ratio of the preferred drug, its interactions with the pathologies that are often associated with hypertension, and its acceptability. Finding for each patient the optimal dosage with maximum effectiveness and minimum undesirable side-effects is of prime importance. 3) If this initial treatment fails, the practitioner must first make sure that his prescription was optimal in dosage and compliance. If this was the case, he must make a choice between another single-drug therapy and a combination therapy, using by preference two synergistic drugs in low doses.

Antihypertensive Agents↗
PubMed1990

Effect of tertatolol and of its metabolites and structural analogues in isolated perfused rat kidney vasculature.

The renal vascular effect of tertatolol and analogues was investigated in isolated rat kidney perfused at constant flow in an open circuit with Krebs-Henseleit solution after vascular tone had been reestablished by bolus injections of serotonin or other vasoconstrictor drugs. Against serotonin-induced vasoconstriction, (+/-)tertatolol (3 X 10(-7)-3 X 10(-5) M) evoked concentration-dependent relaxation (IC 50 = 4.6 +/- 0.4 X 10(-6) M), (-)tertatolol was more active than the racemic and (+)tertatolol was less active. (+/-)Tertatolol competitively antagonized serotonin-induced renal constriction (pA2 = 5.6 +/- 0.2). Tertatolol metabolites (4-OH tertatolol, 4,5-di-OH tertatolol, and sulfoxy tertatolol) were inactive. (+/-)Sotalol and (+/-)nadolol, were also inactive in this model and (-)bunolol induced renal vasodilatation only at concentrations 40 times higher than (-)tertatolol. The renal response to tertatolol was not linked to release of prostaglandins or dopamine or to interaction with the dopamine receptor, since neither indomethacin nor SCH 23390 affected tertatolol-induced renal vasodilatation. Tertatolol also elicited relaxation of N6-cyclohexyladenosine-induced renal vasoconstriction (34 +/- 7% relaxation at 3 X 10(-5) M) but was inactive when renal vascular tone was raised by prostaglandin F2 alpha, angiotensin II, or neuropeptide Y in the presence of norepinephrine.

Adrenergic beta-Antagonists↗
PubMed1990

[Ventricular arrhythmia in moderate essential arterial hypertension. Review of the literature apropos of 2 cases].

The authors report two observations of severe ventricular arrhythmias is two hypertensive patients without coronary disease. In the light of these observations and of a literature review, they recall the frequency of these arrhythmias, their possible role in the event of the sudden death of the hypertensive subject without coronary disease and their physiopathology, where the left ventricular hypertrophy is predominant. They also try to draw the practical guidelines for the management of the hypertensive patient.

Aged↗
PubMed1989

[Vasodilator effect of tertatolol on isolated rat kidney].

Tertatolol, a non cardioselective beta-blocker, maintains or increases renal blood flow in animals and in man. In this work, we confirmed in vitro the renal vasodilator effect of tertatolol and we investigated its mechanism. The rat kidney was isolated and perfused at constant flox in an open circuit with a Krebs-Henseleit solution. A vascular tone was restablished by sequential bolus injections of serotonine (every 5 mn) at a dose increasing perfusion pressure by 40 mm Hg. Tertatolol and other drugs were perfused at increasing concentrations during successive periods of 15 mn. Any relaxation was expressed as percentage inhibition of the initial vaso-constriction induced by serotonine. Tertatolol (3 x 10(-7) to 3 x 10(-5) M) induced a concentration-dependent renal vasodilatation (CI50 = 4.6 +/- 0.4 x 10(-6) M, n = 5) with a maximum effect of nearly 100 p. 100 relaxation. (-) tertatolol and (+) tertatolol were respectively more and less active (CI50 = 1.7 +/- 0.3 x 10(-6) M and 10.6 +/- 2.5 x 10(-6) M, n = 5). Tertatolol metabolites (4-OH tertatolol and sulfoxytertatolol) were inactive, excluding a vascular effect of tertatolol related to its metabolism into vasoactive derivatives. Other beta-blocking drugs, (+/-) sotalol and (+/-) nadolol, were also inactive on the renal vasculature and (-) bunolol only induced renal vasodilatation at concentrations 40 fold higher than that of (-) tertatolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

Orientation and molecular map position of the complement genes in the mouse MHC.

Over the past few years six gene clusters have been isolated from the major histocompatibility complex (MHC) of the BALB/c mouse encompassing a total of 1600 kb of DNA and 48 genes. The molecular distances between these gene clusters and the orientation of four of the six clusters on chromosome 17 is not known. Here we use pulse-field gradient gels and Southern blot hybridization to establish large-scale genomic restriction maps covering several hundreds of kb surrounding the three gene clusters located in the K, I, S, and D regions of the MHC. Comparison of the maps orients the complement gene clusters in the S region with the 21-OHB gene pointing towards the K end and the C2 gene pointing towards the D end of the MHC. The distances between the E alpha and 21-OHB genes is 430 kb and between the C2 and TNF-alpha genes at least 420 kb.

Animals↗
PubMed1986

Organization and evolution of D region class I genes in the mouse major histocompatibility complex.

Chromosome walking has been used to study the organization of the class I genes in the D and Qa regions of the MHC of the BALB/c mouse and in the D region of the AKR mouse. Five and eight class I genes are found in the D and Qa regions of the BALB/c mouse, respectively, while the AKR mouse contains only a single class I D region gene that has been identified by transfection as the Dk gene. Restriction map homologies and crosshybridization experiments suggest that the multiple class I genes in the D region of the BALB/c mouse have been generated by unequal crossing-over involving class I genes from the Qa region. The expanded D region of BALB/c and other H-2d haplotype mouse strains appears to be metastable, since evidence for gene contraction in the Dd region has been found in two mutant strains. Thus the D region and also the Qa region class I genes are in a dynamic state, evolving by gene expansion and contraction.

Animals↗
PubMed1986

Gene organization and recombinational hotspots in the murine major histocompatibility complex.

By chromosome walking in the major histocompatibility complex (MHC) of the BALB/c mouse, we have linked the K region to the I region at the molecular level. Forty-nine overlapping cosmid clones define a stretch of about 600 kb of DNA containing 2 class I and 7 class II genes. Eleven independent recombination events were mapped between the K and the I region marker loci by Southern blot analysis of polymorphic restriction sites. Eight of these events involved crossing-over, at an unusually high frequency of 0.6%-1.5% between genes from Mus musculus castaneus and laboratory mouse strains, and they were confined to two small stretches of DNA. We conclude that recombination hotspots are present at these positions in the two M.m. castaneus MHC haplotypes tested. In contrast, several MHC haplotypes of laboratory mice appear to lack those hotspots.

Animals↗
PubMed1984

Tracts of high or low sequence divergence in the mouse major histocompatibility complex.

The K, I and S regions of the mouse major histocompatibility complex (MHC) are composed of long tracts of DNA which differ in sequence divergence. A correlation exists between the location of an MHC gene in a variable or conserved chromosomal tract and the degree of polymorphism and diversity of the proteins encoded by its alleles. Variable tracts appear to be the result of mechanisms which mutate certain coding and non-coding sequences to the same extent and selective pressures operating on the genes.

Animals↗
PubMed1980

Peroxidase biosynthesis as part of protein synthesis by cultured peanut cells.

Membrane-bound and free ribosomes from cultured peanut cells were separated by differential centrifugation. The former ribosomes were liberated from the 27000 X g pellet with 1% Triton X100. Purification of both polysome populations was obtained by passage through a 1.5 M sucrose cushion. Both populations have a high rate of protein synthesis in vitro in the presence of a wheat germ S30 fraction. Comparisons of protein synthesis in vitro with that in vivo, and also with labelled proteins released by these cells into the medium did not provide significant information regarding peroxidase biosynthesis. However, immunoprecipitation of the products formed in vitro with antibodies raised against a purified cationic peroxidase fraction, resulted in isolating one major radioactive product. The higher molecular weight of this isolated product compared with the molecular weight of the purified peroxidase fraction suggests the occurrence of a single peptide for peroxidase commensurate with its being a secreted protein.

Arachis↗
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

[A new approach to arterial rigidity: ultrasonic tissue mode imaging].

Vascular stiffness is a major contributory factor of cardiovascular morbidity and mortality. Tissue Doppler imaging (TDI) could make it possible to evaluate vascular rigidity in a site by the measurement of the arterial wall velocity. The objective of this work is to validate the use of tissue Doppler imaging in the assessment of carotid rigidity. The following parameters were measured with TDI (ATL HDI 5000 and software HDI Lab): maximum velocity and mean acceleration of parietal motion (VMax and AccMax). These measurements were corrected for the arterial diameter and pulse pressure (VMax cor and AccMax cor). These data have been compared to the calculated parameters of elasticity from a mode M echography. Thirty-one subjects aged of 26 to 77 years (41.6 +/- 10.6 years, m +/- ESM), without atheromatous plaque or high blood pressure, have been included. The VMax is correlated very significantly at the parietal velocity calculated with mode M echography (r = 0.77; p = 0.00002). The VMax cor is correlated significantly with the parameters of stiffness following: distensibility coefficient, compliance coefficient, pulse wave velocity, elasticity modulus of Young, coefficient beta. [table: see text] Tissue Doppler imaging allows an easy evaluation of the carotid stiffness correlated with the parameters of elasticity. Therefore it constitutes a method of evaluation of the cardiovascular risk. Further longitudinal studies will be able to assess the involvement of the carotid stiffness as causal agent of the cardiovascular risk.

Adult↗