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Alain Carre

Publications and source records attributed to Alain Carre.

4 recordsLinked to original sources

Functional GPCR microarrays.

This paper describes G-protein-coupled receptor (GPCR) microarrays on porous glass substrates and functional assays based on the binding of a europium-labeled GTP analogue. The porous glass slides were made by casting a glass frit on impermeable glass slides and then coating with gamma-aminopropyl silane (GAPS). The emitted fluorescence was captured on an imager with a time-gated intensified CCD detector. Microarrays of the neurotensin receptor 1, the cholinergic receptor muscarinic 2, the opioid receptor mu, and the cannabinoid receptor 1 were fabricated by pin printing. The selective agonism of each of the receptors was observed. The screening of potential antagonists was demonstrated using a cocktail of agonists. The amount of activation observed was sufficient to permit determinations of EC50 and IC50. Such microarrays could potentially streamline drug discovery by helping integrate primary screening with selectivity and safety screening without compromising the essential functional information obtainable from cellular assays.

Drug Evaluation, Preclinical↗

Changes in renal blood flow reserve after angioplasty of renal artery stenosis in hypertensive patients.

BACKGROUND: Intra-arterial Doppler is a recent technique which allows assessment of distal vascular disease using measurements of intrarenal blood flow velocities. The purpose of this study was to evaluate intrarenal hemodynamics and renal blood flow reserve before and after percutaneous transluminal angioplasty (PTA) in hypertensive patients with unilateral atherosclerotic renal artery stenosis using intra-arterial Doppler. METHODS: Intra-arterial Doppler was performed during arteriography in 19 hypertensive patients (12 men; mean age, 64 +/- 8 years) in "normal" and in "stenotic" kidneys at baseline, on isosorbide dinitrate, and after selective intra-renal papaverine injection, before, and after PTA. Doppler parameters analyzed were average peak velocity, maximum peak velocity, end diastolic velocity, and renal blood flow (RBF). Changes in Doppler parameters after papaverine injection were also analyzed. RESULTS: The major results were (1) the significant reduction in RBF distal to the stenosis, (2) the lack of arteriolar reactivity in response to papaverine distal to the stenosis, (3) the immediate recovery of arteriolar reactivity after PTA, associated with restoration of RBF in the revascularized kidneys, and (4) no change in arteriolar reactivity in response to papaverine in the "normal" kidneys following PTA. CONCLUSION: Ours results highlighted the benefit of endovascular Doppler to evaluate (1) RBF reserve, and (2) the repercussion of the stenosis on the distal vascularization.

Aged↗

Randomized, comparative, double-blind study of amlodipine vs. nicardipine as a treatment of isolated systolic hypertension in the elderly.

A 90-day, multicenter, randomized, double-blind, parallel-group study was conducted to compare the efficacy of amlodipine (once a day) with nicardipine (two to three times a day), in the treatment of isolated systolic hypertension (ISH) in the elderly. Patients (n = 133) aged > or = 60 years, with ISH were randomized to receive either amlodipine 5 mg/day, or nicardipine 60 mg/day (titrated if necessary to 10 mg/day and 100 mg/day, respectively) for 90 days. Efficacy was assessed by measuring office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM). The two treatments substantially and comparably reduced office systolic blood pressure (SBP) and pulse pressure (PP), and also produced a slight decrease in diastolic blood pressure (DBP). Amlodipine reduced SBP, as assessed by ABPM, to a significantly greater extent than nicardipine. Both treatments were well-tolerated. The sustained effect of amlodipine, compared with nicardipine, was reflected in its significantly greater antihypertensive activity, particularly during the nocturnal period, as assessed by ABPM. The study demonstrates that once a day dose of amlodipine is an effective antihypertensive treatment for elderly ISH patients.

Aged↗

Cortical thickness: an early morphological marker of atherosclerotic renal disease.

BACKGROUND: Although kidney size is still the most commonly used morphological parameter, it is not sensitive enough for early detection of atherosclerotic renal disease (ARD). The purpose of this work was to evaluate morphological abnormalities on both post-stenotic and contralateral kidneys, by using spiral computed tomography angiography (CTA). METHODS: Spiral CTA was performed in 49 hypertensive patients. Renal diameters, renal length, and cortical thickness were measured in 26 post-stenotic kidneys, 26 contralateral kidneys and 46 control kidneys. Mean cortical thickness, cortical area, and medullary length were calculated. RESULTS: The right and left control kidneys were of comparable morphology. The post-stenotic kidneys showed significant cortical atrophy. The contralateral kidneys also underwent cortical disease, as judged by comparison with control kidneys. A threshold of 800 mm2 was identified for the cortical area that allowed us to distinguish control kidneys from post-stenotic kidneys. Similarly, a threshold of 8 mm was identified for mean cortical thickness. Renal length was still within normal range in all kidney groups. The measurement of superior pole segments appeared to be more sensitive than measurement at other locations for identifying significant intrarenal lesions. There was no significant correlation between clinical and morphological parameters. CONCLUSIONS: These results suggest that cortical parameters are more sensitive for early diagnosis of ARD than kidney size. Cortical atrophy should be a useful marker for guidance for revascularization.

Adult↗