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F Paillard

Publications and source records attributed to F Paillard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

Adult↗
PubMed1999

[Development of prediction models for three in vitro embryotoxicity tests which are evaluated in an ECVAM validation study]

In 1997 ZEBET started the co-ordination of a study funded by the European Centre for the Validation of Alternative Methods (ECVAM) with the aim of pre-validation and validation of three in vitro embryotoxicity tests. These tests employ the cultivation of post-implantation whole rat embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass test, MM-Test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test, EST). In the current Validation Study each of the tests is evaluated in four laboratories under blind conditions. In an initial phase of the validation study six out of 20 test chemicals comprising different embryotoxic potential (non, weak and strong embryotoxic) were tested. The results were used to improve the prediction models (PM) for the WEC test and the MM-Test in order to identify the embryotoxic potential of test chemicals. In addition, the existing PM for the EST was evaluated using the results from testing of the initial six chemicals. The PM for the EST was developed using the results of a previous pre-validation study (Scholz et al.,1999), in which 94% of the learning sample were classified correctly. Applying this PM to the results of the initial phase of the current validation study, 80% of the experiments were classified correctly according to the embryotoxic potential of the tested chemicals in vivo. Applying the PM for the MM-Test and the WEC test that were developed during the current validation study in both tests, 79% correct classifications were achieved. Since the PM of the WEC-Test took into account only parameters of growth and development, but not cytotoxicity data, a second PM (PM2) for the WEC was developed that was improved by incorporating cytotoxicity data of the differentiated mouse fibroblast cell line 3T3 derived from the EST. This approach, which has previously never been used as an adjunct to the WEC test, resulted in an increase of correct classifications to 96%.

Journal Article↗
PubMed1998

[Polyuropolydipsic syndromes].

PROGNOSIS: Intracellular dehydration is the major risk in case of a polyuropolydipsic syndrome. Excepting osmotic polyuria, prognosis depends on a possibly progressive functional anomaly of the hypothalamopituitary axis. PATHOPHYSIOLOGY: Polyuropolydipsia occurs when antidiuretic hormone (ADH) secretion is absent (central diabetes insipidis), the kidney does not respond to ADH (nephrogenic diabetes insipidus) or in case of physiological inhibition of ADH secretion (primary polydipsia). EXPLORATION: Dynamic explorations are associated with radioimmunoassay of ADH. They are particularly useful in case of atypical diabetes insipidus and include the water restriction test and a study of the sensitivity to exogenous ADH (dDAVP). The results orient the etiologic diagnosis and allow an evaluation of the fluid intake required as a function of the maximal concentrating capacity of the kidneys. TREATMENT OF CENTRAL DIABETES INSIPIDUS: Treatment is based on ADH analogs (dDAVP). The aim is to obtain a constant antidiuretic effect without hyponatremia or escape. In case of partial central diabetes insipidus, a non-hormone treatment using compounds which increase vasopressin release or its effect on the kidney can be proposed.

Diagnosis, Differential↗