Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

Background: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in , the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability.

Methods: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.

[Clinical case of the month. Thyrotoxic periodic paralysis. Report of a case in a Somalian male].

We report the case of a man hospitalized for tetraparesis related with hypokalemia due to a potassium shift from the extracellular to the intracellular compartment revealing a hyperthyroidism. We will discuss different physiopathological hypotheses giving relating periodic paralysis and hyperthyroidism. Correction of hypokalemia combined with a synthetic antithyroid agent and a beta blocking drug allowed complete motor fonctional recovery.

Peritoneal equilibration test with conventional 'low pH/high glucose degradation product' or with biocompatible 'normal pH/low glucose degradation product' dialysates: does it matter?

Background: The evaluation of the peritoneal transport characteristics is mandatory in peritoneal dialysis (PD) patients. This is usually performed in routine clinical practice with a peritoneal equilibration test (PET) using conventional dialysates, with low pH and high glucose degradation product (GDP) concentrations. An increasing proportion of patients are now treated with biocompatible dialysates, i.

[The cardiorenal syndrome and optimal treatment of renal anemia].

The cardiorenal syndrome is a clinical and pathophysiological concept illustrating the relationship between the two organs, and is mainly based on the control of volemia. Heart failure is an example of this entity: when congestive heart failure becomes refractory, ultrafiltration by various modes of dialysis is needed. Ambulatory peritoneal ultrafiltration is a good alternative for the management of treatment-resistant congestive heart failure.

[Results of rehabilitation on quality of walking and outcome in elderly patients following femoral neck fracture. Development after one year].

Objectives: To examine effects of coordinated multidisciplinary inpatient rehabilitation for older patients with hip fractures.

Material And Method: 187 (42 men and 147 women: mean age 80.9 +/- 8.

Synthesis of a novel class of non-peptide NK-2 receptor ligand, derived from 1-phenyl-3-pyrrol-1-ylindan-2-carboxamides.

A series of trans,trans-1-phenyl-3-pyrrol-1-ylindan-2-carboxamide derivatives has been synthesized in eight steps starting from cinnamic acid or 3,3-diphenylpropionic acid. The trans,trans configuration of these carboxamides has been established by X-ray analysis and by NOE experiments in NMR. These new compounds were evaluated for their potential NK-1, NK-2 and NK-3 receptors binding affinity.

Extended time-to-collision measures for road traffic safety assessment.

This article describes two new safety indicators based on the time-to-collision notion suitable for comparative road traffic safety analyses. Such safety indicators can be applied in the comparison of a do-nothing case with an adapted situation, e.g.

Endoscopic manifestations of Wegener disease.

The diagnostic criteria for upper airway necrotizing diseases such as Wegener's granulomatosis (WG) are well defined. However, the differentiation with other diseases of unknown aetiology remains difficult. Establishing an early diagnosis and prompt treatment is very important to minimize loss of function and cosmetic deformity.

Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp sequence of fibrinogen. (Aminobenzamidino)succinyl (ABAS) series of orally active fibrinogen receptor antagonists.

Our initial orally active fibrinogen receptor antagonist benzamidinopentanoyl (BAP) series which was discovered through truncation of our i.v. antiplatelet agent (SC-52012) demonstrated modest oral activity in canine studies (ethyl [5-(4-amindinophenyl)pentanoyl]-3-amino-3-(3-pyridyl)propionate, 1e).

A novel series of orally active antiplatelet agents.

A novel series of orally active fibrinogen receptor antagonists has been discovered through structural modification of our lead intravenous (iv) antiplatelet agent, 5-(4-amidinophenyl)pentanoyl-Asp-Phe 1 (SC-52012). The Asp-Phe amide bond was removed through truncation to a 3-substituted beta-amino acid aspartate mimetic which resulted in a tripeptide mimetic inhibitor of lower molecular weight (from 482 to the 330-390 g mol-1). The zwitterionic nature of the inhibitor was masked through the preparation of an ethyl ester prodrug.

Design of orally active, non-peptide fibrinogen receptor antagonists. An evolutionary process from the RGD sequence to novel anti-platelet aggregation agents.

The evolutionary process from the Arg-Gly-Asp-Phe (RGDF) tetrapeptide to potent orally active anti-platelet agents is presented. The RGD sequence is an important component in the recognition of fibrinogen by its platelet receptor GP IIb-IIIa (integrin alpha IIb beta 3). This work concentrates on the replacement of the Arg-Gly dipeptidyl fragment by an acylated aminobenzamidine.

Nonpeptide angiotensin II antagonists: N-phenyl-1H-pyrrole derivatives are angiotensin II receptor antagonists.

A series of 5-[1-[4-[(4,5-disubstituted-1H-imidazol-1-yl)methyl]- substituted]-1H-pyrrol-2-yl]-1H-tetrazoles and 5-[1-[4-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-substituted]- 1H-pyrrol-2-yl]-1H-tetrazoles were investigated as novel AT1-selective angiotensin II receptor antagonists. Computer-assisted modeling techniques were used to evaluate structural parameters in comparison to the related biphenyl system. New synthetic procedures have been developed to prepare the novel compounds.

Influence of polyfluorination of the phenylalanine ring of angiotensin II on conformation and biological activity.

[Phe(F5)8]angiotensin II was synthesized by the solid phase method and purified by reverse-phase HPLC. In rat uterus and rabbit aorta bioassays the analogue had 10 and 50%, respectively, of the contractile activity of angiotensin II and demonstrated antagonist properties. These findings illustrate that inversion of the Phe8 ring quadrupole moment in angiotensin II decreases agonist activity and invokes antagonist properties.

Conformationally restricted polysubstituted biphenyl derivatives with angiotensin II receptors antagonist properties.

The synthesis and in vitro activity of new nonpeptide angiotensin II antagonists is presented. Compared to previously reported biphenyl compounds, the new analogues 8 and 9 have reduced conformational freedom derived from steric hindrance. Methyl 4'-methyl-2',6'-dimethoxy[1,1'-biphenyl]-2-carboxylate 4 has been synthesized by a Von Pechmann condensation of orcinol with oxocyclohexane-2-carboxylate followed by dehydrogenation.

Atriopeptin regulation and renal function in conscious spontaneously hypertensive rats.

We examined the interaction of a non-guanylate cyclase-linked atriopeptin (AP) binding site ligand, SC-46542 (des[Phe106,Gly107,Ala115,Gln116]AP-(103-126], and an endopeptidase 24.11 inhibitor, thiorphan, on mean arterial pressure, urinary sodium excretion, urinary cyclic guanosine monophosphate (cGMP) excretion, plasma cGMP concentration, and plasma AP immunoreactivity (ir) in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Compared to vehicle control rats, coadministration of SC-46542 and thiorphan increased urinary sodium excretion in SHR from 2.

Central and peripheral actions of a nonpeptidic angiotensin II receptor antagonist.

Nonpeptidic imidazole derivatives were recently reported to be angiotensin II receptor antagonists with acute blood pressure-lowering activity. In the present study, we characterized the angiotensin II receptor antagonist properties of one such derivative, 4'-([2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl)- [1,1'-biphenyl]-2-carboxylic acid (IMI). In receptor binding studies, IMI displaced bound [125I]angiotensin II from rat uterine membranes with an IC50 of 0.

Structure-activity relationships for the carboxy-terminus truncated analogues of angiotension II, a new class of angiotensin II antagonists.

A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determined in the isolated rabbit aorta assay. In the analogues tested, replacement of aspartic acid in position 1 by sarcosine was found necessary to produce significant antagonist activity.

A synthetic linear decapeptide binds to the atrial natriuretic peptide receptors and demonstrates cyclase activation and vasorelaxant activity.

A linear decapeptide, [cyclohexylalanine 106]ANP-(105-114)NH2 (1), where ANP is atrial natriuretic peptide, was prepared by solid phase synthesis and purified by reverse-phase liquid chromatography. This novel peptide was found to bind to ANP receptors in rabbit lung membranes, to stimulate cGMP production in various tissues, and to fully relax precontracted rabbit aorta in a dose-dependent fashion. The potency of 1 in the various in vitro assays varies between one-twentieth and one-eightieth of the potency of the reference peptide, the 24-mer rat ANP-(103-126).

Interaction of non-guanylate cyclase-linked atriopeptin receptor ligand and endopeptidase inhibitor in conscious rats.

We examined the interaction of SC-46542 [des(Phe106, Gly107, Ala115, Gln116)-AP(103-126)], a non-guanylate cyclase-linked atriopeptin (AP) binding site ligand, with thiorphan, an inhibitor of endopeptidase 24.11, on mean arterial pressure, urine flow, urinary sodium excretion and plasma AP immunoreactivity in conscious rats. The coadministration of SC-46542 (16 micrograms/kg/min) and thiorphan (30 mg/kg i.

Identification of structural requirements for analogues of atrial natriuretic peptide (ANP) to discriminate between ANP receptor subtypes.

The structure-activity relationships for affinity and selective binding of atrial natriuretic peptide (ANP) and analogues to guanylate cyclase coupled (CC) and non-cyclase coupled (NC) receptors in rabbit lung membranes are described. We have designed a series of peptides to try to identify the minimal sequence involved in specific recognition of each receptor subtype. The affinity of the peptides was determined from competitive binding experiments.

Specific inhibitors of endopeptidase 24.11 inhibit the metabolism of atrial natriuretic peptides in vitro and in vivo.

Atrial natriuretic peptides (ANPs) are degraded rapidly by renal brush border membranes in vitro. Here, we report that thiorphan, a specific inhibitor of endopeptidase 24.11, afforded almost complete protection against inactivation of ANPs by a renal brush border membrane preparation.