Biomedical subjects

Dominique Durand

Publications and source records attributed to Dominique Durand.

46 records · Page 3Linked to original sources

PubMed2003

Evidence that clearance of hepatitis C virus RNA after alpha-interferon therapy in dialysis patients is sustained after renal transplantation.

To date, there is no available treatment of hepatitis C virus (HCV) infection after renal transplantation (RT). Among 55 anti-HCV-positive/HCV RNA-positive hemodialysis patients who were treated with IFN-alpha (9 MU/wk during 6 or 12 mo), 21 of them (38%) had a sustained virologic response. Of these, 16 (76%) underwent RT 38 mo (range, 2 to 57 mo) after alpha-IFN therapy. There were 13 men and 3 women aged 46 yr (range, 27 to 68 yr). At RT, HCV serology was still positive in 15 patients, and HCV viremia was negative in all patients. Immunosuppression relied on anticalcineurin agents with or without steroids and/or antimetabolites; in addition, 12 of them received induction therapy with antithymocyte globulins. At the last follow-up after RT, at 22.5 mo (range, 2 to 88 mo), HCV viremia remained negative in all patients. Moreover, HCV RNA was not present in peripheral blood mononuclear cells when assessed in eight patients. HCV serology was found to be still positive in 13 patients. Three patients presented with acute rejection, one presented with a suppurative lymphocele, one died from a sepsis, and four presented with a cytomegalovirus infection. None of them developed posttransplant diabetes mellitus. In conclusion, hemodialysis patients waiting for a RT need to be treated with alpha-IFN because when HCV RNA clearance occurred, they experienced no relapse after transplantation despite chronic immunosuppressive treatment.

Adult↗

PubMed2002

Relation between aggregation and phase separation: three-dimensional Monte Carlo simulations.

We study phase separation of particles in solution using Monte Carlo simulations of reversible aggregation on a cubic lattice. Two stages of the phase separation can be clearly distinguished: initial random aggregation and subsequent densification. Step one leads to a distribution of fractal aggregates close to the binodal and to a temporary gel for large attractive interaction. Step two leads to isolated spherical dense domains close to the binodal and branched wormlike strands for large attractive interactions. The transition between the two types of structure is gradual and there is no clear feature that shows the existence of a spinodal. The first stage of the phase separation is metastable very close to the binodal or at very large interaction energy. In the latter case, the second step can be viewed as an aging process of the gel formed in the first step.

Biophysical Phenomena↗

PubMed2002

[The effect of angiotensin-converting enzyme inhibitors on the progression of chronic renal failure].

SEVERAL MECHANISMS: The progression in renal failure first implies hemodynamic mechanisms and among which angiotensin II has a central role, but also an increase in proteinuria and the induction of many inflammatory and mitogenic mediators that enhance fibrosis (TGF-beta), an effect stimulating the thrombotic mechanism. Among these factors of progression in renal failure, hypertension and proteinuria are the two major factors. Proteinuria is "nephrotoxic" and leads to glomerular and tubulo-interstitial lesions. THE ROLE OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS: Angiotensin-converting enzyme inhibitors (ACE) affect the different mechanisms that lead to glomerulosclerosis: antihypertensive effect, with the normalisation of blood pressure having demonstrated its determining role in the production of nephrosis in various epidemiological studies; hemodynamic effect with a decrease in glomerular capillary pressure, in the filtration fraction, and inhibition of the bradykinin deterioration; antiproteinuric effect superior to that of other anti-hypertensive drugs (excepting angiotensin II-receptor antagonists). Two indications ACE inhibitors have demonstrated their efficacy in slowing the progression of renal failure in two large pathological fields: diabetic nephropathy in which this effect is demonstrated in type I diabetes, although the results are not as obvious in type II diabetes in which the nephropathy is multi-factor. The recent French and American recommendations are that ACE inhibitors should be used in first intention in diabetic nephropathies and aimed at tight blood pressure control; non-diabetic nephropathies Two pivotal studies have demonstrated the efficacy of ACE inhibitors in nephropathies whatever their type. These data have led to propose ACE inhibitors in first intention in patients exhibiting chronic nephropathies, whether hypertensive or not THE COMBINATION WITH OTHER HYPERTENSIVE DRUGS: Calcium channel blockers have a beneficial trophic effect in renoprotection and can be combined with ACE inhibitors, particularly in the case of diabetic nephropathies. ACE inhibitors and angiotensin II-receptor antagonists have comparable effect on hemodynamics and glomerulosclerosis factors. Clinically, the decrease in proteinuria is identical. Endothelin antagonists have also been studied in renoprotection and appear to have a beneficial effect when combined with ACE inhibitors. GLOBALLY: ACE inhibitors remain the only treatment with demonstrated long-term efficacy in the progression of chronic renal failure. However, the concept of renoprotection needs to be widened to all the factors implied in the progression of chronic renal failure, and ACE inhibitors only represent one aspect of treatment. The role of angiotensin II-receptor antagonists, alone or combined, is clearly promising.

Amlodipine↗

PubMed2002

Dynamic transition associated with the thermal denaturation of a small Beta protein.

We studied the temperature dependence of the picosecond internal dynamics of an all-beta protein, neocarzinostatin, by incoherent quasielastic neutron scattering. Measurements were made between 20 degrees C and 71 degrees C in heavy water solution. At 20 degrees C, only 33% of the nonexchanged hydrogen atoms show detectable dynamics, a number very close to the fraction of protons involved in the side chains of random coil structures, therefore suggesting a rigid structure in which the only detectable diffusive movements are those involving the side chains of random coil structures. At 61.8 degrees C, although the protein structure is still native, slight dynamic changes are detected that could reflect enhanced backbone and beta-sheet side-chain motions at this higher temperature. Conversely, all internal dynamics parameters (amplitude of diffusive motions, fraction of immobile scatterers, mean-squared vibration amplitude) rapidly change during heat-induced unfolding, indicating a major loss of rigidity of the beta-sandwich structure. The number of protons with diffusive motion increases markedly, whereas the volume occupied by the diffusive motion of protons is reduced. At the half-transition temperature (T = 71 degrees C) most of backbone and beta-sheet side-chain hydrogen atoms are involved in picosecond dynamics.

Biophysical Phenomena↗

PubMed2002

Salt-induced conformation and interaction changes of nucleosome core particles.

Small angle x-ray scattering was used to follow changes in the conformation and interactions of nucleosome core particles (NCP) as a function of the monovalent salt concentration C(s). The maximal extension (D(max)) of the NCP (145 +/- 3-bp DNA) increases from 137 +/- 5 A to 165 +/- 5 A when C(s) rises from 10 to 50 mM and remains constant with further increases of C(s) up to 200 mM. In view of the very weak increase of the R(g) value in the same C(s) range, we attribute this D(max) variation to tail extension, a proposal confirmed by simulations of the entire I(q) curves, considering an ideal solution of particles with tails either condensed or extended. This tail extension is observed at higher salt values when particles contain longer DNA fragments (165 +/- 10 bp). The maximal extension of the tails always coincides with the screening of repulsive interactions between particles. The second virial coefficient becomes smaller than the hard sphere virial coefficient and eventually becomes negative (net attractive interactions) for NCP(145). Addition of salt simultaneously screens Coulombic repulsive interactions between NCP and Coulombic attractive interactions between tails and DNA inside the NCP. We discuss how the coupling of these two phenomena may be of biological relevance.

Animals↗

PubMed2002

Danon's disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation.

Herein, we report a new case of Danon's disease in a 41-year-old Frenchman. This patient displays the typical clinical triad, with cardiomyopathy, mental retardation and myopathy, and a vacuolar myopathy without acid alpha-glucosidase deficiency. He has also developed a diffuse chorio-capillary ocular atrophy, and represents the second case of successful heart transplantation in this lysosomal disease. Interestingly, analysis of LAMP-2 protein expression in cultured fibroblasts revealed a primary deficiency of this lysosomal membrane protein. This defect resulted from a yet undescribed deletion in exon 7 of lamp-2 gene.

Adult↗

PubMed2002

Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients.

Sirolimus and cyclosporine (CsA) prevent acute rejection in man when used as primary therapies in triple drug regimens. Sirolimus does not act via the calcineurin pathway and therefore is not expected to produce the same renal side-effects. This paper presents the pooled 2-year data analysis of renal function parameters from two open-label, randomized, multicenter studies. Patients (18-68 years) receiving a primary renal allograft were randomized to receive concentration-controlled sirolimus (n = 81) or CsA (n = 80), in combination with azathioprine and steroids (n = 83), or mycophenolate mofetil (MMF) and steroids (n = 78). From week 10 through year 2, calculated glomerular filtration rate (GFR) was significantly higher in sirolimus--than in CsA-treated patients (69.3 vs. 56.8 mL/min, at 2 years, p = 0.004). Serum uric acid was significantly higher in the CsA-treated patients and magnesium was significantly lower; these parameters were more likely to be within normal limits in the sirolimus group. Mean serum potassium and phosphorus were lower in sirolimus-treated patients. In conclusion, sirolimus, when administered as primary therapy in combination with azathioprine or MMF, has a favorable safety profile compared to CsA with regards to renal function.

Adult↗

PubMed2002

Long-term impact of renal transplantation on liver fibrosis during hepatitis C virus infection.

BACKGROUND & AIMS: During hepatitis C virus (HCV) infection, liver fibrosis progression after renal transplantation remains controversial. The aim of this cohort study with controls was to compare liver histopathologic features during HCV infection between renal transplant recipients and matched groups of hemodialyzed patients or controls without renal disease and untreated for HCV. METHODS: Each renal transplant recipient (group 1, n = 30) was matched at first liver biopsy (LB) using the main factors known to influence progression of fibrosis with one HCV hemodialyzed patient (group 2, n = 30) and one HCV-infected patient (nonhemodialyzed, nontransplanted; group 3, n = 30). Patients from group 1 were also matched with those of group 3 on the time between 2 consecutive LBs performed 37 months apart. LBs were evaluated according to the Knodell index, METAVIR score, and rate of fibrosis progression per year (fibrosis unit). RESULTS: The rate of fibrosis progression per year between the first and second LBs was significantly lower (P = 0.03) in group 1 (0.067; 95% confidence interval: -0.05, 0.18) than group 3 (0.20; 95% confidence interval: 0.13, 0.26). At the second LB, the Knodell index and activity or fibrosis in METAVIR were lower in group 1 than group 3 (4.2 +/- 0.4 vs. 7.5 +/- 0.6, 0.5 +/- 0.1 vs. 1.3 +/- 0.2, and 1.4 +/- 0.2 vs. 2.3 +/- 0.2 respectively, P < 0.01). CONCLUSIONS: Our study suggests that liver fibrosis progression is low in most HCV-infected renal transplant recipients with moderate liver disease at baseline.

Adult↗

PubMedDate not supplied

Influence of chain length and polymer concentration on the gelation of (amidated) low-methoxyl pectin induced by calcium.

The gelation of low-methoxyl pectin (LMP) induced by addition of Ca2+ was studied by measuring the storage modulus as a function of temperature during cooling. Samples with different molar masses were prepared by mechanical degradation. The effect of the molar mass and the pectin concentration on the gelation properties was investigated. The effect of partial amidation was studied by comparing LMP and partially amidated LMP with the same molar mass and degree of methylation. The results are compared to those from a model developed for Ca2+-induced pectin gelation, and good agreement is found except at low concentrations and low molar masses where the gels are weaker than predicted. At low concentrations intrachain bonding weakens the gel, while the presence of small pectin chains weakens the gel because it neutralizes binding sites on larger chains.

Amides↗

PubMedDate not supplied

Jamming and gelation of dense beta-casein micelle suspensions.

The rheology of dense suspensions of beta-casein micelles is investigated at pH 6. For a given temperature, the viscosity increases dramatically at a critical concentration (Cc) of about 100 g/L due to jamming of the micelles. For a given concentration close to and above Cc, the viscosity of dense suspensions decreases strongly with increasing temperature because Cc increases. The suspensions show weak shear thickening followed by strong shear thinning. At lower pH, that is, closer to the isoelectric point, spontaneous gelation is observed, which is favored by lowering the temperature and addition of sodium polyphosphate. The gelation process is studied at pH 5.5 by rheology and light scattering.

Animals↗