Biomedical subjects

S Roux

Publications and source records attributed to S Roux.

At least 19 recordsLinked to original sources

PubMed2001

Indapamide, a thiazide-like diuretic, decreases bone resorption in vitro.

We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10(-4) M IDP and 10(-4) M AZ, as well as 10(-5) M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF-1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl- cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10(-4) M IDP as well as 10(-5) M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors.

Animals↗

PubMed2000

Maturation of frontal and temporal components of mismatch negativity (MMN) in children.

The mismatch negativity (MMN) response of auditory ERPs in adults appears to result from several overlapping components involving both frontal and temporal brain areas. Our aim was to test whether a similar configuration could be observed in children, and to examine the maturation rates of the different components. MMN (standard tones: 1000 Hz, deviants: 1100 Hz) was recorded from 28 scalp electrodes in 24 healthy children aged from 5 to 10 and in eight adults for comparison. Scalp current density analysis revealed both temporal and frontal components in children of all ages as well as in adults. Moreover the amplitudes of the temporal components were significantly greater in children than in adults, whereas the frontal components were similar at all ages. The results strongly suggest that MMN is mediated by at least two separate neural systems, and that the frontal system matures earlier than the sensory-specific system.

Acoustic Stimulation↗

PubMed2000

Bone loss. Factors that regulate osteoclast differentiation: an update.

Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bone loss. Among many factors triggering excessive osteoclast activity, cytokines such as IL-1 or tumour necrosis factor (TNF)-alpha play a central role. New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-kappa B [RANK] and RANK ligand [RANKL]) have been discovered whose cross-interaction is mandatory for the differentiation of osteoclasts from hemopoietic precursors, in both physiological and pathological situations. Osteoprotegerin, a decoy receptor which blocks this interaction, decreases osteoclast activity and could have a fascinating therapeutic potential in conditions associated with upregulated bone resorption.

Cell Differentiation↗

PubMed2000

Self-organization, localization of shear bands, and aging in loose granular materials

We introduce a mesoscopic model for the formation and evolution of shear bands in loose granular media. Numerical simulations reveal that the system undergoes a nontrivial self-organization process which is governed by the motion of the shear band and the consequent restructuring of the material along it. High density regions are built up, progressively confining the shear bands in localized regions. This results in an inhomogeneous aging of the material with a very slow increase in the mean density, displaying an unusual glassylike system-size dependence.

Journal Article↗

PubMed2000

Bubbling and large-scale structures in avalanche dynamics.

Using a simple lattice model for granular media, we present a scenario of self-organization that we term self-organized structuring where the steady state has several unusual features: (1) large-scale spatial and/or temporal inhomogeneities and (2) the occurrence of a nontrivial peaked distribution of large events which propagate like "bubbles" and have a well-defined frequency of occurrence. We discuss the applicability of such a scenario for other models introduced in the framework of self-organized criticality.

Journal Article↗

PubMed2000

Evaluation of a ginkgo biloba extract (EGb 761) in functional tests for monoamine oxidase inhibition.

A standardized extract of ginkgo biloba (EGb 761) was evaluated in functional tests for monoamine oxidase (MAO) inhibition in mice: l-dihydroxyphenylalanine (CAS 59-92-7,1-DOPA) potentiation, tryptamine (CAS 61-54-1) potentiation, 5-hydroxytryptophan (CAS 4350-07-6,5-HTP) potentiation and phenylethylamine (CAS 64-04-0) potentiation. The doses investigated (25, 50 and 100 mg/kg p.o once daily for 5 days) were those known to possess anti-stress properties in other animal models. In contrast to the reference substances investigated (nialamide (CAS 51-12-7), clorgyline (CAS 17780-75-5) and 1-deprenyl (CAS 14611-52-01), EGb 761 did not exhibit any activity indicative of MAO inhibition. It was concluded that MAO inhibition was not the mechanism primarily responsible for EGb 761's anti-stress activity.

5-Hydroxytryptophan↗

PubMed2000

Wave scattering from self-affine surfaces

Electromagnetic wave scattering from a perfectly reflecting self-affine surface is considered. Within the framework of the Kirchhoff approximation, we show that the scattering cross section can be exactly written as a function of the scattering angle via a centered symmetric Levy distribution for the general roughness amplitude, Hurst exponent and wavelength of the incident wave. Our prediction is supported by direct numerical simulations.

Journal Article↗

PubMed2000

Thermally activated breakdown in the fiber-bundle model

Guarino et al., (cond-Mat/9908329) have recently introduced a fiber bundle model where fiber fracture can be thermally activated. Under a fixed (subcritical) loading, the mean failure time of the bundle is studied. An analytical expression for the latter is obtained as a function of the load. The effect of a (narrow) quenched disorder in the fracture stress of the fibers with a Gaussian distribution is shown to lead to an effective temperature simply translated with respect to the actual one. Finally, some "critical" properties of fracture precursors which have been proposed are investigated within the present model.

Journal Article↗

PubMed2000

A new model of chronic cardiac ischemia in rabbits.

Chronic cardiac ischemia has mainly been studied in large species such as pigs or dogs. Little research has been performed using small species such as rabbits. In the present study, 1-3 wk after implantation of a novel device (ameroid) on the circumflex coronary artery of New Zealand White rabbits, vessel patency was evaluated by coronary angiography, corrosion cast, and radiolabeled microspheres. Coronary angiograms showed, after 21 days, either total occlusion or severe stenosis in seven of eight arteries, which was confirmed by corrosion casts. The ameroid group had less blood flow in the epicardial (-62%) and endocardial (-54%) layers of the ischemic area compared with sham-operated rabbits (P < 0.05). Blood flow increased in the ischemic area compared with day 0 during acute occlusion, suggesting that progressive coronary occlusion initiated the growth of de novo collateral vessels. Thus we have developed a new model of chronic cardiac ischemia in rabbits with documented progressive coronary stenosis and occlusion that is suitable to test various therapeutic angiogenesis strategies.

Animals↗

PubMed2000

The family history of patients with primary or secondary antiphospholipid syndrome (APS).

OBJECTIVE: To evaluate familial history for evidence of antiphospholipid syndrome (APS) and autoimmune disease in rheumatology department patients with primary or secondary APS. METHODS: We retrospectively studied patients with APS and systemic lupus erythematosus (SLE) managed at the Rheumatology Department of the Bichat University Hospital, Paris, between 1987 and 1996. Data were collected by chart review and by a 1997 standardized telephone interview. RESULTS: We identified 108 patients with APS managed during the ten-year study period. According to classical classification criteria, 39 patients had primary antiphospholipid syndrome (PAPS) and 69 secondary antiphospholipid syndrome (SAPS). Family history data were obtained for 29 (74%) and 55 (80%) PAPS and SAPS patients. respectively (78% of the 108 patients). Twelve PAPS (41% and 19 SAPS (35%) patients had one or more relatives with evidence of at least one clinical feature of APS such as thrombosis or recurrent fetal loss; of these patients, seven in the PAPS (24%) and 11 in the SAPS (20%) group had two or more relatives with evidence of a clinical feature of APS. Three PAPS (10%) and 14 SAPS (25%) patients had one or more family members with an autoimmune disease. CONCLUSION: A positive family history for autoimmune disease and/or antiphospholipid syndrome is common in patients with PAPS or SAPS. This finding supports a genetic contribution to APS. The percentage of a positive family history for autoimmune disease tend to be higher in patients with SAPS than in those with PAPS.

Abortion, Habitual↗

PubMed2000

Private practice interdisciplinary breast centers: their rationale and impact on patients, physicians, and the health care industry: a bicoastal perspective.

This article reports on the experience of two private practice breast centers in New York and California. It demonstrates that comprehensive breast centers directed by full-time breast imagers have a significant impact on medical care from the perspective of the patient, her physicians, and the health care system. These two centers, separated by a continent, disparate in their formation and founding philosophies, yield very similar results in breast cancer diagnosis, reduction of the benign biopsies, and improving the cost of breast biopsies.

Biopsy↗

PubMed2000

[The pharmacology of endothelin and its antagonist bosentan].

Endothelin is one of the most potent vasoconstrictors known, but it also plays a role in inflammation, fibrosis and cellular hypertrophy. Endothelin is a key pathogenic factor in congestive heart failure, essential hypertension and pulmonary hypertension. Bosentan is a specific mixed antagonist of endothelin receptors. Preclinical and clinical data suggest that bosentan might become a new approach for the chronic treatment of these cadiovascular and pulmonary diseases.

Animals↗

PubMed2000

IgG anti-beta2-glycoprotein I antibodies in adult patients with systemic lupus erythematosus: prevalence and diagnostic value for the antiphospholipid syndrome.

OBJECTIVE: To investigate the prevalence of serum anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies and other antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE). To study their diagnostic value for the antiphospholipid syndrome (APS). METHODS: Anti-beta2-GPI and IgG anticardiolipin (aCL) were determined in sera from 102 consecutive patients with SLE using ELISA. Serum and plasma tests were also done for lupus anticoagulant (LAC), syphilis, and antibodies to dsDNA. Clinical and laboratory features of APS were observed. RESULTS: Prevalences were 23.5% for aCL and 18.6% for anti-beta2-GPI. Correlations between the presence of aCL and anti-beta2-GPI and between their titers were statistically significant (p<0.0001). No associations were found between anti-beta2-GPI and disease activity criteria (SLEDAI, ECLAM, dsDNA). Anti-beta2-GPI were significantly associated with LAC (p = 0.005), APS (p = 0.005), and a high aCL titer (aCL > 5 SD; p< or =0.001). LAC was the best diagnostic criterion for APS. CONCLUSION: These data suggest that determination of anti-beta2-GPI in addition to aCL and LAC is unlikely to improve the diagnosis of APS in patients with SLE.

Adolescent↗

PubMed2000

Hematological malignancies and the bone (myeloma excluded).

Bone involvement is a rare event in lymphomas, except in patients with adult T-cell leukemia/lymphoma associated with HTLVI. It is usually characterised by lytic bone lesions located in the metaphysis of long bones or in the axial skeleton. The occurrence of bone lesions reflects a progression of the disease affecting the prognosis that is related to lymphoma histologic features and staging. Bone lesions may occur in some lymphoproliferative disorders such as LLC or Waldenstrom's disease, or in myeloproliferative disorders. They may reflect a progression to a more aggressive disorder with a worse prognosis. The treatment of hematologic malignancies presenting with bone lesions and/or hypercalcemia is similar to the treatment of the systemic disease. In primary lymphomas of bone presenting with an isolated bone lesion, local treatment with radiation therapy and/or surgical ablation is required, and adjuvant chemotherapy may improve the prognosis of these located lymphomas. Glucocorticoid therapy and bisphosphonates are effective in treating associated hypercalcemia. Except for myeloma and ATL, the underlying mechanisms responsible for bone involvement in hematologic malignancies remain poorly understood. The unusual occurrence of bone lesions in these diseases probably implies distinct pathogenic mechanisms, but one can speculate that an increased expression of RANK/RANKL, the common final pathway in bone resorption, may be involved.

Bone Neoplasms↗

PubMed2000

Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents.

Recently, selective and systemically active antagonists for the metabotropic glutamate 5 receptor (mGlu(5)) were discovered, and the most potent derivative was found to be MPEP (2-methyl-6-(phenylethynyl)pyridine). Given the high expression of mGlu(5) receptors in limbic forebrain regions, it was decided to evaluate the anxiolytic potential of MPEP. After an acute oral administration, MPEP attenuated the anxiety-dependent variable in a variety of well established anxiety test paradigms. In rats, MPEP (10, 30, and 100 mg/kg) increased punished responses in the Geller-Seifter test, but none of these effects reached statistical significance. MPEP significantly increased the ratio (open/total arm entries; 0.1, 1, and 10 mg/kg), the number of open arm entries (0.1, 1, and 10 mg/kg), as well as time spent on open arm (0.1 and 1 mg/kg) in the elevated plus maze test. Furthermore, MPEP (0.3 and 1 mg/kg) significantly increased the time spent in social contact in the social exploration test. In mice, MPEP attenuated stress-induced hyperthermia (15 and 30 mg/kg) and decreased the number of buried marbles in the marble burying test (7.5 and 30 mg/kg). Finally, MPEP (0.01, 0.1, 1, 10, and 100 mg/kg) was tested on spontaneous locomotor activity in mice, and only a dose of 100 mg/kg significantly reduced vertical activity; no effect was seen on horizontal activity. MPEP (7.5, 15, and 30 mg/kg) was ineffective on d-amphetamine-induced (2.5 mg/kg) locomotor activity in mice and prepulse inhibition in rats (1, 3, or 10 mg/kg). Thus, these findings indicate that MPEP exhibits anxiolytic-like effects and low risks for sedation and psychotomimetic side-effects in rodents.

Animals↗

PubMed1999

Conformational change in the human glucocorticoid receptor induced by ligand binding is altered by mutation of isoleucine 747 by a threonine.

Limited proteolysis experiments were performed to study conformation changes induced by ligand binding on in vitro produced wild-type and I747T mutant glucocorticoid receptors. Dexamethasone-induced conformational changes were characterized by two resistant proteolysis fragments of 30 and 27 kDa. Although dexamethasone binding affinity was only slightly altered by the I747T substitution (Roux, S., Térouanne, B., Balaguer, P., Loffreda-Jausons, N., Pons, M., Chambon, P., Gronemeyer, H., and Nicolas, J.-C. (1996) Mol. Endocrinol. 10, 1214-1226), higher dexamethasone concentrations were required to obtain the same proteolysis pattern. This difference was less marked when proteolysis experiments were conducted at 0 degrees C, indicating that a step of the conformational change after ligand binding was affected by the mutation. In contrast, RU486 binding to the wild-type receptor induced a different conformational change that was not affected by the mutation. Analysis of proteolysis fragments obtained in the presence of dexamethasone or RU486 indicated that the RU486-induced conformational change affected the C-terminal part of the ligand binding domain differently. These data suggest that the ligand-induced conformational change occurs via a multistep process. In the first step, characterized by compaction of the ligand binding domain, the mutation has no effect. The second step, which stabilizes the activated conformation and does not occur at 4 degrees C, seems to be a key element in the activation process that can be altered by the mutation. This step could involve modification of the helix H12 position, explaining why the conformation induced by RU486 is not affected by the mutation.

Amino Acid Substitution↗

PubMed1999

Endothelin antagonism with bosentan: a review of potential applications.

Endothelin receptor antagonists have been proposed for the treatment of a variety of disorders in which the endothelins may act as pathogenic mediators, such as congestive heart failure, systemic and pulmonary hypertension, and cerebral vasospasm. Bosentan (Ro 47-0203) is a nonpeptide competitive antagonist, which can be a good tool for studying the endothelin system because it may be administered either acutely or chronically. It is specific for the endothelin system and blocks the actions of endothelin at both mammalian receptors (A and B). In experimental models of heart failure bosentan acts as a vasodilator and neurohormonal blocker that improves overall left ventricular performance and reduces renal dysfunction. Furthermore, in chronic studies, bosentan attenuates cardiac remodeling and significantly improves survival. In patients with chronic heart failure bosentan produces pulmonary and systemic vasodilation and may enhance conventional treatment with angiotensin-converting enzyme inhibitors. Long-term studies are being conducted to characterize the full therapeutic potential of bosentan in chronic heart failure. In experimental models bosentan reverses established pulmonary hypertension. Preclinical efficacy has also been demonstrated in essential hypertension, where bosentan can reduce blood pressure and end-organ damage. Clinical trials in hypertensive patients indicate that bosentan reduces blood pressure without heart rate increase or neurohumoral stimulation. Finally, bosentan is being considered for the treatment of cerebral vasospasm following subarachnoid hemorrhage. Bosentan reverses experimentally induced vasospasm of the basilar artery, and preliminary trials indicate that it can increase cerebral blood flow after aneurysmal subarachnoid hemorrhage.

Animals↗

PubMed1999

SAPHO syndrome: a long-term follow-up study of 120 cases.

OBJECTIVE: To assess the long-term outcome of the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. METHODS: All patients with the SAPHO syndrome seen at our unit between 1974 and 1997 were identified. Follow-up was prospective from 1992 to 1997. Data before 1992 were analyzed retrospectively. Clinical symptoms, treatments and biological data, including erythrocyte sedimentation rate and C-reactive protein, were recorded at least yearly. When available, radiological data, HLA B27 status, and findings from bone or skin biopsy specimens were recorded. For each drug, an efficacy index (El) was determined as follows: "0" for less than 30% improvement, as judged by the patient, on horizontal visual analog scale, "0.5" for partial efficacy, and "1" for more than 60% improvement. RESULTS: We identified 120 patients with the SAPHO syndrome (50 men, 70 women), of whom 102 patients were followed-up prospectively after 1992; 3 of these 102 patients were lost to follow-up. Six patients also had Crohn's disease, and three had ulcerative colitis. Except for a significant association of palmoplantar pustulosis (PPP) or psoriasis vulgaris (PV) with axial osteitis (P = .007), the dermatologic presentation had no significant influence on rheumatic symptoms (ie, osteitis or arthritis, peripheral or axial). The HLA B27 antigen was not significantly associated with a particular pattern of distribution of arthritis or osteitis. No severe or disabling complications were noted. In the 47 patients followed-up for more than 5 years (mean, 9.5; range, 5 to 23), the mean number of osteitis or arthritis foci increased during follow-up from 1.57 to 1.91 and from 2.68 to 3.11, respectively. Nonsteroidal antiinflammatory drugs (NSAIDs) were prescribed in 113 of 120 (94%) patients, with a mean El of 0.67 (+/-0.39). Corticosteroid (CS) therapy was used in 23 patients, with a mean El of 0.67 (+/-0.42). Colchicine and sulfasalazine had a mean El of 0.36 (+/-0.44) and 0.16 (+/-0.30), in 28 and 18 patients, respectively. Methotrexate was given to 10 patients (6 with peripheral arthritis), with a mean El of 0.64 (+/-0.48). Doxycyclin (100 mg twice daily) was used in 20 patients, usually to treat osteitis, with a mean El of 0.26 (+/-0.42). Intraarticular injections of a CS or osmic acid were used in 27 patients, with a mean El of 0.77 (+/-0.35). CONCLUSIONS: SAPHO syndrome is a relevant and stable entity, with a good long-term prognosis. NSAIDs and intraarticular injections (CS or osmic acid) most often alleviate rheumatic symptoms, but prednisone or methotrexate are sometimes necessary and appear globally helpful.

Acquired Hyperostosis Syndrome↗