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N Simon

Publications and source records attributed to N Simon.

At least 37 records · Page 2Linked to original sources
PubMed2000

Efficacy of HCV core antigen detection during the preseroconversion period.

BACKGROUND: The purpose of this study was to compare the performances of HCV core antigen (HCV Ag) testing with HCV RNA detection during the preseroconversion period. STUDY DESIGN AND METHODS: Six HCV antibody (HCV Ab)-negative and HCV RNA-positive blood samples from 6 donors and 135 serial samples from 28 patients who had undergone hemodialysis, collected a mean of 90 days before the detection of HCV Ab, were tested by ELISA for the detection of HCV Ag and by PCR to quantify HCV RNA. RESULTS: Five of the six donors were positive for HCV Ag. The donor with a negative HCV Ag test had the lowest viral load. In the hemodialysis patients, the 43 first specimens of the series were HCV RNA negative. Of the 92 specimens that were HCV RNA positive, 81 (88%) were positive for HCV Ag. Among the 74 samples with more than 10(5) RNA copies, 71 (96%) were HCV Ag positive. Average time from first viremic bleed to first HCV Ag-positive bleed was estimated at 2.0 days and that to first HCV Ab-positive bleed at 50.8 days. CONCLUSION: HCV Ag testing permits the detection of an HCV infection about 1.5 months earlier than the HCV Ab screening tests and an average of only 2 days later than quantitative HCV RNA detection in individual specimens.

Antibodies, Viral↗
PubMed2000

Angiostatic effects of suramin analogs in vitro.

Suramin analogs are polyanionic naphthylureas structurally related to suramin, an antitumor agent with a narrow therapeutic window. The angiostatic activities of suramin and 16 suramin analogs were investigated using an easily quantifiable in vitro angiogenesis system. In addition, the antiproliferative activities of the analogs were studied in four different human tumor cell lines and in porcine aortic endothelial cells. The suramin analogs encompassed two main structural variations, i.e. their molecular size, and the number and substitution pattern of the sulfonate groups. Some suramin analogs with a reduced number of sulfonate groups (NF062, NF289 and NF326) showed significant dose-dependent angiostatic and also antiproliferative activities. The disulfonate NF062 was superior to suramin in inhibiting HT29 and T47D tumor cells while demonstrating a similar angiostatic potential as suramin. Therefore, the sulfonate groups in the para position of the amino groups of the naphthyl residues of suramin seem to be of special importance. The very small disulfonates (NF108, NF109, NF499, NF500 and NF241) and the asymmetric compound NF520, one half of the suramin molecule, are inactive. Therefore, a minimal molecule size seems to be essential for the biological activity. Suramin is a rather rigid molecule. The highly flexible analogs (NF527, NF528 and NF529) are inactive. This indicates that the molecular rigidity is important for the biological activity.

Angiogenesis Inhibitors↗
PubMed1998

Glucocorticoids decrease cytochrome c oxidase activity of isolated rat kidney mitochondria.

The importance of mitochondria is rising as a target in pathologic processes such as ischemia. We have investigated the effects of hydrocortisone, prednisolone, dexamethasone and triamcinolone on oxidative phosphorylation, Ca2+ fluxes, swelling and membrane potentials in isolated kidney mitochondria. The measurement of respiration state 3 showed a significant decrease in presence of glucocorticoids whereas the other respiration states were not modified. When mitochondria were uncoupled and either the complexes III and IV or the complex IV were stimulated, the O2 consumption was decreased by glucocorticoids. These results suggest the cytochrome c oxidase is a target of the glucocorticoid effect on the respiratory chain. Indeed, the other mitochondrial functions investigated were unchanged, ruling out a direct effect on Ca2+ fluxes or swelling. A regulation of cytochrome c oxidase activity by glucocorticoids will be of particular interest in pathology involving metabolic insult.

Animals↗
PubMed1998

[Circulatory arrest].

Explore the source record for details and available documents.

Cardiopulmonary Resuscitation↗
PubMed1998

The genetic variant A of human alpha 1-acid glycoprotein limits the blood to brain transfer of drugs it binds.

The objective of this work was to check the effects of alpha-1 acid glycoprotein (AAG) and of its components, A and F1/S genetic variants, on the brain transfer of drugs they bind in plasma. The relevant extractions of six basic drugs, highly bound to AAG, were measured. We chose three drugs selectively bound to the A variant, disopyramide, imipramine and methadone, one drug mainly bound to the mixture F1/S, mifepristone, and two drugs which were simultaneously bound to the variant A and the mixture F1/S, propranolol and chlorpromazine. Their brain extraction were investigated in rats using the carotid injection technique and the capillary depletion method. Injected drugs were dissolved either in buffer, either in native AAG containing the three variants (A, F1 and S), either in variant A or in variant F1/S solutions. Brain extractions of disopyramide, imipramine and methadone were significantly reduced by native AAG and by variant A. Drug's plasma retention was related to their preferential and almost exclusive binding to A variant, both of them exhibiting the same decrease in brain transfer as compared to a buffered solution. At the opposite, there were no significative differences between the extraction either in buffer, either in AAG or in F1/S solutions, of drugs both bound to A variant and F1/S mixture (chlorpromazine and propranolol) or to the F1/S mixture (mifepristone). In serum, the retentional effect of the A variant on the extraction of disopyramide and imipramine was counteracted by the presence of albumin and lipoproteins, which simultaneously bind these two drugs at a high extent and act as permissive binders. We conclude that AAG binding decreases brain drug transfer when the A variant is mainly and almost exclusively involved in the binding. On the contrary, the entire fraction of the tested drugs when bound exclusively or partly to the mixture F1/S is available for transfer into the brain.

Animals↗
PubMed1998

Tacrolimus decreases in vitro oxidative phosphorylation of mitochondria from rat forebrain.

The effects of tacrolimus (FK 506) on brain phosphorylation have been investigated in vitro using mitochondria isolated from rat brain. Respiratory control ratio (RCR), oxygen consumption, ATP synthesis and enzymatic activities of involved complexes have been measured to assess the mechanisms of action of tacrolimus. Our data show that this drug decreases RCR and ATP synthesis. This effect is quantitatively limited after a single application of the drug (14%), concentration-dependent and biphasic, the respective effect 50%-concentration (EC50) being 0.129 and 247 nM, each step corresponding to 50% of the total oxygen consumption inhibition. Tacrolimus acts mainly as an inhibitor of ubiquinol-cytochrome c reductase (complex III), competing at least partly with antimycin A or myxothiazol, the corresponding EC50 being 0.27 and 103 nM respectively. Tacrolimus inhibits also complex V i.e. ATPase activity (40%) and ATP synthase activity (30%) in a concentration-dependent manner, the relevant EC50 being 78 and 394 nM respectively. These data may be relevant for the protective effect of tacrolimus observed in ischemia-reperfusion, which may be due to its inhibition of both complex III, where Reactive Oxygen Species (ROS) are generated, and complex V, where ATP is depleted by ATPase activation. It may also be related to neurotoxicity occurring along chronic administration of tacrolimus in humans.

Adenosine Triphosphate↗
PubMed1998

[Post-lumbar puncture headache in children. Treatment with epidural autologous blood (blood patch)].

UNLABELLED: Post-lumbar puncture headaches (PLPH) are uncommon in children, but when they occur treatment is challenging. PLPH in adults have been successfully treated by the use of the epidural blood patch. This treatment has been very rarely reported in children. CASE REPORT: A 13-year-old boy, weighing 64 kg, had a lumbar puncture as part of a work-up for a 4-day history of right hemithorax pain. This pain was associated with hypoesthesia; there were no cutaneous vesicles. Neurological examination revealed decreased strength in the left upper extremity. A magnetic resonance imaging of the cervicodorsolumbar spine was normal. Three hours after lumbar puncture, the patient complained of bifrontal headaches. The headaches worsened in the upright position and they prevented the boy from ambulating. Treatment with acetaminophen was unsatisfactory. On day 9, the initial symptoms that had motivated the lumbar puncture had disappeared, but PLPH persisted. Therefore, an epidural blood patch was performed (EBP). A 18-gauge 1 Perican needle was introduced into the peridural space at the L3-L4 interspace using the loss of resistance technique. Fifteen milliliters of blood were drawn in a sterile fashion and without anticoagulant from the patient's forearm and injected slowly through the epidural needle. The patient experienced immediate, complete, and definite relief of his PLPH. Follow-up did not show any complication. CONCLUSION: EBP can be useful in the treatment of PLPH lasting more than 5 days in children.

Adolescent↗
PubMed1998

Role of lipoproteins in the plasma binding of SDZ PSC 833, a novel multidrug resistance-reversing cyclosporin.

AIMS: The plasma binding of the cyclosporin D analogue SDZ PSC 833 was investigated in vitro. METHODS: The plasma total binding constant (corresponding to the bound-to-free concentration or binding ratio) was determined at 37 degrees C by the erythrocyte partitioning technique on plasma samples from three healthy volunteers and three cancer patients. Lipoproteins were also removed from plasma samples from three healthy volunteers by a standard ultracentrifugal technique. RESULTS: SDZ PSC 833 plasma binding was 97.8 +/- 1.1% and 97.3 +/- 0.2% in samples from three healthy volunteers and three cancer patients respectively. More than 95% of blood SDZ PSC 833 was distributed in plasma. When the original plasma samples of three individuals were delipidated, SDZ PSC 833 binding was strongly decreased (58% bound to plasma proteins) and when lipoproteins were resuspended in the delipidated plasma samples to produce varying lipoprotein plasma concentrations, the binding increased continuously with the fraction of added lipoproteins. When lipoproteins were resuspended to restore the original lipoprotein plasma content, the % plasma-bound SDZ PSC 833 increased to 98.2%, close to the value observed with the original plasma (98.7%). CONCLUSIONS: These results clearly indicate that SDZ PSC 833 plasma binding is mainly determined by lipoproteins and that in blood, most of SDZ PSC 833 is distributed in plasma.

Cyclosporine↗
PubMed1998

Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences.

BACKGROUND: Coenzyme Q10 or ubiquinone is a redox component of the respiratory chain, which may be involved in the pathogenesis of cancer. METHODS: In order to better understand the role of this vitamin in the pathogenesis of breast cancer, a clinical trial including 200 women hospitalized for the biopsy and/or the ablation of a breast tumor was conducted. Ubiquinone plasma concentrations were determined simultaneously with vitamin E plasma concentrations (as antioxidant reference) by HPLC. RESULTS: A coenzyme Q10 deficiency was noted both in carcinomas (80 patients) and non-malignant lesions (120 patients), while vitamin E concentrations were within the normal range. A correlation was shown between the intensity of the deficiency and the bad prognosis of the breast disease based on high TNM and SBR values or the lack of estrogen receptors. However, neither cathepsin D level nor adenopathy invasion was related to ubiquinone levels. CONCLUSIONS: Since prooxidants may promote tumorigenesis, ubiquinone supplementation in breast cancer could be relevant.

Adult↗
PubMed1997

Population pharmacokinetics of high-dose thiopental in patients with cerebral injuries.

Thiopental monitoring was performed in 95 critically ill patients hospitalized for neurologic damage, High-dose thiopental was infused during long-term treatment. Total dose of 333 +/- 144 mg/kg (449 +/- 185 mg/kg for females and 302 +/- 113 mg/kg for men) were given in 125 +/- 43 hours. Plasma concentration-time data were analyzed according to a population pharmacokinetic approach with an initial group of 65 patients. Clearance (CL) and central volume of distribution (Vc) were modeled alone and under the influence of demographic covariates, assuming a two-compartment open model with first-order elimination. The final population models were as follows: CL (L/hr) = 11.7.weight (kg).age (yr)/(2136 + age2) and Vc = 1.52.weight (kg) + 44.8. Mean CL and Vc mean population estimates were 8.01 L/hr (133 ml/min or 2.02 ml/min/kg) and 145 L (2.19 L/kg). The predictive performance of the population modeling and parameters was evaluated with a bayesian fitting procedure in an independent validation set of 30 patients with similar physical and clinical characteristics. There was no statistically significant bias or imprecision between measured and predicted thiopental plasma concentrations in this validation group. Moreover, there was a good adequation (r = 0.939) between individual CL values predicted from the population formula and estimated with the bayesian approach.

Adolescent↗
PubMed1997

Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative phosphorylation decrease of kidney mitochondria.

We investigated the effects of cyclosporine A, prednisolone and azathioprine on respiration rates, Ca2+-induced swelling and Ca2+ fluxes of rat kidney mitochondria. The three drugs significantly decreased the succinate induced-respiration rates according to concentration-dependent processes. Each drug inhibited about 10% of the respiratory control ratio, with EC50 of 3.7 x 10(-7) M, 5.8 x 10(-9) M for cyclosporine A and azathioprine respectively. Prednisolone was the most effective (19.2%) acting by a two-step process with EC50 of 9.2 x 10(-12) M and 1.9 x 10(-8) M. The combination of the three drugs developed a higher significant decrease of respiratory control ratio than that of each drug but lower than the sum of their respective effects. Inhibitions of swelling and Ca2+ fluxes through mitochondrial membrane due to the combination were not different from those induced by cyclosporine A alone. The action mechanisms of cyclosporine A and prednisolone were total and partial Ca2+ dependent respectively. Azathioprine appears to act by a Ca2+-independent one. It is concluded that azathioprine and prednisolone may worsen cyclosporine A-induced renal mitochondrial alteration of oxidative phosphorylation.

Animals↗
PubMed1997

[The Cochrane Collaboration, support of therapeutic information].

Today, prescribers need to distinguish between the clinical practices based on randomized clinical trialing information and those based on animal physiological data or theory. Now the information on therapeutics is becoming more dense, more complex and less available to the clinicians. Information sources are numerous and varied, including data whose quality differs. These data are unhierarchised in terms of methodological quality and clinical relevance. It will be optimal if each prescriber could himself collect and analyse scientific information. In fact this situation cannot be effective in private physician's practices. An international collaboration, the Cochrane Collaboration, including volunteers, university researchers, and clinical investigators has the following objective: to prepare, maintain and disseminate systematic reviews of the effects of health care. The Cochrane Collaboration is thus the most adapted intermediairy between scientifically actualized data and clinical practitioners.

France↗
PubMed1997

pH dependent binding of ligands to serum lipoproteins.

PURPOSE: The binding interactions of binedaline, nicardipine and darodipine with lipoproteins (HDL, LDL, VLDL) were examined as a function of pH in order to evaluate the role of lipoprotein components and ligand protonation in the binding process. METHODS: Binding studies were performed by equilibrium dialysis with radiolabeled ligands and differential UV-visible spectroscopy. RESULTS: Deprotonated ligands had a markedly higher affinity for lipoproteins than the protonated forms, resulting in a concomitant decrease in the pKa of bound ligands, i.e., a decrease in the basicity of the ligand in the bound state. The UV-visible difference spectra generated upon binding of auramine O to lipoproteins also showed that there was a contribution to the binding arising from the deprotonation of the ligand. Ligand binding was related to the phospholipid and cholesteryl ester content and to a lesser degree to the free cholesterol and protein content of lipoproteins, therefore to the surface monolayer components of lipoproteins. This relationship was even more accurate for the deprotonated, high-affinity, than for the protonated species. CONCLUSIONS: It is suggested that among other possible interactions, ligand binding to lipoproteins involves proton exchange between the reactants and that the high affinity ligand species interact more specifically with the phospholipids of the lipoprotein surface monolayer.

Hydrogen-Ion Concentration↗
PubMed1997

Blood-to-brain transfer of various oxicams: effects of plasma binding on their brain delivery.

PURPOSE: The objective of this work was to assess the influence of binding to plasma proteins and to serum on the brain extraction of four antiinflammatory oxicams. METHODS: The brain extraction of isoxicam, tenoxicam, meloxicam and piroxicam was investigated in rats using the carotid injection technique. Blood protein binding parameters were determined by equilibrium dialysis using human serum, human serum albumin (HSA) and alpha-l-acid glycoprotein (AAG) solutions at various concentrations. RESULTS: All oxicams had low values of brain extraction, between 19% and 39% when dissolved in serum, i.e. under physiological conditions. Brain efflux rate constants calculated from the wash-out curves were the same in the absence or presence of serum. Brain efflux was inversely related to the polarity of the oxicams, such that the higher their H-bonding capacity, the lower their brain efflux. The free dialyzable drug fraction was inversely related to protein concentration. However, rat brain extraction was always higher than expected from in vitro measurements of the dialyzable fraction. CONCLUSIONS: Except for piroxicam whose brain extraction was partially decreased in the presence of proteins, the serum unbound and initially bound fractions of oxicams both seem available for transfer into the brain. Modest affinities for AAG rule out any related effect. More surprising is the apparent lack of effect on brain transfer of the high-affinity binding to HSA and serum. The enhanced brain uptake of meloxicam in the presence of AAG could be a result of interactions between this globular protein and the endothelial wall.

Adult↗