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Biomedical subjects

S Marchand

Publications and source records attributed to S Marchand.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effects of acetylethylcholine mustard on [3H]quinuclidinyl benzilate binding and acetylcholine release in rat brain synaptosomes.

The effects of acetylethylcholine mustard and its aziridinium derivative (AMMA) on acetylcholine (ACh) release and [3H]quinuclidinyl benzilate (QNB) binding were studied in rat cortical synaptosomes. After incubation for 5 min at 37 degrees C, AMMA reduced [3H]QNB binding with an IC50 of 9 microM. Following incubation for 5 min with 50 microM AMMA and washing, there was a 62% reduction in the [3H]QNB binding capacity with no change in the KD value for the remaining receptors, a result indicating the irreversibility of the AMMA binding. AMMA and oxotremorine both reduced the basal and 30 mM K+-induced release of newly synthesized [3H]ACh in dose-dependent manners over a 2.5-min period. At identical 50 microM concentrations, AMMA produced a much longer inhibition of basal [3H]ACh release than oxotremorine did. The inhibition of basal and 30 mM K+-induced [3H]ACh release by AMMA (10-250 microM) was blocked by 2 microM atropine during a 2.5-min release incubation, but not during a 30-min release incubation. After synaptosomes were treated with 50 microM AMMA for 5 min and the unbound drug was washed out from the tissue, [3H]ACh release (basal and K+-induced) was reduced. AMMA (50 microM) reduced high-affinity choline uptake and ACh synthesis by greater than 90% in this tissue, but these effects did not account for the [3H]ACh release inhibition, because they were not atropine sensitive and hemicholinium-3 had no effect on [3H]ACh release under the conditions used in these studies, i.e., after extracellular [3H]choline was washed out. Taken together, these results suggest that AMMA may be an irreversible agonist at presynaptic muscarinic autoreceptors.

Acetylcholine↗
PubMed1987

[Erythromelalgia, arterial hypertension and increased excretion of urinary catecholamines].

A 7 year-old girl was hospitalized with acute, severe and drug resistant erythromelalgia. During her stay in the hospital, she presented with an epileptic seizure associated with hypertension (220-120 mmHg). Catecholamine urinary excretion was markedly increased. Diagnoses of pheochromocytoma and acrodynia were excluded. Erythromelalgia and hypertension both disappeared in a few days without any relapse after a 2 year-follow-up. Catecholamine urinary excretion returned to normal levels in a few weeks. A skin biopsy which was performed in an affected site, showed a slight and questionable reduction of the density of autonomic adrenergic nerve terminals in the periarterial and glandular plexuses. The relevance of transitory excess catecholamine excretion and its link with erythromelalgia and hypertension are discussed. The hypothesis that the disorder could be explained by an abnormality of distal autonomic axons is likely.

Catecholamines↗
PubMed1986

Pharmacokinetics of amikacin in cystic fibrosis: a study of bronchial diffusion.

36 pharmacokinetic studies of amikacin were performed to evaluate the bronchial diffusion of amikacin in 9 children with cystic fibrosis, 3 to 15 years old. Amikacin was administered i.v. according to a variable dosage regimen. Four children without cystic fibrosis were enrolled as controls. The mean half life was 1.1, the volume of distribution averaged 0.26 l/kg, and the mean plasma clearance was 131 ml/min/1.73 m2, which no differed from that of the controls. The mean peak plasma concentration was always above the MIC but its level depended on the unit dose: 18.5 mg/l, 25,95 mg/l and 31,46 mg/l for doses of 5, 7.5 and 12.5 mg/kg, respectively. Between consecutive amikacin infusions, the plasma level was above the MIC for 21% and 46% of the time after the 5 and 7.5 mg/kg doses. The maximum concentration in sputum between H1 and H2 was always below the MIC, except after 15 mg/kg. The ratio AUC sputum/AUC plasma was between 0.028 and 0.61, and it increased from the beginning to the end of the course of treatment. No side effects were observed on hearing, or vestibular and renal function. The results are used to suggest more appropriate dosing regimens.

Adolescent↗
PubMed1985

Age-related changes in cardiac muscarinic receptors: decreased ability of the receptor to form a high affinity agonist binding state.

Cardiac ventricular muscarinic cholinergic receptors and agonist binding properties were determined in Fischer 344 rats at 3, 12, and 24 months of age. Muscarinic receptors were determined by specific (-)-[3H]quinuclidinyl benzilate (QNB) binding, and the agonist binding properties were determined by competition assays. There were no differences in the concentration of the receptor or the dissociation constant of [3H]QNB binding among the three age groups. In cardiac membranes from 3- and 12-month-old animals, 5'-guanylyl-imidodiphosphate (Gpp(NH)p) increased by 16- to 18-fold (p less than .01) the concentration of carbachol required to inhibit [3H]QNB binding by 50% (IC50). At 24 months, however, Gpp(NH)p induced only a 2.7-fold shift in the carbachol IC50 value (p less than .01). The reduced shift was due to an increase in the carbachol IC50 value determined in the absence of Gpp(NH)p (p less than .01). There was no significant differences among the 3-, 12-, and 24-month-old animals in the half-maximal concentration of Gpp(NH)p required to produce the carbachol IC50 shift. The data indicated that with age there is a reduced ability of the muscarinic receptor to form a high affinity agonist binding state.

Aging↗
PubMed1984

[C-reactive protein of the cerebrospinal fluid in children. A new evaluation of its diagnostic value].

The presence of C-reactive protein in the cerebrospinal fluid (CSF) has been proposed as an early indicator of bacterial meningitis in children. A commercial latex agglutination test (CR-test, Hyland) was performed in CSF obtained at first lumbar puncture in 114 children (26 neonates and 88 children aged from 1 month to 15 years) presenting with meningitis-like episodes. The CSF was regarded as normal in 41 cases; 50 had non-bacterial meningitis, and bacterial infection was diagnosed in 14 and suspected in 9. The latex agglutination test was positive in the first CSF sample from 2 neonates with bacterial meningitis, but its specificity was low (= 0.58). In older infants and children the test was positive in 18/21 cases of bacterial meningitis (sensitivity = 0.86) and negative in the 18 cases with normal CSF, as well as in 47/49 cases of non-bacterial meningitis (specificity = 0.97). The presence of C-reactive protein in CSF obtained at first lumbar puncture therefore is unreliable to distinguish between bacterial and aseptic meningitis.

Adolescent↗
PubMed1975

Efficacy of inactivated Mycoplasma pneumoniae vaccine in man.

Inactivated Mycoplasma pneumoniae vaccine produced antibody responses that reached protective levels in most individuals. These were almost equivalent to natural infection in amount and duration, and they persisted more than a year. Adverse effects were inconsequential. At Keesler Air Force Base, Mississippi, where the annual rate of mycoplasma pneumonia varied from 20 to 50 per 1000 since 1959, protection studies were conducted in 21, 199 men in 1964-1966 and in 13, 892 men in 1969-1971. This produced a 36 percent reduction in bronchitis and a 45 percent reduction in pneumonia due to all etiologies in the frist study and 37 percent and 48 percent respectively in the second study. The protective efficacy of the second vaccine was 87 percent for acutebronchitis and 66 percent for pneumonia due to Mycoplasma pneumoniae. Persons who developed Mycoplasma pneumoniae infections in spite of vaccination did not experience more severe illnesses.

Adult↗
PubMedDate not supplied

Kinetic parameters of amikacin in cystic fibrosis children.

35 kinetic studies have been performed, in nine CF children three to 15 years old; six kinetic studies were performed in four non-CF children, one to 12 years old. The dosage was 5 to 12.5 mg/kg, i.v. during 0.5 to 1.0 h, three to four times per day. Amikacin concentrations were measured in the plasma of all children, and in the sputum of CF-patients, by fluorescent polarization (TDX Abbott). The pharmacokinetic parameters in the plasma did not differ significantly in both groups of patients. In CF children t1/2 = 0.94 h (SD = 0.25 h), Vd (area) = 0.257 l/kg (SD = 0.06 l/kg), total body clearance = 130.7 ml/min/1.73 m2 (SD = 32.4 ml/min/1.73 m2). In non-CF children t1/2 = 0.83 h (SD = 0.15 h), Vd (area) = 0.265 l/kg (SD = 0.04 l/kg) and clearance = 155 ml/min/1.73 m2 (SD = 17.4 ml/min/1.73 m2). The parameters were not affected by the dosage of amikacin. The peak plasma concentrations ranged from 19 to 43.8 mg/l. Amikacin peak level in the sputum of CF children never reached the average MIC (4 mg/l) of Pseudomonas aeruginosa strains isolated in these patients. Amikacin concentration in the sputum reached its highest value about 2 h after the completion of i.v. infusion and was directly related to the peak plasma concentration. According to these parameters, the best dosage regimen appeared to be 7.5 to 8 mg/kg or 225 to 240 mg/m2 administered intravenously in 1.0 h, three times per day.

Adolescent↗
PubMedDate not supplied

Targeting of acetylcholine receptor and 43 kDa rapsyn to the postsynaptic membrane in Torpedo marmorata electrocyte.

In this study we have investigated the intracellular routing of two major components of the postsynaptic membrane in Torpedo electrocytes, the nicotinic acetylcholine receptor and the extrinsic 43 kDa protein rapsyn, and of a protein from the non-innervated membrane, the Na+,K+ ATPase. We isolated subpopulations of post-Golgi vesicles (PGVs) enriched either in AChR or in Na+,K+ ATPase. Rapsyn was associated to AChR-containing PGVs suggesting that both AChR and rapsyn are targeted to intracellular organelles in the secretory pathway before delivery to the postsynaptic membrane. In vitro assays further show that rapsyn-containing PVGs do bind more efficiently to microtubules compared to Na+,K+ ATPase-enriched PVGs. These data provide evidence in favor of the contribution of the secretory pathway to the delivery of synaptic components.

Animals↗
PubMedDate not supplied

Post-transplantation polyomavirus infections.

Increasing attention has been recently accorded to BK and JC viruses (BKV and JCV). Both these human polyomavirus (HPV) are members of the papovavirus family which includes the simian virus SV 40. BKV and JCV infect more than 60% of the population worldwide. After primary infection, they remain harboured in the kidneys and may become reactivated in situations of immune impairment. HPV were first described in 1971. BKV was isolated in a renal transplant patient with ureteral stricture and JCV in a patient with progressive multifocal leukoencephalopathy (PML). BKV was known to be involved in post-bone marrow transplantation (BMT) hemorrhagic cystitis. In renal transplantation, BKV and JCV were initially found in the post-transplant ureteric stricture and PML. They are now recognised as a possible cause of transplant interstitial nephritis, mimicking rejection (satisfying the Banff criteria for acute rejection) or drug toxicity. In HPV nephritis there is a mixed interstitial inflammatory infiltrate with focal tubular injury; the tubular epithelium shows marked anisonucleosis, nuclear atypia and basophilic or amphophilic intranuclear inclusions. Tubulitis is frequent. DNA hybridisation or gene amplification by polymerase chain reaction usually demonstrate HPV. Although histology with viral nucleic acid detection may be helpful in differentiating viral infection and rejection, confusion between these complications may lead to either anti-rejection therapy, with the risk of over-immunosuppression, or reduction of immunosuppression, with the risk of graft loss. Confusion may also arise with inclusions of other viruses, such as cytomegalovirus, herpes virus and adenovirus. Reactivation of BKV and JCV infection was demonstrated in respectively 22.2% and 10.9% of renal transplant recipients and 55% and 6.7% of BMT patients. Unfortunately, no routine screening is available for these viruses, so this complication is probably underestimated. No specific therapy of HPV infection is currently available.

Bone Marrow Transplantation↗
PubMedDate not supplied

Ciprofloxacin pharmacokinetics in young cystic fibrosis patients after repeated oral doses.

Until recently, only compassionate use of ciprofloxacin in children with cystic fibrosis was possible despite limited pharmacokinetic data. We studied five subjects with cystic fibrosis and exacerbation of pulmonary infection. A 15 mg/kg b.i.d. regimen of oral ciprofloxacin was administered. On the 15th day, eight blood samples were collected and plasma concentrations were measured by HPLC. The actual dose administered ranged from 10 to 14 mg/kg b.i.d., due to the fixed-dosage formulation. Corresponding AUC0-12 ranged from 8.2 to 11.9 mg.h/L. Plasma concentrations were maintained above individual MICs for a median time of 12.7 h over 24 h. The median area under the inhibitory curve was 52.8, which is about half the proposed target value for ciprofloxacin in pulmonary infections with Gram-negative bacteria such as Pseudomonas aeruginosa. A higher dose, administered from a specific formulation to ensure precise dosing, must be given in order to obtain adequate concentrations in cystic fibrosis children.

Administration, Oral↗