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Biomedical subjects

S Marchand

Publications and source records attributed to S Marchand.

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

In vitro and in vivo investigations on fluoroquinolones; effects of the P-glycoprotein efflux transporter on brain distribution of sparfloxacin.

The role of mdr1a-encoded P-glycoprotein on transport of several fluoroquinolones across the blood-brain barrier was investigated. In vitro, P-glycoprotein substrates were selected by using a confluent monolayer of MDR1-LLC-PK1 cells. The inhibition of fluoroquinolones (100 microM) on transport of rhodamine-123 (1 microM) was compared with P-glycoprotein inhibitors verapamil (20 microM) and SDZ PSC 833 (2 microM). Subsequently, transport polarity of fluoroquinolones was studied. Sparfloxacin showed the strongest inhibition (26%) and a large polarity in transport, by P-glycoprotein activity. In vivo, using mdr1a (-/-) and wild-type mice, brain distribution of pefloxacin, norfloxacin, ciprofloxacin, fleroxacin and sparfloxacin was determined at 2, 4, and 6 h following intra-arterial infusion (50 nmol/min). Brain distribution of sparfloxacin was clearly higher in mdr1a (-/-) mice compared with wild-type mice. Sparfloxacin was infused (50 nmol/min) for 1, 2, 3 and 4 h in which intracerebral microdialysis was performed. At 4 h, in vivo recovery (dynamic-no-net-flux method) was 6.5+/-2.2 and 1.5+/-0.5%; brain(ECF) concentrations were 5.1+/-0.2 and 26+/-21 microM; and total brain concentrations were 7.2+/-0.3 and 23+/-0.3 microM in wild-type and mdr1a (-/-) mice, respectively. Plasma concentrations were similar (18.4+/-0.7 and 17.9+/-0.5 microM, respectively). In conclusion, sparfloxacin enters the brain poorly mainly because of P-glycoprotein activity at the blood-brain barrier.

4-Quinolones↗
PubMed2000

[Mortality in a pediatric hospital. Six-year retrospective study].

AIMS: To define the characteristics of patients dying in a pediatric hospital, including causes and modes of death. PATIENTS AND METHODS: This retrospective, descriptive, epidemiologic study was performed between 1 January 1990 and 31 December 1995. All patients who died in the hospital between these dates were included. Patients already dead on arrival (sudden infant death syndrome, children deceased during their transport), and those whose hospital records could not be found, were excluded. RESULTS: A total of 375 children were studied, including 195 neonates. The sex ratio was 1.3. Ninety-one percent of deaths took place in three departments: intensive care, neurosurgery-neurology and oncology. Median duration of hospitalization was three days. The most common causes of deaths were accidents, neurologic diseases (particularly among neonates) and tumours. Analysis of modes of death revealed that 41.1% occurred following unsuccessful resuscitation, 38.8% were the result of withdrawal of life-support or a 'do not resuscitate' order and 21.6% resulted from brain death. Evolution of modes of death over the six years showed a reduction of cases with unsuccessful resuscitation, an increase in decisions of 'do not resuscitate' orders and withdrawal of life-support and no change in rates of brain death. Organs were made available for transplantation from 12 of the 81 children with brain death (14.8%). CONCLUSION: Accidents were the most common cause of death. The distribution of deaths showed a clear increase in withdrawal or withholding of life-support care, relying on ethical decisions, which are more frequent than some years ago.

Adolescent↗
PubMed2000

Approaches to wine aroma: release of aroma compounds from reactions between cysteine and carbonyl compounds in wine.

Under conditions close to those of wine, that is, low pH, aqueous medium, and low temperatures, this work examines the role of carbonyl (acetoin and acetol) and dicarbonyl (glyoxal, methylglyoxal, diacetyl, and pentane-2,3-dione) compounds associated with cysteine in the formation of odorous products. In particular, thiazole, 4-methylthiazole, 2-acetylthiazole, and trimethyloxazole and two sulfur and oxygenated heterocyclic compounds, 2-furanmethanethiol and thiophene-2-thiol, are examined. For thiophene-2-thiol, the reactional mechanism is proposed. Attempts were made to detect these compounds in wines from various origins. Certain molecules were identified for the first time in wine.

Cysteine↗
PubMed2000

Pharmacokinetic-pharmacodynamic modelling of the convulsant interaction between norfloxacin and biphenyl acetic acid in rats.

Fluoroquinolones (FQs) are associated with a low incidence of central nervous system (CNS) side effects, possibly leading to convulsions, especially when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDS). Although the in vivo pro-convulsant activity of NSAIDS is essentially unknown, the convulsant potential of FQs is traditionally evaluated by in vitro gamma-aminobutyric acid (GABA) binding experiments in the presence of 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen. The aim of this study was therefore to investigate the BPAA-norfloxacin convulsant interaction in vivo. Male Sprague-Dawley rats (n = 27) were given BPAA orally, at various doses 1 h before norfloxacin infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for analysis. An inhibitory E(max) effect model with a baseline effect parameter was fitted to the norfloxacin versus BPAA concentrations in the CSF, previously shown to be part of the biophase. This model includes three parameters: the concentrations of norfloxacin in the absence of BPAA (C(CSF0, Nor)), and when BPAA concentration tends toward infinity (C(CSFbase, Nor)), and the BPAA concentration for which half of the maximal effect is observed (C(CSF50, BPAA)). The maximal proconvulsant effect of BPAA is given by the C(CSF0, Nor) / C(CSFbase, Nor) ratio, estimated to approximately 6 in this study. Derived models were developed in plasma to account for the non-linear CSF diffusion of norfloxacin and protein binding of BPAA. In conclusion this study has shown that the convulsant interaction between norfloxacin and BPAA in rats, can be adequately characterized by modelling of the CSF concentrations of the two drugs at the onset of activity, following their administration in various proportions.

Animals↗
PubMed1999

Studies on calpain expression during differentiation of rat satellite cells in primary cultures in the presence of heparin or a mimic compound.

We have synthesized dextran derivatives called RGTAs (for regenerating agents) that were designed to mimic some of the properties of heparin or heparan sulfate to interact with and protect heparin binding growth factors. Some of these growth factors have been described to be involved in myogenesis control. In previous studies, we have shown that muscle regeneration in adults could be greatly enhanced in vivo by treatment with RGTA. Since muscle regeneration occurs through the activation of satellite cells, in the present study we have used primary cultures of rat satellite cells and treated them with the heparan sulfate analogue RGTA or heparin in order to stimulate their growth and differentiation. We also studied the effect of these substances on calpain (calcium-activated neutral proteases) expression in these cultures. Indeed, several reports, principally based on fetal myoblast cultures or myogenic cell lines, have suggested that calpains might be involved in myoblast fusion during myogenic differentiation. We therefore studied the expression of microcalpain (mu-calpain), millicalpain (m-calpain), and calpain 3 in the course of differentiation of these satellite cell cultures in the absence or in the presence of heparin or of a mimic compound (the RGTA RG1282). RGTA and heparin were shown to have a dual effect on satellite cell proliferation and differentiation: RGTA stimulated proliferation with a maximum dose effect at 1 microgam/ml. Heparin used at concentrations similar to those of RGTA was less efficient at stimulating proliferation. Both substances were shown, however, to induce precocious and enhanced differentiation of satellite cells. We showed by quantitative RT-PCR analysis that mu-calpain, m-calpain, and calpain 3 mRNAs were expressed in satellite cell cultures in proliferating myoblasts (day 3) and differentiating cultures (days 7 and 12). The level of mu-calpain mRNA was increased by a factor of 3 during differentiation of satellite cells, whereas the level of m-calpain mRNAs was slightly increased at day 12 only, and calpain 3 mRNA was slightly reduced in these differentiating cultures. Interestingly enough, RGTA and heparin, which both strongly increased differentiation, reduced the expression of the mu- and m-calpains and slightly increased that of calpain 3 in differentiating cultures. These results showed that there was no correlation between the extent of myoblast differentiation and the level of calpain expression in satellite cells grown in primary cultures and underscored the differences between these adult cells and fetal myoblasts.

Animals↗
PubMed1999

Spinal opioid analgesia: how critical is the regulation of substance P signaling?

Although opioids can reduce stimulus-evoked efflux of Substance P (SP) from nociceptive primary afferents, the consequences of this reduction on spinal cord nociceptive processing has not been studied. Rather than assaying SP release, in the present study we examined the effect of opioids on two postsynaptic measures of SP release, Fos expression and neurokinin-1 (NK-1) receptor internalization, in the rat. The functional significance of the latter was first established in in vitro studies that showed that SP-induced Ca(2+) mobilization is highly correlated with the magnitude of SP-induced NK-1 receptor internalization in dorsal horn neurons. Using an in vivo analysis, we found that morphine had little effect on noxious stimulus-evoked internalization of the NK-1 receptor in lamina I neurons. However, internalization was reduced when we coadministered morphine with a dose of an NK-1 receptor antagonist that by itself was without effect. Thus, although opioids may modulate SP release, the residual release is sufficient to exert maximal effects on the target NK-1 receptors. Morphine significantly reduced noxious stimulus-induced Fos expression in lamina I, but the Fos inhibition was less pronounced in neurons that expressed the NK-1 receptor. Taken together, these results suggest that opioid analgesia predominantly involves postsynaptic inhibitory mechanisms and/or presynaptic control of non-SP-containing primary afferent nociceptors.

Analgesia, Epidural↗
PubMed1999

Developmental regulation of tyrosine phosphorylation of the nicotinic acetylcholine receptor in Torpedo electrocyte.

Tyrosine phosphorylation is thought to play a critical role in the clustering of acetylcholine receptors (AChR) at the developing neuromuscular junction. Yet, in vitro approaches have led to conflicting conclusions regarding the function of tyrosine phosphorylation of AChR beta subunit in AChR clustering. In this work, we followed in situ the time course of tyrosine phosphorylation of AChR in developing Torpedo electrocyte. We observed that tyrosine phosphorylation of the AChR beta and delta subunits occurs at a late stage of embryonic development after the accumulation of AChRs and rapsyn in the membrane and the onset of innervation. Interestingly, in the mature postsynaptic membrane, we observed two populations of AChR differing both in their phosphotyrosine content and distribution. Our data are consistent with the notion that tyrosine phosphorylation of the AChR is related to downstream events in the pathway regulating AChR accumulation rather than to initial clustering events.

Aging↗
PubMed1999

A diagnostic fluorescent marker kit for six limb girdle muscular dystrophies.

The autosomal progressive muscular dystrophies which are grouped together under the term limb girdle muscular dystrophies (LGMD) are diseases characterized by a progressive impairment of the proximal limb muscles and myopathic changes on electromyogram and muscle biopsy. Eight independent purely recessive genetic entities have been recognized in this group of diseases by genetic localization or causative gene identification. We have developed fluorescent genetic markers bracketing six of these loci (LGMD2A-LGMD2F). The marker loci were genotyped in 96 LGMD2 families leading to genetic definition of 25 of them either with a high likelihood or with a suggested localization (7 LGMD2A, 5 LGMD2B, 4 LGMD2C, 4 LGMD2D, 2 LGMD2E and 3 LGMD2F). In addition, 18 families were excluded for all six tested loci; for 45 of the 53 remaining families at least one exclusion could be demonstrated. This kit, which makes the rapid genetic testing of LGMD2 families possible, may be useful in a diagnostic process.

Chromosome Mapping↗
PubMed1999

Human parvovirus B19 infection in organ transplant recipients.

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

DNA, Viral↗
PubMed1998

Evaluation of rubella screening in pregnant women.

BACKGROUND: The rationale for rubella vaccination in the general population and for screening for rubella in pregnant women is the prevention of congenital rubella syndrome. The objective of this study was to evaluate the effectiveness of the prenatal rubella screening program in Quebec. METHODS: A historical cross-sectional study was designed. Sixteen hospitals with obstetric services were randomly selected, 8 from among the 35 "large" hospitals in the province (500 or more live births/year) and 8 from among the 50 "small" hospitals (fewer than 500 live births/year). A total of 2551 women were randomly selected from all mothers of infants born between Apr. 1, 1993, and Mar. 31, 1994, by means of stratified 2-stage sampling. The proportions of women screened and vaccinated were ascertained from information obtained from the hospital chart, the physician's office and the patient. RESULTS: The overall (adjusted) screening rate was 94.0%. The rates were significantly different between large and small hospitals (94.4% v. 89.6%). Five large hospitals and one small hospital had rates above 95.0%. The likelihood of not having been screened was statistically significantly higher for women who had been pregnant previously than for women pregnant for the first time (4.8% v. 1.4%; p < 0.001). Of the 200 women who were seronegative at the time of screening (8.4%), 79 had been vaccinated postpartum, had a positive serological result on subsequent testing or did not require vaccination, and 59 had not been vaccinated postpartum; for 62, subsequent vaccination status was unknown. INTERPRETATION: Continued improvement in screening practices is needed, especially in small hospitals. Because vaccination rates are unacceptably low, it is crucial that steps be taken to address this issue.

Canada↗
PubMed1998

Molecular dynamics study of calbindin D9k in the apo and singly and doubly calcium-loaded states.

Molecular dynamics simulations based on detailed atomic models are used to examine the structure and dynamics of calbindin D9k, a protein possessing a pair of EF-hands able to bind two calcium ions in a cooperative fashion. Trajectories for the apo and singly (in the C-terminal binding site) and doubly loaded structures are generated and analyzed. Each system is solvated in a 27 A radius sphere of 2,285 explicit water molecules. The influence of the remaining bulk is incorporated through a stochastic boundary potential including a solvent reaction field. Long-range electrostatic interactions are treated with a special method and are not truncated. The average structural and dynamic properties upon calcium binding are studied at the atomic level to gain insight into the cooperative interactions between the two binding sites. Results from the trajectories are compared with data from nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. NMR 15N and 13C(alpha) backbone relaxation order parameters and crystallographic B-factors are calculated. Generally, there is a good qualitative agreement between calculated and observed properties. Results confirm that the doubly loaded state is closer, both structurally and dynamically, to the singly loaded state than either of these is to the apo state. It is observed that both hydrogen bonding and the packing of nonpolar side chains contribute to the coupling between the calcium binding sites. Two backbone-to-backbone hydrogen bonds linking the calcium-binding EF-hands (Leu23-0 ... HN-Val61 and Val61-O ... HN-Leu23) are sensitive to the state of occupancy. Residues Leu23 and Val61 exhibit the smallest rms fluctuations of the entire protein in the D state. In addition, the van der Waals interaction of Val61 with the rest of the protein varies with the calcium-binding state.

Binding Sites↗
PubMed1998

Characterization of two distinct P2Y receptors in human tracheal gland cells.

Human submucosal tracheal glands are now believed to play a major role in the physiopathology of cystic fibrosis, a genetic disease in which ATP is used as a therapeutic agent. However, actions of ATP on tracheal gland cells are poorly known. ATP-binding characteristics, and ATP-induced formation of cAMP were investigated in a cell line (MM39) of human tracheal gland cells. The binding of a radiolabelled non-hydrolysable analogue of ATP Adenosine-5'-[35S]thiotriphosphate: [35S]ATP[gammaS] was rapid (within 30 min at 4 degrees C), stable and reversible. Scatchard analysis revealed two classes of [35S]ATP[gammaS]-binding sites. Low-affinity binding sites had a Kd1 of 20 +/- 5 microM (Bmax = 150 nmol/10(6) cells) and the high-affinity binding sites had a Kd2 of 2.5 +/- 0.2 microM (Bmax = 52 nmol/10(6) cells). Competition experiments showed competition with ATP, ADP and 2-methylthio-ATP but no competition with UTP, AMP and adenosine. UTP stimulates protein secretion as well as it induced [Ca2+]i mobilization but did not affect the intracellular cAMP levels. ATP also caused induced [Ca2+]i mobilization and protein secretion but also caused an increase in cyclicAMP content of the cells, reaching a maximum after 1 min. ATP-induced cAMP formation was concentration dependent and inhibited by the P2-antagonist suramin. Reverse-transcription-PCR amplification revealed the presence of the transcripts of both the P2Y2 and the UTP-specific P2Y4 receptors. In conclusion, P2Y2 receptors, UTP-P2Y4 receptors and unidentified ATP-specific receptors seem to be present in MM39 cells which appear to be coupled differently to intracellular second-messenger systems.

Adenosine Triphosphate↗
PubMed1998

A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B.

The limb-girdle muscular dystrophies are a genetically heterogeneous group of inherited progressive muscle disorders that affect mainly the proximal musculature, with evidence for at least three autosomal dominant and eight autosomal recessive loci. The latter mostly involve mutations in genes encoding components of the dystrophin-associated complex; another form is caused by mutations in the gene for the muscle-specific protease calpain 3. Using a positional cloning approach, we have identified the gene for a form of limb-girdle muscular dystrophy that we previously mapped to chromosome 2p13 (LGMD2B). This gene shows no homology to any known mammalian gene, but its predicted product is related to the C. elegans spermatogenesis factor fer-1. We have identified two homozygous frameshift mutations in this gene, resulting in muscular dystrophy of either proximal or distal onset in nine families. The proposed name 'dysferlin' combines the role of the gene in producing muscular dystrophy with its C. elegans homology.

Adolescent↗
PubMed1998

Class, health and justice.

Class inequalities in health are intuitively unjust. Although the link between social class and health status has been fully documented, the precise nature of the injustice has not been made clear. Four alternative views are presented, corresponding to four goals: (1) maximizing the sum total of health; (2) equalizing the health status of higher and lower social classes; (3) maximizing the health status of the lowest social class; and (4) maximizing the health status of the sickest individuals in society. The nature of the injustice is further obscured by several theoretical and empirical questions, like the degree and significance of personal responsibility for illness and the relation of the degree of economic inequality to sum total of health.

Health Care Rationing↗
PubMed1998

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.

Adult↗
PubMed1998

Developmental gene expression and immunohistochemical study of the human endocrine pancreas during fetal life.

The development of human endocrine pancreas has been the subject of many immunohistochemical studies but very little is known at the molecular level. We have determined the patterns of gene expression of glucagon, somatostatin and pancreatic polypeptide during fetal life (16-41 weeks of gestation) using the dot-blot hybridization method. In spite of some dispersion in the mRNA levels, no progressive increase or decrease during this period of fetal life could be found, as previously observed for insulin. In keeping with these molecular data, no increase in immunostaining of the four hormones was observed, but a dispersion of endocrine cells within the exocrine tissue was noticed at 20 weeks of gestation followed by a clear differentiation of the Langerhans islets at 31 weeks. Interestingly, the mRNA levels of the four hormones were always higher in the fetal pancreas than in the adult pancreas.

Blotting, Northern↗
PubMed1998

[Urinary tract infections in pediatric practice--which new aspects must be considered?].

The prevalence of urinary tract infections varies markedly with sex and age. They are caused mainly by colonic bacteria. Acute cystitis should be promptly treated either with cotrimoxazol or coamoxyclav to prevent its possible progression to pyelonephritis. In acute febrile infections suggestive of pyelonephritis, the initial use of broad-spectrum antibiotics capable to reaching significant tissue levels is advised, mostly amoxycillin with an aminoglycoside. A variety of functional voiding disorders including bladder instability, detrusor-sphincter dyscoordination, postponing syndrome or lazy bladder syndrome have been identified since the early 1970s, each with its own characteristics and clinical importance. Functional voiding disorders are nowadays a major cause of recurrent urinary tract infections in children. A careful investigation to confirm or exclude functional voiding disorders is warranted in children with recurrent urinary tract infections. Management will vary according to the type and severity of the dysfunction present.

Acute Disease↗