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J Sénécal

Publications and source records attributed to J Sénécal.

At least 19 recordsLinked to original sources

Catecholaminergic activation of G-protein coupling in rat spinal cord: further evidence for the existence of dopamine and noradrenaline receptors in spinal grey and white matter.

[35S]GTPgammaS autoradiography of slide-mounted tissue sections was used to examine G-protein coupling in the rat spinal cord, as stimulated by dopamine, the D1 receptor agonist SKF 38393, noradrenaline, and noradrenaline in the presence of the alpha adrenoceptor antagonist, phentolamine. Measurements were obtained from the different laminae of spinal grey and from the dorsal, lateral, and ventral columns of white matter, at cervical, thoracic, and lumbar levels. At every level, there was a relatively strong basal incorporation of GTPgammaS in laminae II-III>lamina IV-X of spinal grey, even in presence of DPCPX to block endogenous activation by adenosine A1 receptors. Dopamine, and to a lesser degree SKF 38393, but not the D2 receptor agonist quinpirole, stimulated G-protein coupling in laminae IV-X. Both dopamine and SKF 38393 also induced a weak but significant activation throughout the white matter. In both grey and white matter, the activation by dopamine was markedly reduced in presence of a selective D1 receptor antagonist. Noradrenaline strongly stimulated coupling throughout the spinal grey at all levels, an effect that was uniformly reduced in the presence of phentolamine. With or without phentolamine, there was also significant stimulation by noradrenaline in the white matter. Under the same experimental conditions, alpha 1, alpha 2, and beta adrenergic receptor agonists failed to activate GTPgammaS incorporation in either grey or white matter. However, in the presence of selective alpha 1 or alpha 2 receptor antagonist, significant reductions of noradrenaline-stimulated GTPgammaS incorporation were observed in both grey and white matter. The beta antagonist propanolol reduced GTPgammaS incorporation in grey matter only. Thus, the results confirmed the existence of D1 dopamine receptors and of alpha 1, alpha 2, and beta adrenergic receptors in the grey matter of rat spinal cord. In white matter, they strongly suggested the presence of dopamine D1, and of alpha 1 and alpha 2 adrenergic receptors on glia and/or microvessels, that might be activated by diffuse transmission in vivo.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Decreased G-protein coupling of serotonin 5-HT(1A) receptors in the brain of 5-HT(1B) knockout mouse.

The firing of central serotonin (5-hydroxytryptamine, 5-HT) neurons and their capacity to release 5-HT are subjected to a receptor-mediated auto-control via 5-HT(1A) and 5-HT(1B) receptors respectively located on the somata/dendrites (5-HT(1A) autoreceptors) and preterminal axon arborizations (5-HT(1B) autoreceptors) of these neurons. To further characterize mutual adaptations of these two receptor subtypes in the absence of one of them, activation of G-protein coupling by agonist was measured and compared to wild-type (WT) in 5-HT(1A) and 5-HT(1B) homozygous knockout (KO) mice. As expected, in WT, the non-selective 5-HT(1A/1B) receptor agonist 5-carboxyamidotryptamine (5-CT) stimulated guanosine 5'-O-(gamma-[(35)S]thio)triphosphate ([(35)S]GTP(gamma)S) incorporation in many brain regions endowed with one and/or the other receptor. In the respective KOs, no stimulation was measured in regions known to express only or mainly the deleted receptor. In the 5-HT(1A) KOs, the amplitude of G-protein activation in regions endowed with 5-HT(1B) receptors was unchanged by comparison to WT. In the 5-HT(1B) KOs, the magnitude of the 5-CT stimulation was the same as WT in all regions containing 5-HT(1A) receptors, except in the amygdala, where it was significantly lower, even if this region was one of the most strongly activated in the WT. A similar result was obtained in the amygdala of 5-HT(1B) KOs after activation by the selective 5-HT(1A) receptor agonist R-(+)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Under these conditions, however, there was in addition a significant lowering of the stimulated (but not basal) [(35)S]GTP(gamma)S incorporation by comparison to WT in all regions endowed with 5-HT(1A) receptors, including the dorsal raphe nucleus. Thus, eventhough agonist radioligand binding to either 5-HT(1A) or 5-HT(1B) receptors is unchanged in the reciprocal KOs, it appears that a compensatory decrease in the efficiency of G-protein coupling to 5-HT(1A) receptors has developed in the 5-HT(1B) mutant. This could represent the first indication of a cross-talk between these two 5-HT receptor subtypes, at least in brain regions where they are co localized in the same neurons.

Animals↗

Topology of ionotropic glutamate receptors in brains of heterozygous and homozygous weaver mutant mice.

In weaver mice, mutation of a G-protein inwardly rectifying K(+) channel leads to a cerebellar developmental anomaly characterized by granule and Purkinje cell loss and, in addition, degeneration of dopaminergic neurons. To evaluate other deficits, ionotropic glutamate receptors sensitive to N-methyl-D-aspartate (NMDA), amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainic acid (KA) were examined by autoradiography with [(3)H]MK-801, [(3)H]AMPA, and [(3)H]KA. These surveys were carried out in selected areas of cerebral cortex, hippocampus and related limbic regions, basal ganglia, thalamus, hypothalamus, brainstem, and cerebellum from heterozygous (wv/+) and homozygous (wv/wv) weaver mutants, and compared to wild-type (+/+) mice. In wv/+ and wv/wv mutants, NMDA receptor levels were lower in cortical areas, septum, hippocampus, subiculum, neostriatum, nucleus accumbens, superior colliculus, and in the cerebellar granular layer. Densities of KA receptors were lower in cortical areas, hippocampus, limbic system structures, neostriatum, nucleus accumbens, thalamus and hypothalamus, superior and inferior colliculi, and cerebellar cortex of wv/wv mutants. Levels of AMPA receptors in the weaver were higher than in +/+ mice, particularly in somatosensory and piriform cortices and periaqueductal gray of wv/+, and in somatosensory cortex, CA1 field of Ammon's horn and cerebellar granular layer of wv/wv. Abnormal developmental signals, aberrant cellular responses, or a distorted balance between neurotransmitter interactions may underlie such widespread and reciprocal glutamate receptor alterations, while in the case of cerebellar cortex, NMDA receptors are lacking due to a massive disappearance of cerebellar granule cells and some loss of Purkinje neurons.

Animals↗

Distribution of glutamate receptors of the NMDA subtype in brains of heterozygous and homozygous weaver mutant mice.

In weaver mice, mutation of an G-protein inwardly rectifying K+ channel leads to a cerebellar developmental anomaly characterized by granule and Purkinje cell loss and, in addition, degeneration of dopaminergic neurons. To evaluate other deficits, glutamate receptors sensitive to N-methyl-D-aspartate (NMDA) were examined by autoradiography with [3H]MK-801 in 36 brain regions from heterozygous (wv/+) and homozygous (wv/wv) weaver mutants, and compared to wild type (+/+) mice. In wv/+ and wv/wv mutants labelling decreased in cortical regions, septum, hippocampus, subiculum, neostriatum, nucleus accumbens, superior colliculus and in the cerebellar granular layer. The reductions in [3H]MK-801 binding were particularly specific in the cerebellar granular layer of wv/wv mutants, but an ubiquitous altered NMDA receptor topology was revealed in other brain regions. Abnormal developmental signals, or aberrant cellular responses, may underlie widespread NMDA receptor reductions, while in cerebellar cortex they could be lacking due to the massive loss of cerebellar granule cells.

Animals↗

[Compulsory medical certificates of early childhood: unknown epidemiology tool].

The delivery of three medical certificates has been made compulsory in 1970, the first during the first eight days of life, the second and the third respectively at 9 and 24 months. Thirty years later a survey has been conducted to evaluate the application and the efficiency of the system in 100 french departments. All the medical directors of the departmental MCH service send back the questionnaire. The number of annual birth by department is of 7,665 (mean) with extremities of 800 to 36,457. The covering of the concerned population is very good for the first certificate and increasing from 88.8% in 1992 to 94.9% in 1998; it is less good and not increasing for the CS9 (71.1%) and the CS24 (66%). The answers to each item are also variable according to the department but with an average of 86% (to refer to 650,000 annual births). The computer treatment of the certificates is increasing since ten years but 8 departments are still using manual analysis. In spite of the decentralization of MCH service each department is obliged to send to the Ministry of Health, each year, the results of 22 indicators which makes it possible to follow up the evolution of the situation of young children at the national level and to establish comparasons between departments. Simultaneously the certificates allow to guide the MCH activities, often at the canton level. The first certificate has been very useful for the study of perinatal problems and the third for the vaccination coverage. For example, some results are given and discussed (qualification of the examiner, neonatal mortality and socio-economical categories, mother âge, duration of pregnancy, birth weight, vaccination coverage...). Of course, the system is not perfect but is improving due to a better information of the medical personnel and of the families. It is still necessary to continue the research to underline the deficiencies and to correct them. Probably, in the future, the system will be extended to the registration of data obtained at the maternal school (3-4 years old) and the elementary school (5-6 years old).

Child Welfare↗

[Malaria in the infant in a rural area of maritime Guinea (Guinea Conakry). I. Immune and parasitic status of the mother and the newborn].

Among 216 women who had given birth in the rural health maternity centre of Maférinyah (Guinea), 32% had parasitemia with no clinical signs. Antimalarial antibodies could be measured only for 156 women and were present in all of them. Serological antimalarial tests were carried out on 133 newborns, all of whom had antibodies. The serological results of 122 mother infant pairs are given in this article. The absence of parasitemia in 122 newborns confirms the rarity of congenital malaria and would seem to favour the protective role of transmitted maternal antibodies.

Animals↗

[Malaria in infants in a rural area of maritime Guinea (Guinea Conakry). II. Development of antimalarial antibodies and malaria during the first year of life].

A transversal investigation carried out on 551 children and a longitudinal study of 55 infants showed the disappearance of maternal anti-plasmodium antibodies during the first year of life. Out of 212 new-borns surveyed for one year, 59 (28%) were infested by Plasmodium, but never during the first two months of life. This infestation was not related to the age of the infant nor to the season. For 46% of cases, infestation was completely asymptomatic, for 18% of cases respiratory signs were present and for 20% digestive signs not specific to malaria. Fever was present in 14 cases (24%) and isolated in 6 cases. Only 7 infants received a specific antimalarial treatment. Evolution under medical surveillance was favourable in all cases. These findings prove the difficulties inherent to the diagnosis of malaria, especially in the absence of laboratories for diagnosing other infections--such as typhoid--which do not appear in sanitary statistics. The findings also raise the question as to the efficiency of systematic antimalarial treatment in case of fever in the infant or child. Asymptomatic parasitemia can be explained by the existence of antitoxic immunity different from antiplasmodia immunity.

Aging↗

Glycogen metabolism in dog inner medullary collecting ducts.

The regulation of glycogen degradation and synthesis in canine inner medullary collecting ducts (IMCD) was investigated using IMCD tubules suspensions prepared from dog papilla. A small but significant amount of glycogen was found in dog IMCD. Under aerobic condition and especially when no exogenous substrate is available, glycogen breakdown can support IMCD glycolysis for a short period of time. Increasing concentration of exogenous glucose but not lactate was able to reduce and even to suppress (20 mM glucose) the glycogen breakdown. A net synthesis of glycogen was observed only when the endogenous glycogen pool was previously partially or totally depleted. Under anaerobic condition, glycogenolysis was stimulated. The addition of up to 20 mM glucose now reduced but never suppressed this process. Glycogen metabolism responded to variation in the cells energy needs, since the net glycogen breakdown was diminished and glycogen synthesis increased when the cellular ATP turnover was reduced. The reverse effects were observed when the ATP turnover was increased. At all times, glycogen metabolism correlated well with changes in tissue glucose 6-phosphate concentration. The energy requirement of IMCD cells and the availability of alternative energy sources (active mitochondria, exogenous glucose) are therefore capable of eliciting an integrated and appropriate response of glycogen phosphorylase and synthase in IMCD tubules in suspension studied in vitro.

Adenine Nucleotides↗

Basolateral glucose transport in distal segments of the dog nephron.

The transport of glucose by canine thick ascending limbs (TAL) and inner medullary collecting ducts (IMCD) was studied using tubule suspensions and membrane vesicles. The uptake of D-[14C(U)]glucose by a suspension of intact TAL tubules was reduced largely by phloretin (Pt), moderately by phlorizin (Pz), and completely suppressed by a combination of both agents. A selective effect of Pz on the transport of [14C]alpha-methyl-D-glucoside, but not on 2-[3H]deoxyglucose, was also observed in TAL tubules. In contrast, glucose transport was unaffected by Pz but entirely suppressed by Pt alone in IMCD tubules. The metabolism of glucose was largely suppressed by Pt but unaffected by Pz in both types of tubules. Membrane vesicles were prepared from the red medulla and the white papilla or from TAL and IMCD tubules isolated from these tissues. Vesicle preparations from both tissues demonstrated a predominant carrier-mediated, sodium-independent, Pt- and cytochalasin B-sensitive glucose transport. Following purification of basolateral membrane on a Percoll gradient, the sodium-insensitive D-[14C(U)]glucose transport activity copurified with the activity of the basolateral marker Na(+)-K+ ATPase in both tissues. However, a small sodium-dependent and Pz-sensitive component of glucose transport was found in membrane vesicles prepared from the red medulla or from thick ascending limb tubules but not from the papilla nor collecting duct tubules. The kinetic analysis of the major sodium-independent processes showed that the affinity of the transporter for glucose was greater in collecting ducts (Km = 2.3 mM) than in thick ascending limbs (Km = 4.9 mM). We conclude that glucose gains access into the cells largely through a basolateral facilitated diffusion process in both segments. However a small sodium-glucose cotransport is also detected in membranes of TAL tubules. The transport of glucose presents an axial differentiation in the affinity of glucose transporters in the renal medulla, ensuring an adequate supply of glucose to the glycolytic inner medullary structures.

Aerobiosis↗

Metabolism of lactate by a suspension of dog thick ascending limbs: relations with transport.

The addition of substrate in the form of lactate (L), but not glucose (G), increases the respiration of canine thick ascending limb (TAL) segments in a saturable (above 2 mM) fashion. More than 60% of this stimulation is ouabain-sensitive (1 mM ouabain) even if L and G transport are both sodium-insensitive processes in TAL. Thus L, but not G, specifically stimulates Na+ entry in TAL cells and its subsequent transport by the Na+,K(+)-ATPase. If chloride is substituted for by gluconate, no significant substrate-induced stimulation of ouabain-sensitive respiration is observed. SITS (4-acetamino-4'-isothiocyanostilbene-2,2'-disulfonic acid) also interferes with the L-induced stimulation of respiration. Thus L entry in TAL appears to be directly or indirectly coupled to the transepithelial flux of Cl-. Furosemide (F), but not amiloride, also inhibits this stimulation suggesting that the accelerated Na+ entry triggered by the application of L occurs through the F-sensitive carrier or that lactate transport is F-sensitive in TAL cells. In accord, F specifically impairs the metabolism of L (as compared to G). These data suggest that in intact TAL tubules both lactate uptake and oxidation are directly or indirectly influenced by the transcellular flux of NaCl. This organization may participate to maintain a stoichiometry between the transport of NaCl and the availability of L to support the energetic needs of TAL cells.

Animals↗

Basolateral transport of lactate in dog thick ascending limbs.

Basolateral membrane vesicles (BLMV) isolated from both red outer medulla or from thick ascending limb segments isolated from the dog kidney were used to examine the process of lactate transport in this nephron segment. The BLMV preparation was enriched in Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) that represented 96% of the total ATPase activity of this preparation and the vesicles were largely under the right side-out orientation. On application of a OH- or HCO3- gradient (inside greater than outside), a secondary active lactate accumulation was observed, with characteristic transient overshoot. This phenomenon was shown to occur irrespective of the presence or absence of Na+, K+, or Cl-. The pH, but not the bicarbonate-driven, overshoot was abolished by nigericin (in presence of K+). Studies with valinomycin and K+ demonstrated that the generation of a membrane potential was not responsible for the acceleration of lactate transport, even if the amplitude of lactate accumulation was reduced in the presence of a bicarbonate gradient and valinomycin. A significant trans-stimulation of [14C]lactate transport by cold lactate was observed (under voltage-clamp condition). The transport was 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid insensitive but sensitive to furosemide (IC50 = 0.1 mM) and alpha-hydroxycyanocinnamate (IC50 = 1 mM). The kinetic parameters of the transporter revealed a single carrier with an apparent Michaelis constant of 1.7 mM and an apparent Vmax of 9.7 nmol.mg protein-1.30 s-1. The transporter was shown to be distinct from that of proximal tubule brush-border membrane or mitochondria (pyruvate). Thus thick ascending limbs possess a carrier-mediated lactate transport that can be used for lactate uptake (aerobic condition) or for lactate release (anaerobic glycolysis) according to metabolic processes imposed by the local oxygenation condition.

Animals↗

[The Children's Rights convention].

A Convention project about Children Rights will be soon submitted for ratification to all member states of the United Nations. It is the continuation of several anterior declarations which principles it recalls in its preamble: fundamental responsibility of the family for the care and the protection of the child, necessity of a social and juridical child protection depending on the state, vital role of an international cooperation so that the children rights will become a reality. After having largely analysed the needs of the child in the world, the project proposes the creation, inside the United Nations, of a Committee of the Children Rights with 10 members. Though a progress in comparison with the anterior declarations, many articles won't be easy to apply immediately: furthermore, the problems differ from the industrialized countries to the most disfavored countries. Nevertheless the Convention constitutes an engagement and a line of conduct for the future.

Child↗

[Indications for therapeutic interruption of pregnancy in Ille-et-Villaine from 1982 to 1986. Apropos of 222 cases].

The authors have made the census of all the Medical Terminations of Pregnancy (MTP) which have been carried out in the Department of Ille et Vilaine from 1982 to 1986, i.e. 222 cases, in order to precise the different indications and the diagnosis tools which were used. 132 MTP concern women who live in the Department of Ille et Vilaine. By referring this figure to the total number of pregnancies in this area, one can see that the average incidence is of 1.9%; MTP account for 1% of the total number of Terminations of Pregnancies. Foetal indications are more frequent (188 cases; i.e. 84.7%) than maternal ones (34 cases, 15.3%); these figures remained stable over the 5-year period of study. Chromosomal aberrations and closing defects of the neural tubule are the main causes of MTP (22.9% of foetal indications). Among the 43 chromosomal aberrations, trisomies are the most frequent ones (34.9%) because all women aged 38 or more are proposed a detection. The diagnosis of trisomy was made in 24 cases after tests were programmed either because of the age of the mother or because of family antecedents (amniocentesis: 22 times, punction of foetal blood: once, biopsy of chorion villosities: once), in 6 cases after tests were carried out on the basis of suspect clinical signs amniocentesis: once, punction of foetal blood: 5 times), and in 13 cases after the echography had revealed a major syndrome. Closing defects of the central nervous system mainly concern anencephaly (17.6% of foetal indications) since the echography enables an easy diagnosis. All anencephaly have actually been detected during the reference period of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗

[Stillbirths in Ile-et-Vilaine].

The study of stillbirths is a way to approach foetal medicine and a good opportunity to foster a closer relationship between obstetricians, pediatricians and public health physicians, which will lead to preventive measures known to be effective in decreasing mortality rates. Four hundred and ninety pregnancies which ended in stillbirths were investigated: 61 before 27 weeks of amenorrhea, 228 between 28th and 36th weeks, 194 after 37 weeks. The different causes were identified: intrauterine growth retardation and pathological pregnancies remain the most important causes but the authors attract attention to a category of foetal deaths occurring at the end of the pregnancy without any evident cause and for which "postmaturity" was likely. The data attract attention on the necessity to carry out research on stillbirths through a closer collaboration between obstetricians and pediatricians and suggest that appropriate preventive measures may lead to a significant reduction of the 25% of avoidable deaths.

Female↗

[Fetal death toward the end of pregnancy].

This study is on 171 late fetal deaths. These arose from 508 cases histories that the Group for the Study of Neonatology in Rennes brought together when they were conducting a systematic enquiry into perinatal mortality in Ille-and-Vilaine. These concerned events that occurred from the 37th week of pregnancy onwards and had nothing to do with labour. Their study should make it possible to understand better the importance and the details of fetal deaths occurring in the last weeks of pregnancy. Four facts can be established: 1. The number of fetal deaths occurring at the end of pregnancy seems to be higher than had been thought. They represent 38.39% of fetal deaths occurring independent of labour which the Study Group have registered. 2. In most cases they were unexpected. Their discovery was a surprise. 3. Almost half were due to specific causes: accidents to do with the umbilical cord (21 cases); going past biological term (53 cases) following a theory that the authors suggest should be used in place of the commonly held concept of post-maturity, and based solely on the duration of the pregnancy. 4. In order to reduce this perinatal mortality, which is avoidable in many cases, it is important that the pregnancy should be monitored much more thoroughly at its end and this requires, among other things, that the patients themselves should participate.

Female↗