Biomedical subjects

G Campistron

Publications and source records attributed to G Campistron.

At least 19 recordsLinked to original sources

PubMed1997

Distribution and role of aspartate in the nervous system of the chaetognath Sagitta.

Cholinergic control of locomotory muscles in chaetognaths is monitored by diffuse transmitter release through layers of collagen fibers that form the connective stratum of the hydroskeleton. Despite the lack of morphologically defined synaptic junctions, the control of locomotor activity in chaetognaths is highly specific and allows complex behavioral patterns. This complexity suggests the existence of neuromediators acting to modulate the effects of the main motor neurotransmitter, acetylcholine, on muscular contraction. Immunocytochemical investigations performed in Sagitta friderici by using antibodies directed against L-aspartate revealed the presence of the amino acid within abundant fiber networks regularly distributed in the head, trunk, and tail and within discrete groups of cell bodies. In addition to known components of the sensory and motor nervous systems, L-aspartate immunoreactivity revealed previously undescribed intraepidermal networks of axonal profiles. With the exception of two giant anterior fibers radiating from the ventral ganglion, L-aspartate-immunoreactive processes were usually thin and varicose, occasionally making an anastomosis. As indicated by electron microscopy, L-aspartate-immunoreactive varicosities apposed to the connective stratum were filled with synaptic-like vesicles but displayed no synaptic differentiation. Physiologic investigations suggested a potent inhibitory effect of L-aspartate on acetylcholine-induced muscle contraction. The wide distribution pattern of immunoreactive profiles suggests an important role of L-aspartate in motor and sensory functions in chaetognaths. Although classified among excitatory amino acids in vertebrates, aspartate may function as an inhibitory modulator of acetylcholine-induced muscle contraction in these enterocoelous gastroneuralians.

Animals↗

PubMed1996

Increased content of annexin II (p36) and p11 in human placenta brush-border membrane vesicles during syncytiotrophoblast maturation and differentiation.

Annexins are a group of proteins abundant in placental membranes where they may play diverse functional roles. Annexins are expressed in high levels in mature placenta but little is known about their presence at very early stages of gestation and later. We used the model of brush-border membrane vesicles (BBMV) at different stages of gestation to assess precise localization of some of these proteins in syncytiotrophoblast apical membrane and to determine their appearance along the maturation process of placenta. Here we describe annexins type I, II, IV, V and VI which are present all along gestation in BBMV. Annexin II (p36) is present with the S100 like calcium-binding protein p11 in BBMV, where they can constitute heterotetrameric forms of annexin II linked to cytoskeleton structures. No variation of annexins I, IV and VI content was observed in BBMV along pregnancy. Annexin V undergoes significant decrease after 12th week, which could be related to local anticoagulant activity. Levels of annexin II and p11 increased progressively during gestation suggesting that heterotetrameric forms of annexin II play a role in the differentiation process of placenta and in function of the mature microvilli.

Annexin A2↗

PubMed1994

Quantitative aspects of the GABA circuitry in the primary visual cortex of the adult rat.

The number and size of synaptic contacts made by GABA-immunoreactive axonal boutons were estimated in each layer of the primary visual cortex (area Oc1M) of adult rats by using the dissector method. Immunoreactivity for GABA was detected with the postembedding immunogold technique on ultrathin sections. Targets of GABA synaptic contacts were also identified to predict the sites of GABA influence in the rat visual cortex. For the total cortical depth, 82 million out of an overall population of 666 million synaptic contacts per mm3 of tissue (or 1 in 8 contacts, 12%) were GABA. Layer IV averaged 62% more GABA contacts per unit volume than did any other cortical layer. Consequently, these represented a larger proportion (1 in 6, 17%) of the overall population of layer IV synaptic contacts. This higher number of GABA contacts was not due to a greater density of GABA boutons, but to an increased number of contacts made by each layer IV GABA bouton (mean of 1.4 contacts per bouton compared to 1.1 in other cortical layers). The total area occupied by the contacts on an average GABA bouton was similar in all layers; the higher number of contacts per GABA bouton in layer IV being compensated for by their smaller size. This observed constancy in the area of synaptic contacts suggests the presence of one or more regulatory mechanisms maintaining optimal numbers of the different macromolecules forming the synaptic contacts. The increased density of GABA contacts in layer IV compared to other cortical layers was due to their greater number targeting distal regions of the dendritic tree. Since layer IV receives the vast majority of thalamocortical terminals and since these axons preferentially target dendritic spines, the specific arrangement of GABA synaptic contacts in this layer could be designed to exert a precise inhibition near the site of the thalamic input and thus serve as the structural basis for the strong GABA-related hyperpolarization that followed the excitatory response after physiological stimulations of the thalamocortical pathway.

Animals↗

PubMed1993

Pharmacokinetic and pharmacodynamic study of amodiaquine and its two metabolites after a single oral dose in human volunteers.

The pharmacokinetics of amodiaquine (AQ, Flavoquine, CAS 6398-98-7) and its metabolites, mono (AQml) and bis-desethyl amodiaquine (AQm2) were investigated in 8 healthy volunteers after an oral dose of 306.2 mg of AQ. Metabolic clearance was the main AQ elimination pathway. AQ disappeared rapidly, from the plasma and blood, whereas AQml appeared rapidly in keeping with a hepatic first-pass effect. By contrast, AQ was little excreted in urine and AQm2 formation from AQm1 was low. Blood AQm1 concentrations were higher than plasma levels, with an AQm1/AQ concentration ratio of 5 to 10. This result was related to strong uptake of AQm1 by white blood cells, as shown by an in vitro study. On the basis of plasma concentrations, there was no preferential uptake by red blood cells, the pharmacological target cells; effective AQ concentrations should thus be analyzed in plasma rather than in whole blood. The inhibitory activity of patients' sera on Plasmodium falciparum growth in vitro appears to be directly related to the AQm1 concentration.

Adult↗

PubMed1993

Pharmacokinetic study of fentiazac and its main metabolite hydroxyfentiazac in the elderly.

The pharmacokinetics of fentiazac (F, CAS 18046-21-4) and hydroxyfentiazac (OH-F) were estimated in 12 elderly (> 76 years). After an oral single dose of 200 mg F, the plasma and urine profiles were determined using high-performance liquid chromatography with a fluorescence detection. When compared to results obtained in young adults, the maximum plasma concentrations (5.4 +/- 1.9 mg/l) and-the time to reach them were identical. The terminal half-life (7.0 +/- 9.1 h) was longer, due to a slight increase of the apparent volume of distribution and a decrease of the elimination clearance. The findings suggest that the dosage regimen of this drug should be decreased in the elderly. Moreover, the variability of the pharmacokinetics being larger, individual adaptation of the daily dose should be performed.

Acetates↗

PubMed1993

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 1st Communication: balance of elimination, plasma and blood kinetics, metabolism in rats.

N-N'-Dicyclopropyl-methyl-piperazine-dichlorhydrate (Ino 2628-CZ) is a novel inotropic compound. The absorption, distribution, excretion and metabolism of radiochemically labelled 14C-Ino 2628-CZ has been studied in male and female rats after intravenous and oral administration. The compound was mainly excreted during the first 24 h after both administrations, although traces of radioactivity were still measured at 7 days post-dose. About 20% of the drug is excreted in the urine unchanged. Nine metabolites were separated, four of them being characterized.

Administration, Oral↗

PubMed1993

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 2nd communication: tissue distribution in rats.

The distribution of radioactivity in rats after intravenous or oral administration of 14C-labelled N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate (14C-Ino 2628-CZ) demonstrated that the labelled compound was widely distributed in the body. An important diffusion of the isotope was found in the central nervous system, the gastric mucosa and several glands. Only small amounts of radioactivity were found in these organs 24 h after dosage.

Animals↗

PubMed1991

Maternal and umbilical cord concentrations of fentanyl after epidural analgesia for cesarean section.

The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.

Analgesia, Epidural↗

PubMed1990

Immunocytochemical and autoradiographic studies of the endocrine cells interacting with GABA in the rat stomach.

There are now increasing evidences suggesting that GABA is able of direct interaction with certain endocrine cells. In the present study, highly specific anti-GABA-glutaraldehyde antibodies and 3H-GABA uptake were used at the light and electron microscope levels to investigate the occurrence of cells containing endogenous GABA or taking up exogenous GABA in the mucosal antrum and corpus of the rat stomach. Only certain endocrine cell types of both regions were immunostained or grain-labelled. However, the morphology of their secretory granules did not allow to identify the nature of their hormone with certainty but suggested that somatostatin-like cells could interact with GABA. The combination of gastrin and somatostatin immunodetection with 3H-GABA uptake autoradiography at the light microscope level, revealed that a subpopulation of somatostatin-like cells and other still unidentified endocrine cells are able to take up GABA, while the gastrin-like cells are not. These results reinforce the hypothesis that certain endocrine cell types of the diffuse endocrine system of the digestive tract are able to directly interact with GABA.

APUD Cells↗

PubMed1990

Morphine-6-glucuronide is more mu-selective and potent in analgesic tests than morphine.

6-glucuronidation of morphine confers to this widely used analgesic increased potencies both in terms of receptor binding (selectivity) and of antinociceptive properties. In binding studies, 6-glucuronidation of morphine results in increased mu/kappa selectivity (comparable to DAGO). Na+ ions and Gpp(NH)p inhibit similarly the binding of morphine and M6G at the mu sites, suggesting that M6G is a mu agonist. The agonist nature of M6G was further confirmed by its antinociceptive properties: M6G (i.c.v.) was considerably more potent than morphine in the writhing (45 fold) and in the tail-flick (61 fold) tests. Furthermore, M6G induced a longer lasting analgesic effect than morphine. These data strongly suggest that M6G may significantly contribute to the pharmacological activity of morphine.

Analgesics↗

PubMed1990

[Detection of respiratory allergies using the Phadiatop test in children 1 to 6 years of age].

Phadiatop, a new test for detecting hypersensitivity to airborne allergens, was used in 83 children aged 9 months to 6 years with recurrent respiratory manifestations, i.e. recurrent expiratory obstruction and/or recurrent respiratory infections. A good correlation was found between this test and both the prick tests (95%) and the specific IgE assays (91% for RASTS of classes greater than or equal to 1, and 95% for RASTS of classes greater than or equal to 2). However, the correlation was less strong with the total IgE level (68%). The overall correlation with the specialist's prediction based on history and physical evaluation was excellent (94%). In this study, Phadiatop was found to have a 90% sensitivity and a 98% specificity. Furthermore, this test costs 40% less than the often used strategy combining skin tests and determinations of total and specific IgE levels. In the age group studied, Phadiatop is most useful above the age of two, since in younger patients true respiratory allergies are fairly infrequent in recurrent ENT and lower respiratory tract infections, whereas infections are far more common.

Child↗

PubMed1990

Effects of pH on antipyrine transfer across the human placenta ex vivo.

The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.

Adult↗

PubMed1989

Monoclonal antibody directed against glutaraldehyde conjugated glutamate and immunocytochemical applications in the rat brain.

Like other small-sized neurotransmitter molecules, glutamate (Glu) was conjugated to carrier proteins via glutaraldehyde (G). Human serum albumin (HSA) and thyroglobulin (TH) conjugates were alternately injected into mice. When a relevant immune response was obtained for antibody affinity and specificity, hybridization of spleen activated lymphocytes with SP2/O/Ag myeloma cells was performed. Supernatant culture media of hybridomas were tested for the presence of anti-conjugated Glu antibodies with our ELISA method. Selected hybridomas giving good antibody affinity and specificity were then cloned by the limiting dilution technique. Using DEAE-chromatographed ascites fluid, Glu reactivity was observed on the cortex and the hippocampus. Staining obtained with this monoclonal antibody was in agreement with that observed with previous polyclonal antisera directed against conjugated Glu or monoclonal anti-gamma-glutamyl-Glu antibody.

Aldehydes↗

PubMed1989

Pharmacokinetics of two spiroarsoranes administered intravenously or orally to rabbits.

The pharmacokinetics of two spiroarsorane molecules (1,2) were investigated after both intravenous bolus and an oral administration in rabbits. After iv administration of a 15-mg/kg dose, for the two substances, the plasma concentration-time curves were well described by an open two-compartmental model. The half-lives of the first phase were 0.47 +/- 0.12 and 0.27 +/- 0.02 h for 1 and 2, respectively. The half-lives of the terminal phase were of the same order of magnitude for the two substances: 4.38 +/- 0.24 and 6.03 +/- 1.14 h, respectively. Total plasma clearances were 2.47 +/- 0.44 and 0.81 +/- 0.04 L/h, respectively, and the steady-state volume of distribution of 2 (14.99 +/- 2.57 L) was larger than that of 1 (4.27 +/- 0.28 L). After oral administration, spiroarsorane 2 was not absorbed. The availability of the suspension of 1 was 18%. The rate of the absorption phase of 1 showed a saturation process, probably due to the solubility of the molecule. When increasing oral doses of 1 (15, 30, and 60 mg/kg) were administered, the plasma concentrations did not increase to the same extent.

Administration, Oral↗

PubMed1988

Immunocytochemical detection of GABAergic nerve cells in the human temporal cortex using a direct gamma-aminobutyric acid antiserum.

Recently, an immunocytochemical method using glutaraldehyde fixation and an antiserum developed against a GABA--glutaraldehyde--protein conjugate has permitted direct visualization of GABAergic structures in the brains of perfused animals. This paper reports a successful use of this technique on human temporal cortex fixed by immersion. The cerebral tissue was obtained from patients operated for focal epilepsy. GABA-positive somata, fibres and terminals are observed in all layers of the temporal cortex. Terminals are particularly abundant in the superficial portion of layer I and in layers II, III and IV. Dense plexuses of fibres are located in layers II, III, IV and VI and in the underlying white matter. Somata are found in all cortical layers and in the underlying white matter; they are round, oval, fusiform or triangular and exhibit a multipolar, bitufted or bipolar dendritic pattern. This technique for the visualization of GABAergic structures in the human brain may allow a better understanding of the pathogeny of epilepsy in which the GABAergic transmission has been implicated.

Humans↗

PubMed1988

Pharmacokinetics of veralipride after chronic administration in humans.

A pharmacokinetic study of veralipride (N-[(1-allyl-2-pyrroli dinyl)methyl]-5-sulfamoyl-o-veratramide) was performed in healthy volunteers during a chronic administration. The pharmacokinetic model based on the hypothesis of a double site for drug absorption, previously used after a single-dose oral administration, was developed to fit the data obtained after chronic administration. The empirical model used allows correct depiction of the behavior of the drug in the body, especially secondary peaks. According to the results, veralipride pharmacokinetics did not show any change upon chronic administration.

Adult↗

PubMed1988

The pharmacokinetics of bendazac-lysine and 5-hydroxybendazac, its main metabolite, in patients with hepatic cirrhosis.

We have studied the pharmacokinetics of bendazac and its major metabolite, 5-hydroxybendazac, in 11 patients with hepatic cirrhosis after the oral administration of a single 500 mg tablet of bendazac-lysine, and compared them with those obtained from 10 healthy adults. The rate of absorption of bendazac, as assessed by tmax and Cmax, is similar in patients and in healthy subjects. The drug is eliminated mostly by metabolism in healthy adults, more than 60% of the dose being excreted in the urine as 5-hydroxybendazac and its glucuronide. Hepatic insufficiency impairs this metabolism, a two-fold decrease in apparent plasma clearance (CL/f) being observed in the patients. Although the plasma unbound fraction of bendazac is increased in patients (the drug is highly bound to plasma albumin), the apparent volume of distribution (V/f) is unchanged. In consequence, the half-life of bendazac is increased two-fold in the patients. Impairment of metabolism decreases the formation of 5-hydroxybendazac, but metabolism remains the main route of its elimination. Renal excretion of bendazac accounts for about 10% of the dose in both patients with cirrhosis and healthy subjects. We conclude that in patients with severe hepatic insufficiency the daily dose of bendazac-lysine should be halved.

Adult↗

PubMed1988

Immunocytochemical localisation of GABA in endocrine cells of the rat entero-pancreatic system.

The occurrence of GABA-containing cells in the rat entero-pancreatic system was investigated by using anti-GABA-glutaraldehyde antibodies at the light and electron microscope level. In the pancreas, the B cells showed intense immunoreactivity, contrary to non-B and exocrine cells. Moreover, post-embedding immunogold staining was localised mostly in mitochondria, close to rough endoplasmic reticulum and in the nucleus. The insulin granules appeared nonsignificantly stained, which suggests the lack of cosecretion of GABA together with insulin. In the duodenum, GABA immunoreactivity was detected in certain endocrine cell types, suggesting a possible interaction with this amino acid. The well established GABAergic innervation in the enteric system was also confirmed by immunolabelling.

Animals↗