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Biomedical subjects

M Allard

Publications and source records attributed to M Allard.

At least 73 records · Page 4Linked to original sources

Characteristics and specific localization of receptors for atrial natriuretic peptides at non-neuronal cells in cultured mouse spinal cord cells.

Characteristics of atrial natriuretic peptide receptors were determined in cultured mouse spinal cord cells. Saturation and competition experiments demonstrated the presence of a single class of atrial natriuretic peptide binding sites with high affinity (KD = 0.054 nM) and a density of 1.92 fmoles/10(6) cells. A similar affinity (KD = 0.070 nM) was observed in rat spinal cord membrane preparations. These atrial natriuretic peptide binding sites were functional receptors since the treatment of cells with atrial natriuretic peptide increased cyclic guanosine monophosphate levels within these cells in a classical time-dependent manner. When atrial natriuretic peptide was applied onto the cell body of intracellularly recorded spinal cord neurons, this peptide did not evoke a change of the input resistance or of the resting membrane potential value. Light-microscopic autoradiography studies showed that no atrial natriuretic peptide binding could be detected on typical birefringent neurons but it could be located on astroglial and epithelial cells as identified by immunocytochemical markers. These results show that functional atrial natriuretic peptide receptors with high affinity exist in cultured mouse spinal cord cells and are not located on neurons. The presence of atrial natriuretic peptide receptors on astrocytes suggests that this neuropeptide might be a good candidate for neuron-glial communication. As the atrial natriuretic peptide binding sites previously shown in epithelia responsible for maintaining fluid and electrolyte gradients, the atrial natriuretic peptide receptors on epithelial cells in these spinal cord cultures may be involved in vivo in the control of water balance in the central nervous system.

Animals↗

[Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with monotherapy in a large population].

A multicentre open study to which 229 investigators participated was carried out to demonstrate the safety of cicletanine, a new therapeutic agent, in routine clinical use. Cicletanine was administered alone for three months and normalized blood pressure (less than 160/95 mmHg) in 63 p. 100 of the 1,238 hypertensive patients who entered the study. There was a significant fall of systolic arterial pressure from 178.4 +/- 14.8 to 151.8 +/- 14.2 mmHg and a similar fall of diastolic arterial pressure from 104.0 +/- 6.7 to 86.3 +/- 6.2 mmHg. The reduction of BP values was accompanied by a significant decrease of differential BP (SBP-DBP) from 72.5 to 65.8 mmHg. The initial dosage (50 mg/day) was doubled in only one-third of the patients. The mean daily dose was 66 mg. This antihypertensive effect was paralleled by a significant and major improvement of signs (dyspnoea, oedema of the lower limbs) and symptoms (mainly dizziness, headache, visual and auditory disorders, asthenia) which existed at inclusion. A modest, but significant, reduction of heart rate from 76.7 to 73.9 beats/mn was also noted. Cicletanine produced no toxic or severe adverse events. Clinical side-effects consisted of pruritus, fatigue, headache, vertigo, lower limb oedema and gastrointestinal disorders. These effects were mild and non-specific (doubtful drug imputability); each of them occurred with an incidence ranging from 4.0 to 1.0 p. 100. They were responsible for the withdrawal of about 30 patients (2.4 p. 100). No significant alteration of biochemical or haematological values was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Antihypertensive effectiveness and tolerance of cicletanine. Results obtained with bitherapy].

In a multicentre open trial involving 229 investigators, cicletanine, a new antihypertensive agent, was administered orally in doses of 50 to 100 mg/day either alone (1,238 patients) or combined with another drug (430 patients). In this second group of patients with essential hypertension whose BP had not been normalized by a beta-blocker (n = 157), a calcium inhibitor (n = 67), an angiotensin-converting enzyme inhibitor (n = 134) or an alpha-blocker (n = 7), cicletanine normalized BP (less than 160/95 mmHg) in 48.8% of the patients and significantly lowered BP values which fell from 177.7 +/- 15.9/103.3 +/- 6.3 mmHg to 157.2 +/- 17.6/88.8 +/- 8.7 mmHg. The addition of cicletanine to treatments with beta-blockers, calcium inhibitors and angiotensin-converting enzyme inhibitors normalized BP in 48%, 52% and 47% of patients respectively. A significant reduction of symptoms was noted, notably as regards headache, dizziness, palpitations, lower limb oedema, asthenia, auditory disorders and dyspnoea. The side-effects reported (headache, dizziness, gastralgia, nausea, pruritus) were minor and non-specific; they accounted for the withdrawal of only 8 patients. The only significant, though moderate, biochemical variations observed were decreases in natremia and cholesterolaemia unconfirmed by qualitative analysis. Altogether, cicletanine proved to be effective and well tolerated when administered in combination with other antihypertensive drugs belonging to three main therapeutic classes.

Adrenergic beta-Antagonists↗

Location of angiotensin II binding sites on neuronal and glial cells of cultured mouse spinal cord: an autoradiographic study.

Cultures of mouse spinal cord were used to visualize binding sites for [125I]angiotensin II (AII) by autoradiography. Visualization by light microscopy shows that neurones, but also glial cells possess angiotensin II binding sites which are located both on soma and processes. These findings open a new field of investigation for the understanding of the physiological significance of AII in the CNS.

Angiotensin II↗

Antenatal origin of neurologic damage in newborn infants. I. Preterm infants.

Currently, the diagnosis of white matter necrosis may be performed with echoencephalography when cysts are observed in the white matter adjacent to the lateral ventricles. One hundred twenty-seven infants with a gestational age less than 36 weeks (mean [+/- SE] gestational age = 31 +/- 3.2 weeks) were studied in the neonatal period with echoencephalography to determine the incidence of white matter necrosis and the perinatal variables associated with this complication. Twenty-three infants (18.3%) had white matter necrosis. Thirteen (10.3%) had cysts by day 3 (11 on day 1), indicating that the onset of white matter necrosis occurred antenatally. The incidence of antenatal white matter necrosis was inversely related to birth weight and was more frequent in infants weighing less than 1000 gm (19%). Stepwise logistic regression analysis of 31 antenatal variables showed that placental vascular anastomoses in multiple pregnancies, funisitis, and purulent amniotic fluid were the only complications associated with antenatal white matter necrosis. Follow-up neurologic evaluations were abnormal in four of six patients with antenatal white matter necrosis. The findings in this study focus attention on prenatal, rather than intrapartum and postnatal, factors as causative agents of neurologic morbidity and emphasize the importance of early and sequential evaluation of neonatal brain structures.

Cerebral Hemorrhage↗

Neurotoxicity of hydrosoluble iodine contrast media.

The side effects of the different hydrosoluble iodine contrast media now in use in neuroradiology are analyzed: ionic monomers, ionic monoacid dimers, nonionics. Their neurotoxicity depends on the patient, the product and its chemical structure, and the modes of administration. The available products, neurotoxicity after intravascular injection, and neurotoxicity after intrathecal injection are successively considered. The frequency of different complications and their pathophysiology are detailed for both injection modes. The authors propose a practical approach, choosing in each case the product with the best cost-efficacy coefficient. This choice must take into account the patient, the indications, and the product.

Blood-Brain Barrier↗

Experimental study of DOTA-gadolinium. Pharmacokinetics and pharmacologic properties.

Pharmacokinetic and acute-toxicity studies of Gd-DOTA meglumine (Mgl) were evaluated in various animals and compared with those of Gd-DTPA Mgl. The agents were injected intravenously at two dosages: 0.1 or 0.5 mmol/kg. Various organs and tissues were removed at specified times after injection and assayed for gadolinium (Gd) concentration. The two complexes behave in an identical fashion in their short-term biodistribution and excretion. The very rapid distribution in the body (except in the brain) and the high clearance from blood are due to an extravascular distribution. The small distribution volume and the very high hydrophilicity account for its extracellular localization. There is no accumulation within any organ. Rapid disappearance, short half-life, size, and hydrophilicity of these molecules are in agreement with urinary elimination by free glomerular filtration. Whatever the species or the salt used, Gd-DOTA appears safer in its acute toxicity than Gd-DTPA with an 85% higher safety factor. These results can be explained by the greater stability of Gd-DOTA (very slow kinetics of dissociation and greater specificity of DOTA than DTPA for gadolinium), and the lower osmolality of DOTA than DTPA. The pharmacokinetic characteristics and the very low toxicity of Gd-DOTA Mgl may prove its suitability for intravenous or oral administration in humans.

Animals↗

Effects of cold acclimation, cold exposure, and palatability on postprandial thermogenesis in rats.

Groups of rats were maintained at 24 degrees C and 4 degrees C (WA, CA). At each temperature one group was fed a pelleted stock diet, while another was fed in addition, 3 kJ of palatable food at 1-h intervals for a total of 8 h during the day. After 2 weeks the thermogenic response to both 3 kJ and 30 kJ of palatable food was determined by measuring oxygen consumption over a period of 3 h. Food intake revealed two phases of postprandial thermogenesis. During the initial cephalic phase which lasted 30 min the O2 consumption increased by about 40 percent with both test meals and the response was comparable for WA and CA rats tested at the same temperature. During the subsequent gastrointestinal phase the response was proportional to the size of the meal and the CA rats were always more responsive than the WA rats specially when tested at 4 degrees C. The results suggest that postprandial thermogenesis during the initial cephalic phase is related to food palatability and that cold exposure and cold acclimation cause an enhanced response during the second phase of meal thermogenesis.

Acclimatization↗

Angiotensin II inactivation process in cultured mouse spinal cord cells.

The pattern of hydrolysis of [3H]angiotensin II ( [3H]AII; 20 nM) by intact cells was studied on cultured mouse spinal cord cells. Degradation products were identified by HPLC analysis after incubation for 2 h at 37 degrees C. In the absence of peptidase inhibitors, 70% of [3H]AII was degraded, and the main labeled metabolite was [3H]tyrosine (40% of total radioactivity). Minor quantities of [3H]AII1-5 and [3H]AII4-8 were formed. Results obtained in the presence of various inhibitors indicate that several enzymes were involved in the AII-hydrolyzing process. Dipeptidyl aminopeptidase III (EC 3.4.14.4) could play a critical role, as suggested by the formation of [3H]Val3-Tyr4 and [3H]-Tyr4-Ile5 in the presence of bestatin (2 X 10(-5) M). This hypothesis was confirmed by the potency of dipeptidyl amino-peptidase III inhibitors to inhibit both [3H]AII hydrolysis and formation of these 3H-labeled dipeptides. An arylamidase-like activity could also be participating in [3H]AII hydrolysis, because higher concentrations of bestatin (10(-4) M) in association with dipeptidyl aminopeptidase III inhibitors totally inhibited [3H]tyrosine formation, increased protection of [3H]AII and [3H]AII1-7 formed, and provoked a slight accumulation of [3H]AII2-8. These results suggest that the formation of [3H]AII2-8 is due to the action of a bestatin-insensitive acidic aminopeptidase and that the Pro7-Phe8 cleavage is also a step of AII hydrolysis, resulting from the action of an unidentified peptidase different from prolyl endopeptidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Primary structure of the minor haemoglobins from the sea lamprey (Petromyzon marinus, Cyclostomata).

Erythrocytes of the adult Sea Lamprey Petromyzon marinus contain several haemoglobin species, but only the main constituent has hitherto been sequenced. The present paper describes the determination of the primary structures of the two minor species, whose electrophoretic mobilities are higher and lower than that of the main component. Tryptic peptides from both chains were purified by high-performance liquid chromatography, then sequenced and aligned by homology with the main haemoglobin. The fast and the major components appeared to be very similar, differing in only four positions (pos. 5: Ser----Thr; pos. 33: Thr----Ser; pos. 86: Val----Ala; pos. 99: Gly----Arg). The slow haemoglobin component, however, differed from the main component with respect to 27 amino-acid residues. The position of the three globins of Petromyzon marinus in the phylogenetic tree of haemoglobins is discussed and a relationship with primitive alpha-chains is postulated.

Amino Acid Sequence↗

[Diagnostic and therapeutic angiography in severe retro- and subperitoneal hematomas].

This study of the value of arterial angiography was carried out in 22 patients with serious retroperitoneal hemorrhage. In the first instance, this investigation determines the number of hemorrhages, their sites and flows. Later on it can be used to evaluate the volume of the hemorrhage and its effect on vascularisation of the abdominal viscera so that an initial prognosis can be made. At a later stage it also provider valuable date when setting up an appropriate selective embolisation based on the number of sites involved.

Abdominal Injuries↗

[Methodology for a controlled trial in Alzheimer's disease].

The various evaluation scales available to study the clinical courses of Alzheimer-like dementias are controverted, and the practical aspects of a controlled trial are being considered. A tentative protocol has been designed, in which multiple individual assessments are combined with several validated scales and tests. This protocol would lend itself to a multicentre study, as it only includes evaluation tools that are easy to handle and do not require too much time. It should make it possible to select a relatively homogeneous group of patients and provide an opportunity to quantify the course of Alzheimer's disease over one year. In the discussion, emphasis is laid upon the foreseeable difficulty to evaluate a therapeutic benefit in our present imperfect knowledge of the natural history and prognostic factors of the disease.

Aged↗

[Treatment of the disorders of aging with Ginkgo biloba extract. From pharmacology to clinical medicine].

Ginkgo biloba extract is prescribed in psychic and behavioural disorders of the elderly, in peripheral vascular deficiency and in functional disorders of ischaemic origin in the E.N.T. and eye areas. Numerous controlled clinical trials justify these prescriptions and are in agreement with the pharmacological data currently available. Experimentally, Ginkgo biloba extract has proved active on the circulatory and rheological functions, on neuronal metabolism threatened by ischaemia or hypoxia, on neurotransmission and on membrane lesions caused by free oxygenated radicals. Concerning Alzheimer's disease and dementia, no firm conclusion can be drawn for the time being due to the lack of animal model. However, experimental data suggest that the product may act on a number of major elements of these diseases. From what is already known about Ginkgo biloba extract, it appears that it fulfills the conditions laid down by the W.H.O. concerning the development of drugs effective against cerebral ageing.

Aging↗

Action of gadolinium complexes on different enzyme systems.

Gadolinium complexes have two advantages: their toxicity is very low and the paramagnetic properties are adequate enough to give a useful signal with magnetic resonance imaging (MRI). The effects of several MRI contrast media on the activity of two brain enzymes, glutamate decarboxylase (GAD) and cholineacetyl transferase (ChAT), were investigated. The study was performed on homogenates of rat striatum with variable concentrations of gadolinium sulphate, EDTA, DTPA, DOTA, Gd-EDTA, Gd-DTPA and Gd-DOTA (from 10(-2) mol/l to 10(-9) mol/l. Gadolinium in its ionic form and the chelators of cation agents such as EDTA, DTPA and DOTA inhibit GAD, a calcium dependent enzyme, whereas they have no inhibiting effect on the activity of ChAT, a calcium independent enzyme. Gadolinium complexes inhibit the GAD activity by about 15 per cent whereas they do not modify that of ChAT. The complex form of gadolinium has the advantage of retaining its paramagnetism while drastically lowering its toxicity.

Animals↗