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Biomedical subjects

D Morin

Publications and source records attributed to D Morin.

At least 91 records · Page 5Linked to original sources

[Hereditary nephrogenic diabetes insipidus].

Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder characterized by the inability of the kidney to concentrate urine in response to vasopressin (AVP). Following the recent characterization of the cDNA and genomics sequences encoding the human V2 receptor to AVP (AVPR2), X-linked NDI has been found to be due to mutations in the AVPR2 gene that maps to the chromosome Xq28 region. To date more than 30 mutations, insertions or deletions have been reported in independent families, without any significant differences in the phenotypic expression of the disease. The AVPR2 is a member of the superfamily of 7 transmembrane domain, G protein-coupled receptor, linked to cyclic AMP second messenger system. Other types of inheritance have been described in NDI, and recently, a mutation of the aquaporin-2 gene, encoding a water channel of the renal collecting duct, has been reported in an autosomal recessive form of NDI.

Diabetes Insipidus, Nephrogenic↗

Purification, mass spectrometric characterization, and covalent modification of murine glutathione S-transferases.

Three cytosolic glutathione S-transferase (GST, EC 2.5.1.18) isozymes were purified from livers of male CD-1 mice to homogeneity using affinity chromatography and gradient elution. Isozyme molecular masses and purities were determined using electrospray ionization mass spectrometry (ESI/MS), HPLC, and electrophoretic methods. Isozymes were assigned to alpha, pi, and mu classes based on kinetic and electrophoretic properties. Molecular masses determined by mass spectrometry were 25 271.4 +/- 2, 23 478.8 +/- 2, and 25 838.4 +/- 2 Da for alpha, pi, and mu isozymes, respectively. Molecular masses for pi and mu class isozymes agreed with molecular masses derived from nucleic acid sequences, but the molecular mass of the alpha class isozyme was 42 Da greater than calculated for a reported sequence. Analysis of tryptic digests of GST-alpha using tandem mass spectrometry determined that the molecular weight discrepancy could be attributed to N-terminal acetylation. Effects of covalent attachment of 4-hydroxy-2-nonenal (HNE) on catalytic activities of each GST isozyme were investigated by incubating GSTs with HNE. The extent of HNE-protein adduct formation was determined using ESI/MS. Catalytic activity of HNE-modified GSTs toward CDNB was measured. ESI mass spectra of modified enzymes show that the extent of HNE modification to the isozymes (pi > alpha > mu) coincides with the loss of activity seen for each protein. ESI mass spectra also indicated that glutathione-protein adducts form in isozymes during incubations with HNE even though purified proteins had been dialyzed against water before incubations. Glutathionylation of isozymes increased as the concentration of HNE in the incubations was raised. Dialysis of GSTs against 2 mM S-hexylglutathione (to displace GSH) before incubations eliminated S-glutathionylation. Reactivities of these GSTs toward HNE differed and is related to the number of cysteine residues (alpha < mu < pi) within the amino acid sequence.

Animals↗

[Penal aspects of psychiatric intervention: management modes and impact of new criminal legislation].

Psychiatry and criminal justice have been closely related for a long time. Traces of such ties can already be found during the 19th century through the establishment of the contemporary systems of social control. Various questions that will mark the development of policies in this domain were important objects of discussion and analysis: Is mental illness a cause of criminality? Should the "insane" be held responsible for their crimes? What are the appropriate measures to heal, reform, control? In other words, should we consider the individual as sick or as criminal? If these questions are formulated differently nowadays they haven't lost any of their relevance. In this article, we will briefly present the forms of intervention available to the criminal justice system when dealing with persons suffering from mental health problems. This presentation is based on recent studies conducted in Montreal, elsewhere in Canada, as well as in the United States. The main stages of the criminal justice process will be examined, taking into account the recent modifications to the Canadian Criminal Code and its impact on the relations between the courts and psychiatric facilities. This type of situation is not without impact on community mental health for two main reasons. First, with the diminishing public funding of various health services there seems to be a growing practice of criminalization of persons suffering from mental health problems, especially the most vulnerable segments of this population. Secondly, there is a growing trend, in the criminal justice system, of requiring support from community groups or facilities to deal with these criminalized individuals. In the coming years criminalization will constitute an increasing and complex challenge for community mental health.

Canada↗

Biliary excretion of pyrrolic metabolites of [14C]monocrotaline in the rat.

The biliary excretion of amphoteric pyrroles was studied using in situ isolated rat liver preparations perfused in a recirculatory manner for 60 to 90 min with 14C-monocrotaline (40 mumol/120 ml of Krebs-Henseleit buffer). After 90 min, 20% of the administered 14C and an amount of pyrrole equivalent to 9 mumol of dehydroretronecine was recovered in the bile. Bile collected between 15 and 30 min contained the highest levels of 14C and pyrrolic metabolites. Isoelectric focusing (IEF) and electrophoretic separations on matrices of polyacrylamide and silica were used to isolate and estimate levels of pyrrolic conjugates. IEF and electrophoretic separations on silica revealed the presence of six pyrrole-positive metabolites. Reactions of monocrotaline pyrrole with glutathione produced three conjugates that had the same pI values as components found in bile. Electrophoretic separations on silica and polyacrylamide followed by reversed phase chromatography removed sufficient biliary matrix contaminants to permit identification of glutathione and cysteinyl-glycine conjugates of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine and 1-formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine with fast atom bombardment MS/MS. This study revealed a complexity in the biliary pyrrolic excretion profile that had not previously been realized.

Animals↗

[Are we really talking about psychic symptoms?].

To conceive psychic symptoms as a linguistic sign stemmed from binding a form (the significant) with a meaning (the signified) assumes that rules binding signs of mental illnesses are identical to rules binding linguistic signs, but above all, that those rules are extant. The author exposes that they are not, no rules permitting to associate a linguistic form to a meaning are extant. Consequently the interpretation of psychic symptoms based on the equivalence with linguistic scheme is built on a twisted argument.

Humans↗

Glutathione conjugation with the pyrrolizidine alkaloid, jacobine.

The reaction of glutathione with the epoxide containing pyrrolizidine alkaloid, jacobine, was catalyzed by guinea pig hepatic glutathione-S-transferase enzymes in in vitro experiments; the rate of the reaction in the presence of rat hepatic glutathione-S-transferases did not differ from the non-enzymatic rate. Using ion-pairing liquid chromatography we were able to isolate the conjugate and obtain a daughter ion spectrum using Fast Atom Bombardment Mass Spectrometry together with Collisionally Activated Dissociation/Mass Analyzed Kinetic Energy experiments.

Animals↗

Isoproterenol interacts differently with beta-adrenoceptors in astrocytes and neurons isolated from the adult rat brain.

The interaction of isoproterenol with beta-adrenoceptors has been investigated in astroglial and neuronal cells isolated from adult rat cerebral cortices. Using the non-selective beta-adrenergic antagonist (3H)CGP-12177 as a ligand, binding experiments revealed that both types of cells exhibit beta-adrenoceptors. However the analysis of the isoproterenol displacement curve indicated that only neuronal cells contained the high affinity conformational state of the beta-adrenoceptor.

Animals↗

Isolation and study of two strains of Leptospirillum-like bacteria from a natural mixed population cultured on a cobaltiferous pyrite substrate.

Two strains of Leptospirillum-like bacteria, L6 and L8, have been isolated from a mixed inoculum, also containing Thiobacillus ferrooxidans and T. thiooxidans, cultured for one year with a colbaltiferous pyrite as energy substrate in a 100 l continuous bioleaching laboratory unit. Several physiological properties of the strains are described. The vibrio-shaped microorganisms grew at pH values lower than 1.3. Their growth rate was maximum between 2.5 and 8.0 g l1 ferrous iron. The optimal growth temperature was 37.5 degrees C. Ferric iron had a stimulative effect on bacterial development up to 8 g l-1, and growth was as rapid at 14 g l-1 ferric iron as at 8 g l-1. The negative influence of cobalt on the final cell concentration was observed at 0.5 g l-1, but the growth rate was not affected up to 2 g l-1. The G + C content of strains L8 is 55.6 mol%.

Cobalt↗

Possible involvement of serotonin in obstructive apnea of the newborn.

Experiments were conducted on newborn rats in order to study the serotonergic modulation of the central respiratory activity during the neonatal period. In vitro experiments performed on isolated brainstem spinal cord preparations demonstrated that serotonin exerts a permanent excitatory modulation on the central respiratory rhythm generator but depresses the inspiratory motor output to the genioglossus muscle. In vivo experiments confirmed that increasing endogenous serotonin levels decreases the inspiratory activity of the genioglossus and elicits drastic obstructive apneas.

Animals↗

[Diagnosis, course and prognosis of pulmonary arterial hypertension].

Pulmonary arterial hypertension (PAHT) is defined by an increase in mean pulmonary artery pressure above 20 mmHg. Its diagnosis is often easy by cardiac echo-Doppler. Hemodynamic investigation is required in non-echogenic patients or in order to define the type of PAHT: pre- or post-capillary. It is important to determine, on the basis of non-invasive clinical and paraclinical (echocardiography) studies, those patients in whom catheterisation is indicated. PAHT may be due to chronic respiratory disease, left heart disorders, congenital heart disease or follow pulmonary embolism. It is sometimes apparently primary. The prognosis of PAHT depends upon its etiology: when PAHT is secondary to heart disease, it reflects worsening of the causative cardiac problem, which must be corrected. PAHT is a prognostic factor in chronic obstructive lung disease. The course is particularly grave in primary PAHT.

Echocardiography, Doppler↗

Cyclic AMP and inositol phosphate accumulations in rat brain cortical slices following chronic citalopram or desipramine administration.

The influence of chronic administration of desipramine (16 mg/kg per day for 8 days) or citalopram (1 mg/kg per day for 8 days) on the serotonergic and noradrenergic stimulations of phosphoinositide hydrolysis and cyclic AMP formation was investigated in rat cerebral cortical slices. This was done by means of a prelabelling method allowing the simultaneous measurement of the accumulations of (3H) inositol phosphates ((3H)IP) and of (14C) cyclic AMP. Our results show that neither of the two drugs altered the inhibition of adenylate cyclase activity induced by serotonin1 (5-HT1) receptor agonists nor did they alter 5-HT1A and 5-HT1B receptor densities. Similarly they did not modify the stimulation of the inositol phosphate metabolism induced by 5-HT or norepinephrine (NE). Desipramine treatment decreased both beta-adrenoceptor-elicited cyclic AMP accumulation (-37%) and beta-adrenoceptor density (-29%), whereas citalopram was without effect. These results reinforce the idea that the ability of antidepressants to decrease the activity of the beta-adrenoceptor-adenylate cyclase complex is not common to all antidepressants, and provide no evidence for the involvement of 5-HT1A and/or 5-HT1B in the mechanism of action of these drugs.

Animals↗

Covalent interactions of reactive naphthalene metabolites with proteins.

Naphthalene produces selective necrosis of Clara cells in the mouse but not in the rat. The pulmonary toxicity depends on cytochrome P450-mediated metabolism; however, the selective pulmonary toxicity of naphthalene in the mouse does not correspond to tissue-selective covalent binding of reactive naphthalene metabolites in vivo. These studies compare reactive metabolite binding in target and nontarget cells and in various subcompartments of mouse lung and characterize, by sodium dodecyl sulfate polyacrylamide gel electrophoresis, the proteins to which arylating metabolites are bound. Reactive metabolite binding was substantially higher in incubations of [3H]-naphthalene with distal bronchioles and isolated Clara cells than with explants of trachea or bronchus from the mouse. Likewise, binding was substantially higher in incubations of murine Clara cells than in identical incubations with mouse hepatocytes (nontarget cells) or rat trachea cells (nonsusceptible species). These data show a good correlation between cellular susceptibility to toxicity and the amount of reactive metabolite bound in vitro. Concentrations of adduct were highest in the medium and the nuclear/cell debris fraction (1000 x g pellet) of isolated Clara cells incubated with naphthalene; very small amounts of adduct were noted in pellets isolated at 20,000 or at 100,000 x g (mitochondrial and microsomal fractions) or in cytosol. These observations were consistent with the finding that adduct concentrations in bronchoalveolar lavage were substantially higher than in the lung at low doses of naphthalene and suggest that monitoring adducts in lavage may serve as a useful biomarker of exposure and effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Compared effects of serotonin on the inspiratory activity of glossopharyngeal, vagal, hypoglossal and cervical motoneurons in neonatal rat brain stem-spinal cord preparations.

Experiments were performed on isolated brain stem-spinal cord preparations from neonatal rats, with a view to comparing the effects of serotonin (5-HT) on the rhythmic inspiratory activity recorded in the glossopharyngeal (IX), vagal (X), hypoglossal (XII) and cervical motor roots. Under normal medium, the inspiratory bursts recorded on the different roots presented slight changes in amplitude from one cycle to the other which were significantly correlated only between IX and X nerves. When the normal medium was replaced by a medium containing 5-HT (30 microM), the frequency of occurrence of the inspiratory bursts increased. After 6 min 5-HT superfusion, the inspiratory bursts observed in the IX, X and cervical recordings decreased slightly but significantly, whereas the XII inspiratory discharges decreased drastically. Upon returning to the control conditions, a total recovery was observed in all the recordings apart from the XII discharge, which remained depressed. Although 5-HT qualitatively depressed all the inspiratory motor outputs, the quantitatively drastic and long-lasting depression of the XII inspiratory activity was particularly noteworthy. 5-HT therefore seems to have specific effects on XII inspiratory activity which may be responsible for obstructive apnea in cases involving abnormal 5-HT biosynthesis mechanisms.

Animals↗