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Biomedical subjects

C Morin

Publications and source records attributed to C Morin.

At least 55 records · Page 3Linked to original sources

Transcriptional regulation of pre-pro-endothelin-1 gene by glucocorticoids in vascular smooth muscle cells.

Endothelin is a potent vasoactive peptide involved in the maintenance of vascular tone and in pathophysiological states. Endothelin-1 synthesis is controlled at the transcriptional level. We report that glucocorticoids increase the pre-pro-endothelin-1 gene transcription rate in vascular smooth muscle cells. The effect of glucocorticoids is dose-dependent (EC50 approximately 2-3 nM) and completely blocked by co-incubation with the glucocorticoid antagonist RU 38486. The rise in pp-Et-1 steady state mRNA levels is rapid and transient with a maximal three-fold stimulation within one hour of glucocorticoid administration. Glucocorticoid treatment does not affect the half-life of pre-pro-endothelin-1 mRNA as shown by actinomycin D studies. Furthermore, cycloheximide treatment concomitantly with RU 28362 did not reverse the stimulatory effect of glucocorticoids on pre-pro-endothelin-1 mRNA levels. Nuclear run-on analysis shows that glucocorticoids increase the transcription rate of pre-pro-endothelin-1. Our results suggest a role for glucocorticoids in the regulation of biosynthesis and action of this important vasoactive peptide in vascular smooth muscle cells.

Androstanols↗

Molecular properties and pharmacokinetic behavior of cetirizine, a zwitterionic H1-receptor antagonist.

The ionization and lipophilicity behavior of the antihistamine (H1-receptor antagonist) cetirizine was investigated, showing the drug to exist almost exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its octanol/water lipophilicity is constant and low compared to cationic antihistamines (log D = log PZ = 1.5), whereas its H-bonding capacity is relatively large (delta log PZ > or = 3.1). Conformational, electronic, and lipophilicity potential calculations revealed that zwitterionic cetirizine experiences partial intramolecular charge neutralization in folded conformers of lower polarity. Pharmacokinetic investigations have shown the drug to be highly bound to blood proteins, mainly serum albumin, and to have a low brain uptake, explaining its lack of sedative effects. As such, cetirizine does not differ from "second-generation" antihistamines. In contrast, its very low apparent volume of distribution in humans (0.4 L kg-1, smaller than that of exchangeable water) implies a low affinity for lean tissues such as the myocardium and is compatible with the absence of cardiotoxicity of the drug. The zwitterionic nature and modest lipophilicity of cetirizine may account for this pharmacokinetic behavior. The suggestion is offered that cetirizine and analogous zwitterions, whose physicochemical, pharmacokinetic, and pharmacodynamic properties differ from those of "first-" and "second-generation" drugs in this class, could be considered as "third-generation" antihistamines.

Alkanes↗

Saguenay Lac Saint Jean cytochrome oxidase deficiency: sequence analysis of nuclear encoded COX subunits, chromosomal localization and a sequence anomaly in subunit VIc.

A biochemically distinct form of cytochrome oxidase (COX) deficiency found in the Saguenay region of Quebec is an autosomal recessive trait. The cDNA sequences of all 10 nuclear-encoded subunits from a patient's fibroblasts showed normal coding sequence. Sequences for subunit VIc in two atypical patients showed a heterozygous base substitution. Subunit VIc was localized to chromosome 18.

Animals↗

A Trachylobane Diterpenoid from Xylopia aethiopica

A new trachylobane derivative identified as 7alpha-hydroxytrachyloban-19beta-oic acid (1) has been isolated from the bark of Xylopia aethiopica and its structure elucidated by various NMR techniques and molecular modeling.

Journal Article↗

Tacrolimus decreases in vitro oxidative phosphorylation of mitochondria from rat forebrain.

The effects of tacrolimus (FK 506) on brain phosphorylation have been investigated in vitro using mitochondria isolated from rat brain. Respiratory control ratio (RCR), oxygen consumption, ATP synthesis and enzymatic activities of involved complexes have been measured to assess the mechanisms of action of tacrolimus. Our data show that this drug decreases RCR and ATP synthesis. This effect is quantitatively limited after a single application of the drug (14%), concentration-dependent and biphasic, the respective effect 50%-concentration (EC50) being 0.129 and 247 nM, each step corresponding to 50% of the total oxygen consumption inhibition. Tacrolimus acts mainly as an inhibitor of ubiquinol-cytochrome c reductase (complex III), competing at least partly with antimycin A or myxothiazol, the corresponding EC50 being 0.27 and 103 nM respectively. Tacrolimus inhibits also complex V i.e. ATPase activity (40%) and ATP synthase activity (30%) in a concentration-dependent manner, the relevant EC50 being 78 and 394 nM respectively. These data may be relevant for the protective effect of tacrolimus observed in ischemia-reperfusion, which may be due to its inhibition of both complex III, where Reactive Oxygen Species (ROS) are generated, and complex V, where ATP is depleted by ATPase activation. It may also be related to neurotoxicity occurring along chronic administration of tacrolimus in humans.

Adenosine Triphosphate↗

Temporal and qualitative properties of cold pain and heat pain: a psychophysical study.

Dorsal horn neurons that respond to noxious cold also respond to noxious heat, suggesting the hypothesis that pain evoked by temperature extremes, whether hot or cold, may be processed similarly in the CNS. In this study, we tested perceptual consequences of this hypothesis by comparing characteristics of heat and cold pain, as well as of innocuous warm and cool. Eight healthy subjects performed psychophysical tasks involving hot and cold cutaneous stimuli. Using a 9-cm2 contact thermode, temperatures from -5 degrees to 48 degrees C were each applied for 30 s to the thenar eminence. Subjects gave continuous ratings of perceived temperature and pain intensity, using an electronic VAS. After each stimulus, subjects also reported the maximum stimulus intensity and unpleasantness, and chose appropriate words from a list of qualitative verbal descriptors. We found that larger temperature differences were needed in the noxious cold than in the noxious heat range to produce equal perceptual differences. Further, in the heat range, stimulus-response functions were steeper for noxious than for innocuous temperatures, whereas in the cold range, the opposite held true. The relative unpleasantness of heat pain did not differ from that of cold pain, but subjects used a wider range of qualitative words to describe cold pain. Perceived stimulus intensity was compared to temperature recordings from intradermal and skin surface thermocouples. Heat pain, cool and warmth appeared to depend on surface temperature, whereas cold pain was related to subcutaneous temperature, suggesting different receptors for noxious heat and noxious cold. These data, combined with results of human brain imaging and primate electrophysiological studies, suggest that the unpleasantness associated with both heat pain and cold pain is processed similarly in the CNS, whereas differential information about stimulus quality is preserved in the cerebral cortex.

Adult↗

Biological evaluation of two iodine-123-labeled D-glucose acetals prepared as glucose transporter radioligands.

Two iodinated acetals of D-glucose, 4,6-(R)-O-(2'-iodoethylidene)-alpha, beta-D-glucose (1) and 4,6-(R)-O-(4'-iodobenzylidene)-alpha, beta-D-glucose (2), were prepared and their potential as suitable SPECT radioligands for imaging of glucose transporters was studied. Both are analogs of acetal D-glucose derivatives, which are known to bind to the exofacial sites of the glucose transport protein (GluT). To assess whether iodinated acetals 1 and 2 interacted with the glucose transporter, they were tested in vitro in human erythrocytes (GluT1) and neonatal rat cardiomyocytes (GluT4). The results indicated that 1 and 2 had a very low affinity for the glucose transporter and probably accumulated in cells. Study of their tissue distribution was carried out in the mouse in vivo: Both compounds showed fast tissue clearance with preferential renal elimination. It is concluded that iodinated acetals of D-glucose 1 and 2 are not suitable for GluT targeting in vivo.

Acetals↗

Patients versus rehabilitation practitioners: a comparison of assessments of needs for care.

OBJECTIVE: A group of 47 young adults suffering from schizophrenia was interviewed to garner their views on their needs for care. METHOD: Three members of a specialized multidisciplinary rehabilitation team, who had been caring for these patients, on average, for the past 4 years, completed a questionnaire to assess the needs for care of these individuals. Patient and staff assessments were then compared. RESULTS: Patients and staff do not share similar views on the presence of clinical and social problems. Further analyses of the perceived importance of living-skills deficits, the perceived difficulties in dealing with these, and the recent developments in rehabilitation practices challenge whether patient-staff consensus is indeed essential for rehabilitation. CONCLUSION: We propose that staff should listen to patients' points of view more carefully, especially in the areas of work, studies, and independent living.

Activities of Daily Living↗

Synthetic porous ceramic compared with autograft in scoliosis surgery. A prospective, randomized study of 341 patients.

We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56 degrees, corrected to 24 degrees (57%). At 18 months, the average was 26 degrees (3% loss). In the autograft group the average preoperative upper curve of 53 degrees was corrected to 21 degrees (60%). At 18 months the mean curve was 25 degrees (8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity. Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass.

Adolescent↗

The self-portrait in adulthood and aging.

Ninety-eight participants aged thirty to eighty-five, drew a self-portrait in which the depiction of face features and limb extremities was studied. Statistical multivariate analysis permitted to describe three classes of drawings with different modes of representation of hands and face features. The representation of the hands was problematic in most of the participants regardless of age. There was a relation between age and not representing the face features: 17 percent of the participants over sixty-five did not represent the face features vs. none of the younger participants. Results are discussed from a psychoanalytic perspective. The difficulties in representing the hands are discussed in relation to castration. The absence of face features in the portraits of some elderly drawers could indicate a minimal age-related defect of the network which establishes that the real mouth and eyes are both symbolic body orifices and imaginary face features. The comments made by some drawers strongly suggest that this absence may also represent an incapacity to face the losses imposed by aging.

Adult↗

Patient satisfaction with dentures made by dentists and denturologists.

BACKGROUND: Within Quebec and elsewhere in Canada, patients requiring removable prostheses consult either dentists or denturologists. In this article, we describe the socioeconomic characteristics of 410 edentulous individuals seeking replacement of their dentures, and compare the levels of satisfaction experienced by the patient groups provided with conventional dentures by dentists and by denturologists. METHODS: All subjects responded to announcements seeking participants in a clinical trial. The announcements indicated that all participants would receive new prostheses. Data were collected via telephone interviews. Sociodemographic variables included sex, age, education level and family income. Subjects were asked to evaluate their present maxillary and mandibular prostheses for general satisfaction, stability, comfort, ability to chew, ability to clean and appearance. Age, cost and the provider (dentist or denturologist) of the original prostheses were also recorded, and responses were then compared between the groups of subjects treated by dentists (N = 91) and denturologists (N = 319). RESULTS: There were no significant differences in the sociodemographic characteristics of the two groups, except for a small difference in mean age (two years). Both groups had paid approximately the same amount for their complete prostheses. As expected, most individuals were satisfied with their maxillary prostheses, but dissatisfied with their mandibular prostheses. Significantly more subjects in the denturologist treatment group than the dentist treatment group gave their mandibular prostheses a poor rating for general satisfaction (p = 0.003), comfort (p = 0.04) and stability (p = 0.016). CONCLUSIONS: These results suggest that the edentulous patients treated by dentists and denturologists share similar sociodemographic characteristics, and pay a similar cost for treatment. However, those treated by denturologists seem to be more dissatisfied with their mandibular prostheses than those treated by dentists.

Adult↗

[Simplified technique for thoracic drainage in anterior surgery of scoliosis in the child].

The authors describe a technique of thoracic drainage after anterior surgery of the spine in a pediatric population. A comparative study of drainage using the standard chest tube in one group of patients and small multiperforated vacuum drainage do not show any difference in term of morbidity. As the modified drainage is best tolerated in term of pain, easier to take care of and costless, the authors recommand this technique in children when hermetic closing of the pleura is possible and in absence of air-leakage.

Adolescent↗

Prednisolone and azathioprine worsen the cyclosporine A-induced oxidative phosphorylation decrease of kidney mitochondria.

We investigated the effects of cyclosporine A, prednisolone and azathioprine on respiration rates, Ca2+-induced swelling and Ca2+ fluxes of rat kidney mitochondria. The three drugs significantly decreased the succinate induced-respiration rates according to concentration-dependent processes. Each drug inhibited about 10% of the respiratory control ratio, with EC50 of 3.7 x 10(-7) M, 5.8 x 10(-9) M for cyclosporine A and azathioprine respectively. Prednisolone was the most effective (19.2%) acting by a two-step process with EC50 of 9.2 x 10(-12) M and 1.9 x 10(-8) M. The combination of the three drugs developed a higher significant decrease of respiratory control ratio than that of each drug but lower than the sum of their respective effects. Inhibitions of swelling and Ca2+ fluxes through mitochondrial membrane due to the combination were not different from those induced by cyclosporine A alone. The action mechanisms of cyclosporine A and prednisolone were total and partial Ca2+ dependent respectively. Azathioprine appears to act by a Ca2+-independent one. It is concluded that azathioprine and prednisolone may worsen cyclosporine A-induced renal mitochondrial alteration of oxidative phosphorylation.

Animals↗

Characterization of 6-deoxy-6-iodo-D-glucose: a potential new tool to assess glucose transport.

6-deoxy-6-iodo-D-glucose (6-DIG) was rapidly taken up by adipocytes. Insulin increased 6-DIG transport in adipocytes isolated from both rats and mice. This stimulation was more important in rat than in mouse adipocytes, in agreement with their respective amount of Glut 4 transporters. In two insulin resistant states, the biological behavior of 6-DIG and 3-O-methyl-D-glucose was similar. These results indicated that 6-DIG, which was transported into the cells via the glucose transporters, could be potentially useful to measure modifications of glucose transport.

3-O-Methylglucose↗