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Biomedical subjects

M Cyr

Publications and source records attributed to M Cyr.

At least 19 recordsLinked to original sources
PubMed2001

Estrogenic activity of tamoxifen and raloxifene on rat brain AMPA receptors.

We have previously shown in rats that estradiol has brain regionally specific effects on AMPA receptors. The present study investigated hormonal specificity of AMPA receptors by comparing the effect of estradiol with tamoxifen or raloxifene, which have varying effects on estrogen response in breast, bone and uterus. Ovariectomy in rats decreased uterus weight which was restored by estradiol treatment, whereas tamoxifen and raloxifene had only a weak effect. Ovariectomy left unchanged AMPA receptor specific binding in rat brain whereas estradiol, tamoxifen and raloxifene decreased it in cortical and striatal regions of ovariectomized rats. Hence, tamoxifen and raloxifene showed agonist estrogenic activity on AMPA receptors in specific brain regions, which can be dissociated from their antagonist estrogenic activity in the periphery.

Animals↗
PubMed2001

Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA and AMPA receptors.

Glutamate and glutamate receptors are well known to play a major excitatory role in the brain. Recent findings on ovarian steroids and selective estrogen receptor modulators (SERMs) activity on rat brain AMPA and NMDA receptors are reviewed. Ovarian steroid withdrawal by ovariectomy is without effect on NMDA and AMPA receptors in most brain regions, except in hippocampus, where it decreases NMDA receptor specific binding, compared to intact rat values. Estradiol treatment increases hippocampal NMDA receptor specific binding of ovariectomized rats while it decreases this binding in frontal cortex and striatum. Estradiol treatment has no effect on AMPA receptor specific binding in hippocampus, but decreases binding in frontal cortex, striatum and nucleus accumbens. Progesterone and estradiol+progesterone treatments decrease NMDA, but not AMPA receptors specific binding in frontal cortex compared to ovariectomized rats. No effect was observed in other brain regions. Tamoxifen and raloxifene are SERMs with varying effects on estrogen responses in mammary, bone and uterine tissues. Tamoxifen and raloxifene have estrogenic activity upon modulation of brain NMDA and AMPA receptors. Using specific ligands for binding autoradiography of NMDA receptor subunits and specific probes for subunits measured by in situ hybridization, it was shown that estradiol and SERMs modulate NR1 and NR2B subunits whereas the NR1/2A subunit remains unchanged. In summary, regional agonist estrogenic activity on brain AMPA and NMDA receptors of tamoxifen and raloxifene, like that of estradiol, is observed, whereas progesterone has limited effects or opposes the estradiol effect.

Animals↗
PubMed2001

Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.

Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA, which partially blocks glucocorticoid receptor expression, were used to investigate the long-term effect of hypothalamic-pituitary-adrenal axis dysfunction on brain dopamine transmission. Compared to control mice, the transgenic animals showed increased amphetamine-induced locomotor activity and increased concentrations of striatal dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid. Binding of [3H]SCH 23390 and [3H]spiperone to, respectively, D1 and D2 dopamine receptors was increased in transgenic mice. In contrast, autoradiography of striatal [3H]GBR 12935 binding to the dopamine transporter was decreased and the mRNA levels of this transporter, measured by in situ hybridization, remained unchanged in the substantia nigra pars compacta. The effect of chronic treatment for two weeks with amitriptyline or fluoxetine was compared in control and transgenic mice. No significant changes were observed in control mice following antidepressant treatment, whereas in transgenic mice both antidepressants reduced striatal [3H]SCH 23390 and [3H]raclopride specific binding to D1 and D2 receptors. Amitriptyline, but not fluoxetine, increased striatal [3H]GBR 12935 binding to the dopamine transporter, whereas its mRNA level in the substantia nigra pars compacta was decreased in fluoxetine, compared to vehicle- or amitriptyline-treated transgenic mice. From these results we suggest that hyperactive dopaminergic activity of the nigrostriatal pathway controls motor activity in the transgenic mice. Furthermore, antidepressant treatment corrected the increased striatal D1 and D2 receptors and decreased dopamine transporter levels in the transgenic mice.

Amitriptyline↗
PubMed2001

Estrogen-like activity of tamoxifen and raloxifene on NMDA receptor binding and expression of its subunits in rat brain.

Hormonal specificity of modulation of N-methyl- D-aspartate (NMDA) receptors was investigated by comparing the effects of estradiol with tamoxifen or raloxifene, which display different responses in breast, bone, and uterus. Two weeks ovariectomy in rats decreased uterine weight, which was prevented by a two-week estradiol treatment; tamoxifen and raloxifene had weaker uterine stimulation than estradiol. Ovariectomy in rats decreased L-[3H]glutamate specific binding to NMDA receptors in CA1 and dentate gyrus but not CA2/3 regions of hippocampus and was without effect in cortex, striatum, nucleus accumbens, and olfactory tubercle. [3H]Ro 25-6981 (an NMDA antagonist selective for NR1/NR2B assembly) specific binding and mRNA levels of NMDA receptor subunits 1 and 2B decreased in CA1 after ovariectomy. Estradiol, tamoxifen, and raloxifene decreased L-[3H]glutamate specific binding to NMDA receptors and [3H]Ro 25-6981 specific binding in cortical area of ovariectomized rats and prevented the decrease of [3H]glutamate specific binding to NMDA receptors in CA1 and dentate gyrus, as well as [3H]Ro 25-6981 specific binding in CA1. Estradiol prevented the decrease of NMDA receptor subunits 1 and 2B mRNA levels in CA1 only; tamoxifen and raloxifene prevented the decrease of NMDA receptor subunit 1 mRNA levels in CA1. No effect of ovariectomy or treatments on L-[3H]CGP 39653 (an NMDA antagonist selective for NR1/NR2A assembly) specific binding and NMDA receptor subunit 2A mRNA levels was observed in all brain regions assayed. Our results showed brain regional and subunits specific agonist estrogenic activity of tamoxifen and raloxifene on NMDA receptors.

Animals↗
PubMed2001

Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma.

In the serum of 116 healthy individuals, exogenous bradykinin (BK) half-life (27 +/- 10 s) was lower than that of des-Arg(9)-BK (643 +/- 436 s) and was statistically different in men compared with women. The potentiating effect of an angiotensin-converting enzyme (ACE) inhibitor was, however, more extensive for BK (9.0-fold) than for des-Arg(9)-BK (2.2- fold). The activities of ACE, aminopeptidase P (APP), and kininase I were respectively 44 +/- 12, 22 +/- 9, and 62 +/- 10 nmol x min(-1) x ml(-1). A mathematical model (y = kt(alpha)e(-beta t), t > 0), applied to the BK kinetically released from endogenous high-molecular-weight kininogen (HK) during plasma activation in the presence of an ACE inhibitor, revealed a significant difference in the rate of formation of BK between men and women. For des-Arg(9)-BK, the active metabolite of BK, the rate of degradation was higher in women compared with men, correlating significantly with serum APP activity (r(2) = 0.6485, P < 0.001). In conclusion, these results constitute a basis for future pathophysiological studies of inflammatory processes where activation of the contact system of plasma and the kinins is involved.

Adult↗
PubMed2001

Central 5-hydroxytryptamine-2A receptor expression in transgenic mice bearing a glucocorticoid receptor antisense.

Transgenic mice bearing a transgene coding for a glucocorticoid receptor antisense mRNA that partially blocks glucocorticoid receptor expression were used to investigate the long-term effect of hypothalamic-pituitary-adrenal dysfunction on brain 5-hydroxytryptamine-2A (5-HT2A) receptor expression. The brain 5-HT2A receptor mRNA levels in transgenic mice were measured by in situ hybridization and compared to those in control mice. We also studied the effect of a 3-week treatment with fluoxetine on brain 5-HT2A receptor expression in the transgenic mice. No difference in 5-HT2A mRNA levels was observed between transgenic and control mice in cortical or striatal regions, and fluoxetine treatment was without effect. No difference in hypothalamic 5-HT2A mRNA levels was observed between transgenic and control mice, while fluoxetine treatment increased these levels in both transgenic as well as in the hypothalamic ventromedial and paraventricular nuclei of control mice. 5-HT2A receptor mRNA levels were similar in hippocampal CA1 and CA2 subregions of control and transgenic, but were lower in the CA3 and CA4 subregions of transgenic mice. Fluoxetine had no effect on 5-HT2A mRNA levels of transgenic mice but reduced control mouse 5-HT2A receptor mRNA levels in the CA3 subregion. These results suggest that impaired glucocorticoid receptor function can affect hippocampal 5-HT2A receptor expression in transgenic mice and that this is not corrected by fluoxetine treatment.

Animals↗
PubMed2000

Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain.

Hormonal specificity of modulation of brain 5-HT(2A) receptors was investigated by comparing activity of compounds with varying effects on estrogen response in breast, bone, and uterus. A two-week estradiol treatment stimulated the decreased uterine weight of ovariectomized rats to intact rat values whereas an increase of 29% with tamoxifen and 16% with raloxifene was observed compared to vehicle-treated ovariectomized rats. In 18 assayed brain regions, ovariectomy decreased 5-HT(2A) receptor binding and mRNA levels in anterior cingulate and frontal cortices, striatum, and nucleus accumbens; estradiol restored this decrease to intact rat values. Dehydroepiandrosterone (DHEA) increased ovariectomized rats 5-HT(2A) receptor expression only in striatum and cortical amygdala. Tamoxifen increased 5-HT(2A) receptor density only in striatum. Raloxifene, an uterine estrogen receptor (ER) antagonist, increased, like estradiol, 5-HT(2A) receptor density and expression in cingulate and frontal cortices, striatum, and nucleus accumbens. Brain regional specificity of estradiol, DHEA, tamoxifen, and raloxifene on 5-HT(2A) receptors was observed which can be dissociated from peripheral activity.

Adjuvants, Immunologic↗
PubMed2000

Unmet needs in the community: can existing services meet them?

OBJECTIVE: This prospective study of community cases examined: (a) needs for care; (b) whether services meet the needs; and (c) personal factors associated with unmet needs. METHOD: Two separate 'Needs for Care Assessment Schedule Community version' evaluations identified 38 subjects with No Need (NN), 19 with Met Needs (MN) and 25 with Unmet Needs (UNM). Other instruments included the Diagnostic Interview Schedule-Abridged Version (DISSA) and repeated measures of symptoms and social functioning. RESULTS: (a) Cases did not equate needs. (b) Services utilization did not equate having met needs. (c) Respondents with UNM were more likely to present high rates of lifetime DSM-II-R disorders, no marital relationship ever, no employment, high rates of life events, and physical or sexual abuse in childhood. They have worse outcome in terms of distress and social functioning. CONCLUSION: Personal factors may prevent respondents from seeking, engaging and benefiting from treatment.

Acute Disease↗
PubMed2000

Assessment of a new rehabilitative coping skills module for persons with schizophrenia.

A rehabilitative coping skills module employing problem solving and cognitive behavioral therapy and an experimental repeated-measure design was tested on 55 randomly selected persons severely handicapped by schizophrenia, most of whom had lived almost half of their lives in psychiatric wards. Unlike the control group of 44 comparable schizophrenics, the experimental group exhibited a significant decrease in delusions and increase in self-esteem, and maintained hygiene levels.

Activities of Daily Living↗
PubMed2000

Regional and selective effects of oestradiol and progesterone on NMDA and AMPA receptors in the rat brain.

We investigated the effect of 10 months ovariectomy and a correction therapy, 2 weeks before the rats were killed, of oestradiol, progesterone or their combination on NMDA and AMPA receptor binding in the hippocampus, dentate gyrus, striatum, nucleus accumbens and frontal cortex of the rat brain as well as on amino acid levels in frontal cortex. NMDA and AMPA binding densities were assayed by autoradiography using, respectively, L-[3H]glutamate and [3H]AMPA; amino acid concentrations were measured by high performance liquid chromatograhy (HPLC) coupled with UV detection. Ovariectomy was without effect on NMDA and AMPA binding density in all brain regions assayed except in the hippocampal CA1 region and dentate gyrus where it decreased NMDA binding density compared to intact rats values. Oestradiol restored and increased NMDA binding density in the CA1 subfield and the dentate gyrus of ovariectomized rats but, by contrast, it decreased binding density in the striatum and in the frontal cortex while having no effect in the CA2/3 subfield of the hippocampus and in the nucleus accumbens. Oestradiol was without effect on AMPA binding density in the hippocampus and the dentate gyrus but it reduced AMPA binding density in the striatum, the frontal cortex and the nucleus accumbens. Progesterone, and oestradiol combined with progesterone, decreased NMDA but not AMPA binding density in the frontal cortex of ovariectomized rats, and they were without effect on these receptors in the other brain regions assayed. Amino acid concentrations in the frontal cortex were unchanged after ovariectomy or steroid treatments. The effect of oestradiol in the hippocampus confirmed in the present study and our novel findings in the frontal cortex, striatum and nucleus accumbens may have functional significance for schizophrenia and neurodegenerative diseases.

Animals↗
PubMed2000

Gestational age- and birthweight-specific declines in infant mortality in Canada, 1985-94. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System.

We studied infant mortality rates in Canada within specific gestational age and birthweight categories after using probabilistic techniques to link information in Statistics Canada's live births data base (1985-94) with that in the death data base (1985-95). Gestational age- and birthweight-specific mortality rates in 1992-94 were contrasted with those in 1985-87 with changes expressed in terms of relative risks with 95% confidence intervals [CI]. Statistically significant reductions in infant mortality were observed beginning at 24-25 weeks of gestation and extended across the gestational age range to post-term births. Crude infant mortality rates, infant mortality rates among those > or = 500 g and among those > or = 1000 g decreased by 22%, 25% and 26%, respectively, from 1985-87 to 1992-94. The magnitude of the reductions in infant mortality rates ranged from 14% [95% CI 7, 21%] at 24-25 weeks of gestation to 40% [95% CI 31, 47%] at 28-31 weeks. Almost all reductions in gestational age- and birthweight-specific infant mortality between 1985-87 and 1992-94 were due to approximately equal reductions in neonatal and post-neonatal mortality. Live births > or = 42 weeks of gestation did not follow this rule; post-neonatal mortality rates among such live births decreased significantly by 51% [95% CI 26, 68%], although neonatal mortality rates showed no significant change. The mortality reductions observed across the gestational age and birthweight range are probably a consequence of specific clinical interventions complementing improvements in fetal growth. Temporal changes in the outcome of post-term pregnancies need to be carefully examined, especially in relation to recent changes in the obstetric management of such pregnancies.

Adult↗
PubMed2000

Treatment for posttraumatic stress disorder.

OBJECTIVE: To thoroughly and critically review the pharmacologic treatment of posttraumatic stress disorder (PTSD) and to review the symptomatology, diagnosis, epidemiology, pathophysiology, and assessment of PTSD. DATA SOURCES: A MEDLINE search (1966-October 1999) in the English language specifying PTSD drug treatment as the search term was used to identify articles. STUDY SELECTION AND DATA EXTRACTION: All articles identified were reviewed; emphasis was given to randomized, double-blind, placebo-controlled studies. DATA SYNTHESIS: It appears that a five-week medication trial is necessary to assess clinical effects on PTSD symptoms. The monoamine oxidase inhibitors appear to be superior to the tricyclic antidepressants in improving reexperiencing and avoidance symptoms. Most studies used assessment tools that neglected hyperarousal symptoms; therefore, no conclusions regarding this symptom cluster can be drawn. Other pharmacotherapeutic interventions reported in open-label trials have yielded varying success. CONCLUSIONS: The current literature does not bear a sufficient number of double-blind, placebo-controlled studies using assessment tools that evaluate the three symptom clusters of PTSD to allow for a definite treatment modality to be formulated. Nonetheless, a treatment hierarchy appears to be in order based on the greatest number of double-blind, placebo-controlled studies evaluating antidepressants. Alternate modalities such as mood stabilizers, antipsychotics, anxiolytics, and adrenergic blockers should not be considered the mainstays of therapy.

Humans↗
PubMed2000

Drugs with estrogen-like potency and brain activity: potential therapeutic application for the CNS.

Numerous reports, ranging from molecular investigations to clinical studies, demonstrate the potency of estrogens to modulate brain function and their implications in schizophrenia and depression. Alterations of dopaminergic, cholinergic, GABAergic, glutamatergic and serotonergic neurotransmission through estrogen-mediated mechanisms have been consistently established. Moreover, studies using in vivo and in vitro models as well as epidemiological data suggest that estrogens provide neuroprotection of central nervous system (CNS) cells implicated in the etiology of neurodegenerative disorders such as Alzheimer s (AD) and Parkinson s (PD) diseases. Numerous genomic or non-genomic mechanisms of actions of estrogens in the brain have been documented implicating classical nuclear estrogen receptors as well as possible estrogen membrane receptors, antioxidant activity of steroids, their effect on fluidity as well as on antiapoptotic proteins and growth factors. Selective estrogen receptor modulators (SERMs) have estrogenic and/or antiestrogenic activity depending on the target tissue. Hence, SERMs have the same beneficial effect as estrogen in skeleton and cardiovascular systems but act as antagonists in breast and uterus. The finding of beneficial side effects of SERMs in the CNS might improve their risk-benefit ratio in traditional indications. In this review, we will survey schizophrenia and depression as examples of mental diseases and AD and PD as neurodegenerative diseases. We will review brain effects of estrogens, steroids possibly acting as pro-drugs of estrogens such as testosterone and dehydroepiandrosterone (DHEA) and present novel findings with SERMs. Drugs with estrogen activity in the brain may have therapeutic potential either by modulating brain neurotransmitter transmission or through neuroprotective activity.

Alzheimer Disease↗
PubMed2000

An assessment of the validity of a computer system for probabilistic record linkage of birth and infant death records in Canada. The Fetal and Infant Health Study Group.

Studies on the validity of probabilistic record linkage are sparse. We performed a probabilistic linkage to link the 1984-1994 birth records (obtained from the Canadian Birth Data Base) with 1984-1995 infant death records (from the Canadian Mortality Data Base) in Canada. We extracted the linked birth-death records for Nova Scotia and Alberta (from January 1990 to December 1991) obtained from Statistics Canada's vital registration data and compared them with corresponding records from provincial data (primarily hospital records). The results showed that over 99% of infant deaths (153/155) in the Nova Scotia provincial data were successfully located in the linked Statistics Canada file; the corresponding figure for Alberta neonatal deaths was also 99% (365/367). The distributions of gestational age and birth weight in matched cases demonstrated high agreement between the two data sources. We conclude that the computer system for probabilistic linkage developed by Statistics Canada using the available personal identifying variables in the Canadian Birth Data Base and the Canadian Mortality Data Base is valid.

Alberta↗
PubMed1999

Changes in the registration of stillbirths < 500 g in Canada, 1985-95. Fetal-Infant Mortality Study Group of the Canadian Perinatal Surveillance System.

We assessed recent temporal trends in the registration of stillbirths in Canada, with particular regard to stillbirths < 500 g. Data from the Statistics Canada live birth and stillbirth databases for the period 1985-95 were used for the study. The primary analysis was restricted to data from 10 of the 12 provinces and territories of Canada. Data from Newfoundland were excluded because birthweight distributions were not available prior to 1990, and data from Ontario were excluded because of concerns about data quality. The proportion of stillbirths < 500 g increased by 47% [95% confidence interval (CI) 32, 63%], from 12.7% of stillbirths with known birthweight in 1985-7 to 18.7% in 1993-5. Similarly, the rate of stillbirths < 500 g increased by 36% [95% CI 21, 53%], from 7.2 to 9.8 per 10,000 total births from 1985-7 to 1993-5. Similar increases in stillbirth rates were not observed in other low birthweight categories. Live births < 500 g increased 53% [95% CI 33, 77%], from 4.6 to 7.0 per 10,000 live births. Some provinces and territories had low rates of stillbirths < 500 g and no increasing trend, whereas other provinces showed higher rates and increases over time. These regional differences were consistent with differences in stillbirth definitions across the provinces and territories of Canada. Spatio-temporal comparisons of crude stillbirth rates are likely to be compromised unless differences and changes in birth registration practices are addressed.

Canada↗
PubMed1999

Anomaly of the des-Arg9-bradykinin metabolism associated with severe hypotensive reactions during blood transfusions: a preliminary study.

BACKGROUND: Severe hypotensive reactions have been described after the transfusion of platelets or red cells through negatively-charged bedside white cell-reduction filters. The possibility of a role for bradykinin (BK) in the genesis of these reactions has been raised. STUDY DESIGN AND METHODS: To understand if an anomaly of BK metabolism is associated with these reactions, the metabolism of BK and des-Arg9-BK was studied in the sera of four patients who presented with a severe hypotensive transfusion reaction. Tests were performed in the absence and the presence of complete in vitro inhibition of angiotensin-converting enzyme (ACE) activity by enalaprilat. RESULTS: In the presence of ACE inhibition (enalaprilat), the half-life (t1/2) of BK measured in the sera of patients who presented with a severe hypotensive transfusion reaction (361 +/- 90 sec) was not significantly different from that measured in the sera of normal controls (249 +/- 16 sec). In the presence of ACE inhibition (enalaprilat), the t1/2 of des-Arg9-BK was significantly greater in patients who presented with a severe hypotensive transfusion reaction (1549 +/- 319 sec) than in normal controls (661 +/- 38 sec) (p < 0.001). CONCLUSION: A metabolic anomaly mainly affecting the degradation of des-Arg9-BK could be responsible for its accumulation in vivo. Des-Arg9-BK could be responsible, at least in part, for severe hypotensive transfusion reactions.

Adolescent↗
PubMed1999

Efficacy of a self-esteem module in the empowerment of individuals with schizophrenia.

To enhance empowerment and improve self-esteem among individuals with severe and persistent mental illness, a 12-week "module" (a self-contained program of activities) was created and tested in a randomized clinical trial. Fifty-one individuals with schizophrenia were assigned to the experimental group in addition to regular treatment, and 44 individuals participated in a control group that continued with regular treatment only. Psychosocial, diagnostic, neurocognitive, and symptomatology measures were taken for all 95 subjects before treatment (T0), after treatment (T1), and at a 6-month follow-up (T2). Results indicated module effects on coping skills (active coping skills significantly increased) and psychotic symptoms (positive symptoms significantly decreased), demonstrating the efficacy of this particular type of intervention. Interpretation of the results highlighted the significance of the environment and the role it could potentially play in supporting the empowerment of severely mentally ill individuals.

Adaptation, Psychological↗