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1.
Angew Chem Int Ed Engl ; 61(49): e202210600, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36097796

RESUMO

Understanding the mechanisms that connect heat and electron transport with crystal structures and defect chemistry is fundamental to develop materials with thermoelectric properties. In this work, we synthesized a series of self-doped compounds Cu2+x Mn1-x GeS4 through Cu for Mn substitution. Using a combination of powder X-ray diffraction, high resolution transmission electron microscopy and precession-assisted electron diffraction tomography, we evidence that the materials are composed of interconnected enargite- and stannite-type structures, via the formation of nanodomains with a high density of coherent interfaces. By combining experiments with ab initio electron and phonon calculations, we discuss the structure-thermoelectric properties relationships and clarify the interesting crystal chemistry in this system. We demonstrate that excess Cu+ substituted for Mn2+ dopes holes into the top of the valence band, leading to a remarkable enhancement of the power factor and figure of merit ZT.

2.
Rev Med Liege ; 75(10): 676-681, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-33030845

RESUMO

In Wallonia, almost one fourth of cesarean sections are performed on nulliparous women with vertex nonanomalous singleton gestations who underwent induction of labor. The purpose of this study is to compare maternal and neonatal outcomes with elective induction of labor versus spontaneous onset of labor. Data for all deliveries at CHU de Liège over a two-year period were obtained. Women with vertex nonanomalous singleton gestations who delivered from 3900 to 40+6 weeks were selected. We tested the association of elective induction and operative vaginal delivery, cesarean section, post-partum hemorrhage, episiotomy and perineal lacerations, length of labor, length of stay, 1-min and 5-min APGAR inferior to 7 and admission to neonatal intensive care unit. Length of stay was significantly longer in all induced women. In nulliparous women, there was a 45 % probability of operative vaginal delivery or cesarean section delivery in those who underwent elective induction of labor. In light of these results, it seems that our policy of elective induction of labor in nulliparous women is causing unnecessary and potentially avoidable interventions.


En Wallonie, l'induction du travail chez les patientes nullipares avec grossesse singleton en présentation céphalique recrute près d'un quart de l'ensemble des césariennes réalisées. L'objectif de cette étude est de comparer le travail spontané et l'induction élective du travail en termes d'issues obstétricales et de morbidités maternelles et néonatales. Entre janvier 2015 et décembre 2016, les femmes ayant accouché entre 390 et 40+6 semaines d'aménorrhée (SA) au CHU de Liège et ayant présenté une grossesse singleton avec présentation céphalique, sans pathologie maternelle, gravidique ou fœtale ont été sélectionnées. Les variables suivantes ont été retenues : taux d'extraction instrumentale, taux de césarienne, type d'hémorragie du post-partum, état du périnée, durée du travail, durée d'hospitalisation, APGAR (1-5 min) défavorable (inf�rieur a 7) et passage en néonatologie. La durée d'hospitalisation est augmentée chez toutes les femmes induites. Chez les patientes nullipares, l'induction élective se solde, dans 45 % des cas, par une extraction instrumentale ou une césarienne en cours de travail. Nos pratiques d'induction élective chez les patientes nullipares pourraient être responsables d'un certain nombre d'interventions non nécessaires et évitables.


Assuntos
Cesárea , Trabalho de Parto Induzido , Feminino , Humanos , Gravidez , Estudos Retrospectivos
3.
Allergy ; 71(2): 220-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26485347

RESUMO

BACKGROUND: Understanding patterns of IgE sensitization in Dermatophagoides-allergic patients living in various geographical areas is necessary to design a product suitable for worldwide allergen immunotherapy (AIT). METHODS: Using a HIFI Allergy customized microarray assay, IgEs specific for 12 purified allergens from Dermatophagoides pteronyssinus or D. farinae were assessed in sera from 1302 house dust mite (HDM)-allergic patients living in various areas. Comprehensive mass spectrometric (MS) analyses were conducted to characterize HDM extracts, as well as purified bodies and feces. RESULTS: Patterns of IgE reactivity to HDM allergens are comparable in all cohorts of patients analyzed, encompassing adults and 5- to 17-year-old children, as well as American, Canadian, European, and Japanese patients. Overall, >70% and >80% of HDM-allergic patients are sensitized to group 1 and group 2 allergens, respectively, from D. pteronyssinus and/or D. farinae species. Furthermore, 20-47% of patients also have IgEs to allergens from groups 4, 5, 7, 13, 15, 21, and 23. All patients have IgEs to allergens present in mite bodies and feces. MS-based analyses confirmed the presence of mite allergens recorded by IUIS in D. pteronyssinus and D. farinae extracts, with groups 2, 8, 10, 11, 14, and 20 prominent in bodies and groups 1, 6, 18, and 23 well represented in feces. CONCLUSIONS: Mite-specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination is appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Pyroglyphidae/imunologia , Adolescente , Adulto , Alérgenos/isolamento & purificação , Animais , Especificidade de Anticorpos , Antígenos de Dermatophagoides/isolamento & purificação , Criança , Pré-Escolar , Dessensibilização Imunológica , Europa (Continente) , Feminino , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Imunização , Imunoglobulina E/sangue , Masculino , Adulto Jovem
4.
Allergy ; 70(7): 795-804, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25846209

RESUMO

BACKGROUND: Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical-grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch pollen (BP)-allergic patients. METHODS: Following expression in Escherichia coli and purification, rBet v 1 was characterized using chromatography, capillary electrophoresis, circular dichroism, mass spectrometry and crystallography. Safety and efficacy of rBet v 1 formulated as a sublingual tablet were assessed in a multicentre, double-blind, placebo-controlled study conducted in 483 patients with BP-induced rhinoconjunctivitis. RESULTS: In-depth characterization confirmed the intact product structure and high purity of GMP-grade rBet v 1. The crystal structure resolved at 1.2 Å documented the natural conformation of the molecule. Native or oxidized forms of rBet v 1 did not induce the production of any proinflammatory cytokine by blood dendritic cells or mononuclear cells. Bet v 1 tablets were well tolerated by patients, consistent with the known safety profile of SLIT. The average adjusted symptom scores were significantly decreased relative to placebo in patients receiving once daily for 5 months rBet v 1 tablets, with a mean difference of 17.0-17.7% relative to the group treated with placebo (P < 0.025), without any influence of the dose in the range (12.5-50 µg) tested. CONCLUSION: Recombinant Bet v 1 has been produced as a well-characterized pharmaceutical-grade biological drug. Sublingual administration of rBet v 1 tablets is safe and efficacious in patients with BP allergic rhinoconjunctivitis.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Pólen/imunologia , Proteínas Recombinantes , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Imunoterapia Sublingual , Adolescente , Adulto , Alérgenos/química , Alérgenos/genética , Alérgenos/isolamento & purificação , Antígenos de Plantas/química , Antígenos de Plantas/genética , Antígenos de Plantas/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Conformação Proteica , Testes de Função Respiratória , Rinite Alérgica Sazonal/diagnóstico , Fatores de Risco , Imunoterapia Sublingual/efeitos adversos , Adulto Jovem
5.
Cancer Radiother ; 27(6-7): 531-534, 2023 Sep.
Artigo em Francês | MEDLINE | ID: mdl-37537026

RESUMO

Extreme hypofractionation in adjuvant breast radiotherapy currently generates a lot of interest. We propose here a synthesis of hypofractionation trials and present the DESTHE COL and DESTHE GR projects, encouraged by the French National Cancer Institute (INCa), which experiment care pathways in order to deploy effective strategies to de-escalate the therapeutics and to reduce sequelae after cancer treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Radioterapia Adjuvante
6.
Encephale ; 36(6): 461-71, 2010 Dec.
Artigo em Francês | MEDLINE | ID: mdl-21130229

RESUMO

RATIONALE AND OBJECTIVES: Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake. It has recently been discovered that bupropion may act as a non-competitive cholinergic nicotinic receptor antagonist, and that it may inhibit the activation of reward systems triggered by nicotine. Buproprion's efficacy as a smoking cessation aid has been demonstrated by numerous clinical trials that have compared its effects with those of placebo and other nicotinic substitutes. In 2001, buproprion SR received marketing authorization in France as a smoking cessation aid, under the name ZYBAN®. Tobacco addiction indeed remains a major public health issue. Among patients with psychiatric conditions, chronic tobacco consumption is frequent. The development of non-nicotinic drugs may therefore enhance therapeutic possibilities. However, the psychotropic effects of these molecules should be taken into account. We have recently reported the case of a patient with schizoaffective disorder, who presented two acute bupropion-induced psychotic episodes. We have also undertaken an exhaustive bibliographical research on this subject. The aim of the present study is to present the information available to us, in order to suggest aetiopathogenic hypotheses and therapeutic proposals. DATA SOURCES: The following databases were consulted on a regular basis, with no date restriction: Medline, Cochrane and Elsevier. The present study identified 22 cases of psychotic conditions associated with buproprion, as well as randomized and pharmacovigilance studies published in English, from December 1985 to November 2008. Since 2002, there have been three published case-reports on patients who underwent a tobacco cessation program. DATA SYNTHESIS: Psychotic disorders associated with buproprion appear after an average of 10 days of 300 mg/d bupropion intake. In about two third of cases, the patients have no history of psychiatric conditions. In one third of cases, they have a history of thymic disorders. In our review, auditory, visual or cenaesthetic hallucinations frequently occur (85% of the reported cases), and are sometimes characterized by single episodes and/or are rationalized. Some of them occur along with delusional episodes (mystical, paranoid, etc.). The patients are restless, confused, but seldom exhibit dissociative and thymic symptoms. DISCUSSION AND CONCLUSIONS: From an aetiopathogenic, clinical and evolutive standpoint, buproprion-induced psychotic episodes share many similarities with acute organic or toxic psychosis (notably induced by amphetamines). The hypothesis of a dopaminergic hyper-reactivity should be analyzed. Moreover, most of these patients were taking other medication, and the possibility of a dopaminergic potentialization prior to buproprion intake could be suggested. In such cases, bupropion should be discontinued and complete remission is expected within an average of 10 days. Even though neuroleptic drugs are still frequently used in these cases, benzodiazepines could become a valid alternative, according to the model of amphetamine-induced acute psychosis.


Assuntos
Antidepressivos de Segunda Geração/toxicidade , Bupropiona/toxicidade , Psicoses Induzidas por Substâncias/etiologia , Abandono do Hábito de Fumar , Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Humanos , Psicoses Induzidas por Substâncias/diagnóstico , Psicoses Induzidas por Substâncias/psicologia , Fatores de Risco , Abandono do Hábito de Fumar/psicologia
7.
Hum Reprod ; 24(2): 333-40, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19049990

RESUMO

BACKGROUND: Menstruation is associated with a striking increase in matrix metalloproteinase (MMP) activity. However, it is still unknown whether the level of MMP activity correlates with the amount of menstrual bleeding. METHODS: We used histochemistry to investigate the degradation of the extracellular matrix (ECM), and immunohistochemical labelling and zymographic analysis to determine the level of expression and activity of MMP-2 and -9, and of their tissue inhibitors (TIMPs) -1, -2 and -3, in endometria sampled during menstruation in 14 women experiencing excessive menstrual bleeding and in 10 women successfully treated for menorrhagia by thermal ablation of the endometrium. RESULTS: After thermal ablation, regenerated menstrual endometria showed reduced areas of collagen fibre lysis and increased content of TIMP-1 and TIMP-2 compared with endometria from non-treated menorrhagic women. Surprisingly, treated endometria contained more latent gelatinase A (proMMP-2) but a lower proportion of the active form of gelatinase B (MMP-9) than non-treated endometria. CONCLUSIONS: These results suggest that ECM degradation is decreased at menstruation in the endometrium regenerated after thermal ablation, mostly because of an increased TIMP expression. This represents the first molecular explanation for the decreased amount of menstrual bleeding.


Assuntos
Técnicas de Ablação Endometrial , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Menorragia/metabolismo , Adulto , Matriz Extracelular/metabolismo , Feminino , Humanos , Menorragia/patologia , Menorragia/cirurgia , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Resultado do Tratamento
8.
J Nanosci Nanotechnol ; 9(7): 4215-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19916433

RESUMO

Aligned titanium dioxide nanotubes may be grown on the surface of titanium metal by electrochemical oxidation in the presence of fluoride ion. There are a number of salient parameters that have been reported to affect the nanotube growth i.e., the nature, pH and concentration of the fluoride electrolyte, the cell potential and process time for anodisation. Furthermore, it has been reported that the nanotubes as grown are amorphous and can be converted to a mixture of anatase and rutile crystalline phases by heat treatment at elevated temperatures. There have been no studies reported investigating the effect of surface roughness of the parent titanium metal on nanotube growth. In this work the electrochemical growth of titanium oxide nanotubes on titanium foil was investigated using an ammonium fluoride/ammonium sulphate electrolyte. The results confirm that the anodisation potential controls pore diameter. The surface coverage of nanotubes was dependent on the surface roughness of the parent titanium metal. AFM measurements on untreated titanium foil showed relatively high microscale roughness and low nanoscale roughness. SEM analysis of these samples showed nanotube growth to be confined to depressions or valleys on the surface and the nanotubes were of uniform pore diameter. Mechanically polishing the surface of the parent titanium decreased the microscale roughness and increased the nanoscale roughness which, resulted in more uniform surface coverage. However, this led to an increased variation in pore diameter and shape of the nanotubes. XRD was used to determine crystal structure before and after annealing at 460 degrees C.

9.
Dalton Trans ; 46(7): 2174-2183, 2017 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-28127602

RESUMO

Bornite Cu5FeS4-xSex (0 ≤ x ≤ 0.6) compounds have been synthesized, using mechanical alloying, combined with spark plasma sintering (SPS). High temperature in situ neutron powder diffraction data collected on pristine Cu5FeS4 from room temperature up to 673 K show that SPS enables the stabilization of the intermediate cubic (IC) semi-ordered form (Fm3[combining macron]m, aIC ∼ 10.98 Å) at the expense of the ordered orthorhombic form (Pbca, aO ∼ 10.95 Å, bO ∼ 21.86 Å, cO ∼ 10.95 Å) in the 300-475 K temperature range, whereas above 475 K the IC form coexists with the high temperature cubic (C) form (Fm3[combining macron]m, aC ∼ 5.50 Å). The ability of Se for S substitution to induce disorder and consequently to enhance the IC phase formation is also emphasized. This disordering effect is explained by the high quenching efficiency of the SPS method compared to conventional heating. The existence of topotactic phase transformations, as well as Se for S substitution is shown to have a significant effect on the transport properties. As expected, electrical transport properties indicate a change towards a more metallic behaviour with increasing Se content. The electrical resistivity reduces from ∼21.4 mΩ cm for the pristine Cu5FeS4 to ∼3.95 mΩ cm for Cu5FeS3.4Se0.6 at room temperature. A maximum power factor of 4.9 × 10-4 W m-1 K-2 is attained at 540 K for x = 0.4 composition. The influence of selenium substitution on the carrier effective mass and mobility is discussed based on single parabolic band approximation. Furthermore, a detailed investigation of the thermal conductivity by this isovalent anion substitution reveals a significant reduction of the lattice thermal conductivity due to the alloying effect. Finally, the important role of structural transitions in the thermoelectric properties is addressed. A maximum ZT of 0.5 is attained at 540 K for Cu5FeS3.8Se0.2 composition.

10.
Hear Res ; 208(1-2): 101-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15993014

RESUMO

Benzodiazepines (Bzd) are known to interact with GABAergic inhibitory neurotransmission. Previous research on their effect on human auditory efferent pathways--through evoked otoacoustic emissions suppression by contralateral acoustic stimulation (CAS)--indicated a decrease in medial olivocochlear (MOC) efferent system inhibitory activity, after oral intake of oxazepam--representative of the Bzd drug class. To date, this pharmacological effect was only assessed in the right ear. Since a leftward asymmetry of Bzd receptors localization in human auditory cortex has been described recently, we explored in this study the hypothesis of an asymmetrical action of Bzd on MOC efferent functioning. The results revealed a significant difference of Bzd effect probing the right ear versus the left ear, with CAS-induced suppression being less effective in the right than left ear after oxazepam intake. This finding raises the question of possible neurochemical left-right asymmetry in the descending auditory pathways. The potential localization of this asymmetry is discussed.


Assuntos
Cóclea/efeitos dos fármacos , Moduladores GABAérgicos/farmacologia , Núcleo Olivar/efeitos dos fármacos , Oxazepam/farmacologia , Adulto , Vias Auditivas/efeitos dos fármacos , Vias Auditivas/fisiologia , Cóclea/fisiologia , Vias Eferentes/efeitos dos fármacos , Vias Eferentes/fisiologia , Lateralidade Funcional/fisiologia , Humanos , Masculino , Modelos Neurológicos , Núcleo Olivar/fisiologia , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Emissões Otoacústicas Espontâneas/fisiologia
11.
Ann Fr Anesth Reanim ; 24(7): 802-6, 2005 Jul.
Artigo em Francês | MEDLINE | ID: mdl-15949912

RESUMO

OBJECTIVES: To evaluate if the new anaesthesia platform ZEUS (Dräger Medical) allows the induction of anaesthesia with target-controlled inhalation of sevoflurane. STUDY DESIGN: Prospective clinical study. PATIENTS: Adult ASA I or II patients scheduled for elective surgery under general anaesthesia. METHODS: After preoxygenation during 3 min at 100% oxygen, patients were asked to breathe normally; the target end-tidal concentration of sevoflurane was fixed at 4% without priming of the circuit. Sufentanil (target concentration 0.5 ng/ml) was administered 40 s after. RESULTS: Ten patients (48+/-22 yrs) were included. Sevoflurane was detected in the circuit after 36+/-5 s; the target end-tidal concentration of sevoflurane was obtained at 130+/-19 s. Loss of consciousness was observed after 119+/-7 s. The induction was achieved in all patients without any incident. CONCLUSION: This new anaesthesia system make available the induction of anaesthesia with sevoflurane without priming of the circuit.


Assuntos
Anestesia por Inalação/instrumentação , Anestesiologia/instrumentação , Anestésicos Inalatórios/administração & dosagem , Éteres Metílicos/administração & dosagem , Adulto , Idoso , Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Sistemas de Liberação de Medicamentos , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Éteres Metílicos/efeitos adversos , Pessoa de Meia-Idade , Monitorização Intraoperatória , Medicação Pré-Anestésica , Sevoflurano
12.
Int J Obes Suppl ; 5(Suppl 2): S107-14, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27152178

RESUMO

OBJECTIVES: Within the global context of the nutrition and physical activity transition it is important to determine the relationship between adiposity and active school transport (AST) across different environmental and socio-cultural settings. The present study assessed the association between adiposity (that is, body mass index z-score (BMIz), obesity, percentage body fat (PBF), waist circumference) and AST in 12 country sites, in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). METHODS: The analytical sample included 6797 children aged 9-11 years. Adiposity indicators included, BMIz calculated using reference data from the World Health Organization, obesity (BMIz ⩾+2 s.d.), PBF measured using bioelectrical impedance and waist circumference. School travel mode was assessed by questionnaire and categorized as active travel versus motorized travel. Multilevel linear and non-linear models were used to estimate the magnitude of the associations between adiposity indicators and AST by country site and sex. RESULTS: After adjusting for age, sex, parental education and motorized vehicle availability, children who reported AST were less likely to be obese (odds ratio=0.72, 95% confidence interval (0.60-0.87), P<0.001) and had a lower BMIz (-0.09, s.e.m.=0.04, P=0.013), PBF (least square means (LSM) 20.57 versus 21.23% difference -0.66, s.e.m.=0.22, P=0.002) and waist circumference (LSM 63.73 cm versus 64.63 cm difference -0.90, s.e.m.=0.26, P=0.001) compared with those who reported motorized travel. Overall, associations between obesity and AST did not differ by country (P=0.279) or by sex (P=0.571). CONCLUSIONS: AST was associated with lower measures of adiposity in this multinational sample of children. Such findings could inform global efforts to prevent obesity among school-age children.

13.
J Bone Miner Res ; 11(8): 1146-57, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8854251

RESUMO

Plasminogen activators (PA) are implicated in cell migration and tissue remodeling, two components of the bone resorption processes. Using mice with inactivated tissue PA (tPA), urokinase PA (uPA), or type 1 PA inhibitor (PAI-1) genes, we evaluated whether these processes, or their stimulation by parathyroid hormone (PTH) or 1,25-dihydroxyvitamin (1,25[OH]2D3) are dependent on these genes. Two culture models were used, one involving 19-day fetal calvariae, to evaluate the direct resorptive activity of osteoclasis, and the other involving 45Ca-labeled 17-day fetal metatarsals, in which this activity depends on preliminary (pre)osteoclast migration. PTH similarly increased (about 10-fold) PA activity in calvariae from wild-type tPA+/+ and uPA+/+ or deficient uPA-/- and PAI-/- mice; it affected only tPA, not uPA. In tPA-/- bones, the low PA levels, due to uPA, were not influenced by PTH. Calcitonin did not affect PA responses to PTH. No differences were observed between tPA+/+, tPA-/-, uPA+/+, and uPA-/- calvariae for any parameter related to bone resorption (development of lacunae, release of calcium and lysosomal enzymes, accumulation of collagenase, loss of hydroxyproline), indicating similar responses to PTH or calcitonin. The progressive 45Ca release was largely similar in cultures of tPA+/+, tPA-/-, uPA+/+, uPA-/-, PAI+/+, or PAI-/- metatarsals and it was similarly enhanced by PTH or 1,25(OH)2D3. However, uPA-/- metatarsals released 45Ca at a slower rate at the beginning of the cultures, suggesting an impaired recruitment of the (pre)osteoclasts, which migrate at that time from the periosteum into the calcified cartilage. Thus, it appears that the direct resorptive activity of the osteoclasts does not necessitate the presence of either tPA or uPA, but uPA is likely to facilitate the migration of the (pre)osteoclasts toward the mineralized surfaces. Although considerably enhanced by PTH, tPA does not mediate the actions of PTH (nor of 1,25[OH]2D3) evaluated in these models.


Assuntos
Reabsorção Óssea/genética , Calcitriol/farmacologia , Osteoclastos/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Ativador de Plasminogênio Tecidual/genética , Ativador de Plasminogênio Tipo Uroquinase/genética , Animais , Técnicas de Cultura , Ossos do Metatarso/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Crânio/efeitos dos fármacos , Ativador de Plasminogênio Tecidual/efeitos dos fármacos , Ativador de Plasminogênio Tipo Uroquinase/efeitos dos fármacos
14.
J Clin Endocrinol Metab ; 85(12): 4827-34, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11134150

RESUMO

The pathogenesis of irregular endometrial bleeding, the main reason for stopping contraception with progestins only, is unknown. Based on the recent reappraisal of the mechanisms of menstrual bleeding, we hypothesized that matrix metalloproteinases initiate this disorder. Volunteers upon Norplant treatment provided endometrial biopsies at the start of a bleeding episode and during nonbleeding intervals. Focal stromal breakdown, collagen fiber lysis, and collagenase-1 messenger ribonucleic acid were evidenced in most bleeding endometria, but never in the nonbleeding ones. In the breaking down areas, immunolabeling for gelatinase A was strongly increased, and that of progesterone and estrogen receptors was decreased. Explants from bleeding endometria produced high collagenase and gelatinase activities, whereas release from nonbleeding endometria was negligible. Bleeding endometria released more latent and active forms of collagenase-1 and active gelatinases A and B, but less tissue inhibitor of metalloproteinases-1, than nonbleeding endometria. Collagenase-1 release closely correlated with that of interleukin-1alpha. In contrast, N:-acetyl-beta-hexosaminidase and tissue inhibitor of metalloproteinases-2 were similarly released in both groups. Thus, endometrial bleeding occurs together with focal stromal breakdown, collagen lysis, expression and activation of several matrix metalloproteinases, and decreased production of tissue inhibitor of metalloproteinases-1. These results may lead to new pharmacological treatment of this common medical problem.


Assuntos
Anticoncepcionais Orais Hormonais/efeitos adversos , Endométrio/metabolismo , Levanogestrel/efeitos adversos , Metaloproteinases da Matriz/metabolismo , Menstruação/fisiologia , Progestinas/efeitos adversos , Adulto , Western Blotting , Colagenases/metabolismo , Endométrio/citologia , Feminino , Humanos , Imuno-Histoquímica , Interleucina-1/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , RNA Mensageiro/biossíntese , Células Estromais/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo
15.
Biol Psychiatry ; 30(6): 609-17, 1991 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-1932408

RESUMO

Tianeptine is a new antidepressant drug reported to enhance serotonin (5-hydroxytryptamine [5-HT]) uptake in rat brain. The effect of tianeptine on 5-HT platelet uptake was studied in 10 depressed patients treated for 28 days. Tianeptine increases Vmax of 5-HT platelet uptake during treatment without inducing any change in Km. As early as 2 hr after the first administration, Vmax increased significantly (+23%, alpha = 0.01). Although of a lesser magnitude, 5-HT platelet uptake remains increased after chronic administration (+14% on day 10 and +13% on day 28). This suggests that tianeptine affects 5-HT platelet uptake sites, either directly or via an action on modulators of 5-HT uptake. These results, in contrast with the action of other tricyclic antidepressants, confirm the original action of tianeptine on 5-HT platelet metabolism.


Assuntos
Antidepressivos Tricíclicos/administração & dosagem , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Transtorno Depressivo/sangue , Transtorno Depressivo/tratamento farmacológico , Serotonina/sangue , Tiazepinas/administração & dosagem , Adolescente , Adulto , Idoso , Transtorno Depressivo/psicologia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Personalidade , Tiazepinas/farmacocinética
16.
Neuropsychopharmacology ; 28(4): 778-86, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12655325

RESUMO

The aim of this study was to test for an influence of benzodiazepine (BZD) on various perceptual and/or cognitive auditory processes. Loudness, auditory selective attention, and the ability of subjects to form perceptual streams out of alternating tone sequences were tested. Nine subjects were tested before, 1, 3, 7, and 24 h after a single-dose oxazepam vs placebo administration in a crossover design. A sample of blood allows us to measure plasma oxazepam concentration. The results revealed a significant reduction in stream segregation expressed as d' scores 1 h after oxazepam intake in the test subjects. No significant change occurred across time in the same subjects when they were administrated a placebo in another session. Furthermore, oxazepam had no substantial and systematic influence either on auditory selective attention or on loudness perception. Altogether, these results suggest that the perceptual organization of sound sequences involves inhibitory neural mechanisms, which can be affected by BZDs. This outcome is consistent with existing models of auditory stream segregation and may be paralleled with earlier findings on the effect of BZDs on perceptual binding in the visual modality.


Assuntos
Percepção Auditiva/efeitos dos fármacos , Benzodiazepinas/farmacologia , Estimulação Acústica/métodos , Adulto , Análise de Variância , Percepção Auditiva/fisiologia , Benzodiazepinas/sangue , Método Duplo-Cego , Humanos , Masculino , Oxazepam/sangue , Oxazepam/farmacologia
17.
J Nucl Med ; 35(11): 1822-30, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7965165

RESUMO

UNLABELLED: Radiolabeled ligands of monoamine transporters have already been used to visualize cerebral monoamine innervation by tissue autoradiography and by PET or SPECT in vivo. METHODS: A sampling technique was developed to allow for both the autoradiographic counting of serotonin (5-HT) axonal varicosities, labeled by uptake and storage of [3H]5-HT, and the measurement of the binding of [3H]cyanoimipramine ([3H]CYI), a specific 5-HT transporter ligand, in adjacent slices of adult rat neostriatum. The experiments were conducted in normal, decreased (after 5,7-dihydroxytryptamine lesions in adults) or increased (after 6-hydroxydopamine lesions in neonates) states of neostriatal 5-HT innervation. RESULTS: In normal tissue, the regional density of [3H]CYI binding faithfully reproduced rostrocaudal variations in the number of [3H]5-HT-labeled axonal varicosities. Pairs of values from all three experimental groups showed a highly significant linear correlation (r = 0.93) between the density of [3H]CYI binding and the number of 5-HT varicosities per cubic millimeter of tissue. The intercept of the regression line was close to zero; this confirmed the selectivity of the ligand. CONCLUSION: Under drug-free conditions, specific [3H]CYI binding is a good quantitative index of 5-HT innervation density in brain tissue and is not significantly up- or downregulated on 5-HT denervation or hyperinnervation. When it is adequately labeled, such a ligand might therefore be appropriate to quantify regional 5-HT innervation in vivo by PET or SPECT. The present approach should also be useful to select ligands to quantify 5-HT and monoamine systems.


Assuntos
Imipramina/análogos & derivados , Neostriado/diagnóstico por imagem , Neostriado/metabolismo , Antagonistas da Serotonina , Serotonina/metabolismo , Animais , Autorradiografia , Sítios de Ligação , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Tomografia Computadorizada de Emissão , Tomografia Computadorizada de Emissão de Fóton Único
18.
Drugs ; 38 Suppl 1: 14-6; discussion 49-50, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2612387

RESUMO

Preliminary results are presented from an ongoing study in hospitalised depressed patients. Changes in sleep parameters were assessed on days 1 to 3 and 12 to 14 of a 4-week study in which patients received trimipramine 150 mg on day 1 and 100 mg thereafter. On days 1 to 3 and 12 to 14, 7 depressed patients had a significantly increased total sleep time and sleep efficiency index and a significantly decreased total wake time and number of intrasleep wake episodes per hour of sleep. Trimipramine treatment had no significant effect on REM sleep, percentage of REM sleep, REM duration and REM sleep stability index. However, a significant increase in REM latency was noted on days 1 to 3 but not on days 12 to 14. These polygraphic data suggest that trimipramine effects a very rapid and maintained sleep improvement in these depressed patients without significant alterations to the parameters of REM sleep.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Dibenzazepinas/uso terapêutico , Sono/efeitos dos fármacos , Trimipramina/uso terapêutico , Transtorno Depressivo/psicologia , Humanos , Escalas de Graduação Psiquiátrica , Fases do Sono/efeitos dos fármacos , Sono REM/efeitos dos fármacos
19.
Chest ; 105(6): 1753-8, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8205872

RESUMO

We examined 129 patients recruited from two sleep clinics to study the sleep apnea syndrome (SAS), defined by the apnea-hypopnea index (AHI) > or = 10. Information was registered from a self-administered questionnaire, basal physical measurements, and polysomnography. In 68 subjects recorded for two consecutive nights, a high correlation was found between first- and second-night AHIs (r = 0.89). Habitual loud snoring and breathing arrests during sleep were associated with AHI > or = 10. A model including these two variables, sex, age, and body mass index was created in order to predict AHI > or = 10 and with which it was possible to successfully classify almost three of four patients. Among subjective sleep questionnaire items, only daytime sleepiness was related to drops of transcutaneous oxygen tension. These discrepancies in the observed relationship between sleep parameters and subjective sleep items reduce the questionnaire value in epidemiologic settings where it aimed to detect SAS, as defined solely by the AHI value.


Assuntos
Polissonografia , Síndromes da Apneia do Sono/epidemiologia , Gasometria , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Sono/fisiologia , Síndromes da Apneia do Sono/diagnóstico , Ronco/epidemiologia , Inquéritos e Questionários
20.
Psychopharmacology (Berl) ; 106 Suppl: S118-9, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1546124

RESUMO

A double-blind comparison of moclobemide and toloxatone was performed in adult out-patients diagnosed as suffering from a major depressive disorder. Parallel groups of patients received moclobemide, 450 mg/day (n = 135) or toloxatone, 1000 mg/day (n = 133) for 28 days. Both groups showed a significant clinical improvement while on therapy; the response was most marked and rapid in those receiving moclobemide treatment. Improvement was greatest in those patients with the most severe depression at the time of trial onset. A significantly higher number of patients returned to normal sleep patterns following moclobemide treatment than following toloxatone. Overall, tolerance was rated as good or very good in more than 80% of patients. The most frequent complaints in the moclobemide-treated group were hot flushes, dry mouth, constipation and headache, while an increase in anxiety was associated with toloxatone usage. Moclobemide was found to be as effective as toloxatone in the treatment of major depressive episodes, but with the advantages of improved sleep patterns and reduced anxiety.


Assuntos
Antidepressivos/uso terapêutico , Benzamidas/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Oxazóis/uso terapêutico , Oxazolidinonas , Adulto , Antidepressivos/efeitos adversos , Benzamidas/efeitos adversos , Transtorno Depressivo/psicologia , Método Duplo-Cego , Humanos , Moclobemida , Pacientes Ambulatoriais , Oxazóis/efeitos adversos , Escalas de Graduação Psiquiátrica , Desempenho Psicomotor/efeitos dos fármacos
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