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1.
HIV Med ; 24(8): 938-945, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37046178

RESUMO

INTRODUCTION: Since the advent of HIV pre-exposure prophylaxis (PrEP), stigma has been shown to be a major barrier to its uptake and adherence. It is therefore essential to define the proportion of users who consider that PrEP can negatively impact their image and the factors associated with this perception. METHOD: We performed a multivariable logistic regression on data from the 2567 participants in the ANRS-PREVENIR study who answered the outcome question. RESULTS: Almost one-third of the sample (comprising mostly cisgender men who have sex with men [94.3%]) considered that taking PrEP could give others a negative image of them. Younger participants (adjusted odds ratio [aOR] 0.98; 95% confidence interval [CI] 0.97-0.99) and more psychologically vulnerable participants (i.e., lower self-esteem score [aOR 0.98; 95% CI 0.96-0.99] and higher depression score [aOR 1.02; 95% CI 1.00-1.03]) were also more likely to have this perception. In contrast, participants encouraged to take PrEP by their main partner (aOR 0.67; 95% CI 0.51-0.88) and friends (aOR 0.79; 95% CI 0.66-0.95), and those who protected themselves more because they had knowledge of their most recent sexual partner's HIV status (aOR 0.83; 95% CI 0.69-0.99) and systematic use of PrEP and/or condoms during intercourse in the previous 3 months (aOR 0.80; 95% CI 0.67-0.96) were less likely to have this perception. DISCUSSION: Given the strong interrelation between stigmatization (real or perceived), risky behaviours and adherence, our results emphasize the need for HIV prevention campaigns to promote a positive image of PrEP users. They also show that stigmatization and its effects need to be fully considered to improve HIV prevention offers to current and potential PrEP users who are most likely to be psychologically vulnerable.


Assuntos
Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Comportamento Sexual , Percepção , Profilaxia Pré-Exposição/métodos
2.
J Eur Acad Dermatol Venereol ; 31(8): 1324-1332, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28556418

RESUMO

BACKGROUND: OX40 (CD134) is expressed in lesional but not healthy skin of patients with psoriasis. KHK4083 is a fully human monoclonal antibody against OX40. OBJECTIVE: The primary aim of this first-in-human phase 1 study was to determine the safety and tolerability of ascending single doses of KHK4083 in patients with mild to moderate plaque psoriasis. Secondary aims were to determine the pharmacokinetics and immunogenicity of KHK4083, and an exploratory objective was to assess clinical activity. METHODS: In phase 1a, single doses of KHK4083 0.003 and 0.001 mg/kg IV were administered open label in two cohorts (each n = 6). Phase 1b had a multicentre, randomized, double-blind, placebo-controlled, ascending single-dose design in seven cohorts. Randomization was performed 3 : 1 to KHK4083 (n = 6) or placebo (n = 2) within each cohort. Ascending doses of KHK4083 were 0.03, 0.1, 0.3, 1.0, 3.0 and 10 mg/kg IV, and 1.0 mg/kg SC. RESULTS: There were no severe or serious adverse events (AEs), or discontinuations because of AEs. The most frequent treatment-related AEs in the 55 patients who received KHK4083 were mild or moderate chills (9.1%), and infusion/injection site reactions (7.3%). No clinically meaningful or dose-related changes from baseline in laboratory values, vital signs, ECG recordings or physical examinations were observed. Some KHK4083 recipients (10/54) developed anti-KHK4083 antibodies following treatment. Mean elimination half-life (t1/2 ) increased with dose, maximum serum concentration increased in a dose-proportional manner, and area under the serum concentration-time curve increased in a more than dose-proportional manner with increasing IV dose. Absolute bioavailability following SC administration was 73%. There was some indication of improvement in Psoriasis Area Severity Index (PASI) and sPGA scores at the highest IV doses (1.0 and 10 mg/kg) and the SC dose (1.0 mg/kg). The largest PASI 50 response and improvement in sPGA score ≥2 occurred with KHK4083 1.0 mg/kg SC. CONCLUSION: KHK4083 administration as a single dose up to 10 mg/kg IV or 1.0 mg/kg SC was generally safe and well tolerated in patients with mild to moderate plaque psoriasis with no dose-limiting AEs.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Psoríase/tratamento farmacológico , Receptores OX40/antagonistas & inibidores , Receptores OX40/imunologia , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Humanizados , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Reação no Local da Injeção , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Placebos , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Phys Chem Chem Phys ; 17(14): 8706-13, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25820549

RESUMO

Electrolytes of a room temperature ionic liquid (RTIL), trimethyl(isobutyl)phosphonium (P111i4) bis(fluorosulfonyl)imide (FSI) with a wide range of lithium bis(fluorosulfonyl)imide (LiFSI) salt concentrations (up to 3.8 mol kg(-1) of salt in the RTIL) were characterised using a combination of techniques including viscosity, conductivity, differential scanning calorimetry (DSC), electrochemical impedance spectroscopy (EIS), nuclear magnetic resonance (NMR) and cyclic voltammetry (CV). We show that the FSI-based electrolyte containing a high salt concentration (e.g. 1 : 1 salt to IL molar ratio, equivalent to 3.2 mol kg(-1) of LiFSI) displays unusual transport behavior with respect to lithium ion mobility and promising electrochemical behavior, despite an increase in viscosity. These electrolytes could compete with the more traditionally studied nitrogen-based ionic liquids (ILs) in lithium battery applications.

4.
Climacteric ; 14(2): 282-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21244215

RESUMO

OBJECTIVE: To examine the effect of intravaginal dehydroepiandrosterone (DHEA) on pain at sexual activity (dyspareunia) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1. METHODS: This prospective, randomized, double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone (DHEA) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy, while meeting the criteria for superficial cells ≤ 5% and pH > 5.0 at both screening and day 1. RESULTS: At the standard duration of 12 weeks of treatment, increasing doses of 0.25%, 0.5% and 1.0% DHEA decreased the percentage of parabasal cells by 48.6  ±â€Š 6.78%, 42.4  ±  7.36% and 54.9  ±â€Š 6.60% (p < 0.0001 vs. placebo for all) with no change with placebo (p = 0.769). The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses. The severity score of pain at sexual activity decreased by 0.5, 1.4, 1.6 and 1.4 units in the placebo and 0.25%, 0.5% and 1.0% DHEA groups, respectively, with the p value of differences from placebo ranging from 0.0017 to < 0.0001. CONCLUSIONS: Intravaginal DHEA, through local estrogen and androgen formation, causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues, thus avoiding the recently reported systemic effects of estrogens.


Assuntos
Desidroepiandrosterona/administração & dosagem , Dispareunia/tratamento farmacológico , Administração Intravaginal , Desidroepiandrosterona/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Pós-Menopausa , Resultado do Tratamento
5.
Arch Pediatr ; 24(12): 1287-1292, 2017 Dec.
Artigo em Francês | MEDLINE | ID: mdl-29169715

RESUMO

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.


Assuntos
Assistência Perinatal , Algoritmos , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Gravidez , Fatores de Risco
6.
J Gynecol Obstet Biol Reprod (Paris) ; 45(9): 1172-1178, 2016 Nov.
Artigo em Francês | MEDLINE | ID: mdl-27692519

RESUMO

OBJECTIVES: To study inter-observer variability of decision concerning the route of delivery using pelvimetry in case of one previous cesarean section and abnormal pelvic measures. MATERIALS AND METHOD: Observational study conducted in 2014 in 4 university maternity units among 36 obstetricians. Two groups of obstetricians - as they practiced in a center where pelvimetry was routinely performed (n=12) or not (n=24) - had to choose a route of delivery for 10 clinical cases of women with a single uterine scar and a tight pelvis. The "routine pelvimetry" group had pelvimetry results. The group "no pelvimetry" became aware of pelvimetry results as a second step and had to indicate whether this information changed or not their management. The measurement of the inter-observer variability was estimated by estimating the proportion of agreement according to Grant method. RESULTS: The proportion of agreements of an attempted vaginal delivery between obstetricians in the group "routine pelvimetry" was 64.7% (95% CI [61-68.5]) and 97.3% (95% CI [96.4 to 98.3]) in the group "no pelvimetry", prior knowledge of pelvimetry results. An attempted vaginal delivery was decided in 77.5% versus 98.7% (P<0.001). After knowledge of pelvimetry results in the group "no pelvimetry" had, the number of attempted vaginal deliver was not different (77.5% vs. 78%, P=0.920). CONCLUSION: In women with one previous cesarean section, in case of tight pelvis discovered after pelvimetry, inter-observer variability of decision concerning the route of delivery is increased. Centers that choose to continue using the routine pelvimetry should develop procedures to limit this variability.


Assuntos
Recesariana/métodos , Tomada de Decisão Clínica , Pelvimetria/métodos , Nascimento Vaginal Após Cesárea/métodos , Adulto , Recesariana/normas , Feminino , Humanos , Variações Dependentes do Observador , Pelvimetria/normas , Nascimento Vaginal Após Cesárea/normas
7.
Arch Pediatr ; 22(10): 1056-63, 2015 Oct.
Artigo em Francês | MEDLINE | ID: mdl-26303021

RESUMO

Preterm premature rupture of membranes (PPROM) occurs in 3 % of pregnancies and is responsible for 30 % of premature births. The risks described in cases of PPROM are those of prematurity, acute maternal-fetal infection, cord prolapse, and abruptio placentae. The main objective of prenatal care is to reduce and anticipate the risk of perinatal infection and morbidity superimposed, but the predictive value of prenatal monitoring for the maternal-fetal infection prediction is low. Antibiotics are recommended routinely in PPROM cases. Tocolysis should not be continued more than 48h before 32 weeks gestation. Before 32 or 34 WG, a gain of 1 week of gestational age significantly reduces mortality and neonatal morbidity, and expectant management is usually preferred. French recommendations for clinical practice for expectant management or labor induction leave open either expectant management or labor induction after 34 WG. Between 34 and 37 weeks, the risk of rare severe morbidity related to prematurity are to be balanced against those of an acute infection or a maternal-fetal placental abruption. A large randomized trial comparing expectant and labor induction in cases of PPROM between 33 and 37 weeks showed no benefit of labor induction but did not have the power to explore rare and severe complications.


Assuntos
Ruptura Prematura de Membranas Fetais/terapia , Cuidado Pré-Natal , Antibacterianos/uso terapêutico , Feminino , Idade Gestacional , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Trabalho de Parto Induzido , Gravidez , Complicações Infecciosas na Gravidez , Nascimento Prematuro/prevenção & controle , Tocolíticos/uso terapêutico , Conduta Expectante
8.
PLoS One ; 10(10): e0138122, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26465600

RESUMO

We propose two strategies to improve the quality of tractography results computed from diffusion weighted magnetic resonance imaging (DW-MRI) data. Both methods are based on the same PDE framework, defined in the coupled space of positions and orientations, associated with a stochastic process describing the enhancement of elongated structures while preserving crossing structures. In the first method we use the enhancement PDE for contextual regularization of a fiber orientation distribution (FOD) that is obtained on individual voxels from high angular resolution diffusion imaging (HARDI) data via constrained spherical deconvolution (CSD). Thereby we improve the FOD as input for subsequent tractography. Secondly, we introduce the fiber to bundle coherence (FBC), a measure for quantification of fiber alignment. The FBC is computed from a tractography result using the same PDE framework and provides a criterion for removing the spurious fibers. We validate the proposed combination of CSD and enhancement on phantom data and on human data, acquired with different scanning protocols. On the phantom data we find that PDE enhancements improve both local metrics and global metrics of tractography results, compared to CSD without enhancements. On the human data we show that the enhancements allow for a better reconstruction of crossing fiber bundles and they reduce the variability of the tractography output with respect to the acquisition parameters. Finally, we show that both the enhancement of the FODs and the use of the FBC measure on the tractography improve the stability with respect to different stochastic realizations of probabilistic tractography. This is shown in a clinical application: the reconstruction of the optic radiation for epilepsy surgery planning.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Epilepsia/cirurgia , Algoritmos , Encéfalo/patologia , Simulação por Computador , Epilepsia/patologia , Reações Falso-Positivas , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador , Modelos Estatísticos , Reconhecimento Automatizado de Padrão/métodos , Imagens de Fantasmas , Probabilidade , Processos Estocásticos , Substância Branca/patologia
9.
J Med Chem ; 29(2): 218-23, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3081721

RESUMO

A series of gold(I) coordination complexes including analogues of the antiarthritic agent auranofin 1 were evaluated for in vitro cytotoxic potency against both B16 melanoma cells and P388 leukemia cells and in vivo antitumor activity against P388 leukemia in mice. A number of the complexes showed potent cytotoxic activity in vitro and antitumor activity in vivo, with the phosphine-coordinated gold(I) thiosugar complexes demonstrating the greatest in vitro and in vivo activity. The data compiled for 63 complexes of the general structural formula LAuX provide the basis for the following observations: potent in vitro cytotoxic activity is observed for substituted (phosphine) gold complexes, lack of potency in vitro correlates well with lack of antitumor activity, potent cytotoxicity in vitro is not necessarily predictive of activity in vivo, in vivo antitumor activity is generally optimized by ligation of Au(I) with a substituted phosphine and a thiosugar.


Assuntos
Antineoplásicos/farmacologia , Ouro/farmacologia , Animais , Auranofina , Aurotioglucose/análogos & derivados , Aurotioglucose/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Leucemia P388/tratamento farmacológico , Melanoma/patologia , Camundongos , Solubilidade , Relação Estrutura-Atividade
10.
J Med Chem ; 32(7): 1566-71, 1989 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2738892

RESUMO

A series of 7,8-fused heterocyclic tetrahydroisoquinolines were synthesized and tested as inhibitors of rabbit adrenal phenylethanolamine-N-methyltransferase (PNMT). 6,7,8,9-Tetrahydro[1,2,3]thiadiazolo[5,4-h]isoquinoline 5 (SK&F 86607) was found to be a potent inhibitor of PNMT with an IC50 similar to that of 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (1, SK&F 64139). The isomeric tetrahydro[1,2,3]thiadiazolo[4,5-h]- and tetrahydro[1,2,5]thiadiazolo[3,4-h]isoquinolines, 13 and 20, were also potent PNMT inhibitors. However, substitution of Cl at position 5 (17) resulted in loss of potency similar to the loss observed in the 5-chloro analogue of 1. The 1,2,5 isomer 20 showed only a small drop in activity at 10(-6) M. All of the thiadiazoles were more potent than the 7,8-benzo-fused analogue 36. Fusion of other five-membered heterocyclic ring systems at the 7,8-position, e.g. triazole 22 and imidazoles 24 and 26, resulted in a decrease of PNMT inhibition. The alpha-adrenoreceptor affinities of 1 and 5 were also compared.


Assuntos
Isoquinolinas/síntese química , Feniletanolamina N-Metiltransferase/antagonistas & inibidores , Glândulas Suprarrenais/enzimologia , Animais , Fenômenos Químicos , Química , Técnicas In Vitro , Isoquinolinas/farmacologia , Coelhos , Ratos
11.
J Med Chem ; 36(13): 1880-92, 1993 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-8515425

RESUMO

The further evolution of the imidazole-5-acrylic acid series of nonpeptide angiotensin II receptor antagonists is detailed (for Part 1, see: J. Med. Chem. 1992, 35, 3858). Modifications of the N-benzyl ring substitution were undertaken in an effort to mimic the Tyr4 residue of angiotensin II. Introduction of a p-carboxylic acid on the N-benzyl ring resulted in the discovery of compounds with nanomolar affinity for the receptor and good oral activity. SAR studies of these potent antagonists revealed that the thienyl ring, the (E)-acrylic acid, and the imidazole ring in addition to the two acid groups were important for high potency. Also, overlay comparisons of the parent diacid with both angiotensin II and a representative biphenylyltetrazole nonpeptide angiotensin II receptor antagonist are presented. The parent diacid analog, SK&F 108566 or (E)-3-[2-butyl-1-(4-carboxybenzyl)-1H-imidazole-5-yl]-2-[(2- thienyl)methyl]propenoic acid, is currently in clinical development for the treatment of hypertension.


Assuntos
Acrilatos/síntese química , Acrilatos/farmacologia , Antagonistas de Receptores de Angiotensina , Imidazóis/síntese química , Imidazóis/farmacologia , Tiofenos , Sequência de Aminoácidos , Angiotensina II/antagonistas & inibidores , Animais , Técnicas In Vitro , Modelos Moleculares , Dados de Sequência Molecular , Coelhos , Ratos , Relação Estrutura-Atividade
12.
J Med Chem ; 30(12): 2181-90, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3681888

RESUMO

Bisphosphines related to bis(diphenylphosphino)ethane (dppe) and their gold complexes are described that are active in a spectrum of transplantable tumor models. When administered ip on days 1-5 at its maximally tolerated dose (MTD) of 40 mumol/kg, dppe reproducibly gives 100% increase in life span (ILS) in mice bearing ip P388 leukemia. Coordination of chlorogold(I) to each phosphine in dppe gave a complex that had similar activity but at a much lower dose level than dppe; the MTD for the gold(I) complex was 7 mumol/kg. Among other metal complexes of dppe, the Au(III) complex was active (greater than 50% ILS) whereas Ag(I), Ni(II), Pt(II), Pd(II), and Rh(I) complexes were inactive. Among dppe analogues, replacement of phenyl groups with ethyl or benzyl groups resulted in inactivity for both ligands and the corresponding gold complexes whereas substitution with cyclohexyl or heterocyclic ring systems yielded ligands and/or gold complexes with antitumor activity. Among substituted-phenyl dppe and dppe(AuCl)2 analogues, 3-fluoro, 4-fluoro, perdeuterio, 4-methylthio, and 2-methylthio analogues were active; 4-methyl, 3-methyl, 4-methoxy, 4-dimethylamino, and 4-trifluoromethyl analogues were marginal or inactive. Analogues in which the ethane bridge of dppe or dppe(AuCl)2 was varied between one and six carbons, unsaturated or substituted, revealed that activity was maximal with ethane or cis-ethylene. Compounds with good P388 activity were also active in other animal tumor models.


Assuntos
Antineoplásicos/farmacologia , Ouro/farmacologia , Compostos Organofosforados/farmacologia , Animais , Antineoplásicos/síntese química , Camundongos , Conformação Molecular , Neoplasias Experimentais/tratamento farmacológico , Solubilidade , Relação Estrutura-Atividade
13.
J Med Chem ; 35(21): 3858-72, 1992 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-1433195

RESUMO

A series of novel nonpeptide angiotensin II receptor antagonists containing a substituted (E)-acrylic acid has been developed. The overlay of 1, an imidazole-5-acetic acid found in the patent literature, on a novel pharmacophore model of AII suggested that extension of the acid side chain and attachment of a second aryl residue to mimic the C-terminal phenylalanine region of AII would lead to increased activity. A study of extended acid side chains at C-5 of the imidazole nucleus led to the discovery of the (E)-acrylic acid 5 as a promising starting point for further exploration. As predicted by the modeling, substitution of a benzyl group on the acrylic acid side chain to mimic the phenylalanine gave increased potency. An extensive study of the SAR of the newly introduced aromatic ring revealed that electron-rich heteroaryl rings provided improved activity, most notably in the in vivo rat models. Compound 40, (E)-3-[2-butyl-1- [(2-chlorophenyl)methyl]imidazol-5-yl]-2-[(2-thienyl)methyl]-2- propenoic acid, has been shown to be a potent, competitive, and orally active small molecule AT-1 receptor antagonist. It exhibits a 2 orders of magnitude increase in binding affinity and a 10-fold improvement in in vivo potency as compared to compound 1 and represents an important milestone in the development of even more potent nonpeptide angiotensin II receptor antagonists.


Assuntos
Acrilatos/farmacologia , Antagonistas de Receptores de Angiotensina , Imidazóis/farmacologia , Acrilatos/química , Animais , Desenho de Fármacos , Imidazóis/química , Técnicas In Vitro , Masculino , Coelhos , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Difração de Raios X
14.
J Med Chem ; 28(5): 653-60, 1985 May.
Artigo em Inglês | MEDLINE | ID: mdl-2985785

RESUMO

3-Pyrrolidineacetic acid (1a), certain piperidinecarboxylic acids--i.e., 3-piperidinecarboxylic acid (2a), 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (3a), and cis-4-hydroxy-3-piperidinecarboxylic acid (4a)--cis-3-aminocyclohexanecarboxylic acid (5a, cis-3-ACHC), and gamma-aminobutyric acid (6a, GABA) itself are among the most potent inhibitors of [3H]GABA uptake by neurons and glia in vitro. These hydrophilic amino acids, however, do not readily enter the central nervous system in pharmacologically significant amounts following peripheral administration. We now report that N-(4,4-diphenyl-3-butenyl)-3-piperidinecarboxylic acid (2b) is a specific GABA-uptake inhibitor that is more potent, more lipophilic and, in limited testing, as selective as 2a. Similar results were obtained with the N-(4,4-diphenyl-3-butenyl) derivatives of 1a, 3a, and 4a. By contrast, N-(4,4-diphenyl-3-butenyl) derivatives of 5a and 6a were not more potent than the parent amino acids and appear to inhibit GABA uptake, at least in part, by a nonselective mechanism of action. The N-(4,4-diphenyl-3-butenyl)amino acids 1b-4b exhibit anticonvulsant activity in rodents following oral or intraperitoneal administration [Yunger, L.M.; et al. J. Pharmacol. Exp. Ther. 1984, 228, 109].


Assuntos
Aminoácidos/síntese química , Ácidos Carboxílicos/síntese química , Inibidores da Captação de Neurotransmissores/síntese química , Ácido gama-Aminobutírico/fisiologia , 4-Aminobutirato Transaminase/metabolismo , Administração Oral , Alquilação , Aminoácidos/farmacologia , Animais , Encéfalo/metabolismo , Ácidos Carboxílicos/farmacologia , Glutamato Descarboxilase/metabolismo , Técnicas In Vitro , Masculino , Inibidores da Captação de Neurotransmissores/administração & dosagem , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos , Receptores de GABA-A/metabolismo , Receptores de Neurotransmissores/metabolismo , Estereoisomerismo , Sinaptossomos/metabolismo , Ácido gama-Aminobutírico/metabolismo
15.
J Med Chem ; 33(5): 1386-92, 1990 May.
Artigo em Inglês | MEDLINE | ID: mdl-2329559

RESUMO

We report the cytotoxicity toward B16 cells and antitumor activity in three transplantable tumor models of a series of ionic, tetrahedral, bischelated gold diphosphine complexes of the type [Au1(R2PYPR2')2]X, where Y = (CH2)2, (CH2)3, or cis-CH = CH. The anion (X = Cl, Br, I, CH3SO3, NO3, PF6) had little effect upon activity. The R = R' = phenyl complexes 1, 7, and 8 [Y = (CH2)2, (CH2)3, cis-CH = CH, X = Cl] were the most active against P388 leukemia, with an increase in lifespan ranging from 83 to 92% and were also active against M5076 sarcoma and B16 melanoma. Complexes with pyridyl or fluorophenyl substituents had reduced activities. For the latter, 19F and 31P NMR were used to verify the formation of bischelated gold(I) complexes in solution. The reduced activity of the complex with R = Et and R' = Ph and inactivity with R = R' = Et are discussed in terms of their increased reactivity as reducing agents. 31P NMR studies show that [AuI(Et2P(CH2)2PPh2)2]Cl readily reacts with serum, albumin, and Cu2+ ions to give oxidized ligand.


Assuntos
Antineoplásicos/síntese química , Quelantes/síntese química , Ouro , Compostos Organometálicos/síntese química , Compostos Organofosforados/síntese química , Animais , Fenômenos Químicos , Química , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Compostos Organoáuricos , Compostos Organometálicos/uso terapêutico , Compostos Organofosforados/uso terapêutico , Relação Estrutura-Atividade
16.
J Med Chem ; 23(5): 506-11, 1980 May.
Artigo em Inglês | MEDLINE | ID: mdl-7381849

RESUMO

In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2 greater than 6,7,8-Cl3 greater than 7-Cl approximately 5,6,7,8-Cl4 greater than 5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (13, SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.


Assuntos
Epinefrina/biossíntese , Isoquinolinas/síntese química , Feniletanolamina N-Metiltransferase/antagonistas & inibidores , Glândulas Suprarrenais/metabolismo , Animais , Fenômenos Químicos , Química , Técnicas In Vitro , Isoquinolinas/farmacologia , Cinética , Coelhos , Relação Estrutura-Atividade
17.
Rev Epidemiol Sante Publique ; 37(3): 217-25, 1989.
Artigo em Francês | MEDLINE | ID: mdl-2799013

RESUMO

Clinical trials studying the influence of hospital practices on breast-feeding duration were combined in a meta-analysis. Nine studies were selected. The global quality score was poor, and varied between 11.6 and 71.5 (Chalmers' scale). The results of each study were pooled using Peto's method and showed the following findings. Supplementation demonstrated a negative clinical effect on breast-feeding duration which was not significant (OR: 0.77, 95% CI[0.59, 1.02] p greater than 0.05). Nursing support demonstrated a positive clinical effect on breast-feeding duration which was not statistically significant if there was no telephone follow-up (OR : 2.29, 95% CI [0.87, 6.02] p greater than 0.05), but was significant if there was telephone follow-up (OR : 2.01, 95% CI [1.37, 2.94] p less than 0.05). Early contact revealed a positive clinical effect which was significant (OR : 2.96, 95% CI [1.6, 5.22] p less than 0.05). In conclusion, early contact and nursing support with telephone follow-up appear as enhancing factors of breast-feeding duration.


Assuntos
Aleitamento Materno , Metanálise como Assunto , Serviço Hospitalar de Enfermagem , Adulto , Feminino , Humanos , Fatores de Tempo
18.
Int J Adolesc Med Health ; 6(3-4): 153-83, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-12319493

RESUMO

PIP: In Argentina, an integrated program has been developed to provide health care to adolescents in a hospital setting. In order to describe the structure and operation of the program and the constitution and dynamics of the working team, data were gathered through observations and interviews. The objectives of the program are 1) to provide adolescents with health care which integrates their physical, psychological, and social needs; 2) to detect disorders in early stages; 3) to emphasize reproductive health; 4) to strengthen families; 5) to train health care professionals; 6) to extend the program; 7) to do research on the Argentine adolescent; and 8) to collaborate with professional organizations concerned with adolescents. This report relates the evolution of the program, which has its roots in a 1973 study on the effectiveness of hospital services to adolescents, and describes the building and equipment devoted to the adolescent program. The organization of the program is discussed in terms of administration, material and financial resources, and human resources. The functions of the program are detailed and, as indicated by its goals, include health care (clinical medicine, gynecology, obstetrics, and mental health), teaching (pre/post graduate workshops, annual intensive courses, and scientific meetings), research, and community outreach. Finally, each area of medical care is described, with data tabulated for the most frequent reasons for each type of clinical and gynecological consultation. Reproductive health care includes sex education, counseling, pregnancy or postabortion care, and social services to unmarried adolescent mothers. The mental health staff offers individual, family, linking, and group therapy as well as vocational guidance, parental guidance, and psychopedagogical diagnoses. The social workers on the team interact with the adolescent in question and other professionals. In conclusion, it is noted that adolescent medicine is developing as a distinct field, and there is a need for more medical centers to provide the range of services adolescents require as well as to afford training opportunities for health care professionals. The positive results of this program based on increasing demand and user satisfaction justify the work done to create the service.^ieng


Assuntos
Adolescente , Atenção à Saúde , Planejamento em Saúde , Hospitais , Entrevistas como Assunto , Organização e Administração , Fatores Etários , América , Argentina , Coleta de Dados , Demografia , Países em Desenvolvimento , Saúde , Instalações de Saúde , América Latina , População , Características da População , Pesquisa , América do Sul
19.
Diabetes Metab ; 40(1): 43-48, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24051249

RESUMO

AIM: The study aimed to determine the factors associated with fetal macrosomia following a positive oral glucose challenge test (OGCT). METHODS: In this retrospective single-centre study of 1268 pregnancies with positive 50-g OGCTs (plasma glucose≥130mg/dL, or 7.2mmol/L), gestational diabetes mellitus (GDM) was defined as fasting plasma glucose (FPG)≥95mg/dL (5.3mmol/L) and/or postprandial glucose (PPG)≥120mg/dL (6.7mmol/L). RESULTS: In GDM pregnancies, the odds ratios adjusted for confounders (age, BMI, ethnicity, parity and weight gain) were 2.02 for macrosomia (Z score≥1.28) and 2.62 for severe macrosomia (Z score≥1.88). For each 10-mg/dL increase in FPG, the mean birth-weight increase was 60g. Macrosomia risk did not differ between GDM patients with normal FPG (<95mg/dL, or 5.3mmol/L) and non-diabetics, but increased significantly in cases of FPG≥95mg/dL and regardless of the level of PPG. CONCLUSION: In our study population, birth-weight and macrosomia risk were strongly correlated with FPG, suggesting that it is a simple and efficient marker for the risk of macrosomia.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Macrossomia Fetal/sangue , Macrossomia Fetal/diagnóstico , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Diabetes Gestacional/diagnóstico , Jejum , Feminino , França , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Razão de Chances , Paridade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Aumento de Peso
20.
J Gynecol Obstet Biol Reprod (Paris) ; 41(5): 476-84, 2012 Sep.
Artigo em Francês | MEDLINE | ID: mdl-22748474

RESUMO

OBJECTIVES: Following pregnancies with gestational diabetes mellitus (GDM), to assess: the perception by women of the risk of subsequent type 2 diabetes, the rate of screening for diabetes in the postpartum, and identify the factors leading women to undergo screening, in particular with respect to the information given to the general practitioner (GP) by the obstetrical team. METHODS: A cohort study of all women with GDM who delivered in a single academic hospital between 1st June 2008 and 31st May 2009, based on data extracted from files and from phone interviews made 6 to 12 months after the delivery. RESULTS: Out of 152 GDM cases, 147 medical files were consulted and 124 phone interviews were performed. Fifty-one percent of the interviewed women were aware of the risk of type 2 diabetes. Eighty patients (65%) underwent postpartum glucose testing, out of which 69 were prescribed by the maternity and 27 women (22%) did not get any prescription. The compliance rate was 78% (53/69) for the hospital prescriptions and 100% (18/18) for the GP's prescriptions, a significant difference in uptake (P<0.05). Although it appears that the information given to the GP is the only factor improving patient awareness about type 2 diabetes (P=0.01), as well as their compliance to postpartum glucose testing (P=0.02), only 41 reports (28%) were sent to the GP out of the 63 reports (43%) mentioning the GDM. CONCLUSION: Postpartum testing for type 2 diabetes following a GDM was not optimal in this study. In view of the key role played by the GP in the postpartum period, it appears that cooperation between maternity and GPs needs to be reinforced in order to maximise both proper screening and diabetes primary prevention following GDM.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Gestacional , Período Pós-Parto , Glicemia/análise , Estudos de Coortes , Feminino , Medicina Geral , Hospitais Universitários , Humanos , Programas de Rastreamento , Cooperação do Paciente , Gravidez , Fatores de Risco
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