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1.
Clin Microbiol Infect ; 21(6): 568.e1-11, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25677632

RESUMO

Biofilm formation, intra-osteoblastic persistence, small-colony variants (SCVs) and the dysregulation of agr, the major virulence regulon, are possibly involved in staphylococcal bone and joint infection (BJI) pathogenesis. We aimed to investigate the contributions of these mechanisms among a collection of 95 Staphylococcus aureus clinical isolates from 64 acute (67.4%) and 31 chronic (32.6%) first episodes of BJI. The included isolates were compared for internalization rate, cell damage and SCV intracellular emergence using an ex vivo model of human osteoblast infection. Biofilm formation was assessed in a microbead immobilization assay (BioFilm Ring test). Virulence gene profiles were assessed by DNA microarray. Seventeen different clonal complexes were identified among the screened collection. The staphylococcal internalization rate in osteoblasts was significantly higher for chronic than acute BJI isolates, regardless of the genetic background. Conversely, no differences regarding cytotoxicity, SCV emergence, biofilm formation and virulence gene distribution were observed. Additionally, agr dysfunction, detected by the lack of delta-toxin production using whole-cell matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis (n = 15; 15.8%), was significantly associated with BJI chronicity, osteoblast invasion and biofilm formation. These findings provide new insights into MSSA BJI pathogenesis, suggesting the correlation between chronicity and staphylococcal osteoblast invasion. This adaptive mechanism, along with biofilm formation, is associated with agr dysfunction, which can be routinely assessed by delta-toxin detection using MALDI-TOF spectrum analysis, possibly providing clinicians with a diagnostic marker of BJI chronicity at the time of diagnosis.


Assuntos
Toxinas Bacterianas/análise , Biofilmes/crescimento & desenvolvimento , Osteoartrite/microbiologia , Osteoblastos/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/fisiologia
2.
Transpl Infect Dis ; 14(6): E134-6, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22998023

RESUMO

Bordetella holmesii is a gram-negative rod that was initially identified in 1995. It causes bacteremia, pneumonia, and endocarditis mostly in patients with anatomical or functional asplenia. We report here, to the best of our knowledge, the first case of B. holmesii bacteremia in a renal transplant recipient following rituximab therapy for recurrence of membranoproliferative glomerulonephritis.


Assuntos
Infecções por Bordetella/microbiologia , Bordetella/classificação , Transplante de Rim/efeitos adversos , Adulto , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Infecções por Bordetella/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Masculino , Rituximab
3.
Water Sci Technol ; 64(7): 1533-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22179653

RESUMO

This paper compares several real-time control (RTC) strategies for a generic configuration consisting of a storage tank with two overflow facilities. Two of the strategies only make use of flow rate data, while the third also introduces turbidity data in order to exercise dynamic control between two overflow locations. The efficiency of each strategy is compared over a wide range of system setups, described by two parameters. This assessment is performed by simulating the application of control strategies to actual measurements time series recorded on two sites. Adding turbidity measurements into an RTC strategy leads to a significant reduction in the annual overflow pollutant load. The pollutant spills spared by such a control strategy strongly depend on the site and on the flow rate based strategy considered as a reference. With the datasets used in this study, values ranging from 5 to 50% were obtained.


Assuntos
Simulação por Computador , Eliminação de Resíduos Líquidos/instrumentação , Eliminação de Resíduos Líquidos/métodos , Poluentes da Água/química
4.
Water Sci Technol ; 63(11): 2628-32, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22049758

RESUMO

Real-time control (RTC) of urban drainage systems has been proven useful as a means to reduce pollution by combined sewer overflow discharges. So far, RTC has been investigated mainly with a sole focus on water quantity aspects. However, as measurement techniques for pollution of wastewater are advancing, pollution-based RTC might be of increasing interest. For example, turbidity data sets from an extensive measurement programme in two Paris catchments allow a detailed investigation of the benefits of using pollution-based data for RTC. This paper exemplifies this, comparing pollution-based RTC with flow-based RTC. Results suggest that pollution-based RTC indeed has some potential, particularly when measurements of water-quality characteristics are readily available.


Assuntos
Engenharia Sanitária/métodos , Cidades , Modelos Teóricos , Nefelometria e Turbidimetria , Chuva , Poluição da Água/prevenção & controle
5.
Water Sci Technol ; 59(8): 1471-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19403959

RESUMO

Turbidity sensors can be used to continuously monitor the evolution of pollutant mass discharge. For two sites within the Paris combined sewer system, continuous turbidity, conductivity and flow data were recorded at one-minute time intervals over a one-year period. This paper is intended to highlight the variability in turbidity dynamics during wet weather. For each storm event, turbidity response aspects were analysed through different classifications. The correlation between classification and common parameters, such as the antecedent dry weather period, total event volume per impervious hectare and both the mean and maximum hydraulic flow for each event, was also studied. Moreover, the dynamics of flow and turbidity signals were compared at the event scale. No simple relation between turbidity responses, hydraulic flow dynamics and the chosen parameters was derived from this effort. Knowledge of turbidity dynamics could therefore potentially improve wet weather management, especially when using pollution-based real-time control (P-RTC) since turbidity contains information not included in hydraulic flow dynamics and not readily predictable from such dynamics.


Assuntos
Drenagem Sanitária/estatística & dados numéricos , Monitoramento Ambiental/instrumentação , Monitoramento Ambiental/métodos , Movimentos da Água , Poluentes Químicos da Água/análise , Condutividade Elétrica , Paris , Análise de Componente Principal , Chuva
6.
Water Res ; 43(8): 2179-90, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19303128

RESUMO

This article presents a methodology for assessing annual wet weather Suspended Solids (SS) and Chemical Oxygen Demand (COD) loads in combined sewers, along with the associated uncertainties from continuous turbidity measurements. The proposed method is applied to data from various urban catchments in the cities of Paris and Nantes. The focus here concerns the impact of the number of rain events sampled for calibration (i.e. through establishing linear SS/turbidity or COD/turbidity relationships) on the uncertainty of annual pollutant load assessments. Two calculation methods are investigated, both of which rely on Monte Carlo simulations: random assignment of event-specific calibration relationships to each individual rain event, and the use of an overall relationship built from the entire available data set. Since results indicate a fairly low inter-event variability for calibration relationship parameters, an accurate assessment of pollutant loads can be derived, even when fewer than 10 events are sampled for calibration purposes. For operational applications, these results suggest that turbidity could provide a more precise evaluation of pollutant loads at lower cost than typical sampling methods.


Assuntos
Nefelometria e Turbidimetria/métodos , Esgotos/análise , Poluentes Químicos da Água/análise , Calibragem , Simulação por Computador , Oxigênio/química , Paris , Tempo (Meteorologia)
7.
Eur J Pharmacol ; 394(1): 131-8, 2000 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-10771045

RESUMO

A single oral administration of 1-[4-(N-tert-butylcarbamoyl)-2-methoxybenzene sulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethoxy)cyclohexane]indo l-2 -one SR121463 (0.3-3 mg/kg), a vasopressin non-peptide V(2) receptor antagonist, to rats induced dose-dependent aquaresis which was accompanied by Na(+), K(+), aldosterone and arginine vasopressin excretion over 6 h after dosing. However, no solute excretion was observed over 24 h. As a result of aquaresis, hemoconcentration and increases in plasma angiotensin II and adenocorticotrophin hormone were seen with 3 mg/kg at 2 h after dosing. Chronic treatment with SR121463 (3 mg/kg/dayx28 days) induced a marked aquaresis associated with aldosterone and vasopressin excretion. After a week of treatment, urine volume and aldosterone excretion were reduced ( approximately 40%) and then stabilised, while urine vasopressin excretion remained almost constant throughout the study. There were no changes in arterial pressure, plasma osmolality, plasma sodium concentration, or in number and affinity of liver vasopressin V(1A) and kidney V(2) receptors 24 h after the last treatment. These results indicate that SR121463 is a potent aquaretic agent and might be useful for the chronic management of water-retaining diseases in humans.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Diurese/efeitos dos fármacos , Morfolinas/farmacologia , Compostos de Espiro/farmacologia , Administração Oral , Hormônio Adrenocorticotrópico/sangue , Angiotensina II/sangue , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley
8.
Encephale ; 23(3): 184-93, 1997.
Artigo em Francês | MEDLINE | ID: mdl-9333549

RESUMO

This work was originated from the concern for the availability of a short, acceptable and reliable instrument for self-assessment of perceived stress. The questionnaire was designed to be routinely applied within a visit at an Occupational Medical Center. A new questionnaire was developed with this aim, consisting of 9 subscales presented in a Lickert form, with 4 modes of answer, scored from 0 to 3. The content of the 9 items covers the multiple facets of perceived stress and its consequences: "feeling of being under pressure", "impatience", "irritability", "intrusive thoughts about work", "inability to entertain", "discouragement", "morning fatigue", "food compensation", "compensation by smoking". Stress global score is defined as the sum of the 9 elementary scores. The first 7 items are similar in their construct to the 7 factor solutions of the principal component factor analysis performed on Levenstein Perceived Stress Questionnaire (1993). On the other hand, in comparison with Cohen Perceived Stress Scale (1983), our instrument keeps an important place for affective, physiologic and behavioral impact of stressing situations. A study on the homogeneity of the scale, its factorial structure, and its time reproducibility after 6 weeks of interval, was carried out on a first population of 91 subjects seen during an occupational medical visit in several companies of Paris district (PCV-Metra group). The coefficient of internal consistency is very high (Cronbach's alpha = 0.82). Principal component analysis extracted two factors, which were unchanged after a Varimax rotation and respectively represented 42% and 13% of the total variance: they can be interpretated as a general perceived stress component (being overwhelmed, loss of control) and a behavioral bipolar component opposing food compensation to smoking, whilst facing stressing situations. Test-retest correlation coefficient is 0.88 (Pearson r as well as intraclass correlation coefficient), without any significant gap between the first and the second assessment. A second study was carried out on 761 working individuals seen in the same conditions during an occupational medical visit in the same companies (596 males and 65 females, aged 40.1 +/- 8.8 years). Socio-demographic data analysis showed higher stress scores in females (10.2 +/- 4.0), than in males (8.5 +/- 3.7) (p < 0.0001). Detailed analysis showed differences related to gender in the same direction for the items "irritability", "discouragement", "morning fatigue" and "food compensation". Highest stress scores, for both males and females, were found for the items "intrusive thoughts about work" and "morning fatigue". Stress global score was correlated with socioprofessional status (SPS): unskilled and skilled workers (n = 39) as well as technicians (n = 346) exhibited lower scores than clerical workers (n = 108) or engineers (n = 162) (ANOVA, p < 0.0001). The comparison between mean scores performed separately by gender, given the different sex-ratio according to SPS (employees were mostly females) confirmed the association between stress score and SPS only in males, with blue collars and technicians looking less under stress than engineers. Metrological properties of this Perceived Stress Questionnaire incite to perform studies focused on the associations between such a stress index measured in an occupational setting, and several other clinical or biological variables, especially those supposed to constitute classical cardiovascular risk factors.


Assuntos
Doenças Profissionais/psicologia , Inventário de Personalidade/estatística & dados numéricos , Estresse Psicológico/complicações , Carga de Trabalho/psicologia , Adulto , Mecanismos de Defesa , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Estresse Psicológico/psicologia
9.
J Clin Invest ; 98(12): 2729-38, 1996 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8981918

RESUMO

SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Morfolinas/farmacologia , Compostos de Espiro/farmacologia , Adenilil Ciclases/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Administração Oral , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Arginina Vasopressina/antagonistas & inibidores , Arginina Vasopressina/farmacologia , Autorradiografia , Benzazepinas/farmacologia , Ligação Competitiva , Furosemida/farmacologia , Hidroclorotiazida/farmacologia , Rim/efeitos dos fármacos , Estrutura Molecular , Potássio/urina , Ratos , Sódio/urina , Urina
10.
Eur J Pharmacol ; 264(3): 307-16, 1994 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-7698170

RESUMO

The efficacy of SR 47436 (BMS-186295), 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)- biphenyl-4-yl)methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one, a non-peptide angiotensin AT1 receptor antagonist, was characterized in various conscious hypertensive rat models. In spontaneously hypertensive rats, single intravenous or oral doses of SR 47436 induced mild to modest antihypertensive effects. No tolerance of the antihypertensive effect was observed when the oral treatment was extended to 15 days. SR 47436 was highly effective to lower blood pressure in high renin-dependent hypertensive models such as two-kidney, one-clip renal hypertensive rats and renal artery-ligated hypertensive rats. In this last model, intravenous or oral administration of the angiotensin II antagonist produced a dose-dependent decrease in blood pressure. When injected after the maximal effective dose, enalapril did not induce any further decrease in blood pressure. Furthermore, the antihypertensive effect elicited after a single oral dose (10 mg/kg) was long-lasting (at least 24 h). The simultaneous blunting effect of the angiotensin II-induced blood pressure increase indicated clearly that the antihypertensive effect was due to the blockade of vascular angiotensin AT1 receptors. As expected, the angiotensin AT1 receptor antagonist did not show any efficacy in deoxycorticosterone acetate hypertensive rats, with a suppressed renin-angiotensin system. In genetic and renal hypertensive rats, the antihypertensive effect induced after acute dosing of SR 47436 was similar to that observed after losartan and enalapril. A reflex tachycardia accompanied the antihypertensive effect only after intravenous treatment with either SR 47436 or losartan. These results show that this angiotensin II antagonist, SR 47436, is an effective and long-lasting antihypertensive agent in rats.


Assuntos
Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão Renal/tratamento farmacológico , Tetrazóis/uso terapêutico , Administração Oral , Animais , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/toxicidade , Desoxicorticosterona/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Enalapril/farmacologia , Enalapril/uso terapêutico , Hipertensão Renal/induzido quimicamente , Hipertensão Renal/genética , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Imidazóis/toxicidade , Injeções Intravenosas , Irbesartana , Losartan , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Taquicardia/induzido quimicamente , Tetrazóis/administração & dosagem , Tetrazóis/farmacologia , Tetrazóis/toxicidade
11.
J Hypertens ; 11(11): 1187-94, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8301099

RESUMO

OBJECTIVE: The hypotensive and hormonal responses of an AT1-subtype angiotensin II receptor antagonist, SR 47436, were investigated and compared with those of DuP 753 (losartan), the leading AT1-receptor antagonist, and captopril and enalapril, two major angiotensin converting enzyme (ACE) inhibitors, in conscious, sodium-replete and sodium-depleted non-human primates. DESIGN AND METHODS: Blood pressure and heart rate were measured in conscious, chronically instrumented sodium-replete (n = 3-5) and sodium-depleted (n = 4) cynomolgus monkeys (Macaca fascicularis). Plasma renin activity (PRA), active renin and angiotensin II plasma concentrations were determined. RESULTS: SR 47436 induced a dose- and time-related fall in blood pressure in sodium-depleted monkeys; the blood pressure-lowering effect was obtained at a range of doses from one-third to one-tenth the equihypotensive dose of DuP 753 after intravenous and oral administrations. The hypotensive effect obtained with SR 47436 was similar to that of captopril and was sustained in sodium-replete monkeys, although it was weaker and less long-lasting than that of enalaprilat. In both sodium-depleted and sodium-replete monkeys the AT1 antagonist and ACE inhibitors caused similar increases in PRA and active renin. However, although angiotensin II levels increased after SR 47436 or DuP 753 treatment, they decreased after treatment with enalaprilat. Modest decreases in the heart rate sometimes accompanied the hypotension, irrespective of the compound tested. CONCLUSION: These data demonstrate that the AT1 antagonist SR 47436 is an effective hypotensive agent in both sodium-replete and sodium-depleted monkeys, with an intrinsic potency three to 10 times that of DuP 753 and similar to that of ACE inhibitors.


Assuntos
Angiotensina II/metabolismo , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo/farmacologia , Tetrazóis/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Feminino , Imidazóis/farmacologia , Irbesartana , Losartan , Macaca fascicularis , Masculino , Renina/sangue , Sódio na Dieta/administração & dosagem
12.
Arch Mal Coeur Vaiss ; 86(8): 1177-80, 1993 Aug.
Artigo em Francês | MEDLINE | ID: mdl-8129524

RESUMO

This study was conducted with 58 subjects (31 males and 27 females): a sample of 37 normotensives (NT) (mean age 36 +/- 11) and a sample of 21 hypertensives (HT) without any antihypertensive medication (mean age 46 +/- 9). Cardiovascular reactivity was measured during a sequence of 3 computer assisted mental stress tasks (visual-motor tasks, maze test). Before and following the stress tasks the subjects were asked to respond on the same computer to psychological test and questionnaires measuring anxiety, depression (H.A.D. inventory) type A behavior (impatience, competition and drive for success; Bortner's scale), locus of control (attribution of success or failure to internal or external factors; Levenson's scale), and coping mechanisms used in response to everyday life stresses (Rosenzweig Picture Frustration Test, adapted by S. Consoli and E. Albert). Measurements of systolic (SBP) and diastolic blood pressure and heart rate were obtained automatically every minute during the entire computer session with a Colin Press-Mate BP 8800 sphygmomanometer. Pressure reactivity (PR) was defined as the relative difference between BP measured during mental stress and BP measured during non-stress condition (the reference period). Our hypotheses were that PR would be greater in HT than in NT, and that PR would be correlated with various psychological and behavioral characteristics. During the stress session, SBP in NT increased from 119.8 to 123.7 mmHg (p < 0.001) and in HT from 147.4 to 152 mmHg (p < 0.05): there was no significant difference between the two samples but in HT, SBP elevation persisted after the stress session, contrary to the NT, whose SBP quickly decreased to the reference values.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Adaptação Psicológica , Pressão Sanguínea , Estresse Psicológico , Adulto , Feminino , Humanos , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Técnicas Projetivas , Sístole , Personalidade Tipo A
13.
J Clin Invest ; 92(1): 224-31, 1993 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8392086

RESUMO

SR 49059, a new potent and selective orally active, nonpeptide vasopressin (AVP) antagonist has been characterized in several in vitro and in vivo models. SR 49059 showed high affinity for V1a receptors from rat liver (Ki = 1.6 +/- 0.2) and human platelets, adrenals, and myometrium (Ki ranging from 1.1 to 6.3 nM). The previously described nonpeptide V1 antagonist, OPC-21268, was almost inactive in human tissues at concentrations up to 100 microM. SR 49059 exhibited much lower affinity (two orders of magnitude or more) for AVP V2 (bovine and human), V1b (human), and oxytocin (rat and human) receptors and had no measurable affinity for a great number of other receptors. In vitro, AVP-induced contraction of rat caudal artery was competitively antagonized by SR 49059 (pA2 = 9.42). Furthermore, SR 49059 inhibited AVP-induced human platelet aggregation with an IC50 value of 3.7 +/- 0.4 nM, while OPC-21268 was inactive up to 20 microM. In vivo, SR 49059 inhibited the pressor response to exogenous AVP in pithed rats (intravenous) and in conscious normotensive rats (intravenous and per os) with a long duration of action (> 8 h at 10 mg/kg p.o). In all the biological assays used, SR 49059 was devoid of any intrinsic agonistic activity. Thus, SR 49059 is the most potent and selective nonpeptide AVP V1a antagonist described so far, with marked affinity, selectivity, and efficacy toward both animal and human receptors. With this original profile, SR 49059 constitutes a powerful tool for exploring the therapeutical usefulness of a selective V1a antagonist.


Assuntos
Indóis/farmacologia , Pirrolidinas/farmacologia , Receptores de Vasopressinas/efeitos dos fármacos , Animais , Arginina Vasopressina/antagonistas & inibidores , Bovinos , Membrana Celular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Contração Muscular/efeitos dos fármacos , Piperidinas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Quinolonas/farmacologia , Ratos , Receptores de Vasopressinas/classificação
14.
J Pharmacol Exp Ther ; 265(2): 826-34, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8496828

RESUMO

SR 47436, 2-n-butyl-3-[(2'-(1H-tetrazol-5-yl)-biphenyl-4-yl) methyl]-1,3-diaza-spiro[4,4]non-1-en-4-one, is a new potent and selective AT1 angiotensin II (AII) receptor antagonist. It competitively inhibited [125I]AII binding to AT1 subtype receptors in rat liver membranes (IC50 = 1.7 nM) and did not interact with AT2 subtypes in rat adrenal cortical membranes. In rabbit aorta, SR 47436 inhibited contractions induced by 10 nM AII (IC50 = 4.0 nM) and shifted AII contractile response curves to the right in a parallel fashion, without total recovery of the maximal response. The potency of SR 47436 was higher than that of the lead compound, 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5- yl)biphenyl-4-yl)methyl]imidazole (DuP 753) (rat liver binding: IC50 = 16 nM; rabbit aorta: IC50 = 26 nM), and equivalent to saralasin (IC50 = 1.8 and 2.7 nM, respectively). The high specificity of SR 47436 was demonstrated by its lack of activity (IC50 > 10 microM) on various other receptors, ionic channels and antiports and rabbit aorta contracted by norepinephrine and KCl, and its lack of inhibition of renin and converting enzyme. In conscious rats, SR 47436 as well as DuP 753 (0.1 to 3 mg/kg, i.v., and 0.3 to 30 mg/kg, p.o.) antagonized the AII-pressor response in a dose-related manner. In conscious dogs, SR 47436 (1-10 mg/kg, p.o.) was a more potent antagonist of the AII pressor response than DuP 753. In conscious chronically implanted cynomolgus monkeys, SR 47436 antagonized the AII-pressor response at 1 mg/kg (89% i.v. and 66% p.o.) much more strongly than DuP 753 at 10 mg/kg (83% i.v. and 20% p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo/farmacologia , Tetrazóis/farmacologia , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiologia , Sítios de Ligação , Compostos de Bifenilo/metabolismo , Cães , Feminino , Irbesartana , Fígado/efeitos dos fármacos , Fígado/metabolismo , Macaca fascicularis , Masculino , Contração Muscular/efeitos dos fármacos , Papio , Coelhos , Ratos , Ratos Sprague-Dawley , Suínos , Tetrazóis/metabolismo
15.
Artigo em Francês | MEDLINE | ID: mdl-8121995

RESUMO

Between 1980 and 1990, 60 patients presenting with 62 peri-lunar dislocations of the carpus have been surgically treated. One case was a subluxation of the scaphoid and 61 were posterior perilunar dislocations, among them were 32 grade I, 23 grade II, 4 grade III, 2 unknown grade according to the Witvoët and Allieu scale. In 36 cases the scaphoid was fractured in 5 were associated a fracture of the scaphoid and a scapho-lunar dislocation. 48 cases have been reviewed after a 31 month follow-up average. The result was satisfactory in 83 per cent of these cases, unsatisfactory results being observed in cases of delayed surgery or incomplete reduction. In 36 cases a dynamic radiological examination was available after a 36 month follow-up average. 27 wrists were stable, 9 were not (7 D.I.S.I., 2 V.I.S.I.) 8 of these were related to unsatisfactory reductions. Diagnosis was delayed in 10 cases which ended with less satisfactory results. The authors think that conservative treatment is not adequate, they propose different surgical procedures according to the possible association of a fracture of the scaphoid.


Assuntos
Ossos do Carpo/cirurgia , Luxações Articulares/cirurgia , Instabilidade Articular/cirurgia , Articulação do Punho/cirurgia , Adolescente , Adulto , Ossos do Carpo/diagnóstico por imagem , Ossos do Carpo/lesões , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia
17.
Arch Mal Coeur Vaiss ; 83(8): 1281-4, 1990 Jul.
Artigo em Francês | MEDLINE | ID: mdl-2124468

RESUMO

SR 33557 (SR) is a new calcium channel blocker belonging to the chemical class of indolizinsulfones (IC50 = 0.6 nM, 3H-nitrendipine). Its hypotensive effects were studied in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and compared to those of Nitrendipine (Nit) (IC50 = 0.8 nM, 3H-nitrendipine). SR was given intravenously (IV) at 0.3, 1 and 3 mg/kg (n = 4 to 6) and orally (PO) at 3, 10, 30 and 60 mg/kg (n = 4 to 7). Nitrendipine was studied at 0.3 mg/kg (IV) and 10 mg/kg (PO). Blood pressure (BP) and heart rate (HR) were measured for 120 min, and for 24 h at 30 mg/kg. The IV injection of SR induced an immediate and dose-dependent decrease in BP. The maximal diastolic hypotension was situated between 11 p. 100 at 0.3 mg/kg and 45 p. 100 at 3 mg/kg (basal values: 133 +/- 6 and 131 +/- 5 mmHg). These effects lasted between 30 min and over 2 hours. The oral administration of SR induced a dose-dependent fall in BP at 3 mg/kg and upwards. The maximal diastolic hypotension appeared within 60 and 120 min and were situated between 8 p. 100 at 3 mg/kg and 28 p. 100 at 60 mg/kg (basal values: 130 +/- 7 and 133 +/- 2 mmHg). At 30 mg/kg, the hypotension lasted for 8 hours. SR was roughly 10 times less hypotensive in WKY than in SHR. HR did not change.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Indolizinas/farmacologia , Fenetilaminas/farmacologia , Animais , Frequência Cardíaca/efeitos dos fármacos , Indolizinas/administração & dosagem , Masculino , Nitrendipino/farmacologia , Fenetilaminas/administração & dosagem , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Resistência Vascular/efeitos dos fármacos
18.
J Hypertens Suppl ; 7(2): S33-5, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2666612

RESUMO

The effects of the renin inhibitor, SR 43845 (IC50 = 10(-11) mol/l human and primate plasma renin) and of the angiotensin converting enzyme (ACE) inhibitor captopril on blood pressure and plasma active renin were investigated in conscious, chronically instrumented, sodium-replete macaca (cynomolgus monkeys). Perfusion of SR 43845 at 0.33, 3.3, 33, 100 and 200 micrograms/kg per min for 30 min elicited a dose-related decrease in blood pressure with a notable effect on plasma renin activity (PRA; 90% inhibition), beginning at a dose of 0.33 micrograms/kg per min. The maximal reduction in blood pressure of 22 +/- 2 mmHg (from 110 +/- 5 mmHg) was achieved at 100 micrograms/kg per min and a higher dose (200 micrograms/kg per min) induced no further reduction. Plasma levels of active renin were also significantly increased (to 104%, from 102 +/- 14 pg/ml) at the lower dose. Captopril, tested at 33 micrograms/kg per min under the same experimental conditions, lowered blood pressure in a similar manner and with the same intensity as the renin inhibitor at an equal dose (by 14 +/- 1 mmHg, from 114 +/- 4 mmHg). However, a dose six times as high only influenced the decrease of blood pressure slightly (by 16 +/- 2 mmHg, from 103 +/- 5 mmHg). For the same hypotensive effect, the plasma renin concentration was significantly higher with the renin than with the ACE inhibitor. The recovery of pre-infusion blood pressure was both time- and dose-dependent, the basal value being almost restored after 5 h with both inhibitors, although the initial plasma renin levels were not completely recovered. A comparison of the maximal hypotensive effects and the plasma active renin concentrations elicited by the renin and the ACE inhibitors suggests that there are no major differences between the two types of inhibition and that renin inhibition is slightly more efficient.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Captopril/farmacologia , Dipeptídeos/farmacologia , Renina/antagonistas & inibidores , Animais , Captopril/administração & dosagem , Relação Dose-Resposta a Droga , Macaca fascicularis , Renina/sangue , Renina/metabolismo
19.
Artigo em Francês | MEDLINE | ID: mdl-2781070

RESUMO

The hydatid disease is rare in osseous locations, especially in our country (2.2 per cent). It has some particularities: clinical latency, diagnosis difficulties, surgical treatment often unsatisfactory because of the difficulty of total excision. Pain and sometimes deformity are often the only clinical features at the beginning of the disease. But, the evolution is unfavourable as soon as neurological symptoms appear. Multiple recurrences lead to unavoidable paraplegia. The antihelminthic drug (mebendazole) is disappointing in osseous location. Surgery is the only hope but the excision must be carcinologic. Spinal instrumentation can be improved by the use of acrylic cement whereas osseous grafts can be invaded by hydatidosis extension or recurrence. At present, the prognosis is still poor with constant apparition of cord compression. The authors report two cases of patients with osseous hydatidosis of the spine which illustrate these difficulties.


Assuntos
Equinococose/diagnóstico , Vértebras Torácicas , Adulto , Equinococose/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Coluna Vertebral/diagnóstico , Doenças da Coluna Vertebral/cirurgia
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