Asunto(s)
Costo de Enfermedad , Microcefalia , Atención Perinatal/métodos , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika/fisiología , Brotes de Enfermedades , Femenino , Salud Global , Necesidades y Demandas de Servicios de Salud , Humanos , Recién Nacido , Microcefalia/diagnóstico , Microcefalia/etiología , Microcefalia/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/fisiopatología , Complicaciones Infecciosas del Embarazo/terapia , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/fisiopatología , Infección por el Virus Zika/terapiaRESUMEN
Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1' group. Select compounds were found to be effective in in vivo models of arthritis.
Asunto(s)
Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , Metaloendopeptidasas/antagonistas & inhibidores , Proteínas ADAM , Proteína ADAM17 , Animales , Artritis/tratamiento farmacológico , Artritis/patología , Disponibilidad Biológica , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cartílago/efectos de los fármacos , Cartílago/patología , Bovinos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/síntesis química , Ácidos Hidroxámicos/síntesis química , Ratones , Ratas , Relación Estructura-ActividadRESUMEN
A cluster of infant deaths due to severe metabolic acidosis following immunization was reported in a prosperous farming village in Egypt. Fears that more deaths might occur, and of a deleterious effect on national immunization programs prompted an urgent investigation by national and international partners. The deaths, and other previously unrecognized illness following immunization, were associated with excessive topical application of methanol. Methanol was employed as an anti-pyretic and anti-inflammatory agent following injections. Fear of adverse reactions to vaccine had encouraged increasing use of methanol for these purposes. Local physicians and nurses were unaware of the toxicity of methanol and did not consider it in the differential diagnosis, and thus did not offer appropriate life-saving therapy. The interaction of traditional practices and modern medical interventions can have clinically important consequences, and should be considered when programs are introduced and as they are monitored.
Asunto(s)
Metanol/envenenamiento , Vacunación/efectos adversos , Estudios de Cohortes , Resultado Fatal , Humanos , LactanteRESUMEN
Anthranilic acid derivatives bearing basic amines were prepared and evaluated in vitro and in vivo as inhibitors of MMP-1, MMP-9, MMP-13, and TACE. Piperazine 4u has been identified as a potent, selective, orally active inhibitor of MMP-9 and MMP-13.
Asunto(s)
Aminas/química , Inhibidores Enzimáticos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , ortoaminobenzoatos/farmacología , Proteínas ADAM , Proteína ADAM17 , Animales , Sitios de Unión , Colagenasas/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Ácidos Hidroxámicos/química , Interleucina-1 , Interleucina-1beta , Espectroscopía de Resonancia Magnética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloendopeptidasas , Ratones , Modelos Moleculares , Osteoartritis/tratamiento farmacológico , Ratas , Relación Estructura-Actividad , ortoaminobenzoatos/síntesis química , ortoaminobenzoatos/químicaRESUMEN
A novel series of anthranilic acid-based inhibitors of MMP-1, MMP-9, and MMP-13 was prepared and evaluated both in vitro and in vivo. The most potent compound, 6e, has in vivo activity in a rat sponge-wrapped cartilage model.
Asunto(s)
Inhibidores de la Metaloproteinasa de la Matriz , Inhibidores de Proteasas/síntesis química , ortoaminobenzoatos/farmacología , Animales , Técnicas Químicas Combinatorias , Humanos , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/farmacología , Concentración 50 Inhibidora , Metaloproteinasa 13 de la Matriz , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/química , Sulfonamidas/farmacología , ortoaminobenzoatos/síntesis química , ortoaminobenzoatos/químicaRESUMEN
Interventions for parvovirus B19 infection need to balance the low risk of infection at a population level with the potential for serious adverse outcome for particular groups, notably the fetus, people with haemoglobinopathies and the immunocompromised. This guidance aims to assist the local decision-making process to be as evidence-based as the available evidence allows.
Asunto(s)
Infecciones Comunitarias Adquiridas/prevención & control , Infección Hospitalaria/prevención & control , Eritema Infeccioso/prevención & control , Control de Infecciones/normas , Parvovirus B19 Humano/aislamiento & purificación , Adolescente , Adulto , Niño , Eritema Infeccioso/transmisión , Femenino , Guías como Asunto , Humanos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Factores de Riesgo , Reino UnidoRESUMEN
A novel series of diazepine-based hydroxamic acid inhibitors of MMP-1, MMP-9, and MMP-13 were prepared and evaluated both in vitro and in vivo.
Asunto(s)
Azepinas/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores de la Metaloproteinasa de la Matriz , Compuestos Orgánicos , Pirazinas , Animales , Antineoplásicos/farmacología , Ácidos Hidroxámicos/síntesis química , Ácidos Hidroxámicos/farmacología , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 9 de la Matriz , Ratones , Inhibidores de Proteasas/farmacología , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/farmacologíaRESUMEN
AIMS: In April 1991 additional quality control procedures were introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. Internal quality control (IQC) samples were gradually included in the serological assays performed in the laboratory and supplemented kit controls and standard sera. METHODS: From April 1991 to December 1993, 2421 IQC procedures were carried out with reference sera. RESULTS: The IQC samples were evaluated according to the Westgard rules. Violations were recorded in 60 of 1808 (3.3%) controls and were highest in the IQC samples of complement fixation tests (25/312 (8%) of controls submitted for complement fixation tests). CONCLUSIONS: The inclusion of IQC samples in the serological assays performed in the laboratory has highlighted batch to batch variation in commercial assays. The setting of acceptable limits for the IQC samples has increased confidence in the validity of assay results.
Asunto(s)
Laboratorios de Hospital/normas , Virología/normas , Pruebas de Fijación del Complemento/normas , Inglaterra , Ensayo de Inmunoadsorción Enzimática/normas , VIH-1/aislamiento & purificación , VIH-2/aislamiento & purificación , Humanos , Control de Calidad , Virus/aislamiento & purificaciónRESUMEN
AIMS: In April 1991 an internal quality assessment scheme (IQAS) was introduced into the virology section of the Clinical Microbiology and Public Health Laboratory, Cambridge. The IQAS was established to identify recurring technical and procedural problems, to check the adequacy of current techniques, and to calculate the frequency of errors. METHODS: Between April 1991 and December 1993, 715 anonymous clinical serum samples were submitted to the laboratory to test 3245 individual procedures of diagnostic viral serology. RESULTS: A total of 485 (14.9%) procedural and 61 (1.9%) technical discrepancies were observed, the technical discrepancies mainly being recorded in complement fixation tests. Twenty two (0.7% of total procedures) of the technical discrepancies were diagnostically significant. CONCLUSIONS: Evaluation criteria developed with the introduction of IQAS to viral serology, and technical and procedural discrepancies are assessed. As yet, IQAS has not been introduced to other sections of the diagnostic virology laboratory (virus isolation, electron microscopy, immunofluorescence, and enzyme linked immunosorbent assays for viral and chlamydial antigens).
Asunto(s)
Laboratorios/normas , Garantía de la Calidad de Atención de Salud , Virología/normas , Humanos , Control de Calidad , Virosis/diagnósticoAsunto(s)
Aloxano/farmacología , Butanoles/farmacología , Etanol/farmacología , Glucosa/farmacología , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Animales , Interacciones Farmacológicas , Técnicas In Vitro , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Masculino , Ratas , Factores de TiempoRESUMEN
The uptake of theophylline and caffeine was determined in isolated pancreatic islets employing a dual isotope procedure with sucrose as an extracellular marker. Islets rapidly accumulated caffeine and theophylline with apparent dissociation constants of approximately 23 and 6 mM, respectively. Theophylline inhibited the uptake of caffeine and caused displacement of caffein from islets. These results indicated a competition by theophylline and caffeine for a common site (binding and/or transport carrier). In addition, theophylline and caffeine inhibited D-glucose transport in a dose-dependent manner and within the limits of the experimental system, this inhibition appeared to be non-competitive. (Bu)2cAMP under similar experimental conditions exerted no effect on D-glucose transport. These results present evidence for a rapid uptake of theophylline and caffeine in pancreatic islets, which is compatible with their immediate cellular effects. In addition, these results demonstrate a direct effect by theophylline and caffeine on D-glucose transport which appears independent of their ability to alter intracellular cAMP levels.
Asunto(s)
Cafeína/metabolismo , Glucosa/metabolismo , Islotes Pancreáticos/metabolismo , Teofilina/metabolismo , Animales , Transporte Biológico Activo/efectos de los fármacos , Cafeína/farmacología , Técnicas In Vitro , Islotes Pancreáticos/efectos de los fármacos , Cinética , Masculino , Ratas , Teofilina/farmacologíaRESUMEN
Ninhydrin, a compound which shares chemical properties strikingly similar to alloxan was found to mimic basically the inhibitory effect of alloxan on glucose-induced insulin release. Exposure of pancreatic islets for five minutes to 85 mumol/l ninhydrin produced approximately ninety percent inhibition of subsequent glucose-induced insulin release without altering basal secretion. Both D-glucose and D-mannose provided substantial protection against the inhibitory effect of ninhydrin, and the alpha anomer of D-glucose was more effective than the beta anomer in preventing ninhydrin inhibition of insulin release. Evidence for a common site of inhibition by ninhydrin and alloxan in the insulin release process is discussed.
Asunto(s)
Glucosa/farmacología , Indenos/farmacología , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Ninhidrina/farmacología , Animales , Hexosas/farmacología , Técnicas In Vitro , Secreción de Insulina , Islotes Pancreáticos/efectos de los fármacos , Masculino , RatasRESUMEN
The in vitro inhibition of insulin released by alloxan (20 mg/100 ml) in collagenase isolated rat islets is preferentially prevented by alpha D-glucose at a concentration of 1.0 mg/ml, while at a higher anomer concentration (1.5 mg/ml) both alpha and beta D-glucose provide equal protection. The ability of alpha D-glucose compared with beta D-glucose to stimulate insulin release, in vitro, showed a similar dose-related response, as observed in the alloxan protective studies. Although, both alpha and beta D-glucose compete with mutorated D-glucose for transport into islet cells, neither anomer produced a significantly different degree of inhibition in the transport process. The shared alpha stereospecificity for D-glucose in protection against alloxan and in stimulating insulin secretion in these in vitro studies, suggest a common site of interaction which may involve the beta-cell membrane.