RESUMO
Background: Stroke is a time-dependent emergency. Most patients with acute ischemic stroke are excluded from reperfusion therapies due to late consultation. Aims: To estimate the arrival times of patients with stroke to the Emergency Room (ER) of a public hospital. To identify factors associated with early consultation. Material and Methods: A convenience sample, 583 patients aged 71 ± 13 years (55% males) consulting for stroke at an emergency room was analyzed in terms of delay between onset of symptoms and arrival to the ER, demographics and etiology of stroke. Results: The admission diagnoses were ischemic stroke in 76%, intracerebral hemorrhage in 12%, transient ischemic attack in 9% and subarachnoid hemorrhage in 3%. The median time of arrival was 8 hours and 11 minutes after the onset of symptoms. Nineteen percent of consultations for ischemic stroke occurred within 3 hours of symptom onset, and 38% within 6 hours. In the logistic regression analysis, having an address near the hospital and the severity of stroke were associated with early consultation with a combined odds ratio of 5.97 (95% confidence intervals 3.23-11.04). Conclusions: There were significant differences in the arrival times of patients with stroke. Only a low proportion of patients with ischemic stroke consulted within the window for reperfusion therapies. Severe strokes and living near the hospital were associated with early consultation.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/epidemiologia , Hemorragia Cerebral , Hospitais PúblicosRESUMO
Resumen Antecedentes: El ataque cerebrovascular (ACV) es una urgencia tiempo-dependiente. La mayoría de los pacientes con infarto cerebral quedan excluidos de las terapias de reperfusión por consultar tardíamente. Se desconocen los factores asociados a llegada y evaluación precoz de pacientes con ACV agudo en nuestra población. Objetivos: Identificar los factores asociados, llegada y evaluación precoz de pacientes con ACV agudo. Pacientes y Métodos: Muestra por conveniencia de las consultas por ACV realizadas en el Turno N° 1, del SU del Hospital Dr. Hernán Henríquez de Temuco, entre enero de 2016 y diciembre de 2017. El análisis estadístico se realizó con el software STATA 14.0. Resultados: Se registraron 584 consultas por ACV. La mediana del tiempo de llegada fue de 8 h y 11 min. La mediana del tiempo para la evaluación por neurólogo(a) fue de 66 min. Tener domicilio en Temuco-Padre Las Casas y una mayor severidad del ACV se asociaron a consultar precozmente con un OR = 5,97 (3,23-11,04). Para evaluación dentro de una hora, las variables severidad, llegada en ambulancia y consulta en menos de 3 h, fueron estadísticamente significativas, con un OR combinado de 10,86 (IC 95%: 5,15-22,94). Conclusiones: Los factores más fuertemente asociados a llegada y evaluación precoz incluyen residir en comunas cercanas al hospital y presentar síntomas más severos de ACV. Se sugiere implementar estrategias para aumentar el grado de reconocimiento de síntomas de ACV y para disminuir las barreras de acceso a hospitales que traten a este tipo pacientes.
Introduction: Stroke is a time-dependent emergency. The majority of patients with Acute Ischemic Stroke are excluded from reperfusion therapies due to late consultation. The factors associated with early arrival and evaluation of patients with acute stroke in our population are unknown. The aim of the study was to identify factors associated with early arrival and evaluation of patients with acute stroke. Methods: A convenience sample of the stroke consultations made during shift # 1 at the ER between January 2016 and December 2017, was analyzed. Results: There were 584 stroke consultations in the period. 55.1% were men. The median time of arrival was 8 hours and 11 minutes. The median time for evaluation by neurologist was 66 minutes. Having an address in Temuco-Padre Las Casas and the severity of stroke was associated with early consultation with a combined OR of 5.97 (CI 95% 3.23-11.04). For an evaluation within one hour, in the logistic regression model, the variables severity, arrival in ambulance and consultation in less than 3 hours were statistically significant with a combined OR of 10.86 (CI 95% 5.15-22.94). Conclusions: The factors associated with early consultation and evaluation include residing in communes near the hospital and presenting more severe symptoms of stroke. It is suggested to implement strategies to increase the degree of recognition of stroke symptoms and to reduce barriers to access hospitals that treat patients with stroke.
Assuntos
Humanos , Masculino , Feminino , Pacientes , Infarto Cerebral , Acidente Vascular Cerebral , Emergências , Hospitais , Estudos Prospectivos , Estudo ObservacionalRESUMO
BACKGROUND: Stroke is a time-dependent emergency. Most patients with acute ischemic stroke are excluded from reperfusion therapies due to late consultation. AIMS: To estimate the arrival times of patients with stroke to the Emergency Room (ER) of a public hospital. To identify factors associated with early consultation. MATERIAL AND METHODS: A convenience sample, 583 patients aged 71 ± 13 years (55% males) consulting for stroke at an emergency room was analyzed in terms of delay between onset of symptoms and arrival to the ER, demographics and etiology of stroke. RESULTS: The admission diagnoses were ischemic stroke in 76%, intracerebral hemorrhage in 12%, transient ischemic attack in 9% and subarachnoid hemorrhage in 3%. The median time of arrival was 8 hours and 11 minutes after the onset of symptoms. Nineteen percent of consultations for ischemic stroke occurred within 3 hours of symptom onset, and 38% within 6 hours. In the logistic regression analysis, having an address near the hospital and the severity of stroke were associated with early consultation with a combined odds ratio of 5.97 (95% confidence intervals 3.23-11.04). CONCLUSIONS: There were significant differences in the arrival times of patients with stroke. Only a low proportion of patients with ischemic stroke consulted within the window for reperfusion therapies. Severe strokes and living near the hospital were associated with early consultation.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral , Feminino , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
Synthetic selective modulators of the estrogen receptors (SERMs) have shown to protect neurons and glial cells against toxic insults. Among the most relevant beneficial effects attributed to these compounds are the regulation of inflammation, attenuation of astrogliosis and microglial activation, prevention of excitotoxicity and as a consequence the reduction of neuronal cell death. Under pathological conditions, the mechanism of action of the SERMs involves the activation of estrogen receptors (ERs) and G protein-coupled receptor for estrogens (GRP30). These receptors trigger neuroprotective responses such as increasing the expression of antioxidants and the activation of kinase-mediated survival signaling pathways. Despite the advances in the knowledge of the pathways activated by the SERMs, their mechanism of action is still not entirely clear, and there are several controversies. In this review, we focused on the molecular pathways activated by SERMs in brain cells, mainly astrocytes, as a response to treatment with raloxifene and tamoxifen.
Assuntos
Astrócitos/efeitos dos fármacos , Encefalopatias/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Cloridrato de Raloxifeno/farmacologia , Receptores de Estrogênio/metabolismo , Moduladores Seletivos de Receptor Estrogênico/metabolismo , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/farmacologia , Animais , HumanosRESUMO
BACKGROUND: Neurological emergencies constitute 10-15% of medical emergencies. Doctor Hernán Henríquez Aravena Hospital has in house neurologists present permanently at the Emergency Room since July 2013. AIM: To estimate the waiting times for neurological consultations; to compare the waiting times between neurovascular (UV) and non-vascular (UNV) emergencies; and to compare the waiting times of two prioritization (triage) models. MATERIAL AND METHODS: A convenience sample of the consultations made during shift # 1 at the emergency room between January and December 2016, was analyzed. RESULTS: There were 859 consultations in the period, 570 for UNV and 289 for UV. Mean age of consultants was 57 years and 52% were women. The median time for having an evaluation by a neurologist was 106 min (132 and 81 min for UNV and UV respectively). Twenty seven percent of patients were evaluated in less than one hour (23 and 36% of UNV and UV, respectively). The change of the prioritization model decreased the waiting time by 81 and 32 min for UNV and UV, respectively. CONCLUSIONS: There were significant differences in waiting times between neurovascular and non-vascular emergencies. Most patients were not evaluated in less than 60 minutes. The change in the initial stratification model was associated with a significant reduction in the waiting times for neurological emergencies.
Assuntos
Serviço Hospitalar de Emergência , Doenças do Sistema Nervoso , Encaminhamento e Consulta/estatística & dados numéricos , Tempo para o Tratamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Estudos Prospectivos , Fatores de TempoRESUMO
Background: Neurological emergencies constitute 10-15% of medical emergencies. Doctor Hernán Henríquez Aravena Hospital has in house neurologists present permanently at the Emergency Room since July 2013. Aim: To estimate the waiting times for neurological consultations; to compare the waiting times between neurovascular (UV) and non-vascular (UNV) emergencies; and to compare the waiting times of two prioritization (triage) models. Material and Methods: A convenience sample of the consultations made during shift # 1 at the emergency room between January and December 2016, was analyzed. Results: There were 859 consultations in the period, 570 for UNV and 289 for UV. Mean age of consultants was 57 years and 52% were women. The median time for having an evaluation by a neurologist was 106 min (132 and 81 min for UNV and UV respectively). Twenty seven percent of patients were evaluated in less than one hour (23 and 36% of UNV and UV, respectively). The change of the prioritization model decreased the waiting time by 81 and 32 min for UNV and UV, respectively. Conclusions: There were significant differences in waiting times between neurovascular and non-vascular emergencies. Most patients were not evaluated in less than 60 minutes. The change in the initial stratification model was associated with a significant reduction in the waiting times for neurological emergencies.
Assuntos
Humanos , Masculino , Feminino , Encaminhamento e Consulta/estatística & dados numéricos , Serviço Hospitalar de Emergência , Tempo para o Tratamento , Doenças do Sistema Nervoso , Fatores de Tempo , Estudos Prospectivos , Exame NeurológicoRESUMO
HLA-A*02:481 differs from HLA-A*02:01:01:01 by one nucleotide and was found in four unrelated Brazilians.
Assuntos
Alelos , Antígeno HLA-A2/genética , Sequência de Bases , Brasil , Feminino , Antígeno HLA-B15/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Masculino , Dados de Sequência MolecularRESUMO
The Galpha subunits of heterotrimeric G proteins are constituted by a conserved GTPase "Ras-like" domain (RasD) and by a unique alpha-helical domain (HD). Upon GTP binding, four regions, called switch I, II, III, and IV, have been identified as undergoing structural changes. Switch I, II, and III are located in RasD and switch IV in HD. All Galpha known functions, such as GTPase activity and receptor, effector, and Gbetagamma interaction sites have been found to be localized in RasD, but little is known about the role of HD and its switch IV region. Through the construction of chimeras between human and Xenopus Gsalpha we have previously identified a HD region, encompassing helices alphaA, alphaB, and alphaC, that was responsible for the observed functional differences in their capacity to activate adenylyl cyclase (Antonelli et al. [1994]: FEBS Lett 340:249-254). Since switch IV is located within this region and contains most of the nonconservative amino acid differences between both Gsalpha proteins, in the present work we constructed two human Gsalpha mutant proteins in which we have changed four and five switch IV residues for the ones present in the Xenopus protein. Mutants M15 (hGsalphaalphaS133N, M135P, P138K, P143S) and M17 (hGsalphaalphaS133N, M135P, V137Y, P138K, P143S) were expressed in Escherichia coli, purified, and characterized by their ability to bind GTPgammaS, dissociate GDP, hydrolyze GTP, and activate adenylyl cyclase. A decreased rate of GDP release, GTPgammaS binding, and GTP hydrolysis was observed for both mutants, M17 having considerably slower kinetics than M15 for all functions tested. Reconstituted adenylyl cyclase activity with both mutants showed normal activation in the presence of AlF(4)(-), but a decreased activation with GTPgammaS, which is consistent with the lower GDP dissociating rate they displayed. These data provide new evidence on the role that HD is playing in modulating the GDP/GTP exchange of the Gsalpha subunit.
Assuntos
Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Adenilil Ciclases/metabolismo , Sequência de Bases , Primers do DNA/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/química , Expressão Gênica , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Humanos , Técnicas In Vitro , Modelos Moleculares , Mutagênese Sítio-Dirigida , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , TripsinaRESUMO
Using the yeast two-hybrid system, we studied the physical interaction between the complete C1 and C2 cytosolic domains of Xenopus laevis type 9 (xl9C1, xl9C2) and the C2 domain of rat type 6 (r6C2) adenylyl cyclase (AC). Heterodimerization between xl9C1 and xl9C2 and homodimerization between C2 (but not C1) domains was observed. Interaction between C2 and human G alpha s (hG alpha s) was also detected and was dependent on G alpha s activation. In contrast X. laevis G alpha s (xlG alpha s), which is 92% identical to hG alpha s, was unable to interact with any of the three AC cytosolic domains tested, corroborating previous findings that showed no effector activation. Through the construction of chimeras, we demonstrated that the amino-terminal half of xlG alpha s was responsible for the lack of interaction with AC. Chimeras between mouse G alpha i2 and G alpha s (N-mG alpha i2/C-G alpha s), that have previously shown to activate AC to a higher extent than wild-type G alpha s, also interacted with the C2 cytosolic domain and with a higher affinity. Interestingly, N-mG alpha i2/C-xlG alpha s chimera was not only able to interact with C2 but also with the C1 cytosolic domain.
Assuntos
Adenilil Ciclases/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Animais , Western Blotting , Clonagem Molecular , Citosol/enzimologia , Proteínas de Ligação ao GTP/genética , Humanos , Ligação Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Xenopus laevis , beta-Galactosidase/genéticaRESUMO
We have cloned a cDNA that encodes a novel Xenopus laevis oocyte adenylyl cyclase (xlAC) using oligonucleotides against conserved mammalian adenylyl cyclase regions. The isolated cDNA is 4372 bp long with an open reading frame of 4065 nucleotides which encodes a protein of 1355 amino acids. Comparison of the deduced amino acid sequence with previously cloned mammalian adenylyl cyclases shows a low identity, 19.7% with type 2 rat adenylyl cyclase and 24.2% with type 4 rat adenylyl cyclase, indicating that this Xenopus isoform represents a new member of this protein family. Gene expression studies of the xlAC by reverse PCR showed that this gene is expressed in all oogenesis stages but not during early embryogenesis. Expression of the xlAC in COS-7 cells resulted in increased basal AC activity, that was stimulated by forskolin, Gpp(NH)p and aluminium fluoride, and was insensitive to calcium and calcium-calmodulin (Ca2(+)-CaM).
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Adenilil Ciclases/biossíntese , Adenilil Ciclases/genética , Oócitos/enzimologia , Adenilil Ciclases/química , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Clonagem Molecular , DNA Complementar/isolamento & purificação , Dados de Sequência Molecular , Oócitos/química , Oócitos/crescimento & desenvolvimento , Oogênese/genética , Fases de Leitura Aberta , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Transfecção , Xenopus laevisRESUMO
A probe was constructed by radioactive labelling, and enzymatically a DNA fragment of plasmid pMAM-1, which codes for a beta-lactamase in Shigella flexneri UCSM 129, was obtained by amplification of a small part of the gene using the polymerase chain reaction technique (PCR). Since previous published work indicated that this beta-lactamase was of the TEM type, the primers used to amplify the gene were two highly conserved DNA regions in all TEM beta-lactamases. A 500 bp DNA probe was obtained which, by hybridization assays, facilitated the identification of restriction fragments of the plasmid containing the beta-lactamase gene. Two DNA fragments were sequenced by the Sanger method adapted to the PCR technique, and the sequence obtained showed a 100% homology with beta-lactamases TEM-1, TEM-2, TEM-13 and TEM-19. An intragenic restriction site, detected for Pst I, suggested that there is only one copy of the beta-lactamase gene per plasmid copy.
Assuntos
DNA Bacteriano/genética , Genes Bacterianos , Shigella flexneri/enzimologia , beta-Lactamases/genética , Sequência de Aminoácidos , Sequência de Bases , Southern Blotting , Sondas de DNA , Eletroforese em Gel de Poliacrilamida , Dosagem de Genes , Immunoblotting , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência , Homologia de Sequência de Aminoácidos , Shigella flexneri/genética , beta-Lactamases/químicaRESUMO
The resistance to beta-lactam antibiotics shown by a strain of Shigella flexneri was plasmid-coded. This plasmid, pMAM-1, when transferred to Escherichia coli K-12 by conjugation, presented the same molecular weight (100 kbp) and conferred the same high level of resistance to ampicillin in the transconjugant as in the wild type strains (MIC, 2048-4096). Restriction analysis of the plasmid in transconjugants revealed various restrictive sites to some endonucleases (i.e. Bam HI, Eco RI, Pst I, Nco I, Cla I, Sf I and Sau 3AI, Nhe and Hin dIII), and no restrictive sites at all for other endonucleases (such as Xho I, Dra I, Kpn I, and Sal I). Some restricted DNA fragments were appropriate for cloning and isolation of the beta-lactamase gene present in Shigella flexneri UCSF 129. This work provides the first step in this direction.