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OBJECTIVE: Lumbar spinal stenosis is the most common spinal degenerative disease in patients over 60 years, and the unilateral biportal endoscopic (UBE) spine surgery treatment of lumbar spinal stenosis (LSS) has achieved preliminary clinical results. This systematic review and meta-analysis aimed to reveal the clinical efficacy of UBE for LSS and provide evidence for clinical practice. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for literature. The papers selected were those published from inception till October 2021. The selected pieces of literature were graded for evidence using the Oxford Centre for Evidence-Based Medicine: Levels of Evidence (March 2009). Outcomes measures were operation time, blood loss, complication rate, admission period, Visual Analogue Scale (VAS)-back, VAS-leg, and Oswestry Disability Index (ODI) score, and radiological outcomes. The mean comparisons were based on VAS and ODI scores. RESULTS: A total of 823 patients with a single LSS segment were included from the selected nine studies. There were nine studies comparing UBE clinical outcomes and micro-endoscopic unilateral laminotomy for bilateral decompression (M-ULBD). The meta-analysis revealed that the UBE group had better VAS-leg and -back scores in the first week postoperatively [total: mean difference (MD) = -0.96, 95% confidence interval (CI): -1.19, -0.74, p < 0.00001; total: MD = -1.69, 95% CI: -1.93, -1.45, p < 0.00001], 1st month postoperatively (total: MD = -0.35, 95% CI: -0.61, -0.08, p = 0.01; total: MD = -0.40, 95% CI: -0.68, -0.12, p = 0.005), 6th month postoperatively (total: MD = -0.22, 95% CI: -0.35, -0.08, p = 0.002; total: MD = -0.24, 95% CI: -0.40, -0.07, p = 0.005), and UBE group also performed better in ODI score at 1st month postoperatively (total: MD = -3.36, 95% CI: -4.26, -2.46, p < 0.00001). There was no significant difference in VAS-leg and -back scores between both groups at the 3rd and 12th month postoperatively, and ODI scores did not significantly differ between both groups at 3, 6, and 12 months postoperatively (all p > 0.05). CONCLUSIONS: UBE has achieved good preliminary clinical results and may be a minimally invasive alternative surgery for patients with single segmental LSS.
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Estenose Espinal , Humanos , Estenose Espinal/cirurgia , Vértebras Lombares/cirurgia , Endoscopia/métodos , Laminectomia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: Elizabethkingia species are ubiquitous bacteria but uncommonly cause human infection. An outbreak of Elizabethkingia anophelis bacteraemia was observed in a respiratory care center of a tertiary hospital in Taiwan from 2015 to 2018. METHODS: Clinical and environmental isolates were collected for the outbreak investigation. Pulsed-field gel electrophoresis (PFGE) and complete-genome sequencing were conducted to elucidate the mechanism of transmission. FINDINGS: The three-year outbreak involved 26 patients with E. anophelis bacteraemia and the incidence significantly increased during the outbreak period compared with that observed from 2010 to 2014 (P<0.05). All 26 clinical isolates during the outbreak period belonged to a cluster by PFGE analysis. In contrast, the PFGE pattern was heterogeneous among comparative historical strains. Hospital tap water was highly contaminated by Elizabethkingia species (18/34, 52.9%); among that, five E. anophelis belonged to the outbreak cluster (5/18, 27.8%). As for the inanimate surface survey, 3.4% sites (4/117) revealed positive growth of E. anophelis including two from feeding tubes/bags and two from sputum suction regulators. All four isolates belonged to the outbreak clone. The outbreak strain had no apparent relationship to currently known E. anophelis strains worldwide through complete-genome sequencing analysis. Specific infection control strategies aimed at water source control and environmental disinfection were implemented subsequently and the outbreak ended in mid-2018. CONCLUSIONS: A specific E. anophelis strain was identified from a three-year outbreak. The elucidation of the mechanism of dominance and intra-hospital transmission is crucial for development of corresponsive infection control policies and outbreak control.
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Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Flavobacteriaceae , Flavobacteriaceae/isolamento & purificação , Abastecimento de Água , Infecções por Flavobacteriaceae/epidemiologia , Hospitais , Humanos , TaiwanRESUMO
Epidermal growth factor (EGF) promotes tumourigenesis and tissue repair of epithelial and mesenchymal cells and has a role in chemotaxis, mitogenesis, cell motility, and cytoprotection. It also enhances the growth of cancers. EGF may therefore have a role in the initiation or promotion of oral carcinogenesis. The cases of 152 patients with oral squamous cell carcinoma whose preoperative serum EGF level was determined by enzyme-linked immunosorbent assay were analyzed retrospectively, along with those of 40 age- and sex-matched controls. Patients with higher levels of EGF were more likely to have neck lymph node metastasis (P=0.026), advanced stage cancer (P=0.04), and a worse survival status (P=0.0019). Multivariate analysis using the Cox proportional hazards model indicated that the EGF level was an independent predictor of poor survival (hazard ratio 1.99, P=0.018). Patients with higher preoperative serum EGF levels had significantly poorer cancer-specific survival by Kaplan-Meier analysis (P=0.032). This study indicates that a higher preoperative serum EGF level is associated with neck lymph node metastasis, more advanced stage, and poor survival. EGF should be considered as a potential prognostic biomarker and a therapeutic target for patients with oral cancer.
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Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Fator de Crescimento Epidérmico/sangue , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico por imagem , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico por imagem , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Auto-immune thrombotic thrombocytopenic purpura (TTP) is a morbid multi-organ disorder. Cardiac involvement not recognized in initial disease descriptions is a major cause of morbidity. Therapeutic plasma exchange (TPE) requires exposure to multiple plasma donors with risk of transfusion-transmitted infection (TTI). Pathogen inactivation (PI) with amotosalen-UVA, the INTERCEPT Blood System for Plasma (IBSP) is licensed to reduce TTI risk. METHODS: An open-label, retrospective study evaluated the efficacy of quarantine plasma (QP) and IBSP in TTP and defined treatment emergent cardiac abnormalities. Medical record review of sequential patient cohorts treated with QP and IBSP characterized efficacy by remission at 30 and 60 days (d) of treatment, time to remission, and volume (L/kg) of plasma required. Safety outcomes focused on cardiac adverse events (AE), relapse rates, and mortality. RESULTS: Thirty-one patients (18 IBSP and 13 QP) met study criteria for auto-immune TTP. The proportions (%) of patients in remission at 30 d (IBSP = 61·1, QP = 46·2, P = 0·570) and 60 d (IBSP = 77·8, QP = 76·9, P = 1·00) were not different. Median days to remission were less for IBSP (15·0 vs. 24·0, P = 0·003). Relapse rates (%) 60 d after remission were not different between cohorts (IBSP = 7·1, QP = 40·0, P = 0·150). ECG abnormalities before and during TPE were frequent; however, cardiac AE and mortality were not different between treatment cohorts. CONCLUSIONS: Cardiac and a spectrum of ECG findings are common in TTP. In this study, IBSP and QP had similar therapeutic profiles for TPE.
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BACKGROUND: Amotosalen/UVA-treated platelet concentrates (PCs) have demonstrated efficacy for treating and preventing bleeding in clinical trials and in routine use; however, most studies were performed in haematology/oncology patients. We investigated efficacy during massive transfusion (MT) in general hospitalized patients. METHODS: Universal amotosalen/UVA treatment (INTERCEPT Blood System) of platelets was introduced at a large Austrian medical centre. We performed a retrospective cohort analysis comparing component use, in-hospital mortality and length of stay after MT that included platelet transfusion, for two periods (21 months each) before and after implementation. RESULTS: A total of 306 patients had MT. Patients were mostly male (74%) and ≥18 years old (99%), including 93 liver transplant, 97 cardiac or vascular surgery and 51 trauma patients. There were no differences in demographics between the periods. Component use on the day and within 7 days of the MT event was unchanged post-IBS implementation, except trauma patients received fewer RBCs on the day. The mean ratio of RBC:platelets:plasma on the day of the MT was close to 1:1:1 in both periods, except for liver transplants with MT who received more plasma components. Overall, in-hospital mortality (preimplementation = 27·6% vs. postimplementation = 24·0%; P = 0·51) and median time to discharge (preimplementation = 27 vs. postimplementation = 23 days; P = 0·37) did not change, except for cardiac and vascular surgery patients who were discharged earlier. CONCLUSION: The introduction of amotosalen/UVA-treated, pathogen-reduced PC did not adversely affect clinical outcomes in massively transfused patients in terms of blood product usage, in-hospital mortality and length of stay for a range of clinical indications for platelet transfusion support.
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Plaquetas/efeitos dos fármacos , Furocumarinas/farmacologia , Transfusão de Plaquetas , Raios Ultravioleta , Adolescente , Adulto , Idoso , Áustria , Plaquetas/metabolismo , Plaquetas/efeitos da radiação , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/cirurgia , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar , Hospitais , Humanos , Lactente , Estimativa de Kaplan-Meier , Tempo de Internação , Hepatopatias/mortalidade , Hepatopatias/terapia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/patologia , Adulto JovemRESUMO
BACKGROUND: In clinical studies, pathogen inactivation (PI) of platelet concentrates (PC) with amotosalen and UVA light did not impact patient risk for haemorrhage but may affect transfusion frequency and component utilization. We evaluated the influence of platelet PI on PC, red cell concentrate (RCC) and plasma use and safety in routine practice in a large regional hospital. STUDY DESIGN AND METHODS: Comparative effectiveness of conventional vs. PI-treated PC was analysed during two 21-month periods, before and after PI implementation. RESULTS: Similar numbers of patients were transfused in the pre-PI (control, 1797) and post-PI (test, 1694) periods with comparable numbers of PC (8611 and 7705, respectively). The mean numbers of PC per patient transfused (4·8 vs. 4·5, P = 0·43) were not different but days of PC support (5·9 vs. 5·0, P < 0·01) decreased. Most patients received RCC (86·8% control vs. 84·8% test, P = 0·90) with similar mean numbers transfused (10·8 vs. 10·2 RCC, P = 0·22), and fewer patients (55·4% control vs. 44·7% test, P < 0·01) received less plasma units (mean 9·9 vs. 7·8, respectively, P < 0·01) in the test period. The frequencies of transfusion-related adverse events (AE) were comparable (1·3% vs. 1·4%, P = 0·95). Analysis of haematology-oncology (522 control, 452 test), cardiac surgery (739 control, 711 test), paediatric (157 control, 130 test) and neonate (23 control, 20 test) patients revealed no increase in PC, plasma and RCC utilization, or AE. CONCLUSION: Component utilization and patient safety were not impacted by adoption of PI for PC. RCC use per patient was comparable, suggestive of no increase in significant bleeding.
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Transfusão de Componentes Sanguíneos/efeitos adversos , Plaquetas/citologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Criança , Pré-Escolar , Estudos de Coortes , Transfusão de Eritrócitos/efeitos adversos , Feminino , Furocumarinas/farmacologia , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/efeitos adversos , Fatores de Tempo , Raios Ultravioleta , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiação , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT(™) Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. MATERIALS AND METHODS: This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0-4), and causal relationship to PCT-PLT transfusion. RESULTS: Over the course of 7 years in the study centres, 4067 patients received 19,175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0.6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0.4%) and urticaria (41, 0.2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0.1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. CONCLUSION: This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.
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Segurança do Sangue/métodos , Furocumarinas/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Transfusão de Plaquetas/efeitos adversos , Raios Ultravioleta/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Segurança do Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/estatística & dados numéricos , Estudos ProspectivosRESUMO
MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica , Regulação para Baixo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Masculino , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/genética , Proteínas de Ligação a RNA , TranscriptomaRESUMO
Genotype P[25] rotaviruses are rare and to date have been reported to occur only in a few countries of mainland Asia. Here we report the molecular characterization of a novel human rotavirus genotype combination, G3P[25], detected in a 17-month-old child hospitalized due to severe gastroenteritis during 2009 in central Taiwan. Sequencing and phylogenetic analysis of the VP4 gene demonstrated a distinct origin from other strains bearing the P[25] VP4 gene, whereas the VP7, VP6 and NSP4 gene phylogenies identified common origins with cognate genes of other, presumed human-porcine reassortment Taiwanese strains. These results suggest that interactions between human and animal strains appear to contribute to the generation of genetic and antigenic diversity of rotavirus strains, with potential public health importance in Taiwan.
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Filogenia , Infecções por Rotavirus/virologia , Rotavirus/classificação , Rotavirus/isolamento & purificação , Antígenos Virais/genética , Proteínas do Capsídeo/genética , Diarreia/virologia , Epitopos , Genes Virais , Genótipo , Glicoproteínas/genética , Humanos , Lactente , Masculino , Rotavirus/genética , Rotavirus/patogenicidade , Infecções por Rotavirus/epidemiologia , Taiwan/epidemiologia , Toxinas Biológicas/genética , Proteínas não Estruturais Virais/genéticaAssuntos
Gastroenterite/virologia , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Rotavirus/patogenicidade , Pré-Escolar , Feminino , Gastroenterite/prevenção & controle , Humanos , Masculino , Reação em Cadeia da Polimerase , Rotavirus/classificação , Rotavirus/genética , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/farmacologia , Análise de Sequência de DNA , Taiwan/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Animal experiments indicate that the cerebral thrombin is associated with secondary brain damage after intracerebral hemorrhage (ICH). This study was aimed to investigate the concentrations of thrombin-antithrombin complex (TAT) in hematoma fluid and plasma of the patients with ICH after surgery and analyze the correlation between TAT complex levels and severity of ICH. METHODS: Sixty patients with ICH were enrolled. Craniotomy for removal of intracranial blood clot was performed within 24h after ICH. Hematoma fluid and plasma were collected on postoperative days 1, 2, and 4. The plasma obtained from healthy subjects and cerebrospinal fluid from patients without cerebrovascular diseases served as controls, respectively. Enzyme-linked immunosorbent assay was used to determine the concentrations of TAT complex in the patients and controls. RESULTS: TAT complex concentrations in both postoperative plasma and hematoma fluid of patients with ICH were significantly higher than those of the controls (P<0.01). In patients with ICH, hematoma fluid had a higher TAT complex level than plasma (P<0.01). The preoperative hemorrhage volume and postoperative TAT complex levels in plasma and hematoma fluid correlated positively with National Institutes of Health stroke scale and negatively with Glasgow coma score (P<0.01). CONCLUSION: This study indicates that TAT complex levels of plasma and hematoma fluid correlate positively with the severity of ICH. Determination of the plasma TAT complex concentration is helpful for the evaluation of the severity of post-ICH brain injury.
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Hematoma/sangue , Hemorragia Intracraniana Hipertensiva/sangue , Peptídeo Hidrolases/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombina III/líquido cefalorraquidiano , Feminino , Hematoma/cirurgia , Humanos , Hemorragia Intracraniana Hipertensiva/cirurgia , Hipertensão Intracraniana/sangue , Hipertensão Intracraniana/diagnóstico , Masculino , Pessoa de Meia-Idade , Peptídeo Hidrolases/líquido cefalorraquidiano , Valor Preditivo dos Testes , PrognósticoRESUMO
The complete sequence of an avian paramyxovirus type 1 (APMV-1) strain, FP1/02, isolated from Muscovy duck in China, was determined. Sequence analysis indicated that the complete genome of strain FP1/02 contained 15,192 nucleotides (nt), following the rule of six. The genome contained an extra 6-nt insertion in the non-coding region of the NP gene when compared with other APMV-1 strains, such as strains La Sota and Beaudette C. The cleavage site of the F protein was (112)R-R-Q-K-R↓F(117), indicating that the FP1/02 strain was virulent, but the morbidity and mortality varied with the species of duck. Genotypic analysis based on the F gene revealed that APMV-1 FP1/02 was a member of genotype VII. Phylogenetic analysis showed that the FP1/02 strain shared high identity with other APMV-1 strains such as ZJ1, SF02 and NA-1 isolated from geese.
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Anseriformes/virologia , Avulavirus/genética , Avulavirus/isolamento & purificação , Genoma Viral , RNA Viral/genética , Análise de Sequência de DNA , Animais , Embrião de Galinha , China , Análise por Conglomerados , Dados de Sequência Molecular , Mutagênese Insercional , Nucleoproteínas/genética , Filogenia , Homologia de Sequência , Proteínas Virais de Fusão/genéticaRESUMO
We recorded 872 single units across the complete sleep-waking cycle in the mouse preoptic area (POA) and basal forebrain (BFB), which are deeply involved in the regulation of sleep and wakefulness (W). Of these, 552 were sleep-active, 96 were waking-active, 106 were active during both waking and paradoxical sleep (PS), and the remaining 118 were state-indifferent. Among the 872, we distinguished slow-wave sleep (SWS)-specific, SWS/PS-specific, PS-specific, W-specific, and W/PS-specific neurons, the last group being further divided into specific tonic type I slow (TI-Ss) and specific tonic type I rapid (TI-Rs) both discharging specifically in association with cortical activation during both W and PS. Both the SWS/PS-specific and PS-specific neurons were distributed throughout a wide region of the POA and BFB, whereas the SWS-specific neurons were mainly located in the middle and ventral half of the POA and adjacent BFB, as were the W-specific and W/PS-specific neurons. At the transition from waking to sleep, the majority of SWS-specific and all SWS/PS-specific neurons fired after the onset of cortical synchronization (deactivation), whereas all W-specific and W/PS-specific neurons showed a significant decrease in firing rate >0.5 s before the onset. At the transition from SWS to W, the sleep-specific neurons showed a significant decrease in firing rate 0.1 s before the onset of cortical activation, while the W-specific and W/PS-specific neurons fired >0.5 s before the onset. TI-Ss neurons were characterized by a triphasic broad action potential, slow single isolated firing, and an antidromic response to cortical stimulation, whereas TI-Rs neurons were characterized by a narrow action potential and high frequency burst discharge in association with theta waves in PS. These data suggest that the forebrain sleep/waking switch is regulated by opposing activities of sleep-promoting (SWS-specific and SWS/PS-specific) and waking-promoting (W-specific and W/PS-specific) neurons, that the initiation of sleep is caused by decreased activity of the waking-promoting neurons (disfacilitation), and that the W/PS-specific neurons are deeply involved in the processes of cortical activation/deactivation.
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Neurônios/fisiologia , Prosencéfalo/citologia , Sono , Vigília , Estimulação Acústica , Potenciais de Ação , Animais , Mapeamento Encefálico , Estimulação Elétrica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Área Pré-Óptica/citologia , Área Pré-Óptica/fisiologia , Prosencéfalo/fisiologia , Fases do SonoRESUMO
This study was designed to evaluate anti-Xa activity hourly during the first 3 h after a single intravenous bolus of 0.5 mg/kg enoxaparin in 30 patients with end-stage renal disease (ESRD) who underwent haemodialysis, and in 30 patients with normal or mildly reduced renal function who underwent coronary angiography for chest pain (non-ESRD group). Mean +/- SD haemodialysis time was 3.9 +/- 0.3 h in the ESRD group. Of 24 patients diagnosed with coronary artery disease in the non-ESRD group, 20 underwent percutaneous coronary intervention (PCI). A peak anti-Xa activity > 0.5 IU/ml 10 min after enoxaparin injection was obtained in 90% and 93% of the non-ESRD and ESRD patients, respectively. The percentages of patients with peak anti-Xa activity in the target range (0.5 - 1.5 IU/ml) were similar in the two groups (non-ESRD 80%, ESRD 93%). Adequate anti-Xa activity (> 0.5 IU/ml) lasted about 2 h in both groups. It is concluded that a single intravenous low-dose enoxaparin (0.5 mg/kg) bolus provides anti-Xa activity adequate for elective PCI within 2 h irrespective of whether or not the patient had ESRD.
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Anticoagulantes/administração & dosagem , Anticoagulantes/farmacologia , Enoxaparina/administração & dosagem , Enoxaparina/farmacologia , Fator Xa/metabolismo , Falência Renal Crônica/sangue , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-IdadeRESUMO
Using extracellular single unit recordings alone or in combination with neurobiotin juxtacellular labeling and orexin (hypocretin) immunohistochemistry in the mouse, we have recorded a total of 452 neurons in the orexin neuron field of the posterior hypothalamus. Of these, 76 exhibited tonic discharge highly specific to wakefulness, referred to as waking-active neurons. They showed differences from each other in terms of spike shape, activity profile, and response to an arousing sound stimulus and could be classified into three groups on the basis of spike shape as: 1) biphasic broad; 2) biphasic narrow; and 3) triphasic. Waking-active neurons characterized by biphasic broad spikes were orexin-immunopositive, whereas those characterized by either biphasic narrow or triphasic broad spikes were orexin-immunonegative. Unlike waking-specific histamine neurons, all orexin and non-orexin waking-active neurons exhibited slow (<10 Hz) tonic discharges during wakefulness and ceased firing shortly after the onset of electroencephalogram (EEG) synchronization (deactivation), the EEG sign of sleep (drowsy state). They remained virtually silent during slow-wave sleep, but displayed transient discharges during paradoxical (or rapid eye movement) sleep. During the transition from sleep to wakefulness, both orexin and triphasic non-orexin neurons fired in clusters prior to the onset of EEG activation, the EEG sign of wakefulness, and responded with a short latency to an arousing sound stimulus given during sleep. In contrast, the biphasic narrow non-orexin neurons fired in single spikes either prior to, or after, EEG activation during the same transition and responded to the stimulus with a longer latency. The activity of all waking-active neurons preceded the return of muscle tonus at the transition from paradoxical sleep to wakefulness. These data support the view that the activity of orexin and non-orexin waking-active neurons in the posterior hypothalamus plays an important wake-promoting role and that their activity antagonizes cortical deactivation and loss of muscle tone.
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Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neurônios/fisiologia , Neuropeptídeos/metabolismo , Sono/fisiologia , Vigília/fisiologia , Animais , Sincronização Cortical , Eletroencefalografia , Eletromiografia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tono Muscular/fisiologia , Orexinas , Técnicas de Patch-ClampRESUMO
Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.
Assuntos
Agonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Piperidinas/farmacologia , Receptores Histamínicos H3/efeitos dos fármacos , Acetilcolina/metabolismo , Animais , Gatos , Dopamina/metabolismo , Eletroencefalografia/efeitos dos fármacos , Cobaias , Liberação de Histamina/efeitos dos fármacos , Humanos , Imidazóis/metabolismo , Masculino , Metilistaminas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Piperidinas/farmacocinética , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Receptores Histamínicos H3/fisiologia , Escopolamina/farmacologiaRESUMO
Hippocampal ripple oscillations (140-200 Hz) are believed to be critically involved in the consolidation of memory traces during slow-wave sleep (SWS). We investigated the temporal pattern of ripple occurrence in relation to sleep phases following different types of waking. Amphetamine, the atypical wakening drug modafinil or non-pharmacological sleep deprivation lead to an increased ripple occurrence ("rebound") during the subsequent SWS episode. Waking of the same duration evoked by amphetamine or sleep deprivation led to a ripple rebound of similar extent (approximately 200%). The mean intraripple frequency was also elevated by up to 20 Hz during SWS following all treatments. Ripple amplitude was significantly increased only in experiments with amphetamine. Ripple occurrence but not intraripple frequency clearly correlated with the antecedent waking duration independent of treatment. Recovery of ripple occurrence and frequency to the pretreatment level during SWS depended on SWS duration. At the end of the recovery period paradoxical sleep (PS) acted like waking, elevating ripple occurrence during subsequent SWS episodes. On the other hand, PS decreased ripple occurrence if recovery from the rebound was not yet complete. Thus occurrence and structure of ripple oscillations are regulated by the timing and duration of previous SWS, PS and waking episodes.
Assuntos
Potenciais Evocados/fisiologia , Ventilação de Alta Frequência , Hipocampo/fisiologia , Sono/fisiologia , Vigília/fisiologia , Anfetamina/farmacologia , Animais , Compostos Benzidrílicos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Eletroencefalografia/métodos , Eletromiografia/métodos , Potenciais Evocados/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Modafinila , Ratos , Ratos Wistar , Privação do Sono , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to elucidate the role and identity of cytokines involved in febrile non-haemolytic red cell transfusion reactions (FNHTRs). MATERIALS AND METHODS: Eighty-one patients experiencing transfusion reactions after receiving packed red blood cells (RBCs) were divided into three groups, as follows, based on the reaction experienced: FNHTRs (n = 60); chills without fever (n = 8); and allergic reaction with urticaria (n = 13). The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumour necrosis factor (TNF)-alpha were measured in the packed transfused unit and patients' plasma by using enzyme immunoassays. Wilcoxon's matched-pairs signed test was used to compare the difference in cytokine levels in patients' plasma before and after transfusion. The Kruskal-Wallis test was used first, followed by the Mann-Whitney test, to compare the pretransfusion cytokine levels in patients' plasma between groups and to compare the cytokine levels in packed RBCs transfused to each group of patients. RESULTS: The age of the implicated packed RBC was 11.5 +/- 5.7 days. Significant increases were observed in IL-6 (P < 0.001) and IL-8 (P < 0.001) patients' plasma levels, but not in IL-1beta or TNF-alpha levels, in those patients exhibiting FNHTR. No changes were observed in the patients' plasma samples of the other groups. Cytokine levels in the RBC concentrate supernatants were not appreciably elevated. CONCLUSIONS: Transfusion of packed RBCs may significantly increase intravascular levels of IL-6 and IL-8 in patients with FNHTRs.
Assuntos
Citocinas/metabolismo , Transfusão de Eritrócitos/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Preservação de Sangue , Criança , Feminino , Febre , Humanos , Interleucina-6/sangue , Interleucina-6/metabolismo , Interleucina-8/sangue , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Manejo de EspécimesRESUMO
We show that plane wave ultrasoft pseudopotential methods readily extend to the calculation of the structural properties of lanthanide and actinide containing compounds. This is demonstrated through a series of calculations performed on UO, UO2, UO3, U3O8, UC2, alpha-CeC2, CeB6, CeSe, CeO2, NdB6, TmOI, LaBi, LaTiO3, YbO, and elemental Lu.
RESUMO
The formation of colloidal silica particles and the dynamics of the nanostructure of the particles are investigated by small-angle X-ray scattering (SAXS) technique. Solute concentrations of 0.5 M tetraethylorthosilicate (TEOS), 1.1 or 2.2 M water (H2O), and 0.04 or 0.1 M ammonia base (NH3) in ethanol were used to obtain reaction conditions as close to those of the Stober method as possible and to have reaction kinetics that were slow enough to probe the changes in the nanostructure of the growing particles and to obtain good statistics from the SAXS measurements. We measured the changes in the radius of gyration and the fractal dimension as a function of time during growth. Remarkably, we find that, after an induction period, the first particles to appear in the solution have a radius of gyration of approximately 10 nm and are mass fractals characterized by their polymeric, open structure. This stage is followed by an intraparticle densification process and smoothing of the interface, leading to the usual compact nonfractal, stable structures. The growth models proposed so far cannot account for the observed continuous changes of stages during the formation and growth of the particles. Copyright 1997 Academic Press. Copyright 1997Academic Press