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INTRODUCTION: The Framingham risk model estimates a person's 10-year cardiovascular disease (CVD) risk. This study used this model to calculate the changes in sex- and age-specific CVD risks in the Hong Kong Population Health Survey (PHS) 2014/15 compared with two previous surveys conducted during 2003 and 2005, namely, PHS 2003/2004 and Heart Health Survey (HHS) 2004/2005. METHODS: This study included individuals aged 30 to 74 years from PHS 2014/15 (n=1662; n=4 445 868 after population weighting) and PHS 2003/2004 and HHS 2004/2005 (n=818; n=3 495 074 after population weighting) with complete data for calculating the risk of CVD predicted by the Framingham model. Sex-specific CVD risks were calculated based on age, total cholesterol and high-density lipoprotein cholesterol levels, mean systolic blood pressure, smoking habit, diabetic status, and hypertension treatment. Mean sex- and age-specific CVD risks were calculated; differences in CVD risk between the two surveys were compared by independent t tests. RESULTS: The difference in 10-year CVD risk from 2003-2005 to 2014-2015 was not statistically significant (10.2% vs 10.6%; P=0.29). After age standardisation according to World Health Organization world standard population data, a small decrease in CVD risk was observed, from 9.4% in 2003-2005 to 8.8% in 2014-2015. Analysis according to age-group showed that more participants aged 65 to 74 years were considered high risk in 2003 to 2005 (2003-2005: 66.8% vs 2014-2015: 53.1%; P=0.028). This difference may be due to the decrease in smokers among men (2003-2005: 30.5% vs 2014-2015: 24.0%; P<0.001). CONCLUSION: From 2003-2005 to 2014-2015, there was a small decrease in age-standardised 10-year CVD risk. A holistic public health approach simultaneously targeting multiple risk factors is needed to achieve greater decreases in CVD risk.
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Doenças Cardiovasculares , Inquéritos Epidemiológicos , Humanos , Hong Kong/epidemiologia , Masculino , Pessoa de Meia-Idade , Feminino , Doenças Cardiovasculares/epidemiologia , Idoso , Adulto , Medição de Risco/métodos , Fatores de Risco de Doenças Cardíacas , Fatores de Risco , Fumar/epidemiologia , Fatores Etários , Hipertensão/epidemiologia , Fatores Sexuais , Pressão SanguíneaRESUMO
AIMS: There are many obstacles to overcome in the development of new drugs for metabolic diseases, including efficacy and toxicity problems in later stages of drug development. To overcome these problems and predict efficacy and toxicity in early stages, we constructed a new model of insulin resistance in terms of communication between 3T3-L1 adipocytes and RAW264.7 macrophages by three-dimensional (3D) culture. RESULTS: In this study, results focused on the functional resemblance between 3D co-culture of adipocytes and macrophages and adipose tissue in diabetic mice. The 3D mono-culture preadipocytes showed good cell viability and induced cell differentiation to adipocytes, without cell confluence or cell-cell contact and interaction. The 3D co-cultured preadipocytes with RAW264.7 macrophages induced greater insulin resistance than two-dimensional and 3D mono-cultured adipocytes. Additionally, we demonstrated that 3D co-culture model had functional metabolic similarity to adipose tissue in diabetic mice. We utilized this 3D co-culture system to screen PPARγ antagonists that might have potential as therapeutic agents for diabetes as demonstrated by an in vivo assay. CONCLUSION: This in vitro 3D co-culture system could serve as a next-generation platform to accelerate the development of therapeutics for metabolic diseases.
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Avaliação Pré-Clínica de Medicamentos/métodos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/patologia , PPAR gama/antagonistas & inibidores , Técnicas de Cultura de Tecidos/métodos , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Técnicas de Cocultura/métodos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Modelos Biológicos , Células RAW 264.7 , Alicerces TeciduaisRESUMO
This work examines the extent to which thermal boundary layer effects limit the performance of micromachined microphones. The acoustic impedance of the cavity formed by the microphone enclosure is calculated using both analytical and finite-element methods. A thermal correction to the cavity impedance is included to account for the transition of compression and expansion within the enclosure from adiabatic to isothermal when the thermal boundary layer that forms at the walls of the enclosure becomes large compared to the enclosure dimensions. The thermal correction to the cavity impedance contains a resistive term that results from thermal relaxation losses and contributes thermal-acoustic noise to the system. A lumped-element network model for the microphone response which includes the thermally corrected enclosure impedance is presented and compared to measured results for a case study device. The relative noise power contribution of each noise source considered in the model is calculated. It is shown that the noise due to the resistive term of the enclosure cavity impedance becomes significant when the enclosure volume is small. This sets a theoretical limit on the noise floor that can be achieved by a micromachined microphone with given enclosure dimensions.
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Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators ß-hexosaminidase (ß-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, ß-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.
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Displasia Broncopulmonar/patologia , Exossomos/metabolismo , Hiperóxia/patologia , Mastócitos/metabolismo , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/imunologia , Displasia Broncopulmonar/metabolismo , Células Cultivadas , Humanos , Hiperóxia/imunologia , Hiperóxia/metabolismo , Recém-Nascido , Pulmão/imunologia , Pulmão/patologia , Camundongos , Proteoma/metabolismo , Traqueia/metabolismoRESUMO
A novel device of smart pipette has been suggested to extract and deliver plasma from whole blood in a disposable format. By operating an on-chip disposable micropump, approximately 30 µL of plasma was obtained from 100 µL of whole blood within 5 min without any external equipment for point-of-care blood analysis.
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Separação Celular/instrumentação , Eritrócitos/citologia , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Plasma/química , Desenho de Equipamento , Humanos , Sistemas Automatizados de Assistência Junto ao LeitoRESUMO
STUDY DESIGN: A retrospective study. OBJECTIVE: To identify significant kinematic changes in the cervical spine after cervical artificial disk replacement (ADR) using prostheses with diverse designs. SUMMARY OF BACKGROUND DATA: Various types of artificial disks are used for cervical ADR. However, few clinical studies with a follow-up of 2 or more years have reported on the change in the curvatures and range of motion (ROM) of the cervical spine after cervical ADR in relation to different designs. METHODS: The cohort comprised 58 patients who underwent single-level cervical ADR for radiculopathy. The patients were divided into 4 groups according to the device they received: Mobi-C, Bryan, PCM, and Prestige LP. The radiographs of the cervical spine were obtained preoperatively and at 12, 24, and 36 months after surgery. Several kinematic parameters, including lordotic angles and ROM of the cervical spine, index level, and superior and inferior adjacent disk levels, were assessed preoperatively and at predefined follow-up time points. RESULTS: Cervical sagittal lordosis in patients who received Bryan and PCM prostheses increased at the last follow-up period. The 4 patient groups showed a trend toward an increase of lordosis in the superior adjacent segment with time. The patients who received the Bryan device lost their preoperative lordotic angle at the inferior adjacent level. The ROM of the cervical spine in patients who received Bryan and PCM prostheses increased at the last follow-up compared with preoperative values. The incidence of adjacent segment degeneration in the Mobi-C, Bryan, Prestige LP, and PCM groups were 14.2%, 25%, 9.0%, and 7.6%, respectively. CONCLUSIONS: These results suggest preservation of sagittal ROM and increased superior adjacent segment kinematics, regardless of prosthesis design. Devices with an unconstrained design may not be beneficial to adjacent segment kinematics compared with semiconstrained prostheses.
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Vértebras Cervicais/diagnóstico por imagem , Disco Intervertebral/cirurgia , Próteses e Implantes , Substituição Total de Disco/instrumentação , Adulto , Fenômenos Biomecânicos , Vértebras Cervicais/fisiopatologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lordose/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Radiografia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: To investigate longitudinal changes in retinal nerve fiber layer (RNFL) thickness after panretinal photocoagulation (PRP) in diabetic retinopathy patients. METHODS: This prospective study examined 31 eyes in 25 patients undergoing PRP, who were diagnosed with severe nonproliferative diabetic retinopathy or non-high-risk proliferative diabetic retinopathy. Optical coherence tomography was conducted before PRP and at 3, 6, 12, and 24 months after PRP to investigate changes in peripapillary RNFL thickness. RESULTS: Superior, nasal, inferior, temporal, and mean peripapillary RNFL thickness increased until 6 months after PRP and then decreased. Superior RNFL thickness increased significantly at 3 and 6 months and decreased significantly at 24 months compared with the baseline RNFL thickness. Nasal RNFL thickness declined significantly at 24 months compared with the baseline RNFL thickness without any significant increase in thickness during the follow-up period. Inferior RNFL thickness increased significantly at 6 months and decreased significantly at 24 months compared with its baseline RNFL thickness. Temporal thickness increased significantly at 3, 6, 12, and 24 months compared with the baseline RNFL thickness. Mean RNFL thickness increased significantly at 6 months and decreased significantly at 24 months. Central subfield thickness increased significantly at 3, 6, 12, and 24 months compared with its baseline thickness. CONCLUSION: Peripapillary RNFL thickness increased at 6 months after PRP and then decreased at 24 months after PRP compared with baseline peripapillary RNFL thickness in diabetic retinopathy patients. This finding suggests that in addition to diabetes itself, diabetic retinopathy, and associated glaucoma, PRP may be a cause of RNFL thickness loss in patients with diabetes.
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Retinopatia Diabética/cirurgia , Fotocoagulação a Laser , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Retinopatia Diabética/diagnóstico , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Lasers de Gás/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia de Coerência ÓpticaRESUMO
Campylobacter is a leading causing of bacterial foodborne and zoonotic illnesses in the USA. Pulsed-field gene electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST) have been historically used to differentiate sporadic from outbreak Campylobacter isolates. Whole genome sequencing (WGS) has been shown to provide superior resolution and concordance with epidemiological data when compared with PFGE and 7-gene MLST during outbreak investigations. In this study, we evaluated epidemiological concordance for high-quality SNP (hqSNP), core genome (cg)MLST and whole genome (wg)MLST to cluster or differentiate outbreak-associated and sporadic Campylobacter jejuni and Campylobacter coli isolates. Phylogenetic hqSNP, cgMLST and wgMLST analyses were also compared using Baker's gamma index (BGI) and cophenetic correlation coefficients. Pairwise distances comparing all three analysis methods were compared using linear regression models. Our results showed that 68/73 sporadic C. jejuni and C. coli isolates were differentiated from outbreak-associated isolates using all three methods. There was a high correlation between cgMLST and wgMLST analyses of the isolates; the BGI, cophenetic correlation coefficient, linear regression model R 2 and Pearson correlation coefficients were >0.90. The correlation was sometimes lower comparing hqSNP analysis to the MLST-based methods; the linear regression model R 2 and Pearson correlation coefficients were between 0.60 and 0.86, and the BGI and cophenetic correlation coefficient were between 0.63 and 0.86 for some outbreak isolates. We demonstrated that C. jejuni and C. coli isolates clustered in concordance with epidemiological data using WGS-based analysis methods. Discrepancies between allele and SNP-based approaches may reflect the differences between how genomic variation (SNPs and indels) are captured between the two methods. Since cgMLST examines allele differences in genes that are common in most isolates being compared, it is well suited to surveillance: searching large genomic databases for similar isolates is easily and efficiently done using allelic profiles. On the other hand, use of an hqSNP approach is much more computer intensive and not scalable to large sets of genomes. If further resolution between potential outbreak isolates is needed, wgMLST or hqSNP analysis can be used.
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Campylobacter coli , Campylobacter jejuni , Estados Unidos/epidemiologia , Tipagem de Sequências Multilocus , Campylobacter coli/genética , Filogenia , Surtos de DoençasRESUMO
Salmonella enterica is a leading cause of bacterial foodborne and zoonotic illnesses in the United States. For this study, we applied four different whole genome sequencing (WGS)-based subtyping methods: high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multilocus sequence typing using either all loci [wgMLST (all loci)] and only chromosome-associated loci [wgMLST (chrom)], and core genome multilocus sequence typing (cgMLST) to a dataset of isolate sequences from 9 well-characterized Salmonella outbreaks. For each outbreak, we evaluated the genomic and epidemiologic concordance between hqSNP and allele-based methods. We first compared pairwise genomic differences using all four methods. We observed discrepancies in allele difference ranges when using wgMLST (all loci), likely caused by inflated genetic variation due to loci found on plasmids and/or other mobile genetic elements in the accessory genome. Therefore, we excluded wgMLST (all loci) results from any further comparisons in the study. Then, we created linear regression models and phylogenetic tanglegrams using the remaining three methods. K-means analysis using the silhouette method was applied to compare the ability of the three methods to partition outbreak and sporadic isolate sequences. Our results showed that pairwise hqSNP differences had high concordance with cgMLST and wgMLST (chrom) allele differences. The slopes of the regressions for hqSNP vs. allele pairwise differences were 0.58 (cgMLST) and 0.74 [wgMLST (chrom)], and the slope of the regression was 0.77 for cgMLST vs. wgMLST (chrom) pairwise differences. Tanglegrams showed high clustering concordance between methods using two statistical measures, the Baker's gamma index (BGI) and cophenetic correlation coefficient (CCC), where 9/9 (100%) of outbreaks yielded BGI values ≥ 0.60 and CCCs were ≥ 0.97 across all nine outbreaks and all three methods. K-means analysis showed separation of outbreak and sporadic isolate groups with average silhouette widths ≥ 0.87 for outbreak groups and ≥ 0.16 for sporadic groups. This study demonstrates that Salmonella isolates clustered in concordance with epidemiologic data using three WGS-based subtyping methods and supports using cgMLST as the primary method for national surveillance of Salmonella outbreak clusters.
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Feed accounts for as much as 70% of beef production costs, and improvement of the efficiency with which animals convert feed to product has the potential to have substantial financial impact on the beef industry. The rumen microbiome plays a key role in determining feed efficiency; however, previous studies of rumen microbiota have not focused on protozoal communities despite the estimation that these organisms represent approximately 50% of rumen content biomass. Protozoal communities participate in the regulation of bacterial populations and nitrogen cycling-key aspects of microbiome dynamics. The present study focused on identifying potential associations of protozoal community profiles with feed efficiency. Weaned steers (n = 50) 7 months of age weighing approximately 260 kg were adapted to a growing ration and GrowSafe for 2 weeks prior to a 70-day feed efficiency trial. The GrowSafe system is a feeding system that monitors feed intake in real time. Body weights were collected on the first day and then every 7 days of the feed efficiency trial, and on the final day, approximately 50 mL of rumen content were collected via orogastric tubing and frozen at -80 °C. Body weight and feed intake were used to calculate residual feed intake (RFI) as a measure of feed efficiency, and steers were categorized as high (n = 14) or low (n = 10) RFI based on ±0.5 standard deviations about the mean RFI. Microbial DNA was extracted, and the eukaryotic component profiled by amplification and sequencing of 18S genes using degenerate primers that can amplify this locus across a range of protists. The taxonomy of protozoal sequences was assigned using QIIME 1.9 and analyzed using QIIME and SAS 9.4 with significance determined at α ≤ 0.05. Greater abundances of unassigned taxa were associated with high-RFI steers (p = 0.03), indicating a need for further study to identify component protozoal species. Differences were observed between low- and high-RFI steers in protozoal community phylogenetic diversity, including weighted beta-diversity (p = 0.04), Faith's phylogenetic diversity (p = 0.03), and observed Operational taxonomic unit (OTU) (p = 0.03). The unassigned taxa and differences in phylogenetic diversity of protozoal communities may contribute to divergences observed in feed efficiency phenotypes in beef steers.
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BACKGROUND AND AIM: Selective bile duct cannulation is a prerequisite for performing therapeutic endoscopic biliary intervention. This study aimed to evaluate if using a soft-tipped guidewire to cannulate the bile duct would increase the success rate of needle-knife fistulotomy for difficult bile duct access. METHODS: We reviewed sixty 60 patients with difficult bile duct access who underwent conventional cannulation with radiocontrast dye (29) or guidewire cannulation (31) after needle-knife fistulotomy. RESULTS: There were no significant differences in the demographic data between the two groups. The initial success rate of selective bile duct cannulation was significantly higher in the guidewire cannulation group compared with the conventional cannulation group: 100% versus 79.3%, P = 0.009. The success rate of selective biliary cannulation in the patients with non-dilated common bile duct (< 8 mm) was significantly higher in the guidewire cannulation group compared with the conventional cannulation group: 100% versus 68.4%, P = 0.003. The incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis was not significantly different between the two groups. No serious complications occurred in either group. CONCLUSIONS: In this retrospective and small case series, guidewire cannulation after needle-knife fistulotomy increased the success rate of selective bile duct cannulation in patients with difficult bile duct access.
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Ductos Biliares/cirurgia , Cateterismo , Colangiopancreatografia Retrógrada Endoscópica , Esfinterotomia Endoscópica , Idoso , Cateterismo/efeitos adversos , Cateterismo/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Meios de Contraste , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Punções , Estudos Retrospectivos , Esfinterotomia Endoscópica/efeitos adversos , Esfinterotomia Endoscópica/instrumentação , Resultado do TratamentoRESUMO
The objective of this study was to evaluate the ozone oxidation of dissolved heavy metals in an abandoned mine drainage (AMD) by conducting a pilot-scale operation at two different ozone doses of 7.5 and 24.0 g O(3)/h into an ozone reactor. A portion of the abandoned mine drainage near the Jungam Mine in Samchuck, Korea was pumped into this pilot-scale plant and used as an influent for the ozone oxidation. Some possible precipitates of metal oxides and hydroxides that resulted from the pilot-scale ozone oxidation of the dissolved Fe and Mn ions in the AMD (with a hydraulic retention time of 106 seconds in the ozone reactor) were effectively removed via sand filtration. A six-hour ozone oxidation with an ozone dose of 24.0 g O(3)/h and subsequent sand filtration, before backwashing the sand filter bed, can meet Korean drinking water quality standards (less than 0.3 mg/L) for Fe and Mn in the sand filter effluent under the operating conditions that were used in this study. The SO(4)(-2) concentrations and alkalinities of the influents were not affected by the ozone oxidation. The pH values of the influents were neutral or slightly alkaline, and after the six-hour oxidation, increased very slightly. These experiment results show that the ozone oxidation of dissolved heavy metals and the subsequent sand filtration of metal precipitates are desirable alternatives to removing heavy metals in an abandoned mine drainage.
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Resíduos Industriais/análise , Metais Pesados/química , Mineração , Ozônio , Eliminação de Resíduos Líquidos/métodos , Oxirredução , Projetos PilotoRESUMO
Hemangiomas are benign tumours that commonly develop in the skin, mucosal surfaces, and soft tissues. However, intranodal hemangiomas are extremely rare and are among the benign primary vascular abnormalities of the lymph nodes that include lymphangioma, hemangioendothelioma, angiomyomatous hamartoma and hemangiomas. The hemangioma in the pelvic lymph node has never been reported in the English literature. Herein, we described an extremely rare case of hemangioma in the pelvic lymph node, simulating a benign metastasizing leiomyoma.
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Hamartoma , Hemangioendotelioma , Hemangioma , Linfangioma , Humanos , LinfonodosRESUMO
BACKGROUND: Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) is associated with poor outcomes. However, the clinical features and risk factors of EHM of HCC after radiofrequency ablation (RFA) remain unclear. AIM: To elucidate the characteristics and risk factors of EHM after RFA for HCC. METHODS: From January 2008 to December 2017, we retrospectively enrolled 661 patients who underwent RFA as first-line treatment for HCC at 2 tertiary hospitals. The inclusion criteria were age ≥ 18 years, a diagnosis of HCC, and treatment-naivety. Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and alpha-fetoprotein measurements were routinely performed at 1 mo after RFA and followed-up at intervals of 3-6 mo. Univariate analyses were performed using the chi-squared test or Student's t-test, and univariate and multivariate analyses were performed via logistic regression, as appropriate. RESULTS: EHM was diagnosed in 44 patients (6.7%) during a median follow-up period of 1204 days. The 10-year cumulative rate of HCC recurrence and EHM was 92.7% and 33.7%, respectively. Initial recurrence was most often intrahepatic, and the rate of extrahepatic recurrence at initial recurrence was only 1.2%. The median time to the diagnosis of EHM was 2.68 years, and 68.2% of patients developed EHM within 2 years of the first recurrence, regardless of recurrence-free survival and 75.0% of patients developed EHM within 5 years after first recurrence. EHM was mostly diagnosed via abdominal CT/MRI in 33 (75.0%) and 38 of 44 patients (86.4%) with EHM had either positive abdominal CT scan results or serum AFP level elevation. In multivariate analysis, recurrence-free survival < 2 years, ablation zone/tumor size < 2, and alpha-fetoprotein level > 400 IU/mL were associated with a high EHM risk. CONCLUSION: EHM occurs following multiple intrahepatic recurrences after RFA and combined contrast-enhanced abdominal CT and serum AFP were useful for surveillance. Patients especially with high-risk factors require close follow-up for EHM.
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Carcinoma Hepatocelular , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Adolescente , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/efeitos adversos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Ablação por Radiofrequência/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment in patients with hepatocellular carcinoma (HCC). In the present study, we aimed to investigate the role of urea cream in the prevention of HFSR or amelioration of HFSR severity. PATIENTS AND METHODS: Patients with HCC were treated with either placebo cream or urea cream for 12 weeks concomitantly with sorafenib treatment. HFSR development, the Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire score, and adverse events were assessed at 2, 4, 8 and 12 weeks. RESULTS: Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analysed. The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance. In the incidence by time point, the incidence of severe HFSR of grade II or higher was significantly lower in the urea cream group than in the placebo control group at 2 weeks (13.8% versus 23.9%, P = 0.042). The urea cream group showed a significantly better HF-QoL questionnaire score than the placebo control group (11.8 versus 19.7, P = 0.014) at 12 weeks. CONCLUSIONS: Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03212625).
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Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Creme para a Pele/uso terapêutico , Dermatopatias/induzido quimicamente , Dermatopatias/tratamento farmacológico , Sorafenibe/efeitos adversos , Ureia/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Pele/efeitos dos fármacos , Sorafenibe/uso terapêuticoRESUMO
Detection of the low-frequency (LF; approximately 0.01 Hz) component of renal blood flow, which is theorized to reflect the action of a third renal autoregulatory mechanism, has been difficult due to its slow dynamics. In this work, we used three different experimental approaches to detect the presence of the LF component of renal autoregulation using normotensive and spontaneously hypertensive rats (SHR), both anesthetized and unanesthetized. The first experimental approach utilized a blood pressure forcing in the form of a chirp, an oscillating perturbation with linearly increasing frequency, to elicit responses from the LF autoregulatory component in anesthetized normotensive rats. The second experimental approach involved collection and analysis of spontaneous blood flow fluctuation data from anesthetized normotensive rats and SHR to search for evidence of the LF component in the form of either amplitude or frequency modulation of the myogenic and tubuloglomerular feedback mechanisms. The third experiment used telemetric recordings of arterial pressure and renal blood flow from normotensive rats and SHR for the same purpose. Our transfer function analysis of chirp signal data yielded a resonant peak centered at 0.01 Hz that is greater than 0 dB, with the transfer function gain attenuated to lower than 0 dB at lower frequencies, which is a hallmark of autoregulation. Analysis of the data from the second experiments detected the presence of approximately 0.01-Hz oscillations only with isoflurane, albeit at a weaker strength compared with telemetric recordings. With the third experimental approach, the strength of the LF component was significantly weaker in the SHR than in the normotensive rats. In summary, our detection via the amplitude modulation approach of interactions between the LF component and both tubuloglomerular feedback and the myogenic mechanism, with the LF component having an identical frequency to that of the resonant gain peak, provides evidence that 0.01-Hz oscillations may represent the third autoregulatory mechanism.
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Pressão Sanguínea/fisiologia , Homeostase/fisiologia , Rim/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Reologia/métodos , Algoritmos , Animais , Modelos Animais de Doenças , Retroalimentação/fisiologia , Hipertensão/fisiopatologia , Glomérulos Renais/fisiologia , Masculino , Músculo Liso Vascular/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Long-Evans , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To compare the effect of short-term calorie restriction (CR) on aging with that of already known long-term CR, the anti-inflammatory efficacy of 10-day CR was explored in aged rat kidney. TREATMENT: Two different age groups, 6 months (young) and 24 months (old) were used. In the old group, one sub-group was control, fed ad libitum (AL) and the other was fed CR for 10 days with 40 % of the food intake of the AL subgroup (n = 5). METHODS: Reactive species (RS), lipid peroxides and COX-2 activity were measured. The activities of proinflammatory transcription factors NF-kB and AP-1 were measured by electro-mobility shift assay (EMSA). Upstream signaling cascades of NF-kB and AP-1 as well as proinflammatory gene expression were detected by Western blot. RESULTS: 10-day CR suppressed RS, lipid peroxides, and COX-2 activity in aged rat kidney. CR also inhibited upstream signaling cascades and DNA binding activity of NF-kB and AP-1, and thioredoxin/Ref-1 pathway. CR blocked expression of NF-kB-and AP-1-responsive gene COX-2, iNOS, VCAM-1 and ICAM-1. CONCLUSIONS: We report for the first time that 10-day CR can attenuate the altered signaling transduction for inflammatory processes which is mediated through RS-induced NF-kB and AP-1 in aged kidney.
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Envelhecimento/fisiologia , Restrição Calórica , Inflamação/imunologia , Rim/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Dieta , Peroxidação de Lipídeos , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxirredução , Estresse Oxidativo , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Endogâmicos F344 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologiaRESUMO
In this work, a low-cost PDMS micro-pump and -valve have been designed and developed to control multiple reagents for enzyme-linked immunosorbent assay (ELISA) on a programmable lab-on-a-chip (LOC) platform. The micro pump and valves were precisely controlled by selectively pressurizing the PDMS channels and chamber to actuate the multiple reagents in a controlled manner. Selective pressurizing of the PDMS structures was initiated by a simple system that maneuvered a single roller bar operated by a programmed microprocessor. The performance of the micro-pump was fully characterized and a minimum fluid volume of 1 µL was controlled. Also, the on-chip microvalves were programmed to flow the multiple reagents to automatically process the multi-step ELISA procedures. By applying the proposed platform, 19.40 pg ml-1 cardiac troponin T (cTnT) was successfully detected on the LOC device by using multiple programmed valves as multiple steps of the enzyme-linked sandwich immunoassay. As a result, the developed micro-pump and -valve, which were successfully applied to actuate a series of solutions in a controlled manner, can be widely applied to lab-on-a-chip based bioassays.
Assuntos
Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/instrumentação , Equipamentos Descartáveis , Ensaio de Imunoadsorção Enzimática/instrumentação , Desenho de Equipamento , Limite de Detecção , Modelos Lineares , Microcomputadores , Reprodutibilidade dos TestesRESUMO
The activities of benzaldehyde isolated from Prunus persica seeds and of commercially available aldehydes against Tyrophagus putrescentiae (a stored-food mite) adults were examined and compared with those of the synthetic acaricides benzyl benzoate and N,N-diethyl-m-toluamide. On the basis of the 50% lethal dose (LD50), the compound most toxic to T. putrescentiae adults was salicylaldehyde (LD50 of 1.02 microg/cm2) followed by cinnamaldehyde (1.66 microg/cm2), benzaldehyde (4.23 microg/cm2), phthaldialdehyde (5.16 microg/cm2), benzyl benzoate (9.75 microg/cm2), and N,N-diethyl-m-toluamide (16.26 micorg/cm2). Benzaldehyde was about 2.3 and 3.8 times more toxic than benzyl benzoate and N,N-diethyl-m-toluamide, respectively, against T. putrescentiae adults. These results indicated that benzaldehyde isolated from P. persica seeds and the three aldehydes (cinnamaldehyde, salicylaldehyde, and phthaldialdehyde) are useful as lead compounds for developing acaricidal agents against T. putrescentiae adults. The color of the T. putrescentiae cuticle was changed by treatment with cinnamaldehyde, salicylaldehyde, and phthaldialdehyde.