Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
N Engl J Med ; 381(2): 132-141, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31291515

RESUMO

BACKGROUND: Episodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache. METHODS: We enrolled patients who had at least one attack every other day, at least four total attacks, and no more than eight attacks per day during a baseline assessment, as well as a history of cluster headache periods lasting at least 6 weeks, and randomly assigned them to receive galcanezumab (at a dose of 300 mg) or placebo, administered subcutaneously at baseline and at 1 month. The primary end point was the mean change from baseline in the weekly frequency of cluster headache attacks across weeks 1 through 3 after receipt of the first dose. The key secondary end point was the percentage of patients who had a reduction from baseline of at least 50% in the weekly frequency of cluster headache attacks at week 3. Safety was also assessed. RESULTS: Recruitment was halted before the trial reached the planned sample size of 162 because too few volunteers met the eligibility criteria. Of 106 enrolled patients, 49 were randomly assigned to receive galcanezumab and 57 to receive placebo. The mean (±SD) number of cluster headache attacks per week in the baseline period was 17.8±10.1 in the galcanezumab group and 17.3±10.1 in the placebo group. The mean reduction in the weekly frequency of cluster headache attacks across weeks 1 through 3 was 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (difference, 3.5 attacks per week; 95% confidence interval, 0.2 to 6.7; P = 0.04). The percentage of patients who had a reduction of at least 50% in headache frequency at week 3 was 71% in the galcanezumab group and 53% in the placebo group. There were no substantial between-group differences in the incidence of adverse events, except that 8% of the patients in the galcanezumab group had injection-site pain. CONCLUSIONS: Galcanezumab administered subcutaneously at a dose of 300 mg once monthly reduced the weekly frequency of attacks of episodic cluster headache across weeks 1 through 3 after the initial injection, as compared with placebo. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT02397473.).


Assuntos
Analgésicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Cefaleia Histamínica/prevenção & controle , Adulto , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico
2.
Ocul Immunol Inflamm ; : 1-8, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31116624

RESUMO

Purpose: To evaluate the performance and speed of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) when identifying the pathogenic microorganism of endophthalmitis compared to conventional microbiological culturing. Methods: Forty-four patients with suspected endophthalmitis who had undergone vitrectomy were enrolled. Vitreous specimen was analyzed using either conventional culturing or MALDI-TOF MS. Results: The identification rates of the conventional microbiological culture and MALDI-TOF MS were 45.5% (20/44) and 65.9% (29/44), respectively (Kappa value 0.787, P < 0.000). The mean detection times by the standard culturing method and MALDI-TOF MS were 5.39 ± 0.56d and 3.17 ± 0.40d (P < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MALDI-TOF MS were 70.59%, 54.17%, 80.00%, and 86.67%, respectively. Polymicrobial endophthalmitis was identified in 6.82% of the patients (3/44) using conventional microbiological culturing. However, MALDI-TOF MS failed to identify any polymicrobial infection. Conclusions: With a higher sensitivity, acceptable specificity and a shorter detection time, MALDI-TOF MS was an efficient technique for the rapid identification of a pathogenic microorganism in endophthalmitis.

3.
ACS Nano ; 13(6): 6319-6329, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31091410

RESUMO

Micromotors have promising potential in applications ranging from environmental remediation to targeted drug delivery and noninvasive microsurgery. However, there are inadequacies in the fabrication of artificial micromotors to improve the design of structure and composition for motion performance and multifunctionality. Here, we present a microfluidic fiber-confined approach to creating droplet-templated micromotors with precisely engineered anisotropies in 3D structures and material compositions. The shape anisotropy comes from controllable deformation in droplet templates, and material anisotropy originates from versatile emulsion templates. Containing Pt and magnetic nanoparticles (NPs), micromotors are endowed with both catalytic propulsion and magnetic guidance, which are capable of performing tasks of precise catching, skillful delivering, and on-demand releasing of cargos. Droplet microfluidics allows us to systematically and independently vary the shape and size of micromotors and the distribution and content of NPs for the study of their influences on motors' mobility and improve the design. Our results are useful for fabricating micromotors with well-controlled morphology and composition that is beneficial to designing sophisticated microrobotic systems for real-world applications.

4.
Clin Infect Dis ; 67(suppl_2): S231-S240, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30423048

RESUMO

Background: Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited. Methods: From April 2017 to December 2017, 511 specimens were collected, and their retrospective diagnoses were classified into infectious disease (347 [67.9%]), noninfectious disease (119 [23.3%]), and unknown cases (45 [8.8%]). The diagnostic performance of pathogens was compared between mNGS and culture. The effect of antibiotic exposure on detection rate was also assessed. Results: The sensitivity and specificity of mNGS for diagnosing infectious disease were 50.7% and 85.7%, respectively, and these values outperformed those of culture, especially for Mycobacterium tuberculosis (odds ratio [OR], 4 [95% confidence interval {CI}, 1.7-10.8]; P < .01), viruses (mNGS only; P < .01), anaerobes (OR, ∞ [95% CI, 1.71-∞]; P < .01) and fungi (OR, 4.0 [95% CI, 1.6-10.3]; P < .01). Importantly, for mNGS-positive cases where the conventional method was inconclusive, 43 (61%) cases led to diagnosis modification, and 41 (58%) cases were not covered by empirical antibiotics. For cases where viruses were identified, broad-spectrum antibiotics were commonly administered (14/27), and 10 of 27 of these cases were suspected to be inappropriate. Interestingly, the sensitivity of mNGS was superior to that of culture (52.5% vs 34.2%; P < .01) in cases with, but not without, antibiotic exposure. Conclusions: mNGS could yield a higher sensitivity for pathogen identification and is less affected by prior antibiotic exposure, thereby emerging as a promising technology for detecting infectious diseases.

5.
J Pediatr Hematol Oncol ; 40(7): 499-503, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30044349

RESUMO

We evaluated psychometric properties (validity, reliability, and responsiveness) of a modified Faces Pain Scale-Revised (FPS-R) in 257 patients with sickle cell anemia (SCA) 7 to below 18 years old in a randomized, multinational clinical study. The modified FPS-R asks patients to report, by daily diary, their worst intraday SCA-related pain. Intraclass correlation coefficient assessed test-retest reliability between month 1 and month 2. Pearson correlations between monthly mean SCA-related pain intensity, activity interference score, analgesic use, and opioid use assessed convergent validity. Responsiveness was assessed with correlations of changes of monthly pain rate or intensity and changes in analgesic use or activity interference score from month 1 to month 9. Intraclass correlation coefficients for pain intensity and pain rate were 0.777 and 0.820, respectively, indicating agreement among stable patients. Moderate associations were shown between mean pain intensity and analgesic use (r=0.39) and opioid use (r=0.44), and between monthly pain rate and analgesic use (r=0.38). Moderate-to-large associations were observed between change in mean pain rate or intensity and changes in analgesic use (r=0.38 to 0.39, both P<0.001) and in activity interference scores (r=0.82 to 0.92, both P<0.001). These results support use of the modified FPS-R across cultures in children and adolescents aged 7 to below 18 years with SCA.

6.
Nat Commun ; 8(1): 1080, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-29057877

RESUMO

Large-scale and high-efficient water collection of microfibers with long-term durability still remains challenging. Here we present well-controlled, bioinspired spindle-knot microfibers with cavity knots (named cavity-microfiber), precisely fabricated via a simple gas-in-water microfluidic method, to address this challenge. The cavity-microfiber is endowed with unique surface roughness, mechanical strength, and long-term durability due to the design of cavity as well as polymer composition, thus enabling an outstanding performance of water collection. The maximum water volume collected on a single knot is almost 495 times than that of the knot on the cavity-microfiber. Moreover, the spider-web-like networks assembled controllably by cavity-microfibers demonstrate excellent large-scale and high-efficient water collection. To maximize the water-collecting capacity, nodes/intersections should be designed on the topology of the network as many as possible. Our light-weighted yet tough, low-cost microfibers with high efficiency in directional water transportation offers promising opportunities for large-scale water collection in water-deficient areas.

7.
Lab Chip ; 17(19): 3310-3317, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28861566

RESUMO

Existing approaches for droplet generation with an ultra-low interfacial tension using aqueous two-phase systems, ATPS, are either constricted by a narrow range of flow conditions using passive methods or subjected to complex chip fabrication with the integration of external components using active actuation. To address these issues, we present a simple approach to produce uniform ATPS droplets facilitated by oil-droplet choppers in microfluidics. Our solution counts on the synchronized formation of high-interfacial-tension oil-in-water and low-interfacial-tension water-in-water droplets, where the ATPS interface is distorted by oil droplets and decays into water-in-water droplets. In the synchronization regime, the size and generation frequency of ATPS droplets can be controlled independently by tuning the flow rates of the dispersed aqueous and oil phases, respectively. Our method demonstrates high uniformity of droplets (coefficient of variation between 0.75% and 2.45%), a wide range of available droplet size (droplet radius from 5 µm to 180 µm), and a maximum generation frequency of about 2.1 kHz that is nearly two orders of magnitude faster than that in existing methods. We develop theoretical models to precisely predict the minimum and maximum frequencies of droplet generation and the droplet size. The produced ATPS droplets and oil choppers are separated in the channel using density difference. Our method would boost emulsion-based biological applications such as cell encapsulation, biomolecule delivery, bioreactors, and biomaterials synthesis with ATPS droplets.

8.
Biosci Rep ; 37(5)2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-28811358

RESUMO

Studies on elevated fasting insulin or insulin resistance (IR) and cardiovascular or all-cause mortality risk in non-diabetic individuals have yielded conflicting results. This meta-analysis aimed to evaluate the association of elevated fasting insulin levels or IR as defined by homeostasis model assessment of IR (HOMA-IR) with cardiovascular or all-cause mortality in non-diabetic adults. We searched for relevant studies in PubMed and Emabse databases until November 2016. Only prospective observational studies investigating the association of elevated fasting insulin levels or HOMA-IR with cardiovascular or all-cause mortality risk in non-diabetic adults were included. Risk ratio (RR) with its 95% confidence intervals (CIs) was pooled for the highest compared with the lowest category of fasting insulin levels or HOMA-IR. Seven articles involving 26976 non-diabetic adults were included. The pooled, adjusted RR of all-cause mortality comparing the highest with the lowest category was 1.13 (95% CI: 1.00-1.27; P=0.058) for fasting insulin levels and 1.34 (95% CI: 1.11-1.62; P=0.002) for HOMA-IR, respectively. When comparing the highest with the lowest category, the pooled adjusted RR of cardiovascular mortality was 2.11 (95% CI: 1.01-4.41; P=0.048) for HOMA-IR in two studies and 1.40 (95% CI: 0.49-3.96; P=0.526) for fasting insulin levels in one study. IR as measured by HOMA-IR but not fasting insulin appears to be independently associated with greater risk of cardiovascular or all-cause mortality in non-diabetic adults. However, the association of fasting insulin and HOMA-IR with cardiovascular mortality may be unreliable due to the small number of articles included.


Assuntos
Doenças Cardiovasculares/etiologia , Jejum , Resistência à Insulina , Insulina/sangue , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Homeostase , Humanos , Fatores de Risco
9.
Clin Trials ; 14(6): 563-571, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28743191

RESUMO

BACKGROUND/AIMS: Patients with sickle cell anemia can experience recurrent pain episodes, which affect quality of life. The reported prevalence of pain is higher in studies using patient diaries than in healthcare facility utilization data. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events was a multinational study that assessed the efficacy and safety of prasugrel in reducing the rate of vaso-occlusive events in children with sickle cell anemia (NCT01794000) and included an electronic patient-reported outcome diary to record pain occurrence. We aimed to capture diary completion rates and compliance in children who used the electronic patient-reported outcome diary during the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events study and examine factors contributing to diary completion rates and compliance. METHODS: Daily electronic patient-reported outcome diary data were collected for up to 9 months in Determining Effects of Platelet Inhibition on Vaso-Occlusive Events participants aged 4 to <18 years in Africa, the Americas, Europe, and the Middle East. The questionnaires were available in 11 languages/dialects for collecting subjective (pain intensity, activity interference) and objective (study drug use, analgesic use, school attendance) data. Pain intensity was measured using the Faces Pain Scale-Revised. Data were entered by participants or caregivers and transferred wirelessly each day to a central database. Diary completion rates were the number of daily diary entries divided by the total number of expected daily diary entries. Percentages of participants who were compliant with the diary (≥80% diary completion) were calculated. RESULTS: A total of 311 participants received a diary; 268 provided diary data through Month 9. Diary completion rates and compliance were high throughout the collection period and across all groups and regions, despite no games being included on the device. For subjective data, the overall completion rate was 94.4%, and 92.6% of participants were compliant. For objective data, the overall completion rate was 93.3%, and 89.7% of participants were compliant. Completion rates and compliance differed significantly by age and region and were higher for 4 to <12 year olds and very much higher for participants from Africa and the Middle East. Caregivers almost always entered data for participants <6 years and rarely entered data for participants ≥12 years. Comparing participant-entered and caregiver-entered data, pain intensity score data were more consistent for 4 to <12 year olds than older children, but pain intensity scores for older children were higher when entered by caregivers. CONCLUSION: With appropriate design, participant training, and sufficient monitoring, an electronic patient-reported outcome diary can capture daily sickle cell-related pain data in large multinational studies. Providing a mechanism for caregiver reporting is particularly valuable for participants <6 years and may also facilitate compliance in older children who experience high levels of pain.


Assuntos
Anemia Falciforme/complicações , Medição da Dor/métodos , Dor/epidemiologia , Cooperação do Paciente/estatística & dados numéricos , Qualidade de Vida , Autorrelato/estatística & dados numéricos , Adolescente , África , Fatores Etários , Cuidadores/estatística & dados numéricos , Criança , Pré-Escolar , Computadores de Mão , Europa (Continente) , Feminino , Humanos , Masculino , Oriente Médio , Dor/etiologia , Método Simples-Cego , Estados Unidos
10.
Clin Chem ; 63(7): 1214-1226, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28515099

RESUMO

BACKGROUND: There are conflicting data on whether changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) concentrations between time points (delta NT-proBNP and hs-CRP) are associated with a change in prognosis. METHODS: We measured NT-proBNP and hs-CRP at 3 time points in 1665 patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Cox proportional hazards was applied to the delta between temporal measurements to determine the continuous association with cardiovascular events. Effect estimates for delta NT-proBNP and hs-CRP are presented per 40% increase as the basic unit of temporal change. RESULTS: Median NT-proBNP was 370.0 (25th, 75th percentiles, 130.0, 996.0), 340.0 (135.0, 875.0), and 267.0 (111.0, 684.0) ng/L; and median hs-CRP was 4.6 (1.7, 13.1), 1.9 (0.8, 4.5), and 1.8 (0.8, 4.4) mg/L at baseline, 30 days, and 6 months, respectively. The deltas between baseline and 6 months were the most prognostically informative. Every +40% increase of delta NT-proBNP (baseline to 6 months) was associated with a 14% greater risk of cardiovascular death (adjusted hazard ratio (HR) 1.14, 95% CI, 1.03-1.27) and with a 14% greater risk of all-cause death (adjusted HR 1.14, 95% CI, 1.04-1.26), while every +40% increase of delta hs-CRP (baseline to 6 months) was associated with a 9% greater risk of the composite end point (adjusted HR 1.09, 95% CI, 1.02-1.17) and a 10% greater risk of myocardial infarction (adjusted HR 1.10, 95%, CI 1.00-1.20). CONCLUSIONS: Temporal changes in NT-proBNP and hs-CRP are quantitatively associated with future cardiovascular events, supporting their role in dynamic risk stratification of NSTEACS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00699998.


Assuntos
Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Biomarcadores/análise , Infarto do Miocárdio/etiologia , Proteogenômica , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/genética , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Peptídeo Natriurético Encefálico/sangue , Fatores de Risco , Fatores de Tempo
11.
Thromb Haemost ; 117(3): 580-588, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-27929203

RESUMO

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8 ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.


Assuntos
Anemia Falciforme/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Monitoramento de Medicamentos/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Testes de Função Plaquetária , Testes Imediatos , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Doenças Vasculares/prevenção & controle , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Plaquetas/metabolismo , Criança , Pré-Escolar , Método Duplo-Cego , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Masculino , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos , Valor Preditivo dos Testes , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Doenças Vasculares/sangue , Doenças Vasculares/diagnóstico
12.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 34(2): 130-5, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27443002

RESUMO

OBJECTIVE: We explored the expressions of the Notch and Wnt signaling pathways and their significance in the repair process of alveolar bone defects by establishing animal models with a composite of autologous bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) to repair bone defects in the extraction sockets of rabbits. METHODS: A total of 36 two-month-old male New Zealand white rabbits were randomly divided into four groups, and the left mandibular incisors of all the rabbits were subjected to minimally invasive removalunder general anesthesia. BMSC-PRF compounds, single PRF, and single BMSC were implanted in Groups A, B, and C. No material was implanted in Group D (blank control). The animals were sacrificed at 4, 8 and 12 weeks after surgery, the bone defect was immediately drawn, and the bone specimens underwent surgery after four, eight, and twelve weeks, with three rabbits per time point. The expressions of Notch1 and Wnt3a in the repair process of the bone defect were measured via immunohistochemical and immunofluorescence detection. RESULTS: Immunohistochemistry showed that the expressions of Notch1 and Wnt3a in Groups A, B, and C were higher than that in Group D at the fourth and eighth week after operation (P<0.05). By contrast, the expressions of Notch1 and Wnt3a in Group D were higher than those in Groups A, B, and C at the twelfth week (P<0.05). Immunofluorescence showed that the expressions of both Notch1 and Wnt3a reached their peaks in the new bone cells of the bone defect after four weeks following surgery and gradually disappeared when the bone was repaired completely. CONCLUSION: Notch1 and Wnt3a signaling molecules are expressed in the process of repairing bone defects using BMSC-PRF composites and can accelerate the healing by regulating the proliferation and differentiation of BMSCs. Moreover, the expressions of Notch and Wnt are similar, and a crosstalk between them may exist it.


Assuntos
Enxerto de Osso Alveolar/métodos , Células da Medula Óssea/citologia , Transplante Ósseo/métodos , Fibrina/administração & dosagem , Transplante de Células-Tronco Mesenquimais/métodos , Receptor Notch1/metabolismo , Proteína Wnt3A/metabolismo , Animais , Plaquetas , Osso e Ossos/anormalidades , Diferenciação Celular , Masculino , Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Coelhos , Distribuição Aleatória , Engenharia Tecidual , Via de Sinalização Wnt , Cicatrização
13.
J Thromb Thrombolysis ; 42(3): 369-75, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27165280

RESUMO

UNLABELLED: Platelet P-selectin and activated glycoprotein IIb-IIIa (GPIIb-IIIa) are markers of platelet activation and mediates platelet aggregation. Prasugrel (Pras) 5 mg may be used in very elderly (VE) acute coronary syndrome (ACS) patients undergoing PCI, but its effect on platelet P-selectin and activated GPIIb-IIIa in those patients is not known. Stable ACS patients, VE (78 ± 5 years, n = 23) and non-elderly (NE) (55 ± 5 years, n = 22) were randomized to Pras (5 or 10 mg) or clopidogrel (Clop) 75 mg during three 12-day periods. Platelet activation markers were measured by flow cytometry on unstimulated or stimulated (adenosine diphosphate (ADP) 20 µM) platelets, before and after each dosing period. RESULTS: At baseline there was no difference in platelet activation markers, either unstimulated or ADP-stimulated, between NE and VE. Pras 5 mg reduced both ADP-stimulated platelet P-selectin and activated GPIIb-IIIa in VE (p < 0.01 for both analyses) and NE (p < 0.001 and p < 0.05, respectively). Clop 75 mg had a similar effect as Pras 5 mg but did not significantly reduce activated GPIIb-IIIa in VE. Prasugrel 10 mg resulted in decreased platelet activation in both age groups compared to Clop 75 mg (p < 0.01). CONCLUSIONS: In VE and NE-patients, Pras 5 mg inhibited platelet P-selectin expression similar to Clop 75 mg and Pras 10 mg. Prasugrel 10 mg inhibited platelet P-selectin expression better than Clop 75 mg. Prasugrel 10 mg and 5 mg, but not Clop 75 mg, significantly inhibited activated GPIIb-IIIa in VE. This platelet reactivity data support the use of Pras 5 mg for VE patients.


Assuntos
Selectina-P/antagonistas & inibidores , Ativação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Cloridrato de Prasugrel/farmacocinética , Síndrome Coronariana Aguda/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Doença da Artéria Coronariana/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Selectina-P/metabolismo , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/farmacocinética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/uso terapêutico , Ticlopidina/administração & dosagem , Ticlopidina/análogos & derivados , Ticlopidina/farmacocinética , Ticlopidina/uso terapêutico
14.
Chem Asian J ; 11(12): 1842-8, 2016 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-27123892

RESUMO

Two new quaternary thioarsenates(III), SrAg4 As2 S6 ⋅2 H2 O (1) and BaAgAsS3 (2), have been prepared through a hydrazine-hydrothermal method at low temperature. Compound 1 possesses a two-dimensional (2D) layer network, while compound 2 features a one-dimensional (1D) column structure. The detailed structure analysis indicates that Sr(2+) and Ba(2+) cations have different directing effects on the structures of thioarsenates(III). Both experimental and theoretical studies demonstrate that compounds 1 and 2 are narrow-gap semiconductors. Our success in synthesizing these two quaternary thioarsenates(III) proves that the hydrazine-hydrothermal technique is a powerful yet facile synthetic method for exploring new complex chalcogenides with diverse crystal structures and interesting physical properties.

15.
Pediatr Blood Cancer ; 63(2): 299-305, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26402148

RESUMO

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder characterized by painful vaso-occlusive crises (VOC) with limited treatment options, particularly for children. Emerging knowledge of the pathophysiology of SCD suggests antiplatelet therapies may hold promise for treatment of VOC. Multiple small studies have evaluated antiplatelet agents on the frequency of VOC with varying results, but there has not been an adequately powered study to definitively determine the effect of antiplatelet agents on VOC. Prasugrel, a third-generation thienopyridine that irreversibly inhibits platelet activation and aggregation, is approved in adults with acute coronary syndrome managed with percutaneous coronary intervention. PROCEDURE: Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) is a double-blind, randomized study with planned enrollment of >220 children from 14 countries across the Americas, Europe, Asia, and Africa, designed to test the hypothesis that prasugrel reduces the rate of VOC in children with sickle cell anemia (SCA) (homozygous hemoglobin S [HbSS] and hemoglobin Sß(0) thalassemia [HbSß(0)]). Secondary study endpoints include reductions in rate and intensity of vaso-occlusive pain as recorded in daily electronic diaries. Safety assessments include incidence of hemorrhagic events requiring medical intervention and treatment-emergent adverse events. DOVE incorporates a dose-titration strategy to reduce potential bleeding risks inherent with antiplatelet therapy while maintaining blinded treatment assignment. CONCLUSIONS: DOVE presents a unique opportunity to determine whether antiplatelet therapy reduces frequency of patient-reported VOC and daily vaso-occlusive pain in a global study of children with SCA.


Assuntos
Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Doenças Vasculares/prevenção & controle , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Dor/etiologia , Projetos de Pesquisa
16.
N Engl J Med ; 374(7): 625-35, 2016 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-26644172

RESUMO

BACKGROUND: Sickle cell anemia is an inherited blood disorder that is characterized by painful vaso-occlusive crises, for which there are few treatment options. Platelets mediate intercellular adhesion and thrombosis during vaso-occlusion in sickle cell anemia, which suggests a role for antiplatelet agents in modifying disease events. METHODS: Children and adolescents 2 through 17 years of age with sickle cell anemia were randomly assigned to receive oral prasugrel or placebo for 9 to 24 months. The primary end point was the rate of vaso-occlusive crisis, a composite of painful crisis or acute chest syndrome. The secondary end points were the rate of sickle cell-related pain and the intensity of pain, which were assessed daily with the use of pain diaries. RESULTS: A total of 341 patients underwent randomization at 51 sites in 13 countries across the Americas, Europe, Asia, and Africa. The rate of vaso-occlusive crisis events per person-year was 2.30 in the prasugrel group and 2.77 in the placebo group (rate ratio, 0.83; 95% confidence interval, 0.66 to 1.05; P=0.12). There were no significant differences between the groups in the secondary end points of diary-reported events. The safety end points, including the frequency of bleeding events requiring medical intervention, of hemorrhagic and nonhemorrhagic adverse events that occurred while patients were taking prasugrel or placebo, and of discontinuations due to prasugrel or placebo, did not differ significantly between the groups. CONCLUSIONS: Among children and adolescents with sickle cell anemia, the rate of vaso-occlusive crisis was not significantly lower among those who received prasugrel than among those who received placebo. There were no significant between-group differences in the safety findings. (Funded by Daiichi Sankyo and Eli Lilly; ClinicalTrials.gov number, NCT01794000.).


Assuntos
Síndrome Torácica Aguda/prevenção & controle , Anemia Falciforme/tratamento farmacológico , Dor/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Síndrome Torácica Aguda/etiologia , Administração Oral , Adolescente , Anemia Falciforme/complicações , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Dor/etiologia , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Cloridrato de Prasugrel/efeitos adversos
17.
Zhonghua Yi Xue Za Zhi ; 95(22): 1739-46, 2015 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-26704158

RESUMO

OBJECTIVE: To investigate the spectrum and antimicrobial resistance of major pathogensthat causing nosocomial infections in China, 2013. METHODS: Nosocomial cases as well as pathogens causing bloodstream infections (BSI), hospital-acquired pneumonia (HAP) and intra-abdominal infections (IAI) from 13 teaching hospital around China were collected. The minimum inhibitory concentrations (MICs) were determined by the agar dilution method. The CLSI M100-S23 criteria were used for interpretation. RESULTS: Of all cases, 1 022 cases were from BSI, 683 from HAP and 674 from IAI.Escherichia coli and Klebsiella pneumoniae were the most prevalent pathogens causing BSI and IAI while Acinetobacter baumanii (34.6%) and Pseudomonas aeruginosa were dominated in HAP. Tigecycline, imipenem and meropenem exhibited high potency against Enterobacteriaceae and the susceptibilities rates were 95.6%, 94.2%and 95.2% respectively. Enterobacteriaceae demonstrated high resistance against cephalosporins (52.3%) and fluoroquinolones (38.9%) but were susceptible to ß-lactam+inhibitor. Of all the Enterobacteriaceae, 30.5% were ESBLs positive and 4.3% were carbapenem resistant. Acinetobacter baumanii showed low susceptibilities to the microbial agents except for tigecycline (90.5%) and colistin (100%). The rate of carbapenem resistant Acinetobacter baumanii was 76.6%. Amikacin, ciprofloxacin, cefepime and piperacillin/tazobactam showed high antibacterial activity against Pseudomonas aeruginosa with susceptible rate 88.5%, 77.6%, 72.7% and 64.5% respectively. The resistant rate to imipenem and meropenem were 42.1% and 32.2%. All Staphylococcus aureus (166 strains) were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. MRSA accounted for 46.9% of all the Staphylococcus aureus. The prevalence of MRSA in IAI (55.2%) and HAP (54.4%) were higher that that in BSI (35.0%). No Enterococcus strains were found resistant to tigecycline, linezolid and daptomycin. VRE was found in Enterococcus faecium, accounting for 1.9% of all Enterococcus faecium strains. CONCLUSIONS: Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are the most common pathogens causing nosocomial infections. Nosocomial pathogens showed high susceptibilities against tigecycline. For ESBLs-producing Enterobacteriaceae strains, ß-lactam+Inhibitor show high antibacterial activities. Vancomycin, teicoplanin and linezolid exhibit high potency to Staphylococcus aureus and Enterococcus.


Assuntos
Infecção Hospitalar , Infecções Intra-Abdominais , Pneumonia , Antibacterianos , Bacteriemia , Carbapenêmicos , Cefepima , Cefalosporinas , China , Hospitais de Ensino , Humanos , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Tigeciclina , Vancomicina
18.
Chem Asian J ; 10(12): 2604-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26381694

RESUMO

Two novel porous three-dimensional (3D) quaternary thioantimonates(III) ACuSb2S4 (A = Rb, Cs) were successfully synthesized by employing the neutral surfactant PEG-400 (PEG = polyethyleneglycol) as reaction media, these are significantly different from the known quaternary A-Cu-Sb-S thioantimonates(III) with two-dimensional (2D) crystal structures. This is the first time that crystalline quaternary chalcogenides have been prepared in surfactant media. Both experimental and theoretical studies confirm they are semiconductors with narrow band gaps. Our results demonstrated that the surfactant-thermal strategy could offer a new opportunity to explore novel chalcogenides with diverse crystal structures and interesting physicochemical properties.

19.
Inorg Chem ; 54(18): 8931-6, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26331785

RESUMO

The two new quaternary thioantimonates(III) BaAgSbS3 (1) and BaAgSbS3·H2O (2) have been synthesized through a hydrazine-hydrothermal method at low temperature. Compound 1 possesses a two-dimensional (2D) layer structure, while compound 2 features a three-dimensional (3D) channel framework. The optical band gaps of 1 and 2 are approximately 2.2 and 2.4 eV, respectively. Our results clearly indicated that the hydrazine-hydrothermal method could offer exciting opportunities for exploring novel multinary chalcogenides with diverse crystal structures and interesting physical properties.

20.
Inflammation ; 38(5): 2007-16, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26059910

RESUMO

The present study aimed to determine the protective effects and the underlying mechanisms of astragalin (AG) on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Our study demonstrated that AG inhibited OVA-induced increases in eosinophil count; IL-4, IL-5, IL-13, and IgE were recovered in bronchoalveolar lavage fluid, and increased IFN-γ level in bronchoalveolar lavage fluid. Histological studies demonstrated that AG substantially inhibited OVA-induced eosinophilia in lung tissue. Western blot analysis demonstrated that AG treatments markedly inhibited OVA-induced SOCS-3 expression and enhancement of SOCS-5 expression in an asthma model. Our findings support the possible use of AG as a therapeutic drug for patients with allergic asthma.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/induzido quimicamente , Asma/tratamento farmacológico , Quempferóis/uso terapêutico , Animais , Asma/metabolismo , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/toxicidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA