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1.
J Headache Pain ; 23(1): 90, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35896988

RESUMO

BACKGROUND: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia. METHODS: This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score. RESULTS: In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo). CONCLUSIONS: Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.


Assuntos
Transtornos de Enxaqueca , Qualidade de Vida , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Reação no Local da Injeção/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico , Resultado do Tratamento
2.
Chem Commun (Camb) ; 56(55): 7669-7672, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32520023

RESUMO

Photoinduced direct hydration of dipyridylacetylenes (DPAs) in acidic aqueous solution was achieved upon UV irradiation at room temperature. This is a catalyst-free reaction with moderate-to-good yields, and asymmetric dipyridylacetylenes afford the corresponding Markovnikov addition products.

3.
Org Biomol Chem ; 15(44): 9424-9432, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-29095466

RESUMO

Stereochemical models and mechanistic insights are proposed for [2t + 2i + 2i] annulations of thioketenes and imines on the basis of experimental and computational investigations. In the [2t + 2i + 2i] annulations involving cyclic imines, the zwitterionic intermediates generated from monosubstituted thioketenes and the cyclic imines undergo a stepwise nucleophilic endo-addition/Si-face attack pathway with a second imines molecule, giving initially (2,4)-cis-(4,5)-cis-[2t + 2i + 2i] annuladducts, which completely epimerize into the corresponding (2,4)-cis-(4,5)-trans-annuladducts under basic reaction conditions. The annuloselectivity of thio-Staudinger cycloadditions is dependent on the substituents of both thioketenes and imines. The reactivities and annuloselectivities of Staudinger, thio-Staudinger, and sulfa-Staudinger intermediates are compared.


Assuntos
Etilenos/química , Iminas/química , Cetonas/química , Enxofre/química , Ciclização , Reação de Cicloadição , Cinética , Modelos Moleculares , Conformação Molecular , Estereoisomerismo
4.
Org Biomol Chem ; 15(26): 5541-5548, 2017 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-28632259

RESUMO

The [2 + 2] cycloadditions of thioketenes and imines are named as thio-Staudinger cycloadditions. The diastereoselectivity in thio-Staudinger cycloaddtions of alkyl/alkenyl/aryl-substituted thioketenes is rationalized. The steric effects of the thioketenes play an extremely important role in deciding the diastereoselectivity (cis/trans selectivity) through controlling exo- and endo-attack and subsequent ring closure. The conclusion is further supported by our additional experimental and calculational results. The isomerization of the iminium moiety in zwitterionic intermediates generated from the thioketenes and linear imines also affects the diastereoselectivity. The electronic effect of imine substituents slightly impacts the diastereoselectivity, while epimerization of cis-ß-thiolactams to trans-diastereomers is a significant factor in the thio-Staudinger cycloadditions of mono-substituted thioketenes under basic conditions.

5.
J Org Chem ; 81(18): 8312-8, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27559925

RESUMO

We demonstrate the preparation of diacenaphthopentalene derivatives via a palladium-catalyzed dimerization of 1-iodo-2-arylethynyl-acenaphthylenes. The resulting 7,14-diarylpentaleno[1,2-a:4,5a']diacenaphthylenes, which contain four linearly fused five-membered rings, are benchtop stable and behave as hole-transporting or ambipolar semiconductors in organic field effect transistors. The X-ray crystal structure shows the important role of the fused naphthalene unit that enforces a formal pentalene subunit at the central five-membered rings and [5]-radialene-like structures at the proximal five-membered rings. Nucleus-independent chemical shift (NICS) calculations show the internal pentalene rings are intermediate in antiaromaticity character between known pentalene and dibenzopentalenes derivatives. The diacenaphthopentalene derivatives give high optical gap materials owing to a forbidden HOMO to LUMO transition, yet have narrow electrochemical gaps and are reduced at small negative potentials giving LUMO energy levels of -3.57 to -3.74 eV.

6.
J Atheroscler Thromb ; 22(10): 1061-70, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25958930

RESUMO

AIMS: Considering that cerebral infarction (CI) may share a common etiological basis with coronary artery disease (CAD), we evaluated six CAD-related single-nucleotide polymorphisms (SNPs) on 9p21 for investigating the effect of 9p21 on CI or carotid plaque in the Chinese Han population. METHODS: Altogether, 528 patients with noncardioembolic CI (375 with carotid plaque and 153 without carotid plaque) and 258 control subjects were genotyped. Six SNPs previously shown to be associated with CAD were sequenced and assessed for association with CI and carotid plaque using odds ratio (OR) and 95% confidence interval (CI) from logistic regression models. RESULTS: The G allele frequencies of rs2383206 (OR=1.472, p=0.021) and rs4977574 (OR=1.519, p=0.013) significantly increased in patients with CI without carotid plaque compared with middle-aged patients in the control group. The CI risk was higher among the GG genotype carriers than among GA + AA genotype carriers (OR=1.794, 95% CI=1.059-3.039, p=0.030 for rs2383206; OR=1.866, 95% CI=1.088-3.201, p=0.023 for rs4977574). In comparison with the non-GG genotype, the GG genotype of rs2383206 and rs4977574 combined had a 1.733-fold greater risk of CI in the middle-aged group. SNPs rs2383206 and rs4977574 were also associated with a risk of carotid plaque among patients with CI aged > 65 years (OR=2.329, p=0.018 and OR=1.997, p=0.049, respectively). Moreover, six SNPs were strongly correlated with linkage disequilibrium. CONCLUSIONS: Genetic variations of rs2383206 and rs4977574 on 9p21 are potentially associated with CI and carotid plaque in the Chinese Han population. Our results provide further evidence that the 9p21 region represents a major risk locus for cerebrovascular diseases.


Assuntos
Povo Asiático/genética , Doenças das Artérias Carótidas/genética , Infarto Cerebral/genética , Cromossomos Humanos Par 21/genética , Predisposição Genética para Doença , Placa Aterosclerótica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/etnologia , Infarto Cerebral/diagnóstico , Infarto Cerebral/etnologia , Feminino , Frequência do Gene , Haplótipos , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/etnologia , Fatores de Risco , Ultrassonografia Doppler
7.
Angew Chem Int Ed Engl ; 54(52): 15762-6, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26768696

RESUMO

A new class of stabilized pentacene derivatives with externally fused five-membered rings are prepared by means of a key palladium-catalyzed cyclopentannulation step. The target compounds are synthesized by chemical manipulation of a partially saturated 6,13-dibromopentacene precursor that can be fully aromatized in a final step through a DDQ-mediated dehydrogenation reaction (DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The new 1,2,8,9-tetraaryldicyclopenta[fg,qr]pentacene derivatives have narrow energy gaps of circa 1.2 eV and behave as strong electron acceptors with lowest unoccupied molecular orbital energies between -3.81 and -3.90 eV. Photodegradation studies reveal the new compounds are more photostable than 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pentacene).

8.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 3): o311, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24765012

RESUMO

The title compound, C30H32N4, was synthesized by the photodimerization of trans-4-{2-[4-(di-methyl-amino)-phen-yl]ethen-yl}pyridine in benzene upon irradiation with UV light. This photodimer has a puckered cyclo-butane ring with the four aryl substituents in an r-1,t-2,c-3,t conformation. The puckering angle of the cyclo-butane ring is 32.22 (7)°, which is the largest among reported tetra-aryl-substituted cyclo-butanes. In the crystal, the mol-ecules form a hollow, one-dimensional structure extending parallel to the c axis via two different pairs of C-H⋯π inter-actions.

9.
Dement Geriatr Cogn Disord ; 37(3-4): 223-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24193223

RESUMO

BACKGROUND/AIMS: As a suitable test to screen for Alzheimer's disease (AD) or mild cognitive impairment (MCI), studies to validate the Chinese version of Addenbrooke's Cognitive Examination-Revised (ACE-R) are rare. METHODS: A total of 151 subjects were recruited and the neuropsychological assessments were employed. One-way analysis of variance and Bonferroni correction were used to compare scores of different psychometric scales. Intraclass correlation coefficient (ICC) and Cronbach's coefficient α were used to evaluate the reliability of psychometric scales. The validity of ACE-R to screen for mild AD and amnestic subtype of MCI (a-MCI) was assessed by receiver operating characteristic (ROC) curves. RESULTS: The Chinese ACE-R had good reliability (inter-rater ICC = 0.994; test-retest ICC = 0.967) as well as reliable internal consistency (Cronbach's coefficient α = 0.859). With its cutoff of 67/68, the sensitivity (0.920) and specificity (0.857) were lower than for the Mini-Mental State Examination (MMSE) cutoff (sensitivity 1.000 and specificity 0.937) to screen for mild AD. However, the sensitivity of ACE-R to screen for a-MCI was superior to the MMSE with a cutoff of 85/86. The specificity of ACE-R was lower than that of the MMSE to screen for a-MCI. The area under the ROC curve of ACE-R was much larger than that of the MMSE (0.836 and 0.751) for detecting a-MCI rather than mild AD. CONCLUSION: The Chinese ACE-R is a reliable assessment tool for cognitive impairment. It is more sensitive and accurate in screening for a-MCI rather than for AD compared to the MMSE.


Assuntos
Doença de Alzheimer/diagnóstico , Povo Asiático/psicologia , Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/normas , Psicometria/normas , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Disfunção Cognitiva/psicologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
10.
J Alzheimers Dis ; 39(4): 891-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24321891

RESUMO

BACKGROUND: The prevalence of cognitive impairment (CI) and its associated risk factors among elderly peoples in China has been investigated. However, dynamic studies revealing the risk factors associated with cognitive decline from follow-up observations in China are rarely performed. OBJECTIVE: The present study aimed to identify factors predicting late-life cognitive decline in China. METHODS: Participants were 223 community-dwelling residents (≥65 years old) from the urban community of Shanghai with no CI upon comprehensive assessments at baseline. Cognitive decline at 2-year follow-up was defined as a drop of two or more points from baseline score in the Mini-Mental State Examination (MMSE). Associations with baseline demographic, lifestyle, health, and medical factors were then determined within the population. RESULTS: After 2 years, cognitive decline and incident CI developed in 75 (33.6%) and 25 (11.2%) participants, respectively. Across all participants, risk factors for cognitive decline included low education, high body mass index, and diabetes mellitus. Among participants with cognitive decline, points were predominantly lost in items relating to time orientation and complex commands in the MMSE. CONCLUSION: This study confirms the differences in risk factors between cross-sectional and longitudinal studies for cognitive decline among the elderly population in urban Shanghai. Interventions tailored to potential risk factors associated with cognitive decline may offer further benefits.


Assuntos
Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Características de Residência , População Urbana/tendências , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , China/epidemiologia , Transtornos Cognitivos/psicologia , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/psicologia , Escolaridade , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Fatores de Risco
11.
J Alzheimers Dis ; 36(2): 245-51, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23587747

RESUMO

BACKGROUND: Given the increasing prevalence of dementia, any intervention that can effectively slow the deterioration of cognitive function is of great importance. OBJECTIVE: This study investigated the efficacy of a human-computer interaction-based comprehensive cognitive training program in cognitively impaired elderly individuals living in a nursing home. METHODS: All subjects, who were aged ≥70 years and had cognitive impairment, were randomly allocated to an intervention group (n = 19) or a control group (n = 14). The intervention group received human-computer interaction-based comprehensive cognitive training for 24 weeks. Neuropsychological examinations were conducted before and after this period. The intervention group was subdivided into two groups according to the scores of global cortical atrophy (GCA) to evaluate the impact of training effectiveness on GCA. RESULTS: After 24 weeks, neither group showed a significant change compared with baseline cognitive examinations. However, there was a tendency for greater improvement in memory, language, and visuospatial abilities for the intervention group as compared with controls. Patients with mild cognitive impairment showed improvements in language and visuospatial capacity, while patients with dementia showed improvements in attention/orientation, memory, language, and fluency. However, none of these findings were statistically significant. The results for the intervention subgroups showed that visuospatial ability improvement was significantly greater among those with a global cortical atrophy score of ≤15 (p < 0.05). CONCLUSION: Human-computer interaction-based comprehensive training may improve cognitive functions among cognitively impaired elderly individuals. The training effect was most prominent among those with milder cerebral atrophy.


Assuntos
Envelhecimento , Disfunção Cognitiva/reabilitação , Compreensão/fisiologia , Terapia Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Atenção , Feminino , Humanos , Aprendizagem , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Casas de Saúde/estatística & dados numéricos , Percepção Espacial , Comportamento Verbal
12.
Transl Neurodegener ; 1(1): 22, 2012 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-23210893

RESUMO

OBJECTIVES: Our study aimed to investigate the prevalence of cognitive impairment(CI) and the associated risk factors among elderly people in Shanghai urban area, China. METHODS: A population-based survey was conducted among people aged 55 years or older in urban areas of Shanghai. Face-to-face interviews were carried out to collect information including demographic characteristics, medical history, and medication use, etc. The validated Chinese version of the Mini-Mental State Examination(MMSE) was used to screen subjects with CI, and the criteria of CI were adjusted for education levels. RESULTS: A total of 3,176 home-living residents (≥55 years old) were included in the study. Among them, 266 people (102 men and 164 women) were identified as cognition impaired, with a prevalence of 8.38% (266/3,176, 95% CI: (8.26, 8.49)) for both genders, 9.21% (102/1,107,95% CI: (9.18, 9.33)) for men and 7.93% (164/2,069, 95% CI: (7.80, 8.09)) for women, respectively. Furthermore, we found that several significant risk factors, including social factors(education, number of children, marriage status, and family structure), physiological factors (age, blood glucose level, and obesity), factors on living styles(physical exercise, diet & chronic diseases), and genetic factor(ApoE), associated with CI onset. CONCLUSIONS: This study confirms the high prevalence of CI among the elderly population in the Shanghai urban in China, similar to previous epidemiologic studies in Western countries. The putative risk factors associated with CI merit further investigated.

13.
Hum Genet ; 131(7): 1245-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22382309

RESUMO

CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD). One recent genome-wide association study has revealed that the rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A gene are associated with susceptibility to AD in Caucasians. To evaluate the relationship between the polymorphism of the CD33, MS4A6A gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to determine the prevalence of single-nucleotide polymorphism of two genes in patients with AD in Chinese population of Mainland, and clarified whether these polymorphisms are risk factors for AD. The prevalence of the allele (T) in the rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism of the MS4A6A gene was significantly different in AD patients and control subjects (P < 0.001, respectively), and the results were not influenced by age, gender, or APOE status. Our data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to AD risk in the Chinese Han population.


Assuntos
Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Povo Asiático/genética , Proteínas de Membrana/genética , Idoso , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico
14.
Chemphyschem ; 6(3): 481-6, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15799473

RESUMO

An ultrathin composite film containing anionic Ag-His complexes (His: L-Histidine) and oppositely charged BH-PPV was fabricated by means of the electrostatic layer-by-layer self-assembly technique. UV/Vis spectra showed a continuous deposition process of Ag-His complexes and BH-PPV. The film structure was characterized by using small-angle X-ray diffraction, AFM, and SEM. The nonlinear optical properties of the ultrathin film were studied by using the Z-scan technique with a laser duration of 8 ns at a wavelength of 532 nm. The film sample exhibited a strong nonlinear saturated absorption, with an alpha2 value of -3.9 x 10(-5) mW(-1) and a self-defocusing effect with an n2 value of -4.78 x 10 (-12) m2W(-1).

15.
J Am Chem Soc ; 127(4): 1120-1, 2005 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-15669849

RESUMO

In this contribution, large-area organic charge-transfer complex (AgTCNQ and CuTCNQ) nanowires were synthesized by organic vapor-solid-phase reaction at mild experimental conditions. These nanowires were facilitated on the surface of Cu and Ag foils or different kinds of substrates coated with a layer of silver and copper on a large scale. The excellent field emission properties were observed in the as-grown AgTCNQ and CuTCNQ nanowires. They should have great potential in vacuum device applications.

16.
J Org Chem ; 69(26): 9049-54, 2004 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-15609937

RESUMO

A class of bis-urea compounds with perylene bisimide was synthesized and characterized successfully. (1)H NMR and fluorescence spectra confirmed that strong hydrogen-bonding interactions between neighboring urea groups were formed. Interestingly, the photocurrent measurement showed that the self-assembled films of bis-urea compounds could produce steady and rapid anodic photocurrent responses. The TEM images indicated that well-defined nanoscale rods with uniform diameter distribution could be fabricated by self-assembly of hydrogen-bonding interactions and pi-pi stacking interactions of perylene rings.

17.
Chemphyschem ; 5(8): 1210-5, 2004 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-15446744

RESUMO

A supramolecular system of a perylene derivative containing bis(2,6-diacylaminopyridine) units and a perylene bisimide bound through three hydrogen-bonds was synthesized and characterized. 1H NMR spectra confirmed the existence of hydrogen-bonding interactions between the perylene derivative (3) and the perylene bisimide (7). The photocurrent generation of the self-assembled 3.7 film was measured, and a cathodic photocurrent response was obtained. SEM images indicated that well-defined long fibers could be fabricated by self-assembly, by exploiting the hydrogen bonding interactions and pi-pi stacking interactions of perylene rings.

18.
J Phys Chem B ; 108(20): 6256-60, 2004 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-18950109

RESUMO

A novel hydrogen-bonded supramolecular system of a [60]fullerene derivative with perylene bisimide was synthesized and characterized. 1H NMR spectra confirmed the existence of strong hydrogen-bonding interaction between compounds 1 and 5. Transmission electron microscopy images of 1.5 aggregates showed spherical particles having a mean diameter of 50 nm. The photocurrent response of the film was measured, and a steady and rapid anodic photocurrent response was obtained.

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