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1.
Clin Exp Optom ; : 1-7, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37557167

RESUMEN

CLINICAL RELEVANCE: The decision to have a routine eye examination involves individual- and service-level judgement. A deeper understanding of patient access barriers and expectations could facilitate the design of better-aligned service models in optometric practice, improving the utilisation rate of an important facet of primary healthcare services. BACKGROUND: Routine eye examinations achieve several health objectives, including mitigation of sight-threatening risk factors. However, there are barriers to service uptake. Through the qualitative approach, a deeper understanding of these barriers can be realised and enhanced strategies designed to improve the uptake of the routine eye examination. A qualitative study was conducted to identify the factors influencing the decision-making process of older adults to use the routine eye examination service. METHODS: This study was guided by the grounded theory approach. Participants were purposively recruited from six community elderly centres. Semi-structured interviews were conducted with 25 community-dwelling adults aged 65 years or above in Hong Kong. Data were transcribed and constant comparison techniques were used for data analysis. RESULTS: Difficulty in prioritising and including the routine eye examination in the existing health service utilisation was the central theme associated with its lower use. Four sub-themes were identified to explain this phenomenon: (1) previous health care service utilisation as a reference for judging primary eye care; (2) low perceived primary eye care service needs; (3) low perceived self-efficacy on routine eye care utilisation; (4) service expectations. CONCLUSION: Multiple modifiable factors influence decision-making by older adults, suggesting that their routine eye care seeking behaviour might be altered through behaviour change intervention. The context in which services are delivered requires further study, with a focus on exploring the factors influencing service experience and its subsequent impact on regular eye care seeking behaviour.

2.
Front Neurosci ; 17: 1109735, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36743805

RESUMEN

The decline of visual plasticity restricts the recovery of visual functions in adult amblyopia. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in treating adult amblyopia. However, the underlying mechanisms of rTMS on visual cortex plasticity remain unclear. In this study, we found that low-frequency rTMS reinstated the amplitude of visual evoked potentials, but did not influence the impaired depth perception of amblyopic rats. Furthermore, the expression of synaptic plasticity genes and the number of dendritic spines were significantly higher in amblyopic rats which received rTMS when compared with amblyopic rats which received sham stimulation, with reduced level of inhibition and perineuronal nets in visual cortex, as observed via molecular and histological investigations. The results provide further evidence that rTMS enhances functional recovery and visual plasticity in an adult amblyopic animal model.

3.
Clin Exp Optom ; 106(8): 905-910, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-36062754

RESUMEN

CLINICAL RELEVANCE: Understanding the impact of a health care voucher scheme and service access barriers could facilitate optometry service promotion to the older population. BACKGROUND: A voucher is one strategy to improve the utilisation of the different health care services available in the private sector. This study aims to explore how a health care voucher system for older people impacts utilisation of optometry services from the perspective of service users and service providers. METHODS: People aged 65 years or above were recruited to fill in a structured questionnaire studying the usage characteristics and access barriers of optometry services and the health care voucher. Views from the optometrists about the voucher scheme were collected by questionnaire. RESULTS: A total of 1156 valid questionnaires from eligible voucher users was collected. Results showed that 53.7% (621/1156) of participants had used optometry services within the past 2 years. Lack of familiarity with services provided, professional fees, and prices of spectacles were the main barriers to using optometry services. Of those participants who had used the voucher for optometry services previously, 80.4% (284/353) had an eye examination in the past 2 years. Among 389 optometrists who participated in the study, over 80% agreed that the voucher scheme improved awareness of major eye conditions and access to prescription spectacles when necessary. CONCLUSION: The health care voucher for older people improved access to optometry services. Access could be further improved by increasing price transparency of professional services and prescription spectacles. Responses from optometry service providers supported the view that the voucher scheme improved access to, and utilisation of, preventive care services.


Asunto(s)
Oftalmopatías , Optometristas , Optometría , Humanos , Anciano , Atención a la Salud , Encuestas y Cuestionarios , Accesibilidad a los Servicios de Salud
4.
BMC Geriatr ; 22(1): 711, 2022 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-36030213

RESUMEN

BACKGROUND: This study evaluated the real-world effectiveness and potential cost-effectiveness of a community-based vision care programme for the elderly population aged 60 years or above. METHODS: Data from a total of 8899 subjects participating in a community-based comprehensive vision care programme from 2015 to 2019 were analysed to evaluate the effectiveness of the programme in terms of the prevalence of distance visual impairment (VI), the change in the prevalence of distance VI after refractive error correction, and the types of ocular disorders suspected. Distance VI was defined as a) visual acuity (VA) worse than 6/18 in any eye (worse eye) and b) VA worse than 6/18 in the better eye. The cost-effectiveness from the funder's perspective was also estimated in terms of cost per distance VI avoided. RESULTS: Based on the presenting vision of the worse eye, the prevalence of distance VI was 39.1% (3482/8899, 95% CI: 38.1%-40.1%) and reduced to 13.8% (1227/8899, 95% CI: 13.1%-14.5%) based on best-corrected VA. Referenced to the presenting vision of the better eye, the prevalence of distance VI was 17.3% (1539/8899, 95% CI: 16.5%-18.1%) and decreased to 4.2% (373/8899, 95% CI: 3.8%-4.6%) with best optical correction. Uncorrected refractive error was the major cause of presenting distance VI. From the funder's perspective, the cost per distance VI case prevented was HK$1921 based on VA in the worse eye and HK$3715 based on the better eye. CONCLUSION: This community-based programme identified distance VI in the best eye of 17 out of every 100 subjects. With appropriate new or updated distance optical corrections, distance VI was reduced to about 4 in 100 subjects. Visual impairment in the elderly is common even in a relatively affluent city. A model of care which could minimise avoidable distance VI would bring benefits at individual and societal levels.


Asunto(s)
Errores de Refracción , Baja Visión , Anciano , Estudios Transversales , Humanos , Prevalencia , Trastornos de la Visión , Agudeza Visual
5.
Health Expect ; 24(4): 1242-1253, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33949749

RESUMEN

BACKGROUND: Financial incentive is increasingly used as a mean to promote preventive care utilization (PCU), but the current Elderly Health Care Voucher Scheme (EHCVS) in Hong Kong is ineffective for encouraging PCU. OBJECTIVE: To explore the older people's barriers to PCU and their views on financial incentive, including EHCVS, for improving private PCU. DESIGN AND SETTING: Focus-group discussions were conducted in community elderly centres located in five districts of Hong Kong. PARTICIPANTS: Community-dwelling older people aged 60 years or above. RESULTS: Lack of understanding about preventive care and low awareness of the need for preventive care were key factors for the low motivation for PCU. Uncertainty over the level of service fee charged and concerns over service quality hindered the choice of using the private service providers under the current EHCVS. Financial incentives specific for preventive care services were thought to be cues to actions and guides for service promotion. However, some flexibility in service coverage and a set time limit of the financial incentives were preferred to accommodate individual needs. CONCLUSIONS: Apart from promoting knowledge of preventive care, official monitoring for service fee and quality is important for empowering older people to choose private service providers for preventive care. Financial incentives for preventive care services should be more specific to cue service promotion and uptake of preventive care while maintaining flexibility to accommodate individual needs. PATIENT OR PUBLIC CONTRIBUTION: Participants were recruited using purposive sampling with the coordination of community elderly centres. Data were analysed using thematic coding.


Asunto(s)
Vida Independiente , Motivación , Anciano , Grupos Focales , Hong Kong , Humanos
6.
Acta Ophthalmol ; 99(7): e1027-e1040, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33665973

RESUMEN

PURPOSE: To evaluate the influence of 2.2 mm clear corneal incision (CCI) features in surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) after cataract surgery. METHODS: Right eyes of 92 subjects receiving 2.2 mm incision cataract surgery were involved. A total of 38 eyes were categorized as the intact incision group, and 54 eyes were the defective incision group. Pre- and postoperative (1 month and 6 months) corneal astigmatism and HOAs on anterior and posterior corneal surfaces, corneal volume, and corneal thickness (CT) were measured using Pentacam. The CCI features including incision length (IL), incision angles, distance from incision to central cornea (Dis-En/Ex), and CT at incision site were quantified using AS-OCT. RESULTS: The defective incision group showed shorter IL and larger incision angles [false discovery rate (FDR) - p < 0.05]. Changes in CT at incision site were more pronounced for the defective incision group (FDR - p < 0.05). Some SIA parameters were related to the certain specific CCI features, especially IL (FDR - p < 0.05). Both groups exhibited significant increased 6 mm posterior corneal tHOAs at 1 month (Bonferroni corrected - p < 0.01) and the defective incision group showed increased 6 mm posterior tHOAs at 6 months (Bonferroni corrected - p = 0.023). There were characteristic correlations between Zernike terms and CCI features including IL, CT, Dis-En/Ex, and incision angles at 1 month, especially over 6 mm zone. CONCLUSION: The CCI deformities can affect corneal recovery and induce more HOAs at 1 month postoperatively. Such effects became minor, but could persist until 6 months. The IL combined with Angle-En/Ex was important factor influencing CCI integrity and corneal optical quality.


Asunto(s)
Astigmatismo/etiología , Extracción de Catarata/efectos adversos , Córnea/diagnóstico por imagen , Topografía de la Córnea/métodos , Complicaciones Posoperatorias/epidemiología , Refracción Ocular/fisiología , Agudeza Visual , Anciano , Astigmatismo/epidemiología , Astigmatismo/fisiopatología , China/epidemiología , Córnea/cirugía , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
7.
Acta Ophthalmol ; 98(5): e649-e655, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32336042

RESUMEN

PURPOSE: The SARS-CoV-2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS-CoV-2 in a group of patients with COVID-19. METHOD: Fifty-six patients infected with SARS-CoV-2 were recruited as subjects. Relevant medical histories were obtained from the electronic medical record system. Ocular history and ocular symptoms data were obtained by communicating directly with the subjects. The Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ) were used to assess the anterior ocular surface condition before and after the onset of disease. RESULTS: Patients classified as severe COVID-19 cases were more likely to have hypertension compared to mild cases (p = 0.035). Of the 56 subjects, thirteen patients (23%) were infected in Wuhan, 32 patients (57%) were community-infected, 10 patients (18%) were unknown origin, 1 (2%) was a physician likely infected by a confirmed patient. Three patients wore face mask with precaution when contacting the confirmed patients. Fifteen (27%) had aggravated ocular symptoms, of which 6 (11%) had prodromal ocular symptoms before disease onset. The differences in mean scores of OSDI questionnaire and SEEQ between before and after onset of COVID-19 were all significant (p < 0.05 for both). CONCLUSIONS: Ocular symptoms are relatively common in COVID-19 disease and may appear just before the onset of respiratory symptoms. Our data provided the anecdotal evidences of transmission of SARS-CoV-2 via ocular surface.

8.
Commun Biol ; 3(1): 133, 2020 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-32193507

RESUMEN

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.


Asunto(s)
Longitud Axial del Ojo/patología , Córnea/patología , Topografía de la Córnea , Sitios Genéticos , Miopía/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico/genética , Bases de Datos Genéticas , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Miopía/etnología , Miopía/patología , Fenotipo , Refractometría , Medición de Riesgo , Factores de Riesgo , Población Blanca/genética
9.
J Cell Mol Med ; 24(7): 4341-4349, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32119762

RESUMEN

SARI (Suppressor of AP-1, regulated by IFN-ß) is known to play an important role in some systemic disease processes such an inflammatory conditions and cancer. We hypothesize that SARI may also play a role in ocular diseases involving inflammation and neovascularization. To explore our hypothesis, further, we investigated an endotoxin-induced uveitis (EIU) and experimental argon laser-induced choroidal neovascularization (CNV) model in SARI wild-type (SARIWT ) and SARI-deficient (SARI-/- ) mice. Through imaging, morphological and immunohistochemical (IHC) studies, we found that SARI deficiency exacerbated the growth of CNV. More VEGF-positive cells were presented in the retina of SARI-/- mice with CNV. Compared to SARIWT  mice, more inflammatory cells infiltrated the ocular anterior segment and posterior segments in SARI-/- mice with EIU. Collectively, the results point to a potential dual functional role of SARI in inflammatory ocular diseases, suggesting that SARI could be a potential therapy target for ocular inflammation and neovascularization.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Neovascularización Coroidal/genética , Inflamación/genética , Retina/metabolismo , Uveítis/genética , Animales , Neovascularización Coroidal/patología , Citocinas/genética , Modelos Animales de Enfermedad , Endotoxinas/toxicidad , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Láseres de Gas/efectos adversos , Ratones , Ratones Noqueados , Retina/patología , Retina/efectos de la radiación , Uveítis/inducido químicamente , Uveítis/patología , Factor A de Crecimiento Endotelial Vascular/genética
10.
Cont Lens Anterior Eye ; 43(2): 178-184, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31466907

RESUMEN

PURPOSE: To evaluate the risk factors associated with contamination of lens cases in a group of orthokeratology (ortho-k) lens wearers. METHOD: Ortho-k patients attending the Contact Lens Clinic of the Hospital were required to complete a checklist about their routine daily care and handling of lens cases. Their cases were then collected for analysis. Contamination was evaluated by determining the optical density (OD) of crystal violet stained biofilm present in the cases. OD values were divided into three groups, lower, middle, and upper tertiles, and associations between risk factors were determined by multivariate analysis. RESULTS: A total of 194 subjects were recruited. Twenty-five subjects used cylindrical lens cases (CC), 98 flat cases with ridges (FCR), and 71 flat cases without ridges (FC). FCRs were the most heavily contaminated and CC showed least contamination (FCR > FC, OR 2.16, CI 1.11-4.18, p =  0.023; FCR > CC, OR 8.86, CI 2.97-26.44, p <0.001; FC > CC, OR 2.33, CI 1.35-12.45, p =  0.013). Replacing lens cases monthly significantly reduced the risk of high contamination (OR 0.013, CI 0.06-0.30, p <  0.001), compared to those used for three months. Cases that were not rinsed (OR 3.44, CI 1.50-7.86, p =  0.003) or rinsed by other methods (OR 4.07, CI 1.67-9.92, p =  0.002) had significantly more contamination, compared to those rinsed with multipurpose solution. Lens cases, which were not dried (OR 11.36, CI 2.06-62.93, p =  0.005) or air-dried (OR 8.71, CI 1.16-65.56, p =  0.036), showed more contamination compared to those wiped with tissue daily. CONCLUSION: Case design (cylindrical), monthly replacement, daily rinsing with MPS, and wiping with tissue daily can effectively reduce biofilm formation in contact lens cases.


Asunto(s)
Soluciones para Lentes de Contacto/efectos adversos , Lentes de Contacto/efectos adversos , Contaminación de Equipos , Oftalmopatías/etiología , Adolescente , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Factores de Riesgo , Factores de Tiempo
11.
Sci Rep ; 9(1): 18165, 2019 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-31796800

RESUMEN

Myopia is the commonest eye disorder in the world. High myopes are predisposed to ocular pathologies. The vasoactive intestinal peptide receptor 2 (VIPR2) gene was identified as a myopia susceptibility locus by our group and another group. We continued to fine-map this locus. A case-control study was performed in 4 sequential stages with a total of 941 highly myopic subjects and 846 control subjects, all unrelated Chinese. Stage 1 experimentally genotyped 64.4% of the entire cohort for 152 single-nucleotide polymorphisms (SNPs) and Stage 2 the remaining subjects for 21 SNPs. Stage 3 combined the genotypes for 21 SNPs for the entire cohort, and identified one group of high-risk haplotypes and one group of protective haplotypes significantly associated with high myopia. Stage 4 imputed genotypes for variants in the VIPR2 region and identified two independent groups of variants: one group with high-risk minor alleles and another with protective minor alleles. Variants within each group were generally in strong linkage disequilibrium among themselves while high-risk variants were in linkage equilibrium with protective variants. Therefore, the VIPR2 locus seems to contain variants with opposite effects. This is the first study that has examined the genetic architecture of a myopia susceptibility locus in detail.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Miopía Degenerativa/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Tipo II del Péptido Intestinal Vasoactivo/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Genotipo , Haplotipos/genética , Humanos , Desequilibrio de Ligamiento/genética , Masculino
12.
BMJ Open ; 8(4): e019989, 2018 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-29654021

RESUMEN

OBJECTIVE: To assess the association between awareness of diabetic retinopathy (DR) and actual attendance for DR screening. DESIGN: Cross-sectional study. SETTING: Two public general outpatient clinics. PARTICIPANTS: The subjects were people with diabetes mellitus (DM) who participated in a randomised controlled trial, set up in 2008, to test the impact of a copayment on attendance for DR screening. PRIMARY AND SECONDARY OUTCOME MEASURES: The subjects' awareness of DR was evaluated using a structured questionnaire conducted via a telephone interview. The attendance for screening was from the actual attendance data. Association between awareness and attendance for screening was determined using multivariate logistic regression model and was reported as ORs. RESULTS: A total of 2593 participants completed the questionnaire. A total of 42.9% (1113/2593) said they would worry if they had any vision loss and 79.6% (2063/2593) knew that DM could cause blindness. Only 17.5% (453/2593) knew that treatment was available for DR and 11.5% (297/2593) knew that early DR could be asymptomatic. The importance of having a regular eye examination was acknowledged by 75.7% (1964/2593), but 34% (881/2593) did not know how frequently their eyes should be examined. Worry about vision loss (OR=1.72, P<0.001), awareness of the importance of regular eye examination (OR=1.83, P=0.002) and awareness of the frequency of eye examinations ('every year' (OR=2.64, P<0.001) or 'every 6 months' (OR=3.27, P<0.001)) were the most significant factors associated with attendance. CONCLUSIONS: Deficits in knowledge of DR and screening were found among subjects with DM, and three awareness factors were associated with attendance for screening. These factors could be targeted for future interventions.


Asunto(s)
Concienciación , Retinopatía Diabética , Conocimientos, Actitudes y Práctica en Salud , Cooperación del Paciente , Anciano , Estudios Transversales , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/terapia , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
13.
Biomed Res Int ; 2017: 3024156, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28884119

RESUMEN

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give Pasym values, and multiple comparisons were corrected by permutation test to give Pemp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63-0.90; Pemp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64-0.89; Pemp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.


Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Canales de Potasio KCNQ/genética , Miopía/genética , Adolescente , Adulto , Alelos , Pueblo Asiatico , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Miopía/patología , Polimorfismo de Nucleótido Simple/genética , Adulto Joven
14.
Pest Manag Sci ; 73(4): 752-760, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27414472

RESUMEN

BACKGROUND: The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism. RESULTS: Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pKa and increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog. CONCLUSIONS: Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism. © 2016 Society of Chemical Industry.


Asunto(s)
Clonidina/análogos & derivados , Clonidina/farmacología , Hemípteros/efectos de los fármacos , Insecticidas/farmacología , Animales , Áfidos/efectos de los fármacos , Áfidos/crecimiento & desarrollo , Hemípteros/crecimiento & desarrollo , Ninfa/efectos de los fármacos , Hojas de la Planta/fisiología , Pupa/efectos de los fármacos
15.
Pest Manag Sci ; 73(4): 761-773, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27414747

RESUMEN

BACKGROUND: Optimization studies on a high-throughput screening (HTS) hit led to the discovery of a series of N-(6-arylpyridazin-3-yl)amides with insecticidal activity. It was hypothesized that the isosteric replacement of the pyridazine ring with a 1,3,4-thiadiazole ring could lead to more potent biological activity and/or a broader sap-feeding pest spectrum. The resulting N-(5-aryl-1,3,4-thiadiazol-2-yl)amides were explored as a new class of insecticides. RESULTS: Several methods for 2-amino-1,3,4-thiadiazole synthesis were used for the preparation of key synthetic intermediates. Subsequent coupling to variously substituted carboxylic acid building blocks furnished the final targets, which were tested for insecticidal activity against susceptible strains of Aphis gossypii (Glover) (cotton aphid), Myzus persicae (Sulzer) (green peach aphid) and Bemisia tabaci (Gennadius) (sweetpotato whitefly). CONCLUSION: Structure-activity relationship (SAR) studies on both the amide tail and the aryl A-ring of novel N-(5-aryl-1,3,4-thiadiazol-2-yl)amides led to a new class of insecticidal molecules active against sap-feeding insect pests. © 2016 Society of Chemical Industry.


Asunto(s)
Hemípteros/efectos de los fármacos , Insecticidas/farmacología , Animales , Áfidos/efectos de los fármacos , Áfidos/crecimiento & desarrollo , Hemípteros/crecimiento & desarrollo , Insecticidas/síntesis química , Ninfa/efectos de los fármacos , Relación Estructura-Actividad , Tiadiazoles/síntesis química , Tiadiazoles/farmacología
16.
Pest Manag Sci ; 73(4): 782-795, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27766752

RESUMEN

BACKGROUND: Optimization studies on compounds initially designed to be herbicides led to the discovery of a series of [6-(3-pyridyl)pyridazin-3-yl]amides exhibiting aphicidal properties. Systematic modifications of the amide moiety as well as the pyridine and pyridazine rings were carried out to determine if these changes could improve insecticidal potency. RESULTS: Structure-activity relationship (SAR) studies showed that changes to the pyridine and pyridazine rings generally resulted in a significant loss of insecticidal potency against green peach aphids [Myzus persicae (Sulzer)] and cotton aphids [(Aphis gossypii (Glover)]. However, replacement of the amide moiety with hydrazines, hydrazones, or hydrazides appeared to be tolerated, with small aliphatic substituents being especially potent. CONCLUSIONS: A series of aphicidal [6-(3-pyridyl)pyridazin-3-yl]amides were discovered as a result of random screening of compounds that were intially investigated as herbicides. Follow-up studies of the structure-activity relationship of these [6-(3-pyridyl)pyridazin-3-yl]amides showed that biosteric replacement of the amide moiety was widely tolerated suggesting that further opportunities for exploitation may exist for this new area of insecticidal chemistry. Insecticidal efficacy from the original hit, compound 1, to the efficacy of compound 14 produced greater than 10-fold potency improvement against Aphis gossypii and greater than 14-fold potency improvement against Myzus persicae. © 2016 Society of Chemical Industry.


Asunto(s)
Áfidos/efectos de los fármacos , Insecticidas/síntesis química , Insecticidas/farmacología , Amidas/síntesis química , Amidas/farmacología , Animales , Áfidos/crecimiento & desarrollo , Hidrazonas/síntesis química , Hidrazonas/farmacología , Ninfa/efectos de los fármacos , Piridazinas/síntesis química , Piridazinas/farmacología , Relación Estructura-Actividad
17.
Biochim Biophys Acta Gen Subj ; 1861(2): 335-353, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27888147

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) is a major method for studying the genetics of complex diseases. Finding all sequence variants to explain fully the aetiology of a disease is difficult because of their small effect sizes. To better explain disease mechanisms, pathway analysis is used to consolidate the effects of multiple variants, and hence increase the power of the study. While pathway analysis has previously been performed within GWAS only, it can now be extended to examining rare variants, other "-omics" and interaction data. SCOPE OF REVIEW: 1. Factors to consider in the choice of software for GWAS pathway analysis. 2. Examples of how pathway analysis is used to analyse rare variants, other "-omics" and interaction data. MAJOR CONCLUSIONS: To choose appropriate software tools, factors for consideration include covariate compatibility, null hypothesis, one- or two-step analysis required, curation method of gene sets, size of pathways, and size of flanking regions to define gene boundaries. For rare variants, analysis performance depends on consistency between assumed and actual effect distribution of variants. Integration of other "-omics" data and interaction can better explain gene functions. GENERAL SIGNIFICANCE: Pathway analysis methods will be more readily used for integration of multiple sources of data, and enable more accurate prediction of phenotypes.


Asunto(s)
Polimorfismo de Nucleótido Simple/genética , Transducción de Señal/genética , Estudio de Asociación del Genoma Completo/métodos , Humanos , Programas Informáticos
18.
Invest Ophthalmol Vis Sci ; 57(15): 6591-6595, 2016 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-27918833

RESUMEN

Purpose: Acanthamoeba keratitis (AK), which is associated with noncompliant use of contact lenses, remains difficult to treat due to delayed diagnosis and paucity of therapeutic agents. Although improvements in activity against Acanthamoeba infection have been achieved in disinfecting solutions for soft contact lenses, such modifications have not been extended to those for special rigid gas permeable (RGP) contact lenses, which are increasingly used for myopia control in children. Phytochemicals present in herbs used for traditional Chinese medicine may be effective as therapeutic or preventive agents. The purpose of this study was to investigate amoebicidal properties of lead phytochemicals of Radix scutellariae alone and in combination with multipurpose (disinfecting) solutions (MPS) for RGP lenses. Methods: Viability of Acanthamoeba castellani and A. polyphaga trophozoites was determined following exposure to four phytochemicals: baicalin, baicalein, wogonoside, and oroxylin A and both alone and in combination with four RGP MPS, using a modified stand-alone technique. Results: As individual agents, wogonoside and oroxylin A showed highest activity against A. castellani and A. polyphaga trophozoites, respectively. For both organisms, the combination of baicalein and oroxylin A was superior. Effectiveness of MPS alone did not exceed 0.27 log reduction, but addition of combined baicalein and oroxylin A resulted in 0.92 and 0.64 log reductions of A. castellani and A. polyphaga, respectively. Conclusions: The combination of baicalein and oroxylin A enhanced the activity of MPS for RGP contact lenses against trophozoites of two pathogens, A. castellani, and A. polyphaga, and offers a potential therapeutic and/or preventative agent for AK.


Asunto(s)
Queratitis por Acanthamoeba/prevención & control , Acanthamoeba/efectos de los fármacos , Lentes de Contacto Hidrofílicos/parasitología , Desinfectantes/farmacología , Desinfección/métodos , Plomo/farmacología , Fitoquímicos/farmacología , Queratitis por Acanthamoeba/parasitología , Animales , Antioxidantes/farmacología , Soluciones para Lentes de Contacto/farmacología , Flavanonas/farmacología , Flavonoides/farmacología , NAD(P)H Deshidrogenasa (Quinona)
20.
Cont Lens Anterior Eye ; 39(2): 128-32, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26421730

RESUMEN

BACKGROUND: Many herbs are used in traditional Chinese medicine TCM) for treatment of infections but their properties, in particular, their effects on normal cells have received little attention. This study investigated the cytotoxic properties of three TCM herbs with potential use in prevention and treatment of ocular infections, including Acanthamoeba keratitis. METHOD: The study investigated cytotoxic effects of the herbal extracts of Rhizoma coptidis, Radix scutellariae, and Cortex phellodendri on human corneal epithelial cells using trypan blue staining, MTT production, and flow cytometry. Differences between herbs were determined using repeated measures one-way analysis of variance, followed by paired t-tests where appropriate. RESULTS: These three herbs appeared to lack cytotoxicity when tested with trypan blue and MTT, but flow cytometry revealed that R. coptidis led to cell membrane damage. CONCLUSION: Lack of cytotoxicity of R. scutellariae and C. phellodendri extracts suggest that these are potentially suitable for use in ocular preparations. Only flow cytometry was able to accurately predict cytotoxic effects of extracts of TCM herbs on HCEC, demonstrating the importance of using a sensitive method of detection of cytotoxicity.


Asunto(s)
Coptis/química , Medicamentos Herbarios Chinos/toxicidad , Epitelio Corneal/efectos de los fármacos , Phellodendron/química , Extractos Vegetales/toxicidad , Scutellaria baicalensis/química , Anexina A5/metabolismo , Línea Celular , Supervivencia Celular , Colorantes , Epitelio Corneal/patología , Citometría de Flujo , Humanos , Medicina Tradicional China , Coloración y Etiquetado , Sales de Tetrazolio , Tiazoles , Pruebas de Toxicidad/métodos , Azul de Tripano
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