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1.
Eur J Pharmacol ; 872: 172978, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014487

RESUMO

Evidences from human and animal studies indicate that exposure to infection during early life act as a stressor to impair the hypothalamic-pituitary-adrenal (HPA) axis and may be one of the contributing factors of mental illness of later life. Several atypical antipsychotic drugs (AAPDs) proved to be effective in alleviating psychiatric illness through normalization of HPA axis. However, AAPD are least tried to evaluate their efficacy in modulation of HPA axis impaired under infection. The present study elucidated that the treatment with AAPD paliperidone (PAL: 0.025 mg/kg/bw and 0.05 mg/kg/bw) during periadolescence period (postnatal day 35- postnatal day 56) dose-dependently normalized the HPA axis of the female mice who were gestationally (gestational day 15 and 17) exposed to bacterial endotoxin lipopolysaccharide (LPS: 800 µg/kg/bw; intraperitoneally). The effectiveness of PAL treatment in counteracting the LPS induced hyperactivity of HPA axis was age-related, better observed at postnatal day 120 than at postnatal day 200. The PAL modulation of HPA axis reflected at different levels: inhibition of hypothalamic CRF expression and reduction in plasma levels of adrenocorticotropin and corticosterone. Histopathological alterations such as hypertrophy and/or hyperplasia in cortical zona fasciculata as well as medullary chromaffin cells of adrenal also normalized on PAL treatment. The comparatively long wash out period after drug treatment (postnatal day 57- postnatal day 200) along with age related hormonal imbalance could be correlated to less effectiveness of PAL on HPA axis at postnatal day 200. PAL modulation of HPA axis might be through maintenance of cytokines and reproductive axis homeostasis.

2.
Int J Biol Macromol ; 147: 177-186, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917989

RESUMO

Sphingosine kinase 1 (SphK1) is a lipid kinase which plays vital role in the regulation of varieties of biological processes including, cell growth, apoptosis and mitogenesis. In the present study, we investigated the guanidinium chloride (GdmCl)-induced denaturation of SphK1 at pH 8.0 and 25 °C using two different spectroscopic probes, i.e., mean residue ellipticity at 222 nm ([θ]222) and fluorescence emission maxima (λmax). A significant overlap between the transition curves obtained from both the spectral properties indicate that GdmCl-induced unfolding of SphK1 follows two-state process i.e., Native (N) â‡Œ Denatured (D) state. Interestingly, a visible protein aggregation was observed at low concentrations of GdmCl ([GdmCl] ≤ 1.5 M). The analysis of transition curves was done to estimate the thermodynamic parameters associated with the stability of SphK1. To complement our experimental findings, 100 ns molecular dynamics (MD) simulations were performed. Spectroscopic studies together with MD simulations provided mechanistic insights of unfolding pathway of SphK1 along with its stability parameters.

3.
Int J Biol Macromol ; 147: 768-777, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31982536

RESUMO

Pyruvate dehydrogenase kinase-3 (PDK3) plays important role in the glucose metabolism and is associated with cancer progression, and thus being considered as an attractive target for cancer therapy. In this study, we employed spectroscopic techniques to study the structural and conformational changes in the PDK3 at varying pH conditions ranging from pH 2.0 to 12.0. UV/Vis, fluorescence and circular dichroism spectroscopic measurements revealed that PDK3 maintains its native-like structure (both secondary and tertiary) in the alkaline conditions (pH 7.0-12.0). However, a significant loss in the structure was observed under acidic conditions (pH 2.0-6.0). The propensity of aggregate formation at pH 4.0 was estimated by thioflavin T fluorescence measurements. To further complement structural data, kinase activity assay was performed, and maximum activity of PDK3 was observed at pH 7.0-8.0 range; whereas, its activity was lost under acidic pH. To further see conformational changes at atomistic level we have performed all-atom molecular dynamics at different pH conditions for 150 ns. A well defined correlation was observed between experimental and computational studies. This work highlights the significance of structural dependence of pH for wide implications in protein-protein interaction, biological function and drug design procedures.

4.
Int J Biol Macromol ; 143: 472-482, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31778702

RESUMO

Point mutations in gene sequence often lead to protein misfolding or destabilization which is a well-known cause of a number of loss-of-function diseases. The carriers of point mutations in the human carbonic anhydrase II (HCAII) gene have been recognized to display carbonic anhydrase II deficiency syndrome (CADS). Two such single point mutations linked with CADS involve Gly145Arg and His94Tyr substitution. In the present study, we obtained these two single mutants of HCAII using site-directed mutagenesis, and successfully expressed and purified them. To examine the effect of mutations on the structure and function of HCAII, we carried out circular dichroism, intrinsic fluorescence, NMR measurements and activity assays. Studies suggest that the mutant proteins undergo local structural perturbations and have compromised native state stability. HCAIIH94Y (H94Y), being an active site mutant, shows larger destabilization effect as compared to HCAIIG145R (G145R). GdnHCl-denaturation studies showed that HCAII unfolding is a two-step process (N â‡Œ I â‡Œ U) and the free energy of first transition (N â‡Œ I) decreases by 1.5 kJ mol-1 and 4.9 kJ mol-1 for G145R and H94Y, respectively. Conformational changes and enzyme activity were established through various spectroscopic techniques.

5.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117453, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446356

RESUMO

Sphingosine kinase 1 (SphK1) catalyzes the conversion of sphingosine to sphingosine-1-phosphate that acts as a bioactive signalling molecule, and regulates various cellular processes including lymphocyte trafficking, angiogenesis and response to apoptotic stimuli. Abnormal expression of SphK1 has been observed in a wide range of cancers highlighting their role in tumour growth and metastasis. This enzyme also plays a critical role in metabolic and inflammatory diseases, including pulmonary fibrosis, diabetic neuropathy and Alzheimer's disease. In the present study, we have investigated the structural and conformational changes in SphK1 at varying pH using various spectroscopic techniques. Consistent results were observed with the function of SphK1 at corresponding pH values. SphK1 maintains its secondary and tertiary structure in the pH range of 7.5-10.0. However, protein aggregation was observed in the acidic pH range (4.0-6.5). At pH 2.0, the SphK1 exists in the molten-globule state. Kinase assay also shows that SphK1 activity was optimal in the pH range of 7.5-8.5. To complement in vitro results, we have performed 100 ns molecular dynamics simulation to examine the effect of pH on the structural stability of SphK1 at molecular level. SphK1 maintains its native conformation in the alkaline pH range with some residual fluctuations detected at acidic pH. A considerable correlation was noticed between spectroscopic, enzymatic activity and MD simulation studies. pH dependent structural changes can be further implicated to understand its association with disease condition, and cellular homeostasis with respect to protein function under variable pH conditions.

6.
Sci Rep ; 9(1): 18727, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822735

RESUMO

Sphingosine kinase 1 (SphK1) has recently gained attention as a potential drug target for its association with cancer and other inflammatory diseases. Here, we have investigated the binding affinity of dietary phytochemicals viz., ursolic acid, capsaicin, DL-α tocopherol acetate, quercetin, vanillin, citral, limonin and simvastatin with the SphK1. Docking studies revealed that all these compounds bind to the SphK1 with varying affinities. Fluorescence binding and isothermal titration calorimetric measurements suggested that quercetin and capsaicin bind to SphK1 with an excellent affinity, and significantly inhibits its activity with an admirable IC50 values. The binding mechanism of quercetin was assessed by docking and molecular dynamics simulation studies for 100 ns in detail. We found that quercetin acts as a lipid substrate competitive inhibitor, and it interacts with important residues of active-site pocket through hydrogen bonds and other non-covalent interactions. Quercetin forms a stable complex with SphK1 without inducing any significant conformational changes in the protein structure. In conclusion, we infer that quercetin and capsaicin provide a chemical scaffold to develop potent and selective inhibitors of SphK1 after required modifications for the clinical management of cancer.

7.
Popul Health Metr ; 17(1): 17, 2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806040

RESUMO

BACKGROUND: To explore the prevalence and determinants of unawareness of diabetes, hypertension and hypercholesterolemia and its association with poor disease control in a multi-ethnic Asian population without cardiovascular disease (CVD). METHODS: We included 6904 Chinese, Malay and Indian individuals (mean age [SD] 58.2 [10.2] years; 52.6% female) with diabetes, hypertension and/or hypercholesterolemia from the cross-sectional population-based Singapore Epidemiology of Eye Diseases study (2004-2011). Diabetes was defined as random blood glucose ≥ 11.1 mmol/L or HbA1c > 6.5% or self-reported use of diabetes medication; hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg or self-reported use of anti-hypertensive treatment; and hypercholesterolemia as total cholesterol ≥ 6.2 mmol/L or self-reported use of lipid-lowering medications. Unawareness was based on participants' answers to the questions: "Did your medical practitioner ever tell you that you have diabetes/hypertension/high cholesterol?" The determinants of unawareness, and its association with poor disease control, were assessed using multivariable binary logistic regression models adjusted for known potential confounders. RESULTS: Of the 2380 (34.5%), 5386 (78.0%) and 3607 (52.2%) with diabetes, hypertension and hypercholesterolemia, respectively, unawareness rates were 30.7%, 43.1% and 40.9%, respectively. Having a higher BMI, particularly if obese, and Malay ethnicity were associated with greater unawareness of diabetes; Malay and Indian ethnicities and current smoking with greater unawareness of hypertension; and education ≤6 years, current smoking, and blue collar jobs or unemployment with greater unawareness of hypercholesterolemia (all P < 0.05). Lack of awareness of each condition was independently associated with poorer disease control in the case of hypertension and hypercholesterolemia, while the converse was true for diabetes (all P < 0.05). CONCLUSIONS: Unawareness of diabetes, hypertension, or hypercholesterolemia is high in Singapore, with risk factors varying across all three diseases, although Malay ethnicity is a consistent one. Unawareness was also associated with poor management for hypertension and hypercholesterolemia. Public health education and screening programs should target at-risk individuals, especially Malays, to reduce the likelihood of incident CVD.

8.
Acta Ophthalmol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31833241

RESUMO

PURPOSE: To assess the repeatability of retinal vascular metrics using different postprocessing methods as obtained from the swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Thirty-two participants (63% males; mean [SD] age, 70 [7] years) underwent SS-OCTA imaging (PLEX® Elite 9000, Carl Zeiss Meditec, Inc., Dublin, USA). Each participant underwent 2 repeated scans of 2 scan protocols: a macular-centred 3 × 3-mm2 and a widefield 12 × 12-mm2 for a total of 4 acquisitions. Images of superficial vascular plexuses (SVP) and deep vascular plexuses (DVP) were processed using different filters to generate the perfusion density (PD) and vessel density (VD). Vessel enhancement filters ranged from vessel targeted (Hessian and Gabor filters), classical denoising (Gaussian filter), to a scale-selective adaption (modified Bayesian residual transform [MBRT]). Intra-session repeatability of the different filters and their correlation with the original data set were calculated with the intraclass correlation coefficient (ICC) and Pearson's r. RESULTS: Of the 32 eyes, 17 and 15 were right and left eyes, respectively. For 3 × 3-mm2 scans, both MBRT and Gabor filters yielded very good repeatable PD and VD (both ICCs > 0.87) values. Gabor filter was the most correlated with the original data set for the OCTA metrics (r = 0.95-0.97). For 12 × 12-mm2 scans, MBRT filter produced good-to-moderate ICC values for SVP (ICC>0.89) and DVP (ICC>0.73) metrics. Both the MBRT and Gabor filters were highly correlated with the original 12 × 12-mm2 scan data set (r = 0.96-0.98). The ICCs for the agreement between 3 × 3-mm2 and cropped 12 × 12-mm2 were high only for the PD values at the SVP layer and were poor for the VD at SVP and DVP measurements (ICC < 0.50). CONCLUSION: Our findings show that with the proper choice of postimaging processing methods, SS-OCTA metrics can be obtained with high repeatability, which supports its use in various clinical settings.

10.
Br J Ophthalmol ; 103(11): 1605-1609, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31645330

RESUMO

BACKGROUND/AIM: The relationship between diabetic retinopathy (DR) and cognitive impairment (CI) is unclear due to equivocal findings from cross-sectional studies and a lack of long-term data. In this population-based cohort study, we investigated the longitudinal association between the severity of DR and the incidence of CI. METHODS: 682 participants with diabetes, gradable retinal photographs and no CI at baseline 2004-2011) and complete relevant data at follow-up 2010-2016 from the Singapore Epidemiology of Eye Disease Study were included. CI was assessed using the validated Abbreviated Mental Test (AMT), defined as scores of ≤6 and ≤8 for those with 0-6 and >6 years of formal education, respectively. Six-year incident CI was defined as having no CI at baseline but present at the follow-up visit. RESULTS: Of the 682 included participants, 483 (70.8%) had no DR and 199 (29.2%) had any DR. Of those with DR, 142 (20.8%) had minimal/mild DR and 57 (8.4%) had moderate or worse DR at baseline. At the follow-up visit, 40 (5.9%) participants had incident CI based on AMT. In multivariate analysis compared with participants without DR, those with any DR had more than twofold increased odds of incident CI (OR (95% CI): 2.32 (1.07 to 5.03)). Participants with moderate or worse DR had threefold increased odds of developing CI (3.41 (1.06 to 11.00)), compared with those with no DR. CONCLUSIONS: DR, particularly at the more severe stages, is associated with increased risk of developing CI, independent of vision and other risk factors.

12.
JAMA Netw Open ; 2(9): e1910915, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539074

RESUMO

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (ß = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

13.
Sci Rep ; 9(1): 12634, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477766

RESUMO

The association between objective measures of body composition (BC) with type 2 diabetes (T2DM) is inconclusive. We conducted a systematic review and meta-analysis to examine the association between several body composition (BC) indices assessed using dual energy X-ray absorptiometry (DXA), and T2DM. Using PRISMA guidelines, we searched for observational studies investigating BC measures, including total body fat mass (BFM), visceral fat mass (VFM), subcutaneous fat mass (SFM), and fat free mass (FFM); and T2DM. Of 670 titles initially identified, 20 were included. High VFM was consistently associated with T2DM. For every kg increase in VFM, the odds of having T2DM increased by two-fold for males (OR 2.28 [95% CI 1.42 to 3.65], p = 0.001) and more than 4-fold for females (OR 4.24 [1.64 to 11.02], p = 0.003). The presence of T2DM was associated with 2-fold higher odds of low FFM (OR 2.38 [1.44 to 3.95]). We found evidence that greater VFM is a risk factor for prevalent and incident T2DM. While the presence of T2DM is associated with reduced FFM; the relationship between FFM and BFM with T2DM remains unclear. Reducing VFM and increasing FFM through lifestyle changes may reduce the risk of T2DM and mitigate its deleterious effect on BC, respectively.

14.
Med J Armed Forces India ; 75(3): 344-346, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31388242
15.
Biomed Pharmacother ; 118: 109245, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352240

RESUMO

Sphingosine kinase 1 (SphK1) is one of the central enzymes of sphingolipid metabolism whose high expression level is presumed to be correlated with cancer and other inflammatory diseases. Using a virtual screening approach and in vitro studies, we have identified the ellagic acid (EA), a dietary polyphenol, as a potent inhibitor of SphK1. Molecular docking study has suggested a strong binding affinity of EA to the SphK1. Fluorescence binding and isothermal titration calorimetry (ITC) measurements has also indicated an appreciable binding affinity. Kinase inhibition assay revealed an excellent inhibitory action of EA towards SphK1 (IC50 = 0.74 ±â€¯0.06 µM). Cell viability studies point towards the antiproliferative effects of EA on lung cancer cell line (A549) without affecting human embryonic kidney cells (HEK293). Binding and inhibition mechanism of EA was unveiled by docking analysis of SphK1-EA complex. EA binds to the SphK1 and forms several interactions with catalytically important residues of ATP-binding pocket. Structural stability and dynamics analysis of SphK1-EA complex during 100 ns molecular dynamic simulation studies suggested that EA forms a stable complex with SphK1 without inducing any significant conformational shift. Taken together, our study suggests that EA can be utilized as a chemical prototype to develop potent therapeutics targeting SphK1-associated pathologies.

16.
Int J Biol Macromol ; 136: 1076-1085, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31233792

RESUMO

Pyruvate dehydrogenase kinase 3 (PDK3) is a mitochondrial protein, has recently been considered as a potential pharmacological target for varying types of cancer. Here, we report the binding mechanism of quercetin to the PDK3 by using molecular docking, simulation, fluorescence spectroscopy and isothermal titration calorimetric assays. Molecular docking along with simulation provided an in-depth analysis of protein-ligand interactions. We have observed that quercetin interacts to the important residues of active site cavity of PDK3 and shows a well-ordered conformational fitting. The stability of quercetin-PDK3 complex is maintained by several non-covalent interactions throughout the simulation. To complement in silico findings with the experiments, we have successfully expressed and purified human PDK3. Both fluorescence and isothermal titration calorimetric experiments showed excellent binding affinity of quercetin to the PDK3. Kinase inhibition assay further revealed a significant inhibitory potential of quercetin to the PDK3 with the IC50 values in µM range. Quercetin is non-toxic to HEK293, and significantly inhibits the proliferation of cancer (HepG2 and A549) cell lines. All these observations clearly indicate that quercetin may be further evaluated as promising therapeutic molecule for PDK3 with required modifications and in vivo validation.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Quercetina/farmacologia , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Estrutura Secundária de Proteína/efeitos dos fármacos , /metabolismo , Quercetina/metabolismo
17.
Am J Ophthalmol ; 208: 226-233, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31103525

RESUMO

PURPOSE: We sought to determine the association of refractive error and its associated determinants (axial length [AL], anterior chamber depth, and corneal curvature) with the incidence and progression of diabetic retinopathy (DR). DESIGN: Population-based cohort study. METHODS: A total of 1562 eyes of 840 individuals with diabetes and gradable retinal photographs (mean age [SD], 57.0 [8.3] years, 48.2% female) from the Singapore Malay and Indian Eye Studies at baseline (2004-2009) and follow-up (2011-2015) examinations were included in the analyses. Refractive error was calculated as sphere plus half negative cylinder, while AL, anterior chamber depth, and corneal curvature were assessed using optical biometry. Incident DR was defined as having no baseline DR and any DR at follow-up; incident vision-threatening DR as no baseline vision-threatening DR but present at follow-up; and DR progression as an increase in severity at follow-up from at least minimal baseline DR. Eye-specific data and generalized estimating equation models were used to account for between-eye correlation to determine the relationships between the exposures and outcomes, adjusted for traditional DR risk factors. RESULTS: At follow-up, 164 of 1273 (12.9%) eyes had incident DR, 17 of 1542 (1.1%) eyes had incident vision-threatening DR, and 75 of 269 (27.9%) eyes with baseline DR experienced progression. A longer AL (per millimeter increase) (risk ratio 0.58 [95% confidence interval 0.38-0.88) was associated with a lower risk of incident DR. No other associations were found. CONCLUSION: Our findings show that a longer AL is protective of incident DR.

18.
Eur J Med Chem ; 176: 343-377, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31112894

RESUMO

α-Glucosidase enzyme inhibition is an effective therapeutic decorum in the treatment of type 2 diabetes mellitus. Since 1990, three α-glucosidase inhibitors are known to exist clinically, Acarbose, Voglibose and Miglitol. Side effects and long synthetic routes to access them forced the researchers to move their focus to discover simple and small heterocyclic motifs that work as promising α-glucosidase inhibitors and may eventually lead to the management of postprandial hyperglycemic condition in T2DM. In this regards, this review deals with recently discovered heterocyclic molecules that have been evaluated to exhibit inhibition of α-glucosidase enzyme.


Assuntos
Inibidores de Glicosídeo Hidrolases/química , Compostos Heterocíclicos/química , Animais , Linhagem Celular Tumoral , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/toxicidade , Compostos Heterocíclicos/metabolismo , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/toxicidade , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
19.
Qual Life Res ; 28(8): 2017-2039, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30879245

RESUMO

IMPORTANCE: Previous work has reported a link between diabetic retinopathy/diabetic macular edema (DR/DME) and psychosocial functioning, although the extent and direction of the association remains uncertain. OBJECTIVE: To determine the relationship between DR/DME and psychosocial functioning, the latter an umbrella term used to capture the emotional and social aspects of functioning which may include, for example, depression; depressive disorder; anxiety; vision-specific distress; diabetes-specific distress and emotional and social well-being. EVIDENCE REVIEW: PubMed, Embase, Medline and the Cochrane Central register were systematically searched for relevant interventional and observational quantitative studies using standardised criteria. Studies with DR/DME and psychosocial functioning as exposures or outcomes were accepted. Study quality was evaluated using the modified Newcastle-Ottawa scale for observational studies, and the modified Down's and Black checklist for interventional studies. FINDINGS: Of 1827 titles initially identified, 42 were included in the systematic review. They comprised of four interventions (one RCT, three non-RCTs) and 38 observational studies (33 cross sectional, five prospective). In studies with DR/DME as the exposure (n = 28), its severity and related vision impairment were consistently associated with poor psychosocial outcomes, mostly higher incidence of depression and depressive symptoms. Baseline depression and depressive symptoms were also associated with greater DR incidence and progression of DR. Medical intervention strategies showed significant improvement in psychosocial outcomes in patients with DR, such as significant improvements in mental health domain scores of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ 25). CONCLUSION AND RELEVANCE: Severity of DR, DME and associated vision loss are significantly associated with poor psychosocial outcomes. Aspects of depression and its symptoms show a bi-directional association, with increased incidence and progression of DR significant in those with baseline depression or depressive symptoms. Based on these findings, we propose two areas that may benefit from targeted interventions: (1) Prevention of development of poor psychological outcomes by preventing and delaying progression of DR/DME; and (2) Improved detection and management of poor psychological functioning by improving screening tools and multidisciplinary care for patients. Subsequent longitudinal studies can further help establish the underlying relationship between the two measures.


Assuntos
Retinopatia Diabética/epidemiologia , Retinopatia Diabética/psicologia , Edema Macular/epidemiologia , Edema Macular/psicologia , Qualidade de Vida/psicologia , Transtornos da Visão/psicologia , Ansiedade/psicologia , Estudos Transversais , Depressão/psicologia , Transtorno Depressivo/psicologia , Humanos , Incidência , Masculino , Saúde Mental , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
20.
Br J Ophthalmol ; 103(9): 1314-1319, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30361276

RESUMO

BACKGROUND/AIMS: To assess the independent impact of diabetic retinopathy (DR) on three domains of vision-related quality of life (VRQoL) in a Chinese Singapore population. METHODS: The Singapore Chinese Eye Study (n=3353; 2009-2011) was a population-based, prospective, cross-sectional study conducted at the Singapore Eye Research Institute. The study population included 292 adults with diabetes, with and without DR. DR (better eye) was categorised as presence and absence of any DR; severity of DR (no vision-threatening DR (VTDR); severe non-proliferative DR (NPDR); PDR and/or clinically significant macular oedema and VTDR). Our main outcome was VRQoL which was measured using Rasch-calibrated scores from the 'Reading', 'Mobility' and 'Emotional' domains of the Impact of Vision Impairment questionnaire. The relationship between DR and VRQoL was assessed using multiple linear regression models. RESULTS: Of the 292 individuals (mean age 61.35 ± 9.66 years; 55.8% male), 201 (68.8%), 49 (16.8%), 20 (6.8%), 22 (7.5%) and 27 (9.2%) had no DR, minimal-mild NPDR, moderate-severe NPDR, PDR and VTDR, respectively. Any DR and VTDR were independently associated with 6% and 12% worse Reading scores and 7% and 18% poorer Emotional well-being, respectively, compared with those without DR. These associations persisted after separate adjustment for visual impairment and presenting visual acuity. No significant difference was found in the Mobility domain between persons with and without DR. CONCLUSIONS: We documented that DR, particularly VTDR, was independently associated with restrictions in Reading and Emotional well-being. Understanding factors underlying the detrimental DR-VRQoL relationship may optimise rehabilitation outcomes for individuals with DR.

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