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1.
Psychiatry Clin Neurosci ; 78(10): 612-619, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39109557

RESUMO

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.


Assuntos
Hidrocortisona , Neuroticismo , Personalidade , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Neuroticismo/fisiologia , Masculino , Hidrocortisona/sangue , Feminino , Adulto , Pessoa de Meia-Idade , Personalidade/fisiologia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Seguimentos , Adulto Jovem
2.
Chemosphere ; 364: 143086, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39146990

RESUMO

The risk of chronic inflammatory diseases has been linked to exposure to polycyclic aromatic hydrocarbons (PAHs). However, limited data are available regarding their impact on periodontitis. This study aims to explore the association between PAHs and periodontitis while also evaluating the potential modifying effects of healthy lifestyles. We included 17,031 participants from the US National Health and Nutrition Examination Survey (NHANES, 2001-2004 and 2009-2014). A meta-analysis-based environment-wide association study (EWAS) was adopted to identify environmental chemicals for the mean probing pocket depth (PPD) and the mean attachment loss (AL). PAHs were further evaluated concerning the cross-sectional association with Mod/Sev periodontitis using multivariable logistic regression models. Moreover, healthy lifestyle scores were estimated to assess their modifying effect on the PAH-periodontitis association. EWAS analysis identified several urinary PAH metabolites as significant risk factors for the mean PPD and AL (false discovery rate <0.05, Q > 0.05). Periodontitis severity was positively associated with eight individual and total PAH concentrations. Stratifying the participants in terms of healthy lifestyle scores did not reveal any association in the healthy group. Moreover, the association weakened in never-smokers and individuals with sufficient physical activity and normal weight. PAH exposure was a risk factor for periodontitis. A healthier lifestyle was observed to offset the risk potentials of PAHs for periodontitis. Smoking cessation, physical activity, and weight loss might be recommended as a healthy lifestyle strategy for ameliorating PAH-related periodontitis.


Assuntos
Estilo de Vida Saudável , Periodontite , Hidrocarbonetos Policíclicos Aromáticos , Humanos , Hidrocarbonetos Policíclicos Aromáticos/análise , Periodontite/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Estudos Transversais , Inquéritos Nutricionais , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais
3.
Gac Sanit ; 38: 102408, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38941885

RESUMO

OBJECTIVE: To evaluate the modifying effect of social capital on the relationship between living in violent communities and the presence of psychological distress in adolescents and youth in Mexico. METHOD: The analysis of the Social Cohesion Survey for the Prevention of Violence and Crime (ECOPRED, by its acronym in Spanish) was conducted. The analytic sample consisted of 39,639 participants aged 12 to 29 years. Community violence and social capital were measured at the census tract level using the average answers of a household's head sample. These environmental variables were independent of the experiences of the participants. Social capital variables included structural (social ties, recreational participation, collaborative participation, and social cohesion), and cognitive (trust in neighbors) dimensions. Multilevel structural equation models were used. RESULTS: Recreational participation, collaborative participation, and social cohesion modified the relationship between community environments and psychological distress. In females who lived in places with less recreational participation or less social cohesion, the higher the social disorder, the higher the psychological distress. A similar relationship between vandalism and psychological distress was identified, but only in males who lived in places with less collaborative participation, and in females with less social cohesion. CONCLUSIONS: Our results suggest that dimensions of the structural social capital (organization and interest in the community and its members) were the ones that had the buffering effect of the exposure to disordered community environments on psychological distress.

4.
Rinsho Ketsueki ; 65(5): 375-384, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38825516

RESUMO

Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Some of these agents not only achieve hematologic complete response, reduce spleen size, and alleviate constitutional symptoms, but also induce molecular response, which means that they reduce the allele burden of driver gene mutations. These agents also prevent and alleviate fibrosis in bone marrow, which reduces the incidence of thrombotic events and disease progression and might improve prognosis. This article discusses the latest findings and promising treatments, including ongoing clinical trials, in PV, ET, and PMF.


Assuntos
Transtornos Mieloproliferativos , Humanos , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/terapia , Transtornos Mieloproliferativos/diagnóstico , Mutação , Terapia de Alvo Molecular
5.
Ter Arkh ; 95(12): 1141-1150, 2023 Dec 28.
Artigo em Russo | MEDLINE | ID: mdl-38785054

RESUMO

AIM: To evaluate the efficacy of Artneo (AN) in comparison with a combination of glucosamine hydrochloride and chondroitin sulfate (GC) in patients with osteoarthritis (OA) of the knee joint (KJ). MATERIALS AND METHODS: 70 patients with stages I-III of primary knee OA were randomized into 2 groups. Participants in the 1st (n=35) took AN 1 caps/day, in the 2nd (n=35) GC according to the standard regimen. After 7, 30, 90, 180 days, the Lequesne index (severity of OA), pain when moving according to VAS, WOMAC score were assessed, after 1, 3, 6 months - quality of life SF-36 and morning stiffness, after 6 months - MRI with T2 mapping, laboratory safety indicators. RESULTS: Over the course of 6 months of use, an improvement in the WOMAC index and a decrease in pain were observed without intergroup differences, and a greater decrease in stiffness in the AN group. After 3 months, the severity of OA decreased from moderate to mild in the AN group and was significantly lower compared to the GC group; quality of life (physical component of SF-36) was higher in the AN group. After 6 months, there was an improvement in cartilage ultrastructure (T2 relaxation time) in both groups and a more pronounced reduction of the synovitis area (MRI) in the AN group (2.95 and 1.37 times in the AN and GC group, respectively). There were no clinically significant adverse reactions observed in both groups. CONCLUSION: The use of AN in patients with stage I-III primary knee OA was not inferior in efficacy to the combination of GC. Further studies with greater statistical power (sample size) and follow-up period are warranted including in real clinical practice.


Assuntos
Sulfatos de Condroitina , Glucosamina , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Masculino , Feminino , Glucosamina/administração & dosagem , Glucosamina/farmacologia , Pessoa de Meia-Idade , Sulfatos de Condroitina/administração & dosagem , Sulfatos de Condroitina/farmacologia , Resultado do Tratamento , Dimetil Sulfóxido/administração & dosagem , Dimetil Sulfóxido/farmacologia , Triterpenos/administração & dosagem , Triterpenos/farmacologia , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Idoso , Colágeno Tipo II/administração & dosagem , Qualidade de Vida , Índice de Gravidade de Doença , Medição da Dor , Quimioterapia Combinada , Sulfonas/administração & dosagem , Sulfonas/farmacologia
6.
Vnitr Lek ; 68(8): 517-524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36575070

RESUMO

Currently, the approach to a patient with asthma is in accordance with personalized medicine wherein the decision on the treatment pathway is based on the type of asthmatic inflammation and other comorbidities that accompany asthma. For an allergic asthma patient, allergen immunotherapy (AIT), which has a disease-modifying effect and the potential to prevent further progression of allergic symptoms, is one of the treatment modalities. It is an effective treatment that, unlike pharmacotherapy, modifies the course of allergic respiratory diseases and induces allergen specific immune tolerance that persists for up to several years after treatment cessation. Therapeutic allergens of high quality, efficacy, and safety according to European regulatory authorities are an integral part of the treatment of respiratory allergies. It is a safe treatment option which still remains the only causal immuno¬modulatory therapy for allergic eosinophilic asthma.


Assuntos
Asma , Hipersensibilidade , Humanos , Hipersensibilidade/tratamento farmacológico , Asma/terapia , Dessensibilização Imunológica , Alérgenos/uso terapêutico , Resultado do Tratamento
7.
Front Psychiatry ; 13: 1046715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451764

RESUMO

Background: This study investigated the associations of sleep disturbance and serum serotonin levels with suicidal ideation, and evaluated the potential modifying effects of serotonin on these associations in patients with the acute coronary syndrome (ACS). Methods: In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of sleep disturbance (using the Leeds Sleep Evaluation Questionnaire), serum serotonin levels, and suicidal ideation (using the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of suicidal ideation. Logistic regression analysis was performed with adjustment for covariates. Results: Sleep disturbance was significantly associated with suicidal ideation at baseline and follow-up. Serum serotonin showed no such association but modified the association of sleep disturbance with suicidal ideation such that it was significant only in the lower serum serotonin group, with significant interaction terms obtained after adjustment for relevant covariates. Conclusion: Evaluating sleep disturbance and serum serotonin levels could improve the accuracy of clinical predictions of suicidal ideation in the acute and chronic phases of ACS.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35565005

RESUMO

The association of gestational weight gain (GWG) with perinatal outcomes seems to differ between women with and without gestational diabetes mellitus (GDM). Whether GDM is an effect-modifier of the association has not been verified. This study aimed to assess the modifying effect of GDM on the association of GWG with perinatal outcomes. Data on 12,128 pregnant women (3013 with GDM and 9115 without GDM) were extracted from a prospective, multicenter, cohort study in China. The associations of total and trimester-specific GWG rates (GWGR) with perinatal outcomes, including small size for gestational age, large size for gestational age (LGA), preterm birth, cesarean delivery, and gestational hypertension disorders, were assessed. The modifying effect of GDM on the association was assessed on both multiplicative and additive scales, as estimated by mixed-effects logistic regression. As a result, total GWGR was associated with all of the perinatal outcomes. GDM modified the association of total GWGR with LGA and cesarean delivery on both scales (all p < 0.05) but did not modify the association with other outcomes. The modifying effect was observed in the third trimester but not in the first or the second trimester. Therefore, maternal GWG is associated with perinatal outcomes, and GDM modifies the association with LGA and cesarean delivery in the third trimester.


Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Nascimento Prematuro , Índice de Massa Corporal , China/epidemiologia , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Aumento de Peso
9.
Int J Hyg Environ Health ; 241: 113933, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35134745

RESUMO

BACKGROUND: Previous studies have shown that exposures to ambient particulate matter with aerodynamic diameter <2.5 µm (PM2.5) and stress are associated with adverse cardiovascular health effects. OBJECTIVES: To investigate the potential modifying effect of trait anxiety on the association between short-term exposures to PM2.5 and HRV variables. METHODS: A panel of 92 middle-aged and elderly adults in Tianjin and Shanghai were recruited for repeated follow-ups with measurements of 24-h personal exposures to air pollutants and Holter ECG monitoring. Heart rate variability (HRV) variables calculated over 5-minute segments during the 24 h, including low frequency power (LF), high frequency power (HF), standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (rMSSD), were included in the analysis. The Trait Anxiety Inventory was used to investigate the long-term general anxiety level of the participants. Generalized linear mixed-effects model was used to analyze the association between exposure factors and HRV variables, and potential effect modification by trait anxiety. RESULTS: Data on 87 participants were included in final analysis after exclusions. Higher exposure to PM2.5 was associated with lower levels of LF, HF, SDNN and rMSSD, and the largest decreases in LF, HF, SDNN and rMSSD were found at 3-h moving average. Trait anxiety significantly modified the associations of PM2.5 with LF, HF, SDNN and rMSSD, with stronger inverse associations found in high trait anxiety group than in low trait anxiety group. For an IQR (27.3 µg/m³) increase in PM2.5 at 3-h moving average, there were decreases of 3.50% (95% CI: -4.46%, -2.54%) and 3.50% (95% CI: -4.49%, -2.50%) in the high trait anxiety group, and decreases of 0.81% (95% CI: -1.22%, -0.40%) and 0.65% (95% CI: -1.07%, -0.23%) in the low trait anxiety group in HF and rMSSD, respectively (both p for interaction<0.01). CONCLUSION: Our study suggests that trait anxiety could modify the association of short-term exposure to PM2.5 with HRV variables, indicating that higher trait anxiety may increase the cardiac susceptibility to air pollution in the study participants.


Assuntos
Poluentes Atmosféricos , Material Particulado , Adulto , Idoso , Poluentes Atmosféricos/análise , Ansiedade , China , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Material Particulado/análise
10.
Euro Surveill ; 26(32)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34387185

RESUMO

BackgroundMost reports of influenza vaccine effectiveness consider current-season vaccination only.AimWe evaluated a method to estimate the effect of influenza vaccinations (EIV) considering vaccination history.MethodsWe used a test-negative design with well-documented vaccination history to evaluate the average EIV over eight influenza seasons (2011/12-2018/19; n = 10,356). Modifying effect was considered as difference in effects of vaccination in current and previous seasons and current-season vaccination only. We also explored differences between current-season estimates excluding from the reference category people vaccinated in any of the five previous seasons and estimates without this exclusion or only for one or three previous seasons.ResultsThe EIV was 50%, 45% and 38% in people vaccinated in the current season who had previously received none, one to two and three to five doses, respectively, and it was 30% and 43% for one to two and three to five prior doses only. Vaccination in at least three previous seasons reduced the effect of current-season vaccination by 12 percentage points overall, 31 among outpatients, 22 in 9-65 year-olds, and 23 against influenza B. Including people vaccinated in previous seasons only in the unvaccinated category underestimated EIV by 9 percentage points on average (31% vs 40%). Estimates considering vaccination of three or five previous seasons were similar.ConclusionsVaccine effectiveness studies should consider influenza vaccination in previous seasons, as it can retain effect and is often an effect modifier. Vaccination status in three categories (current season, previous seasons only, unvaccinated) reflects the whole EIV.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/prevenção & controle , Estações do Ano , Vacinação
11.
Environ Res ; 195: 110738, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33485910

RESUMO

BACKGROUND: As the global climate continues to warm, there is an increased focus on heat, but the role of low temperatures on health has been overlooked, especially for developing countries. Methods We collected the admission data of childhood asthma in 2013-2016 from Anhui Provincial Children's Hospital, as well as meteorological data from the Meteorological Bureau for the study period and collected data of pollutants from 10 monitoring stations around Hefei city. Poisson's generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to estimate the short-term effects of cold spell on childhood asthma in cold seasons (November to March). 16 definitions of cold spells were clearly compared, which combining 4 temperature indexes (daily minimum and mean temperature; daily minimum and mean apparent temperature), 2 temperature thresholds (2.5th and 5th) and 3 durations of at least 2-4 days. We then have an analysis of the modifying effect of characteristics of cold spells and individuals(gender and age), with a view to discovering the susceptible population to cold spell. Results There was significant association between cold spells and admission risk for childhood asthma. And the definition, in which daily minimum apparent temperature falls below 5th percentile for at least 3 consecutive days, produced the optimum model fit performance. Based on this optimal fit we found that, for the total population, the effect of cold spell lasted approximately five days (lag1-lag5), with the largest effect occurring in lag 3 (RR = 1.110; 95% CI: 1.052-1.170). In subgroup analysis, the cumulative effect of lag0-7 was higher in males and school-age children than in females and other age groups, respectively. In addition, we found that the effect of is higher as the duration increases. Conclusion This study suggests an association between cold spell and childhood asthma, and minimum AT may be a better indicator to define the cold spells. Boys and school-age children are more vulnerable to cold spell. And one of our very interesting findings is that if a cold spell lasts for several days, the impact of the cold spell on those later days is likely to be greater than that of the previous days. In conclusion, we should pay more attention to the protection of boys and school-aged children in our future public health protection and give more attention to those cold spells that last longer. Therefore, we recommend that schools and health authorities need to take targeted measures to reduce the risk of asthma in children during the cold spell.


Assuntos
Asma , Temperatura Baixa , Asma/epidemiologia , Criança , China , Cidades , Feminino , Hospitalização , Humanos , Masculino , Temperatura
12.
Mov Disord ; 36(2): 306-316, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33184908

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra and accumulation of iron and alpha-synuclein; it follows a characteristic pattern throughout the nervous system. Despite decades of successful preclinical neuroprotective studies, no drug has then shown efficacy in clinical trials. Considering this dilemma, we have reviewed and organized solutions of varying importance that can be exclusive or additive, and we outline approaches to help generate successful development of neuroprotective drugs for PD: (1) select patients in which the targeted mechanism is involved in the pathological process associated with the monitoring of target engagement, (2) combine treatments that target multiple pathways, (3) establish earliest interventions and develop better prodromal biomarkers, (4) adopt rigorous methodology and specific disease-relevant designs for disease-modifying clinical trials, (5) customize drug with better brain biodistribution, (6) prioritize repurposed drugs as a first line approach, and (7) adapt preclinical models to the targeted mechanisms with translational biomarkers to increase their predictive value. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Substância Negra/metabolismo , Distribuição Tecidual , alfa-Sinucleína/metabolismo
13.
Cartilage ; 11(1): 60-70, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-29972025

RESUMO

OBJECTIVES: Hyaluronic acid viscosupplementation is a commonly used intra-articular treatment for osteoarthritis (OA). Some recent preclinical and clinical trials have demonstrated a potential for its disease-modifying effects. The goal of this expert opinion, consensus-driven exercise is to provide guidelines for the design and conduct of clinical trials assessing the disease-modifying effect of viscosupplementation in the knee. METHODS: The EUROVISCO group constitutes 10 members who had expertise in clinical research methodology in the field of OA and viscosupplementation. They initially drafted issues through an iterative process and had to vote on their degree of agreement on these recommendations. The scores were pooled to generate a median agreement score for each recommendation. RESULTS: The document includes 31 recommendations regarding study population, imaging, clinical and biological assessment of disease-modifying effects of viscosupplementation. Agreements were reached on some recommendations. In particular, the experts reached unanimous agreement on double-blind study design, imaging primary outcomes, time interval between 2 radiographs, x-ray procedure standardization, and the combined use of imaging and biological markers. The group did not recommend the use of ultrasonography, computed tomography (CT) scan and CT arthrography as a tool for OA diagnosis or to assess progression over time. CONCLUSION: In summary, the working group identified 31 recommendations that represent the current best practices regarding clinical trials that target the assessment of viscosupplementation disease-modifying effects in patients with knee OA. These recommendations integrate new imaging technologies and soluble biomarkers.


Assuntos
Monitoramento de Medicamentos/métodos , Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementação/métodos , Viscossuplementos/administração & dosagem , Comitês Consultivos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Humanos , Articulação do Joelho/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Biosci Biotechnol Biochem ; 82(3): 383-394, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29488453

RESUMO

The structures, flavor-modifying effects, and CaSR activities of γ-glutamyl peptides comprising sulfur-containing amino acids were investigated. The chemical structures, including the linkage mode of the N-terminal glutamic acid, of γ-L-glutamyl-S-(2-propenyl)-L-cysteine (γ-L-glutamyl-S-allyl-L-cysteine) and its sulfoxide isolated from garlic were established by comparing their NMR spectra with those of authentic peptides prepared using chemical methods. Mass spectrometric analysis also enabled determination of the linkage modes in the glutamyl dipeptides by their characteristic fragmentation. In sensory evaluation, these peptides exhibited flavor-modifying effects (continuity) in umami solutions less pronounced but similar to that of glutathione. Furthermore, the peptides exhibited intrinsic flavor due to the sulfur-containing structure, which may be partially responsible for their flavor-modifying effects. In CaSR assays, γ-L-glutamyl-S-methyl-L-cysteinylglycine was most active, which indicates that the presence of a medium-sized aliphatic substituent at the second amino acid residue in γ-glutamyl peptides enhances CaSR activity.


Assuntos
Alho/química , Ácido Glutâmico/química , Peptídeos/química , Peptídeos/farmacologia , Enxofre/química , Paladar/efeitos dos fármacos , Humanos
16.
Neurobiol Dis ; 103: 24-31, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28363801

RESUMO

In Parkinson's disease (PD) depletion of dopamine in the nigro-striatal pathway is a main pathological hallmark that requires continuous and focal restoration. Current predominant treatment with intermittent oral administration of its precursor, Levodopa (l-dopa), remains the gold standard but pharmacological drawbacks trigger motor fluctuations and dyskinesia. Continuous intracerebroventricular (i.c.v.) administration of dopamine previously failed as a therapy because of an inability to resolve the accelerated dopamine oxidation and tachyphylaxia. We aim to overcome prior challenges by demonstrating treatment feasibility and efficacy of continuous i.c.v. of dopamine close to the striatum. Dopamine prepared either anaerobically (A-dopamine) or aerobically (O-dopamine) in the presence or absence of a conservator (sodium metabisulfite, SMBS) was assessed upon acute MPTP and chronic 6-OHDA lesioning and compared to peripheral l-dopa treatment. A-dopamine restored motor function and induced a dose dependent increase of nigro-striatal tyrosine hydroxylase positive neurons in mice after 7days of MPTP insult that was not evident with either O-dopamine or l-dopa. In the 6-OHDA rat model, continuous circadian i.c.v. injection of A-dopamine over 30days also improved motor activity without occurrence of tachyphylaxia. This safety profile was highly favorable as A-dopamine did not induce dyskinesia or behavioral sensitization as observed with peripheral l-dopa treatment. Indicative of a new therapeutic strategy for patients suffering from l-dopa related complications with dyskinesia, continuous i.c.v. of A-dopamine has greater efficacy in mediating motor impairment over a large therapeutic index without inducing dyskinesia and tachyphylaxia.


Assuntos
Dopamina/administração & dosagem , Discinesia Induzida por Medicamentos/tratamento farmacológico , Infusões Intraventriculares , Transtornos Parkinsonianos/tratamento farmacológico , Índice de Gravidade de Doença , Animais , Células Cultivadas , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Esquema de Medicação , Discinesia Induzida por Medicamentos/metabolismo , Humanos , Mesencéfalo/citologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Parkinsonianos/metabolismo , Ratos , Ratos Wistar , Resultado do Tratamento
17.
Environ Res ; 148: 277-284, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27093470

RESUMO

BACKGROUND: Exposure to ubiquitous polycyclic aromatic hydrocarbons (PAHs) has been associated with decreased heart rate variability (HRV). Evidence accumulates that microRNAs (miRNAs) might be the intermediate factors between environmental exposures and their adverse health effects. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect phenotypes and disease morbidity. OBJECTIVE: We sought to investigate the influences of four well-studied SNPs in miRNA genes (rs2910164, rs11614913, rs2292832, and rs3746444) on HRV, and their modifying effects on the associations between PAH exposure and HRV. METHODS: We measured the concentrations of ten urinary monohydroxy PAHs (OH-PAHs), seven HRV parameters, and genotypes of these four SNPs in 1222 coke oven workers. RESULTS: There were significant differences among different rs2910164 genotype carriers in terms of all seven HRV indices: workers with rs2910164 CC genotype had significant lower HRV than those with GG or GC genotype (P<0.05). The number of rs2910164 C allele was negatively associated with HRV indices in the high PAH exposure group (ß<0, P<0.05), and the association between rs2910164 and high-frequency (HF) power was significantly stronger in high exposure group (Pinteraction=0.042). Interestingly, the negative associations between the sum of 10 OH-PAHs and HRV (ß<0, P<0.05) were significantly or marginally significantly stronger in workers with rs2910164 CC genotype (Pinteraction≤0.050). CONCLUSIONS: Coke oven workers with miR-146a rs2910164 CC genotype may be more susceptible to decreased HRV. The modifying effect of rs2910164 on the PAHs-HRV associations suggested miR-146a may mediate the effects of PAH exposure on HRV.


Assuntos
Poluentes Ocupacionais do Ar/urina , Frequência Cardíaca/genética , MicroRNAs/genética , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Monitoramento Ambiental , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
Environ Res ; 140: 354-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25913154

RESUMO

BACKGROUND: Phthalates were reported to be associated with increased risk of LBW in newborns, but the mechanism and potential influencing factor was still unclear. The objectives of this study were to investigate whether paraoxonase-2 (PON2) Ala148Gly (A148G) polymorphisms have impacts on fetal growth, and evaluate potential modifying effect on the association between phthalate exposures and LBW and short birth length. METHODS: In the current case-control study, 185 mother-newborn pairs including 74 low birth weight (LBW) cases and 111 controls were enrolled. Newborns' meconium specimens were collected and detected for mono-n-butyl phthalate (MBP) and mono-2-ethyhexyl phthalate (MEHP) by the method of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Umbilical vein blood samples were used to identify PON2 A148G polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Newborns prenatally exposed to higher level of phthalates had lower birth weight (ß=-0.92. p=0.045 for MBP, ß=-0.62, p=0.013 for MEHP) and short birth length (SBL) (ß=-0.024. p=0.049 for MBP, ß=-0.023, p=0.007 for MEHP). Comparing with low-phthalate-exposed subjects with PON2 148AA genotype, newborns with PON2 148AG/GG genotype exposed to high concentrations of MBP and MEHP had higher risks of LBW and short birth length (LBW: OR: 5.0, p=0.017 for MEHP; OR: 2.6, p=0.023 for MBP; SBL: OR: 6.6, p=0.005 for MEHP; OR: 6.4, p=0.017 for MBP). Effects of MBP and MEHP on LBW were significantly modified by PON2 A148G (p=0.044 and 0.034, respectively), while the modifying effect of PON2 A148G polymorphisms on the association of two phthalate metabolites with SBL was not significant. CONCLUSION: Prenatal exposure to phthalates affected birth weight and length in newborns. PON2 A148G polymorphisms modified the effects of prenatal phthalates' exposure on fetal development. Newborns with PON2 148AG/GG genotype and exposed to high concentrations of MBP and MEHP had higher risks of LBW and SBL.


Assuntos
Arildialquilfosfatase/genética , Exposição Materna , Ácidos Ftálicos/toxicidade , Polimorfismo Genético , China , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Gravidez , Espectrometria de Massas em Tandem
19.
JPEN J Parenter Enteral Nutr ; 39(3): 322-30, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24291737

RESUMO

BACKGROUND: Handgrip strength (HGS) is a marker of nutrition status. Many factors are associated with HGS. Age, height, body mass index, number of diagnoses, and number and type of drugs have been shown to modify the association between undernutrition and HGS. Nevertheless, other patient characteristics that could modify this association and its joint modifier effect have not been studied yet. OBJECTIVE: To evaluate the association of inpatients' HGS and undernutrition considering the potential modifier effect of cognitive status, functional activity, disease severity, anthropometrics, and other patient characteristics on HGS. METHODS: A cross-sectional study was conducted in a university hospital. Sex, age, abbreviated mental test score, functional activity score, Charlson index, number of drugs, Patient-Generated Subjective Global Assessment (PG-SGA) score, body weight, mid-arm muscle circumference, adductor pollicis muscle thickness, body height, wrist circumference, hand length, and palm width were included in a linear regression model to identify independent factors associated with HGS (dependent variable). RESULTS: The study sample was composed of 688 inpatients (18-91 years old). All variables included in the model were associated with HGS (ß, -0.16 to 0.38; P ≤ .049) and explained 68.5% of HGS. Age, functional activity decline, Charlson index, number of drugs, PG-SGA score, body weight, and wrist circumference had a negative association with HGS. All other studied variables were positively associated with HGS. CONCLUSION: Nutrition status evaluated by PG-SGA was still associated with HGS after considering the joint effect of other patient characteristics, which reinforces the value of HGS as an indicator of undernutrition.


Assuntos
Força da Mão , Hospitalização , Desnutrição/fisiopatologia , Músculo Esquelético/fisiologia , Avaliação Nutricional , Estado Nutricional , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Pesos e Medidas Corporais , Comorbidade , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Atividade Motora , Preparações Farmacêuticas/administração & dosagem , Adulto Jovem
20.
J Biomed Mater Res A ; 103(5): 1713-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25131611

RESUMO

This study aimed to investigate the ability of dopamine (DA)-loaded polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogel [synthesized by gamma (γ) radiation-induced template polymerization] [Nano-DA] to deliver DA across the blood brain barrier, and to evaluate the efficacy and safety of the acute and subchronic administration of Nano-DA in modulating motor activity and/or the biochemical changes in rat brain; induced by different models of Parkinsonism. In this respect, (PVP/PAAc) nanogel was synthesized by gamma radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of PVP as a template polymer, and then, it was used as a nano-drug carrier for DA. The PVP/PAAc and (PVP/PAAc loaded-DA nanogel particles were characterized by dynamic light scattering, infrared spectroscopy, and field emission-scanning electron microscopy. The loaded gel was administered in different doses and dosing regimens to Parkinsonian rats, and the catalepsy score and striatal DA levels were assessed. Then, the potential disease-modifying activity of this form of DA was investigated, through the assessment of the improvement in mitochondrial function, following the subchronic administration of Nano-DA to Parkinsonian rats. Significant disease-modifying effects were observed upon the administration of Nano-DA; in addition to normalization in their motor activity.


Assuntos
Resinas Acrílicas/química , Dopamina/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Transtornos Parkinsonianos/patologia , Polietilenoglicóis/química , Polietilenoimina/química , Povidona/química , Animais , Catalepsia/complicações , Catalepsia/tratamento farmacológico , Di-Hidroxifenilalanina/administração & dosagem , Di-Hidroxifenilalanina/farmacologia , Modelos Animais de Doenças , Dopamina/administração & dosagem , Dopamina/farmacologia , Masculino , Nanogéis , Transtornos Parkinsonianos/complicações , Ratos Wistar , Rotenona , Espectroscopia de Infravermelho com Transformada de Fourier , Resultado do Tratamento
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