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1.
Bioorg Med Chem Lett ; 98: 129596, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142914

RESUMO

To identify new compounds that can effectively inhibit Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), we screened, synthesized, and evaluated a series of novel aryl fluorosulfate derivatives for their in vitro inhibitory activity against Mtb. Compound 21b exhibited an in vitro minimum inhibitory concentration (MIC) of 0.06 µM against Mtb, no cytotoxicity against both HEK293T and HepG2 mammalian cell lines, and had good in vivo mouse plasma exposure and lung concentration with a 20 mg/kg oral dose, which supports advanced development as a new chemical entity for TB treatment.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Animais , Humanos , Camundongos , Antituberculosos , Células HEK293 , Mamíferos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico , Ésteres do Ácido Sulfúrico/química , Ésteres do Ácido Sulfúrico/farmacologia
2.
Genet Test Mol Biomarkers ; 26(11): 543-549, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36378841

RESUMO

Background: Previous studies have reported conflicting results regarding the potential association between the risk of Parkinson's disease (PD) and the single nucleotide polymorphism, rs11558538 (Thr105Ile), in the histamine N-methyltransferase (HNMT) gene. We performed a systematic review and meta-analysis to improve our understanding of the association between them. Methods: We systematically searched several online databases to identify relevant studies regarding the association between rs11558538 and PD. We extracted data on the frequencies of genotypes (Thr/Thr, Thr/Ile, and Ile/Ile) and alleles (Thr and Ile) at the rs11558538 locus in patients with PD and healthy controls. Associations between genotype and PD risk were assessed in terms of odds ratios (OR) and 95% confidence intervals (CI). Results: The final meta-analysis included six case-control studies and data from the International Parkinson's Disease Genomics Consortium (IPDGC) data base on the association between HNMT rs11558538 and PD, involving 22,855 patients and 65,367 controls. Among the studies, substantial heterogeneity was observed (I2 = 84.42 for genotype and I2 = 73.39 for allele). Both the Ile (log OR: -0.31; 95% CI: -0.5 to -0.12; p < 0.001) and Thr/Ile+Ile genotypes (log OR: -0.32; 95% CI: -0.55 to -0.08; p < 0.001) were associated with a decreased risk of sporadic PD across all study populations. Subgroup analysis showed the protective effect of Thr/Ile+Ile genotypes in non-Chinese cohorts (log OR: -0.66; 95% CI: -0.67 to -0.04; p < 0.001) but not in Chinese cohorts (log OR: -0.26; 95% CI: -0.63 to 0.11; p = 0.13). Conclusion: Our findings suggest that the HNMT rs11558538T polymorphism may protect against PD, particularly in patients from the United States and Europe.


Assuntos
Histamina N-Metiltransferase , Doença de Parkinson , Humanos , Histamina N-Metiltransferase/genética , Doença de Parkinson/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/genética
3.
Front Aging Neurosci ; 14: 957997, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118705

RESUMO

Objective: This study aimed to investigate the association of altered cortical thickness and functional connectivity (FC) with depression in Parkinson's disease (PD). Materials and methods: A total of 26 non-depressed PD patients (PD-ND), 30 PD patients with minor depression (PD-MnD), 32 PD patients with major depression (PD-MDD), and 30 healthy controls (HC) were enrolled. Differences in cortical thickness among the four groups were assessed, and the results were used to analyze FC differences in regions of cortical atrophy. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and neuroimaging biomarkers that might help in the prediction of PD-MDD. Results: Patients with PD-MDD showed decreased cortical thickness compared to patients with PD-ND in the left superior temporal and right rostral middle frontal gyri (RMFG), as well as weak FC between the left superior temporal gyrus and right cerebellum posterior lobe and between right RMFG and right inferior frontal gyrus and insula. The combination of cortical thickness, FC, and basic clinical features showed strong potential for predicting PD-MDD based on the area under the ROC curve (0.927, 95% CI 0.854-0.999, p < 0.001). Conclusion: Patients with PD-MDD show extensive cortical atrophy and FC alterations, suggesting that cortical thickness and FC may be neuroimaging-based diagnostic biomarkers for PD-MDD.

4.
Brain Imaging Behav ; 16(6): 2586-2600, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36044168

RESUMO

We aimed to perform a combined analysis of cortical thickness and functional connectivity to explore their association with cognitive impairment in Parkinson's disease (PD). A total of 53 PD and 15 healthy control subjects were enrolled. PD patients were divided into PD with normal cognition (PD-NC, n = 25), PD with mild cognitive impairment (PD-MCI, n = 11), and PD with dementia (PDD, n = 17). In some analyses, the PD-MCI and PDD groups were aggregated to represent "PD patients with cognitive impairment". Cognitive status was assessed with the Mini-Mental State Examination (MMSE). Anatomical magnetic resonance imaging and resting-state functional connectivity analysis were performed in all subjects. First, surface-based morphometry measurements of cortical thickness and voxels with cortical thickness reduction were detected. Then, regions showing reduced thickness were analyzed for changes in resting-state functional connectivity in PD involving cognitive impairment. Our results showed that, compared with PD-NC, patients with cognitive impairment showed decreased cortical thickness in the left superior temporal, left lingual, right insula, and right fusiform regions. PD-MCI patients showed these alterations in the right lingual region. Widespread cortical thinning was detected in PDD subjects, including the left superior temporal, left fusiform, right insula, and right fusiform areas. We found that cortical thinning in the left superior temporal, left fusiform, and right temporal pole regions positively correlated with MMSE score. In the resting-state functional connectivity analysis, we found a decrease in functional connectivity between the cortical atrophic brain areas mentioned above and cognition-related brain networks, as well as an increase in functional connectivity between those region and the cerebellum. Alterations in cortical thickness may result in a dysfunction of resting-state functional connectivity, contributing to cognitive decline in patients with PD. However, it is more probable that the relation between structure and FC would be bidirectional,and needs more research to explore in PD cognitve decline.


Assuntos
Disfunção Cognitiva , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Imageamento por Ressonância Magnética/métodos , Afinamento Cortical Cerebral , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Atrofia
5.
Neurol Sci ; 43(4): 2839-2843, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35088243

RESUMO

The present study aimed to explore the association of plasma neurofilament light chain (NfL) levels with depression and anxiety in Parkinson's disease (PD). This prospective study enrolled 116 patients with PD and 38 healthy controls, and found plasma NfL levels were higher in patients with depression or anxiety than in those without these symptoms. Binary logistic regression identified NfL concentration as an independent predictor of depression and anxiety in PD. In conclusion, elevated plasma NfL may be associated with severity of depression and anxiety in PD patients and may serve as a diagnostic biomarker of PD with moderate to severe depression or anxiety.


Assuntos
Doença de Parkinson , Ansiedade/etiologia , Biomarcadores , Depressão/etiologia , Humanos , Filamentos Intermediários , Proteínas de Neurofilamentos , Doença de Parkinson/diagnóstico , Estudos Prospectivos
6.
J Neuroimmunol ; 358: 577662, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34311152

RESUMO

This study investigated the potential association between levels of plasma neurofilament light chain (NfL) and cognitive function in patients suffering from Parkinson's disease (PD) in P.R. China.We collected a total of 168 participants (130 PD patients and 38 healthy controls),and evaluated the relationship of plasma NfL levels with cognitive dysfunction in PD patients. Our results shown that plasma NfL levels increased with an increase in cognitive impairment across the three groups of PD patients: PD with normal cognition (PD-NC), 17.9 ± 8.9 pg/ml; PD with mild cognitive impairment (PD-MCI),21.9 ± 10.3 pg/ml; and PD dementia (PDD), 35.7 ± 21.7 pg/ml. Higher MMSE scores were associated with lower plasma NfL levels (r = -0.49, 95% CI -0.61 to -0.34, p < 0.0001). Our results associating plasma NfL levels with cognitive dysfunction in PD are consistent with previous studies carried out in several countries/district, based on our meta-analysis.


Assuntos
Disfunção Cognitiva/sangue , Disfunção Cognitiva/psicologia , Proteínas de Neurofilamentos/sangue , Doença de Parkinson/sangue , Doença de Parkinson/psicologia , Idoso , Biomarcadores/sangue , Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Doença de Parkinson/diagnóstico
7.
J Neuroimmunol ; 353: 577504, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33548620

RESUMO

PURPOSE: Up to 20-30% of patients with Guillain-Barré syndrome (GBS) suffer serious clinical manifestations such as respiratory failure. We aim to determine whether two new prognostic biomarkers, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), could reliably predict respiratory failure in GBS.we MATERIALS AND METHODS: Data from 426 patients diagnosed at our center with GBS between January 2015 and July 2019 were retrospectively analyzed. Data were collected from the hospital database. Logistic regression and receiver operating characteristic curves were used to examine whether NLR alone, PLR alone or the combination, as measured at admission, could predict respiratory failure during hospitalization. Nomograms for predicting respiratory failure in GBS individuals were established, and predictive accuracy was evaluated using Harrell's concordance index (C-index). RESULTS: A total of 74 (17%) patients developed respiratory failure during hospitalization, and this was predicted independently by neutrophil count, NLR, PLR, and a combined "NLR-PLR" index, with the combined index performing best. The C-index of nomograms was 0.952 (95%CI 0.930-0.974) when NLR-PLR was included, or 0.933 (95%CI 0.911-0.955) when it was excluded. CONCLUSIONS: The prognostic biomarkers NLR and PLR may be independent predictors of respiratory failure in GBS. Combining the two indices may be more effective than either one on its own.


Assuntos
Biomarcadores/sangue , Síndrome de Guillain-Barré/complicações , Contagem de Linfócitos , Insuficiência Respiratória/etiologia , Adulto , Feminino , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos
8.
Neuromolecular Med ; 23(2): 242-246, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33387304

RESUMO

The aim of this study is to explore whether the single nucleotide polymorphism rs2275294 in the ZNF512B gene is related to the length of survival of patients with amyotrophic lateral sclerosis (ALS). This prospective study examined 212 patients with ALS, who were genotyped at the rs2275294 locus in ZNF512B using the ligase method. Genotype was compared with clinical data and survival. Kaplan-Meier survival analysis and Cox hazard regression were used to identify risk factors of shorter survival. Our results were meta-analyzed together with previous work in order to examine the potential association between the rs2275294-C allele and survival. Of the 212 patients, 166 carried the CC + CT genotype at the rs2275294 locus, while 46 carried the TT genotype. Patients with the C allele showed significantly shorter survival than those without it (34.13 ± 1.9 vs. 45.32 ± 5.7 months, p = 0.036). Cox analysis identified the C allele and time from symptom onset to diagnosis as risk factors for shorter survival. Meta-analysis of 447 patients in China and Japan confirmed the rs2275294-C allele to be an independent risk factor of shorter survival in ALS patients. The C allele at the rs2275294 locus in ZNF512B is a risk factor for shorter survival in patients with ALS.


Assuntos
Esclerose Amiotrófica Lateral/genética , Proteínas de Transporte/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Esclerose Amiotrófica Lateral/mortalidade , China/epidemiologia , Diagnóstico Tardio , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
9.
Neurol Sci ; 42(2): 625-631, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32651855

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS. METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed. RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201). CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/epidemiologia , Esclerose Amiotrófica Lateral/genética , Povo Asiático , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Humanos , Proteínas Mitocondriais/genética , População Branca
10.
Neurol Sci ; 42(1): 267-274, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32643134

RESUMO

BACKGROUND: Deep-brain stimulation is a well-established, effective treatment for patients with advanced Parkinson's disease. Recent studies examining rates of suicide attempts and suicides after deep-brain stimulation in the bilateral subthalamic nucleus have reported varying results. Using this systematic review and meta-analysis, we aim to obtain a comprehensive understanding of suicidality in Parkinson's patients after subthalamic nucleus deep brain stimulation. METHODS: We systematically examined Medline, PubMed, Web of Science, and Embase databases to identify studies published before November 2019 that measured rates of suicidality in Parkinson's patients who underwent subthalamic nucleus stimulation. A meta-analysis of the data from the included studies was conducted using Stata 12.0. RESULTS: A total of 18 studies met the eligibility criteria of this study. We found that the pooled rate of suicidal ideation was 4% (95% CI 0.00-7.2%, range 2-17%). The pooled rate of suicide attempts was 1% (95% CI 1.0-2.0%), while the pooled rate of suicide was 1% (95% CI 0.0-1.0%). CONCLUSIONS: Our findings indicate a relatively high rate of suicidality among Parkinson's patients after subthalamic nucleus deep-brain stimulation. It is important for clinicians to carefully monitor psychiatric disorders, especially suicidal ideation and suicide attempts, in Parkinson's patients before and after subthalamic nucleus deep-brain stimulation.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/terapia , Tentativa de Suicídio , Resultado do Tratamento
11.
Neurol Sci ; 42(8): 3275-3283, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33247320

RESUMO

BACKGROUND: Respiratory failure in patients with Guillain-Barré syndrome (GBS) can lead to serious complications and dysfunctions, emphasizing the importance of early detection. The C-reactive protein-to-albumin ratio (CAR) is emerging as a novel inflammatory marker for predicting neurological outcome. We aimed to identify the association of CAR with respiratory failure and short-term outcome in GBS patients. METHODS: A total of 200 patients diagnosed with GBS were retrospectively analyzed. Data were collected from an electronic database. The associations of C-reactive protein (CRP), albumin, and CAR at admission with outcomes were evaluated by logistic regression analysis. Using receiver operating characteristic curves, we calculated the cutoff value for the CAR and compared its discriminatory power with that of C-reactive protein alone. RESULTS: Fifty-two (26%) patients showed poor short-term outcome, and 50 (25%) developed respiratory failure. CAR > 0.21 was an independent predictor of respiratory failure, and CAR > 0.19 was an independent predictor of poor short-term outcome. CAR showed a better predictive value than CRP alone. In addition, the c-index of the predictive nomogram for respiratory failure was higher when it included CAR (0.962) than when it did not (0.958). A similar result was observed for the predictive nomogram for poor short-term outcome (0.953 vs 0.947). CONCLUSION: CAR > 0.21, a novel inflammatory biomarker, is independently associated with the occurrence of respiratory failure in GBS patients, while CAR > 0.19 is independently associated with poor short-term outcome. CAR may help identify GBS patients at high risk of poor prognosis.


Assuntos
Proteína C-Reativa , Síndrome de Guillain-Barré , Albuminas , Biomarcadores , Proteína C-Reativa/análise , Síndrome de Guillain-Barré/diagnóstico , Humanos , Prognóstico , Estudos Retrospectivos
12.
Acta Neurol Scand ; 142(5): 466-474, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32497277

RESUMO

INTRODUCTION: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis, with up to 20%-30% of patients requiring mechanical ventilation. The aim of our study was to develop and validate a mechanical ventilation risk nomogram in a Chinese population of patients with GBS. METHODS: A total of 312 GBS patients were recruited from January 1, 2015, to June 31, 2018, of whom 17% received mechanical ventilation. The least absolute shrinkage and selection operator (LASSO) regression model was used to select clinicodemographic characteristics and blood markers that were then incorporated, using multivariate logistic regression, into a risk model to predict the need for mechanical ventilation. The model was characterized and assessed using the C-index, calibration plot, and decision curve analysis. The model was validated using bootstrap resampling in a prospective study of 114 patients recruited from July 1, 2018, to July 10, 2019. RESULTS: The predictive model included hospital stay, glossopharyngeal and vagal nerve deficits, Hughes functional grading scale scores at admission, and neutrophil/lymphocyte ratio (NLR). The model showed good discrimination with a C-index value of 0.938 and good calibration. A high C-index value of 0.856 was reached in the validation group. Decision curve analysis demonstrated the clinical utility of the mechanical ventilation nomogram. CONCLUSIONS: A nomogram incorporating hospital stay, glossopharyngeal and vagal nerve deficits, Hughes functional grading scale scores at admission, and NLR may reliably predict the probability of requiring mechanical ventilation in GBS patients.


Assuntos
Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/terapia , Nomogramas , Paralisia Respiratória/etiologia , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Paralisia Respiratória/terapia , Estudos Retrospectivos , Fatores de Risco
13.
Eur Arch Otorhinolaryngol ; 277(1): 169-177, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630244

RESUMO

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) was the most common neuro-otological disorder manifests as recurrent positional vertigo, but its risk factors are elusive. Recent studies suggest that decreased Vitamin D level may be a risk factor, but the literature is inconsistent. METHODS: The databases PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, SinoMed, and Embase were systematically searched for studies on the association between BPPV and  serum Vitamin D levels published up to June 2019. Data from eligible studies were meta-analyzed using Stata 12.0. RESULTS: A total of 18 studies were included in the analysis. Serum Vitamin D levels were significantly lower in individuals with BPPV than in controls (WMD - 2.46, 95% CI - 3.79 to - 1.12, p < 0.001). Subgroup analysis by geographical area showed that vitamin D level was significantly lower in BPPV than in controls in China (WMD - 3.27, 95% CI - 4.12 to - 2.43, p < 0.001), but not outside China (WMD - 0.90, 95% CI - 4.36 to 2.56, p = 0.611). Vitamin D levels were significantly lower in recurrent than non-recurrent BPPV across all countries in the sample (WMD 2.59, 95% CI 0.35-4.82, p = 0.023). Vitamin D deficiency emerged as an independent risk factor of BPPV (OR 1.998, 95% CI 1.400-2.851, p < 0.001). CONCLUSION: The available evidence suggests that BPPV is associated with decreased levels of serum Vitamin D, and vitamin D deficiency was an independent risk factor for BPPV.


Assuntos
Vertigem Posicional Paroxística Benigna/sangue , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Vertigem Posicional Paroxística Benigna/etiologia , Humanos , Estudos Observacionais como Assunto , Recidiva , Fatores de Risco , Deficiência de Vitamina D/complicações
14.
Clin Auton Res ; 30(3): 239-245, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832904

RESUMO

OBJECTIVE: The aim of this study was to investigate the prevalence of rapid eye movement behavior disorder (RBD) in Chinese patients with multiple system atrophy (MSA) and to compare motor and non-motor symptoms and sleep disturbance of MSA patients with and without RBD. METHODS: A total of 55 patients who were consecutively admitted to West China Hospital of Sichuan University from 2016 to 2019 and subsequently diagnosed with probable MSA were enrolled in this cross-sectional study. The diagnosis of RBD was based on the results of video polysomnography (PSG) and a history of abnormal sleep-related behaviors. The patients were divided into two groups: those with RBD and those without. These two groups were then compared in terms of severity of motor symptoms (Unified Multiple System Arophy Rating Scale) and non-motor symptoms (Non-Motor Symptoms Scale, Mini-Mental State Examination score, Epworth Sleepiness Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale) and sleep parameters as recorded on PSG. RESULTS: Of the 55 patients (35 males), 18 (33%, 13 males) were diagnosed with RBD. Patients with or without RBD did not differ in demographic characteristics, clinical features, or sleep parameters based on PSG. CONCLUSION: There was no difference in motor and non-motor symptoms between MSA patients with or without RBD, indicating that the presence of RBD may not be significantly associated with the severity of motor or non-motor dysfunction in MSA.


Assuntos
Atrofia de Múltiplos Sistemas , Transtorno do Comportamento do Sono REM , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Atrofia de Múltiplos Sistemas/complicações , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/epidemiologia , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/epidemiologia , Sono REM
15.
Sleep Med ; 61: 110-117, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395522

RESUMO

OBJECTIVE: Restless legs syndrome (RLS) is a common neurological disorder of unclear pathophysiology that appears to involve an iron deficiency in the brain. Some studies, but not others, suggest that intravenous injection of iron can reduce RLS severity. METHOD: The databases Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were searched for randomized controlled trials, cohort studies and case-control studies of intravenous iron therapy to treat RLS. Eligible studies were meta-analyzed using Stata 12.0. RESULTS: This analysis indicated that IV iron was more efficacious than placebo in treating RLS (OR: 4.71,95%CI 4.21-5.21,p < 0.0001). According to sub-group analysis, either IV ferric carboxymaltose (FCM) or iron sucrose was more efficacious than placebo in treating RLS. Adverse events did not differ significantly between patients receiving intravenous iron or placebo (OR 1.68, 95%CI 0.92-3.07, p = 0.093). The present study also indicated after accepting IV iron treatment the IRLS score in RLS patients decreased (OR = 6.75,95%CI 4.02-9.49, p < 0.0001). The subgroup analysis showed that IV iron dextran, iron sucrose, and FCM could alleviate the IRLS score. CONCLUSION: The available evidence suggests that intravenous iron is effective and tolerable for patients with RLS regardless of peripheral iron status.


Assuntos
Compostos Férricos/uso terapêutico , Óxido de Ferro Sacarado/uso terapêutico , Complexo Ferro-Dextran/uso terapêutico , Maltose/análogos & derivados , Síndrome das Pernas Inquietas/tratamento farmacológico , Humanos , Injeções Intravenosas , Maltose/uso terapêutico , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Neurol Sci ; 40(11): 2293-2302, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31201598

RESUMO

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed. RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001). CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.


Assuntos
Esclerose Amiotrófica Lateral , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Esclerose Amiotrófica Lateral/etnologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/mortalidade , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Humanos , Risco
18.
Sci Transl Med ; 11(491)2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31068442

RESUMO

Parasitic filarial nematodes cause debilitating infections in people in resource-limited countries. A clinically validated approach to eliminating worms uses a 4- to 6-week course of doxycycline that targets Wolbachia, a bacterial endosymbiont required for worm viability and reproduction. However, the prolonged length of therapy and contraindication in children and pregnant women have slowed adoption of this treatment. Here, we describe discovery and optimization of quinazolines CBR417 and CBR490 that, with a single dose, achieve >99% elimination of Wolbachia in the in vivo Litomosoides sigmodontis filarial infection model. The efficacious quinazoline series was identified by pairing a primary cell-based high-content imaging screen with an orthogonal ex vivo validation assay to rapidly quantify Wolbachia elimination in Brugia pahangi filarial ovaries. We screened 300,368 small molecules in the primary assay and identified 288 potent and selective hits. Of 134 primary hits tested, only 23.9% were active in the worm-based validation assay, 8 of which contained a quinazoline heterocycle core. Medicinal chemistry optimization generated quinazolines with excellent pharmacokinetic profiles in mice. Potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease and in vitro selectivity against Loa loa (a safety concern in endemic areas). The favorable efficacy and in vitro safety profiles of CBR490 and CBR417 further support these as clinical candidates for treatment of filarial infections.


Assuntos
Antibacterianos/uso terapêutico , Descoberta de Drogas , Filariose/tratamento farmacológico , Filariose/parasitologia , Filarioidea/fisiologia , Quinazolinas/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Modelos Animais de Doenças , Feminino , Filarioidea/efeitos dos fármacos , Filarioidea/microbiologia , Ensaios de Triagem em Larga Escala , Camundongos , Fenótipo , Quinazolinas/química , Quinazolinas/farmacologia , Bibliotecas de Moléculas Pequenas , Wolbachia/efeitos dos fármacos
19.
Artigo em Inglês | MEDLINE | ID: mdl-30931632

RESUMO

Studies have suggested that obesity is associated with better prognosis among individuals with various types of neurodegenerative diseases, and while some studies suggest that the same is true of amyotrophic lateral sclerosis (ALS), other works cast doubt on this conclusion. Therefore, we conducted a meta-analysis to systematically evaluate the role of body mass index in the prognosis of ALS. PubMed was systematically searched to identify eligible articles, and data on long-term survival were meta-analyzed in terms of hazard ratios (HR) with corresponding 95% confidence intervals (CI). Level of heterogeneity among studies and publication bias were estimated. A total of 17 studies with 9991 ALS patients were included in the review. Each increase of 1 kg/m2 in body mass index was associated with significantly better long-term overall survival (HR 0.95, 95%CI 0.93-0.97; p < 0.001). Obesity may also be a strong predictor of favorable long-term prognosis (HR 0.73; 95%CI 0.62-0.86; p < 0.001). Our results suggest that higher body mass index and obesity are associated with better long-term survival of ALS patients.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Esclerose Amiotrófica Lateral/epidemiologia , Índice de Massa Corporal , Obesidade/diagnóstico , Obesidade/epidemiologia , Ensaios Clínicos como Assunto/métodos , Humanos , Estudos Multicêntricos como Assunto/métodos , Prognóstico , Fatores de Risco
20.
Front Neurol ; 10: 91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828314

RESUMO

Objective: The objective of the present study was to meta-analyze relevant literature to gain a comprehensive understanding of the potential relationship between serum uric acid levels and risk of benign paroxysmal positional vertigo (BPPV). Methods: The databases of PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed were systematically searched for observational case-control studies of the association between BPPV and serum uric acid levels published up to October 2018. Data from eligible studies were meta-analyzed using Stata 12.0. Results: A total of 12 studies were included in the analysis. There was a strong tendency for serum uric acid levels to be associated with risk of BPPV among studies conducted in China (OR 0.69, 95%CI 0.01-1.40, p = 0.053), but not among studies outside China (OR 1.07, 95%CI 1.08-3.22, p = 0.33). Across all studies, serum uric acid level was significantly higher among individuals with BPPV than among controls (OR 0.78, 95%CI 0.15-1.41, p = 0.015), yet it did not independently predict risk of the disorder (OR 1.003, 95%CI 0.995-1.012, p = 0.471). Conclusion: The available evidence suggests that BPPV is associated with elevated levels of serum uric acid, but these levels may not be an independent risk factor of BPPV.

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