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1.
J Pediatr ; 271: 114037, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38580191

RESUMO

OBJECTIVE: To identify perinatal factors in children born extremely preterm (EP) that were associated with motor impairment (MI) at 2 and 10 years of age and develop a predictive algorithm to estimate the risk of MI during childhood. STUDY DESIGN: Participants of the Extremely Low Gestational Age Newborns Study (ELGANS) were classified as: no MI, MI only at 2 years, MI only at 10 years, and MI at both 2 and 10 years, based on a standardized neurological examination at 2 and the Gross Motor Function Classification System (GMFCS) at 10 years of age. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to develop the final predictive model. RESULTS: Of the 849 study participants, 64 (7.5%) had a diagnosis of MI at both 2 and 10 years and 63 (7.4%) had a diagnosis of MI at 1 visit but not the other. Of 22 total risk factors queried, 4 variables most reliably and accurately predicted MI: gestational age, weight z-score growth trajectory during neonatal intensive care unit (NICU) stay, ventriculomegaly, and cerebral echolucency on head ultrasound. By selecting probability thresholds of 3.5% and 7.0% at ages 2 and 10, respectively, likelihood of developing MI can be predicted with a sensitivity and specificity of 71.2%/72.1% at age 2 and 70.7%/70.7% at age 10. CONCLUSION: In our cohort, the diagnosis of MI at 2 years did not always predict a diagnosis of MI at 10 years. Specific risk factors are predictive of MI and can estimate an individual infant's risk at NICU discharge of MI at age 10 years.


Assuntos
Paralisia Cerebral , Lactente Extremamente Prematuro , Humanos , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/epidemiologia , Feminino , Masculino , Recém-Nascido , Pré-Escolar , Criança , Idade Gestacional , Fatores de Risco
2.
Disabil Rehabil Assist Technol ; 19(7): 2498-2505, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38217485

RESUMO

PURPOSE: Assistive technologies based on IoT can contribute to improve quality of living of patients with severe motor difficulties by providing partial or total independence. The aim of this work was to analyse the usability and performance of an assistive system based on the IoT when is evaluated by a child patient with spinal muscular atrophy type 1 (SMA-I). MATERIALS AND METHODS: The study involved a child with SMA-I and his caregiver. The materials used include an M5Stack Core2 kit, a mobile app, and a smart switch based on the ESP-01S card. The patient sends requests to the caregiver from the app installed on the M5Stack Core2 to a mobile app, and controls smart switches located in the rooms. The system was tested by the participants for a period of 30 days to later evaluate its usability and performance. RESULTS: The results show that the control function of smart switches is the most used and there is no decrease in interactions over the days for the system in general. In addition, the scores obtained from both usability tests (patient and caregiver) were 87.5% and 90%, respectively. The average performance of the entire system was 93.33%. CONCLUSION: The application of assistive technologies based on the IoT allows obtaining a practical solution that improves the development of daily activities in a patient with SMA-I.


A low-cost device can contribute to improve the quality of living of spinal muscular atrophy patients by favouring partial or total independence.IoT-based assistive technologies allow obtaining practical solutions that improve the development of daily activities.


Assuntos
Aplicativos Móveis , Tecnologia Assistiva , Humanos , Masculino , Atrofias Musculares Espinais da Infância/reabilitação , Internet das Coisas , Criança , Atrofia Muscular Espinal/reabilitação , Cuidadores
3.
Haemophilia ; 29(6): 1604-1610, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37729473

RESUMO

INTRODUCTION: The impact of joint damage on functional capacity in patients with mild haemophilia (PwMH) has yet to be well studied. The primary aim of this study was to investigate the effect of joint impairment on the functional capacity of the lower limb in PwMH. The secondary aim was to identify physical predictors of lower limb functional capacity. METHOD: Forty-nine PwMH were evaluated. Dynamic balance was assessed using Time Up and Go (TUG). Thirty-second sit-to-stand (30-STS) and 60-second-STS (60-STS) were used to assess muscle power and endurance, respectively. Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) was used to assess joint damage. PwMH were divided based on HEAD-US: with joint damage (≥3 points) and without or with very low joint damage (0-2 points). Univariate ANOVA and multiple regression analyses were performed to identify differences in functional capacity and potential physical predictors. RESULTS: Only 30-STS showed significant differences between groups (p = .002). TUG and 60-STS were primarily explained by age (r2  = .21 and r2  = .44, respectively), while for 30-STS, age combined with joint damage and pain level explains 54% of the variance. CONCLUSION: Our findings indicate that the 30-STS is useful for assessing functional deterioration in people with early-stage haemophilia-related arthropathy. Our results also indicate that joint damage, combined with ageing and pain, may impact 30-STS outcomes in PwMH. Furthermore, our findings show that the loss in TUG and 60-STS performance in PwMH is related to ageing.


Assuntos
Artrite , Hemofilia A , Artropatias , Humanos , Hemofilia A/complicações , Artropatias/complicações , Artrite/complicações , Extremidade Inferior , Dor/complicações
4.
Rev. Bras. Neurol. (Online) ; 59(2): 16-21, abr.-jun. 2023. tab, ilus
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1443704

RESUMO

Trata-se de um estudo transversal retrospectivo que incluiu 27 pessoas com doença de Parkinson (DP), diagnosticados por neurologista. O objetivo do estudo foi analisar o tipo de correlação entre o grau de comprometimento motor e grau de depressão em pessoas com DP, tendo como hipótese que quanto maior o grau de comprometimento motor proporcionado pela doença, maior o grau de depressão. Foram utilizados os instrumentos Inventário de Depressão de Beck (BDI II) para a medida de sintomas depressivos e do grau de depressão, e a escala Hoehn & Yahr foi aplicada para identificação do grau de comprometimento motor. Foram excluídos indivíduos que não preencheram um dos instrumentos do estudo, selecionando apenas as pessoas com DP que preencheram ambos os instrumentos. Verificou-se uma correlação positiva e significativa entre os resultados do BDI -II e a escala Hoehn & Yahr modificada (r = 0,41, p = 0,035). O estudo identificou, portanto, uma associação crescente e positiva entre o grau de comprometimento motor das pessoas com DP e a presença de sintomas de depressão. Com isso, foi possível concluir que, uma pessoa com DP e maior grau de comprometimento motor, tende a apresentar maior número de sintomas depressivos e, consequentemente maior grau de depressão e vice-versa. Portanto, deve-se dedicar maior atenção à saúde mental dos casos em que a doença se expressa com maior comprometimento motor.


This is a retrospective cross-sectional study that included 27 people with Parkinson's disease (PD), diagnosed by a neurologist. The objective of the study was to analyze the type of correlation between the degree of physical impairment and degree of depression in people with PD, having as hypothesis that the greater the degree of physical impairment provided by the disease, the greater the degree of depression. The Beck Depression Inventory (BDI II) was used to measure depressive symptoms and the degree of depression, and the modified Hoehn & Yahr scale was applied to identify the degree of physical impairment. Individuals who did not complete one of the study instruments were excluded, selecting only those people with PD who completed both instruments. A positive and significant correlation can be verified between the results of the BDI -II and the Hoehn & Yahr scale (r = 0.41, p = 0.035). The study identified, therefore, an increasing and positive association between the degree of motor impairment of people with PD and the presence of symptoms of depression. With this, it was possible to conclude that, a person with PD and a higher degree of motor impairment, tends to present a higher number of depressive symptoms and, consequently, a higher level of depression and vice versa. Thus, the more physically compromised the person with PD is, the greater the association with a more severe depression. Therefore, greater attention should be paid to mental health in cases in which the disease is expressed with greater physical impairment.

5.
Naunyn Schmiedebergs Arch Pharmacol ; 396(11): 2957-2975, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37097335

RESUMO

Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) which was designed from molecular hybridization of trimetozine lead compound and 2,6-di-tert-butyl-hydroxytoluene to develop new anxiolytic drugs. Here, we conduct molecular dynamics simulations, docking studies, receptor binding assays, and in silico ADMET profiling of LQFM289 before its behavioral and biochemical assessment in mice within the dose range of 5-20 mg/kg. The docking of LQFM289 showed strong interactions with the benzodiazepine binding sites and matched well with receptor binding data. With the ADMET profile of this trimetozine derivative that predicts a high intestinal absorption and permeability to blood-brain barrier without being inhibited by the permeability glycoprotein, the oral administration of LQFM289 10 mg/kg consistently induced anxiolytic-like behavior of the mice exposed to the open field and light-dark box apparatus without eliciting motor incoordination in the wire, rotarod, and chimney tests. A decrease in the wire and rotarod´s fall latency coupled with an increase in the chimney test´s climbing time and a decrease in the number of crossings in the open field apparatus at the dose of 20 mg/kg of this trimetozine derivative suggest sedative or motor coordination impairment at this highest dose. The attenuation of the anxiolytic-like effects of LQFM289 (10 mg/kg) by flumazenil pretreatment implicates the participation of benzodiazepine binding sites. The lowering of corticosterone and tumor necrosis factor alpha (cytokine) in LQFM289-treated mice at a single oral (acute) dose of 10 mg/kg suggests that the anxiolytic-like effect of this compound also involves the recruitment of non-benzodiazepine binding sites/GABAergic molecular machinery.


Assuntos
Ansiolíticos , Camundongos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Benzodiazepinas/farmacologia , Hipnóticos e Sedativos/farmacologia , Ansiedade/tratamento farmacológico , Morfolinas/farmacologia , Comportamento Animal
6.
Front Aging Neurosci ; 13: 757714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759815

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10-15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.

7.
J Exerc Rehabil ; 17(4): 241-246, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34527635

RESUMO

This study evaluated the impact of motor impairment (MI) on exercise capacity and quality of life in patients with Parkinson disease (PD). One hundred ninety-two patients (≥50 years old) were divided according to the Hoehn and Yahr stages in: mild (stage I), mild to moderate (stage II), moderate (stage III), and advanced MI (stage IV). Exercise capacity (6-min walk test [6MWT]) and quality of life (Parkinson's Disease Questionnaire [PDQ-39]) were obtained. In this context, 6MWT was progressively worse with increasing the severity of MI (P<0.01). Patients with advanced MI achieved 39% of predicted 6MWT of healthy subject, while subjects with mild MI achieved 83% of healthy subject (P<0.01). In addition, patients with advanced MI presented higher (i.e., worse) PDQ-39 scores in summary index, cognition, mobility and activities of daily live domains compared to other groups (P<0.01). Patients with moderate MI also presented worse scores in PDQ-39 summary index, mobility and activities of daily live domains in comparison with mild MI patients (P<0.01). Higher MI was correlated with worse exercise capacity (6MWT: r=-0.46, P<0.01), with worse PDQ-39 summary index and the mobility and activities of daily live domains scores (r=0.38, r=0.46, and r=0.43, P<0.01). In conclusion, MI is related to lower exercise capacity and quality of life (i.e., PDQ-39 summary index and mobility and activities of daily live domains) in patients with PD.

8.
Neurochem Int ; 150: 105188, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34536545

RESUMO

After different types of acute central nervous system insults, including stroke, subarachnoid haemorrhage and traumatic brain and spinal cord injuries, secondary damage plays a central role in the induction of cell death, neurodegeneration and functional deficits. Interestingly, secondary cell death presents an attractive target for clinical intervention because the temporal lag between injury and cell loss provides a potential window for effective treatment. While primary injuries are the direct result of the precipitating insult, secondary damage involves the activation of pathological cascades through which endogenous factors can exacerbate initial tissue damage. Secondary processes, usually interactive and overlapping, include oxidative stress, neuroinflammation and dysregulation of autophagy, ultimately leading to cell death. Resveratrol, a natural stilbene present at relatively high concentrations in grape skin and red wine, exerts a wide range of beneficial health effects. Within the central nervous system, in addition to its inherent free radical scavenging role, resveratrol increases endogenous cellular antioxidant defences thus modulating multiple synergistic pathways responsible for its antioxidant, anti-inflammatory and anti-apoptotic properties. During the last years, a growing body of in vitro and in vivo evidence has been built, indicating that resveratrol can induce a neuroprotective state and attenuate functional deficits when administered acutely after an experimental injury to the central nervous system. In this review, we summarize the most recent findings on the molecular pathways involved in the neuroprotective effects of this multi target polyphenol, and discuss its neuroprotective potential after brain or spinal cord injuries.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Resveratrol/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Lesões Encefálicas/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Humanos , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Resveratrol/farmacologia , Traumatismos da Medula Espinal/metabolismo
9.
Mol Cell Neurosci ; 115: 103643, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34186187

RESUMO

The taiep rat undergoes hypomyelination and progressive demyelination caused by an abnormal microtubule accumulation in oligodendrocytes, which elicits neuroinflammation and motor behavior dysfunction. Based on taurine antioxidant and proliferative actions, this work explored whether its sustained administration from the embryonic age to adulthood could prevent neuroinflammation, stimulate cell proliferation, promote myelination, and relieve motor impairment. Taurine (50 mg/L of drinking water = 50 ppm) was given to taiep pregnant rats on gestational day 15 and afterward to the male offspring until eight months of age. We measured the levels of nitric oxide (NO), malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), CXCL1, CXCR2 receptor, growth factors (BNDF and FGF2), cell proliferation, and myelin content over time. Integral motor behavior was also evaluated. Our results showed that taurine administration significantly decreased NO and MDA + 4-HDA levels, increased cell proliferation, and promoted myelination in an age- and brain region-dependent fashion compared with untreated taiep rats. Taurine effect on chemokines and growth factors was also variable. Taurine improved vestibular reflexes and limb muscular strength in perinatal rats and fine movements and immobility episodes in adult rats. These results show that chronic taurine administration partially alleviates the taiep neuropathology.


Assuntos
Destreza Motora , Taurina , Animais , Masculino , Doenças Neuroinflamatórias , Estresse Oxidativo , Ratos , Ratos Mutantes , Ratos Sprague-Dawley
10.
J Neurosci Res ; 99(9): 2287-2304, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34061383

RESUMO

The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.


Assuntos
Cerebelo/metabolismo , Cerebelo/patologia , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/patologia , Locomoção/fisiologia , Derivação Portocava Cirúrgica/tendências , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Cerebelo/cirurgia , Encefalopatia Hepática/cirurgia , Masculino , Microglia/metabolismo , Microglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Ratos , Ratos Wistar
11.
Neurotox Res ; 39(3): 787-799, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860897

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. In this study, we compared the effects of new curcumin-loaded nanoemulsions (NC) and free CUR in an experimental model of PD. Adult Swiss mice received NC or CUR (25 and 50 mg/kg) or vehicle orally for 30 days. Starting on the eighth day, they were administered rotenone (1 mg/kg) intraperitoneally until the 30th day. At the end of the treatment, motor assessment was evaluated by open field, pole test, and beam walking tests. Oxidative stress markers and mitochondrial complex I activity were measured in the brain tissue. Both NC and CUR treatment significantly improved motor impairment, reduced lipoperoxidation, modified antioxidant defenses, and prevented inhibition of complex I. However, NC was more effective in preventing motor impairment and inhibition of complex I when compared to CUR in the free form. In conclusion, our results suggest that NC effectively enhances the neuroprotective potential of CUR and is a promising nanomedical application for PD.


Assuntos
Curcumina/administração & dosagem , Emulsões/administração & dosagem , Nanopartículas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Transtornos Parkinsonianos/prevenção & controle , Rotenona/toxicidade , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Curcumina/química , Emulsões/química , Masculino , Camundongos , Nanopartículas/química , Fármacos Neuroprotetores/química , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo
12.
J Pediatr ; 231: 61-67.e2, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33340547

RESUMO

OBJECTIVE: To examine the stability of developmental coordination disorder (DCD) throughout childhood in children born very preterm and term. Further, in the very preterm group, to compare perinatal variables and neurobehavioral outcomes at 13 years of age for children with persisting DCD and those with typical motor development. STUDY DESIGN: Prospective study of 180 very preterm and 73 term-born children assessed at 5, 7, and/or 13 years of age using the Movement Assessment Battery for Children, with scores ≤16th percentile used to classify DCD. Children with cerebral palsy or an IQ of <80 were excluded. RESULTS: Children born very preterm had increased odds for DCD at 5 (OR, 5.53; 95% CI, 2.53-12.0; P < .001), 7 (OR, 3.63; 95% CI, 1.43-9.18; P = .06), and 13 years (OR, 4.34; 95% CI, 1.61-11.7; P = .004) compared with term-born children. The rates of DCD in very preterm children reduced from 47.9% at 5 years of age, to 28.5% at 7 years and 27.8% at 13 years of age (OR per year of age, 0.81; 95% CI, 0.75-0.87; P < .001), but less so for term-born children (15.3%, 10.0%, and 8.5% at 5, 7, and 13-years respectively [OR, 0.91; 95% CI, 0.75-1.09; P = .31]). Within the very preterm group at 13 years of age, there was evidence that children with persisting DCD performed poorer across several cognitive domains compared with children with typical motor development, with differences in the order of 0.5-1.0 SD. CONCLUSIONS: Although the rates of DCD decreased across middle childhood for both groups, the odds for DCD were consistently higher for very preterm children compared with term, with important implications for cognitive functioning in the very preterm group.


Assuntos
Deficiências do Desenvolvimento/epidemiologia , Lactente Extremamente Prematuro , Doenças do Prematuro/epidemiologia , Transtornos das Habilidades Motoras/epidemiologia , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/etiologia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/etiologia , Estudos Longitudinais , Masculino , Transtornos das Habilidades Motoras/diagnóstico , Transtornos das Habilidades Motoras/etiologia , Testes Neuropsicológicos , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Vitória/epidemiologia
13.
Front Immunol ; 11: 591563, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193433

RESUMO

Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 µg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.


Assuntos
Crotoxina/administração & dosagem , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/metabolismo , Imunomodulação/efeitos dos fármacos , Dióxido de Silício , Nanomedicina Teranóstica , Animais , Biomarcadores , Biópsia , Crotoxina/efeitos adversos , Crotoxina/química , Citocinas/metabolismo , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Encefalomielite Autoimune Experimental/diagnóstico , Feminino , Camundongos , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Índice de Gravidade de Doença , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Avaliação de Sintomas
14.
Viruses ; 12(10)2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992985

RESUMO

Clinical outcomes related to congenital Zika syndrome (CZS) include microcephaly accompanied by specific brain injuries. Among several CZS outcomes that have been described, epilepsy and motor impairments are present in most cases. Pharmacological treatment for seizures resulting from epilepsy is performed with anticonvulsant drugs, which in the long term are related to impairments in the child's neuropsychomotor development. Here, we describe the results from a two-year follow-up of a cohort of children diagnosed with CZS related to the growth of the head circumference and some neurological and motor outcomes, including the pharmacological approach, and its results in the treatment of epileptic seizures. This paper is part of a prospective cohort study carried out in the state of Mato Grosso Sul, Brazil, based on a Zika virus (ZIKV)-exposed child population. Our data were focused on the assessment of head circumference growth and some neurological and motor findings, including the description of seizure conditions and pharmacological management in two periods. Among the 11 children evaluated, 8 had severe microcephaly associated with motor impairment and/or epilepsy. Seven children were diagnosed with epilepsy. Of these, 3 had West syndrome. In four children with other forms of epilepsy, there was no pharmacological control.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Microcefalia/virologia , Espasmos Infantis/tratamento farmacológico , Infecção por Zika virus/patologia , Brasil , Pré-Escolar , Epilepsia/virologia , Feminino , Cabeça/anatomia & histologia , Humanos , Lactente , Recém-Nascido , Microcefalia/patologia , Hipertonia Muscular/virologia , Malformações do Sistema Nervoso/virologia , Paresia/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Reflexo Anormal/fisiologia , Espasmos Infantis/virologia , Zika virus/patogenicidade
15.
Neurol Sci ; 41(9): 2591-2598, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32253636

RESUMO

OBJECTIVE: To compare the interhemispheric asymmetry of the motor cortex excitability of chronic stroke patients with healthy and to observe if the magnitude of this asymmetry is associated to sensory-motor impairment and stroke chronicity. METHODS: This cross-sectional study was performed with chronic stroke and aged and sex-matched healthy individuals. The interhemispheric asymmetry index was calculated by the difference of rest motor threshold (rMT) of the brain hemispheres. The rMT was assessed by transcranial magnetic stimulation over the cortical representation of the first dorsal interosseous muscle. To investigate the relationship of the asymmetry with sensory-motor impairment and injury chronicity, the stroke patients were grouped according to the level of sensory-motor impairment (mild/moderate, moderate/severe, and severe) and different chronicity stages (> 3-12, 13-24, 25-60, and > 60 months since stroke). RESULTS: Fifty-six chronic stroke and twenty-six healthy were included. We found higher interhemispheric asymmetry in stroke patients (mean, 27.1 ± 20.9) compared to healthy (mean, 4.9 ± 4.7). The asymmetry was higher in patients with moderate/severe (mean, 35.4 ± 20.4) and severe (mean, 32.9 ± 22.7) impairment. No difference was found between patients with mild/moderate impairment (mean, 15.5 ± 12.5) and healthy. There were no differences of the interhemispheric asymmetry between patients with different times since stroke (> 3-12, mean, 32 ± 18.1; > 13-24, mean, 20.7 ± 16.2; > 25-60, mean, 29.6 ± 18.1; > 60 months, mean, 25.9 ± 17.5). CONCLUSION: Stroke patients showed higher interhemispheric asymmetry of the motor cortex excitability when compared to healthy, and the magnitude of this asymmetry seems to be correlated with the severity of sensory-motor impairment, but not with stroke chronicity. SIGNIFICANCE: Higher interhemispheric asymmetry was found in stroke patients with greatest sensory-motor impairment.


Assuntos
Córtex Motor , Transtornos Motores , Acidente Vascular Cerebral , Idoso , Estudos Transversais , Potencial Evocado Motor , Humanos , Acidente Vascular Cerebral/complicações , Estimulação Magnética Transcraniana
16.
Front Immunol, v. 11, 591563, out. 2020
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3312

RESUMO

Crotoxin (CTX), the main neurotoxin from Crotalus durissus terrificus snake venom, has anti-inflammatory, immunomodulatory and antinociceptive activities. However, the CTX-induced toxicity may compromise its use. Under this scenario, the use of nanoparticle such as nanostructured mesoporous silica (SBA-15) as a carrier might become a feasible approach to improve CTX safety. Here, we determined the benefits of SBA-15 on CTX-related neuroinflammatory and immunomodulatory properties during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis that replicates several histopathological and immunological features observed in humans. We showed that a single administration of CTX:SBA-15 (54 μg/kg) was more effective in reducing pain and ameliorated the clinical score (motor impairment) in EAE animals compared to the CTX-treated EAE group; therefore, improving the disease outcome. Of interest, CTX:SBA-15, but not unconjugated CTX, prevented EAE-induced atrophy and loss of muscle function. Further supporting an immune mechanism, CTX:SBA-15 treatment reduced both recruitment and proliferation of peripheral Th17 cells as well as diminished IL-17 expression and glial cells activation in the spinal cord in EAE animals when compared with CTX-treated EAE group. Finally, CTX:SBA-15, but not unconjugated CTX, prevented the EAE-induced cell infiltration in the CNS. These results provide evidence that SBA-15 maximizes the immunomodulatory and anti-inflammatory effects of CTX in an EAE model; therefore, suggesting that SBA-15 has the potential to improve CTX effectiveness in the treatment of MS.

17.
Folia Neuropathol ; 57(3): 258-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588712

RESUMO

The peripheral inflammatory stimulus could induce cell damage in peripheral organs and activate microglial cells in the brain. One such stimulus was given to adult male Wistar rats by injecting different concentrations of lipopolysaccharide (LPS; 50, 300, 500 g/kg and 5 mg/kg i.p.). To verify the systemic effect of the LPS administration, the serum content of C-reactive protein (CRP), the variation of body weight and cellular changes in the spleen, liver and kidney were determined. Motor impairment was evaluated by rotarod and open field tests. Microglia activation and dopaminergic degeneration was confirmed by immunolabelling for CD11b/c (microglia) and tyrosine hydroxylase (TH), respectively. The cell counting was performed in substantia nigra pars compacta (SNpc), microglial activation was explored in SNpc, substantia nigra pars reticulata (SNpr), substantia nigra pars compacta dorsal (SNcd) and the ventral tegmental area (VTA). For the statistical analysis, one-way ANOVA followed by Tukey post hoc test (p ≤ 0.05) was used. On day 7 post intraperitoneal administration of LPS, cellular atrophy was detected in the liver, kidney and spleen at 5 mg/kg, without significant changes in CRP levels. Body weight loss and motor impairment was present only on day 1 post LPS administration. The dosage of 500 g/kg and 5 mg/kg of LPS caused the loss of dopaminergic neurons (40%) in SNpc and microglia migration in a dose-dependent manner in SNcd, SNpc and SNpr. LPS-induced endotoxemia favours damage to the peripheral organs and microglial migration in a dose-dependent manner in rat substantia nigra.


Assuntos
Endotoxemia/patologia , Lipopolissacarídeos/toxicidade , Microglia/patologia , Substância Negra/patologia , Animais , Movimento Celular , Neurônios Dopaminérgicos/patologia , Endotoxemia/induzido quimicamente , Masculino , Ratos , Ratos Wistar
18.
Ecotoxicology ; 28(7): 744-753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31254187

RESUMO

Wild and managed bees are essential for crop pollination and food production. However, the widespread use of insecticides such as neonicotinoids may affect the survival, development, behavior, and maintenance of bee colonies. Therefore, in this study we evaluated the impacts of three neonicotinoid insecticides on the survival and walking abilities of the Africanized honeybee A. mellifera and stingless bee S. postica. A. mellifera was more susceptible than S. postica to all neonicotinoids tested. The median lethal concentrations LC50 values estimated for acetamiprid, imidacloprid, and thiacloprid were 189.62, 22.78, and 142.31 ng µL-1 of diet for A. mellifera, and 475.94, 89.11, and 218.21 ng µL-1 of diet for S. postica, respectively. All tested neonicotinoids affected the speed, distance traveled, duration and frequency of resting, and continuous mobility of both bee species. The results showed that in spite of the different susceptibility to compounds with cyano and nitro radicals, the behavioral variables showed different levels of commitment according to the molecule insecticide and bee species. These results contribute not only to the understanding of the effects of neonicotinoid insecticides on A. mellifera and S. postica, but also to help in the development of protocols that aim to reduce the impact of these insecticides in Neotropical environments.


Assuntos
Abelhas/efeitos dos fármacos , Inseticidas/toxicidade , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Tiazinas/toxicidade , Animais , Dose Letal Mediana , Locomoção/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Especificidade da Espécie , Testes de Toxicidade Aguda , Caminhada
19.
Rev. ecuat. neurol ; Rev. ecuat. neurol;27(1): 72-79, sep.-dic. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1004012

RESUMO

Resumen La musicoterapia neurológica (NMT) está siendo implementada en hospitales y centros de neurorrehabilitación alrededor del mundo gracias a la abundante evidencia neurocientífica y al creciente interés por los efectos de la música en el cerebro. Siendo reconocida y avalada por la World Federation for Neurorehabilitation, la musicoterapia neurológica es utilizada como intervención no-farmacológica y no-invasiva para tratar a pacientes con trastornos neurológicos que presentan disfunciones cognitivas, motoras, y/o del lenguaje. Este artículo busca dar a conocer a esta disciplina como un método efectivo y basado en evidencia para tratar los desórdenes neurológicos.


Abstract Neurologic music therapy (NMT) is being implemented in hospitals and neurorehabilitation facilities around the world, thanks to the abundant neuroscience research and to the growing interest in the effects of music on the brain. Recognized and endorsed by the World Federation for Neurorehabilitation, neurologic music therapy is utilized as a non-pharmacological, non-invasive intervention to treat patients with neurologic disease that present cognitive, motor, and/or language impairments. This article aspires to introduce this discipline as an effective, evidence-based method of treatment for neurologic disease.

20.
Res. Biomed. Eng. (Online) ; 34(2): 166-175, Apr.-June 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-956295

RESUMO

AbstractIntroduction: Communication is a fundamental element for the development of human beings, promoting their coexistence in society. However, changes in muscle tone, associated with cerebral palsy (CP), among other conditions, cause phono-articulatory dysfunctions hindering speech capabilities. Although there are resources for augmentative and alternative communication (AAC), most of them do not completely satisfy the needs of individuals with motor impairment. Therefore, this study proposes a tool based on mobile technology for AAC, which can be adapted to the characteristics of the motor limitations of CP users. Methods Mobile system development was conducted employing user-centered design and development methods. Functions were developed allowing the communication of phrases through pictographic resources and a mechanism of speech synthesis, that can be customized according to specific communication needs. To validate this system, 20 CP volunteers with speech difficulties and motor impairment were recruited from two institutions in the State of São Paulo, Brazil. They operated the system following a pre-defined test protocol, and they answered a system usability scale (SUS) questionnaire, to rate the ease of learning, memorization, efficiency, occurrence of runtime errors, and the level of user satisfaction. Results The results showed a score of 85.85 ± 2.28 above the average SUS scale, for each one of the quality components assessed by the volunteers. Conclusion The developed software is user-friendly, representing a new option for AAC, and is customized according to the communication needs of people with speech disorder and motor impairment.

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