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1.
J Biochem Mol Toxicol ; 34(1): e22415, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31682045

RESUMO

The aim of this study was to assess the therapeutic potential of oxytocin and liraglutide (LIR), a GLP-1 analogue, in a rat model of vincristine-induced neuropathy. Rats were injected with vincristine (VCR) at a dose of 4 mg/kg twice a week for 5 weeks. The VCR-administered rats were divided into three groups and received saline, oxytocin, or liraglutide simultaneously with VCR. After the treatment period, electrophysiological, biochemical, histological, and immunohistochemical investigations were performed. Electromyography (EMG) recordings demonstrated significant alterations in the VCR + saline group (p < .001). Also, motor performance was decreased in the VCR + saline group (p < .05). Histologically, the axonal diameter was decreased in all groups. VCR + saline group showed significantly increased lipid peroxidation and decreased nerve growth factor (NGF) expression. However, the administration of oxytocin and liraglutide significantly prevented the EMG alterations, lipid peroxidation, and reduction in neuronal NGF expression. On the basis of these findings, oxytocin and liraglutide may be considered as potential agents for the prevention of VCR-induced neuropathy.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Liraglutida/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Ocitocina/uso terapêutico , Vincristina/toxicidade , Animais , Liraglutida/administração & dosagem , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Ocitocina/administração & dosagem , Ratos , Ratos Sprague-Dawley
2.
Mol Cell Biochem ; 465(1-2): 175-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853800

RESUMO

Cutaneous changes like rash and hair loss, as well as other neurogenic inflammation side effects, occur frequently during anticancer treatment with the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), erlotinib. These adverse events may be so severe that they impair the patient's compliance with the treatment or even cause its discontinuation. In the current preclinical study, rats (9.2 weeks) were treated with erlotinib (10 mg/kg/day) ± aprepitant (2 mg/kg/day) for 12 weeks. Visual changes in the development of facial skin lesions/hair loss and SP-receptor expression (immunohistochemically) in facial skin tissue were assessed; also changes in plasma magnesium, 8-isoprostane, substance P (SP), neutrophil superoxide production, and cardiac function (echocardiography) were measured. Erlotinib lowered plasma magnesium 14%, elevated SP 65%, caused 3.7-fold higher basal superoxide production, 2.5-fold higher 8-isoprostane levels, 11.6% lower cardiac systolic, and 10.9% lower diastolic function. Facial dermatological changes (alopecia, skin reddening, scabbing, nose crusting) occurred by 4 weeks (± + to ++) in erlotinib-treated rats, and progressively worsened (±++ to +++) by week 12. Facial skin SP-receptor upregulation (78% higher) occurred in epidermal and hair follicle cells. All adverse effects were substantially and significantly mitigated by aprepitant, including a 62% lowering of skin SP-receptors (p < 0.05). Elevated SP levels mediated the side effects of erlotinib treatment, but aprepitant's significant prevention of the systemic and cutaneous adverse events indicates a novel potential therapy against the side effects of this anticancer treatment.


Assuntos
Aprepitanto/farmacologia , Erupção por Droga , Cloridrato de Erlotinib/efeitos adversos , Doenças do Sistema Nervoso , Antagonistas do Receptor de Neuroquinina-1/farmacologia , Animais , Erupção por Droga/tratamento farmacológico , Erupção por Droga/metabolismo , Erupção por Droga/patologia , Cloridrato de Erlotinib/farmacologia , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Ratos , Ratos Sprague-Dawley
3.
Int. arch. otorhinolaryngol. (Impr.) ; 23(4): 389-395, Out.-Dez. 2019. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1024150

RESUMO

Introduction: Agrochemicals, also known as pesticides, are widely used in agriculture and in public health. They are organic and inorganic chemical substances with a high level of toxicity not only for the environment, but also for human health. Objective: To verify findings on labyrinthine assessment in endemic disease control agents, and to recommend the inclusion of the vestibular exam in the set of tests for pesticide-exposed populations. Methods: Descriptive, prospective, cross-sectional study with a sample comprising 15 endemic disease control agents, males, mean age of 51.6 years old (standard deviation [SD] = 5.9). All of the participants were submitted to anamnesis, otorhinolaryngological screening, and vestibular assessment. Results: Regarding the most reported complaints, dizziness (73.4%), headache (60%), and tingling in the extremities (53.4%) were observed. The findings of the vestibular exams were normal in 53.3%, while 46.7% showed peripheral vestibular disorder, of which 26.7% were of deficitary type, and 20% of the irritative type. Conclusions: Alteration in the vestibular system was verified in 50% of the workers, with a greater prevalence in the caloric testing. Several disorders related to pesticides intoxication are scientifically known. Actions promoting knowledge and qualification of this population for the proper handling of chemicals are suggested, in addition to the elaboration and inclusion of protocols of vestibular assessment in hearing health programs for the prevention, diagnosis and treatment of vestibular disorders (AU)


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Doenças Vestibulares/diagnóstico , Exposição Ocupacional , Exposição a Praguicidas , Doenças dos Trabalhadores Agrícolas/diagnóstico , Doenças Vestibulares/induzido quimicamente , Estudos Transversais , Estudos Prospectivos , Agroquímicos/efeitos adversos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/induzido quimicamente
4.
Toxicol Lett ; 315: 96-106, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31386889

RESUMO

We investigate the long-term effect of very-low dose exposure to a mixture of six pesticides associated with hydrophilic vitamin deficiency on the neurobehavioral outcomes of rats. Two hundred Wistar rats were divided into four groups, two control groups, a vitamin sufficient control group and a vitamin deficiency control group and 2 test groups, a vitamin sufficient test group, and a vitamin deficiency group. The test groups were exposed for 9 months to a mixture of diquat, imazamox, imazethapyr, tepraloxydin, bentazone and acifluorfen in doses of 0.01xNOAEL (mg/kg bw/day). After 9 months of exposure, the behavior changes were evaluated by open field test and elevated plus maze test and the memory was assessed by passive avoidance test. Chronic vitamin deficiency decreased locomotor and special orientation activity and increased anxiety-like behavior in rats. Exposure to very low doses of a mixture of 6 pesticides caused central nervous effects, manifested as decreased locomotor activity, and increased anxiety levels. Vitamin deficiency and low dose chronic pesticides mixture exposure thus affected the central nervous system, especially long-term memory.


Assuntos
Deficiência de Vitaminas/complicações , Deficiência de Vitaminas/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/fisiopatologia , Praguicidas/toxicidade , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar
5.
Medicine (Baltimore) ; 98(30): e16588, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348299

RESUMO

Pesticide exposure is a major health risk factor among agricultural workers, and poor protective behavior and a lack of awareness concerning the risks of pesticide use in developing countries may increase the intensity of pesticide exposure. This cross-sectional study aimed to explore the relationship between neurologic symptoms and protective behavior and awareness in relation to pesticide use in China. Latent class cluster analysis was used to categorize participants into 3 latent cluster subgroups, namely, a poor protective behavior subgroup, an excellent protective awareness and behavior subgroup, and a poor protective awareness subgroup, using a person-centered approach. Multivariate regression models were used to detect the association between the latent class cluster subgroups and self-reported neurologic symptoms. The results showed that poor protective behavior in pesticide use was an important negative predicator of neurologic symptoms such as reduced sleep quality, frequency of nightmares, debility, hypopsia, and hypomnesis. These findings suggest that targeted interventions for agricultural workers, especially local greenhouse farmers, are urgently needed to improve pesticide protection behavior.


Assuntos
Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/prevenção & controle , Exposição Ocupacional/prevenção & controle , Praguicidas/toxicidade , Roupa de Proteção , Adulto , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Doenças dos Trabalhadores Agrícolas/prevenção & controle , China , Estudos Transversais , Fazendeiros , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos
6.
Curr Drug Saf ; 14(3): 199-208, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31195950

RESUMO

INTRODUCTION: Antibiotic abuse is a common phenomenon in Egypt as medications are prescribed without supervision. It is suggested that the excess use of antibiotics modifies the gut microbiota and plays a role in the development of neurological and psychiatric disorders. OBJECTIVE: The aim of the present study was to use bulb-c mice as models for curam (amoxicillin /clavulanic acid) abuse compared to the locally acting neomycin model, then restoring the probiotic balance to look at the possible effects on the animal brains. METHODS: The results showed early excitable brains demonstrated by S100b immunohistochemistry in both cortexes and hippocampuses of neomycin-treated mice. Staining with PAS stain showed no suggested neurodegenerative changes. Treatment with probiotics improved the S100b immunohistochemistry profile of the curam group partially but failed to overcome the neuroinflammatory reaction detected by hematoxylin and eosin stain. Curam was possibly blamed for the systemic effects. RESULTS: The neurobehavioral tests showed delayed impairment in the open field test for the curam group and impaired new object recognition for the neomycin group. These tests were applied by video recording. The neurobehavioral decline developed 14 days after the end of the 3-week antibiotic course. Unfortunately, curam abuse induced animal fatalities. CONCLUSION: Antibiotic abuse has a neurotoxic effect that works by both local and more prominent systemic mechanisms. It can be said that antibiotic abuse is a cofactor behind the rise of neuropsychiatric diseases in Egypt.


Assuntos
Amoxicilina/toxicidade , Antibacterianos/toxicidade , Comportamento Animal/efeitos dos fármacos , Ácido Clavulânico/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Animais , Microbioma Gastrointestinal , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo
7.
Bull Cancer ; 106(9): 805-811, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31171345

RESUMO

Testicular cancers are the most frequent and the most curable cancers in young men. Treatments of these cancers represent a great success with cure rate over to 95 %. However, chemotherapy side effects may occur during or after several years post-treatment. This review aimed to highlight complications and physical and psychological side effects occurring mainly after chemotherapy treatment for testicular cancer, and to propose a personalized post-cancer plan specific for patients treated for testicular cancer. Treatments of these cancers can cause short-term complications (asthenia, nausea, vomiting, alopecia..). These side effects disappear within a few months after the end of the treatments. Late complications may occur several years post-treatment. Cardiovascular disease, metabolic syndrome and secondary neoplasia represent the most severe late effects among patients treated for testicular cancer. Given the increased incidence of these chemotherapy-induced side effects, it is indispensable to establish a specific follow up which must include a particular vigilance on the risk of occurrence of second cancer, a follow-up of the cardio-vascular risk factors, pulmonary and auditory follow-up, and early detection of psychosocial disorders.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Testiculares/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Cognição/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Síndrome de Fadiga Crônica/induzido quimicamente , Fertilidade/efeitos dos fármacos , Seguimentos , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/prevenção & controle , Pneumopatias/induzido quimicamente , Masculino , Síndrome Metabólica/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Neoplasias Testiculares/psicologia , Fatores de Tempo
8.
Int. j. morphol ; 37(2): 509-514, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002252

RESUMO

Cisplatin is an antineoplastic agent with neuropathy as one of its major side effect. However, effective treatment is lacking. Increasing evidence suggests that cisplatin might damage nerve capillaries leading to impaired functions of blood-nerve barrier (BNB) and neuropathy. This study was aimed to examine the effects of cisplatin on pericytes. Rats were either treated with intraperitoneal injection of cisplatin 2 mg/kg twice a week for five continuous weeks. Cisplatin-treated rats showed reduced body weight, thermal hypoalgesia and slow sciatic motor nerve conduction velocity, indicating neuropathy. The density of pericytes in the distal sciatic nerves determined by immunohistochemistry to desmin was significantly reduced in the cisplatin compared with that of the control groups. Electron microscopic analysis demonstrated the detachment of pericytes from endothelial cells including the disruption of shared basement membrane in the sciatic nerves from cisplatin-treated rats. These data indicate the pericyte loss and detachment caused by cisplatin. Future studies of the BNB components and functions after cisplatin treatment are needed and will be essential for the development of effective treatments against cisplatin-induced neuropathy.


El cisplatino es un agente antineoplásico y presenta como uno de sus principales efectos secundarios, la neuropatía. Sin embargo, falta un tratamiento eficaz. La creciente evidencia sugiere que el cisplatino podría dañar los capilares nerviosos, lo que puede provocar una alteración de las funciones de la barrera hematoencefálica (BHE) y neuropatía. Este estudio tuvo como objetivo examinar los efectos del cisplatino en los pericitos. Las ratas se trataron con inyección intraperitoneal de cisplatino (2 mg/kg) dos veces por semana durante 5 semanas seguidas. Las ratas tratadas con cisplatino mostraron una reducción del peso corporal, hipoalgesia térmica y una velocidad de conducción del nervio ciático lenta, lo que indicaría neuropatía. La densidad de los pericitos en los nervios ciáticos distales determinada por inmunohistoquímica para desmina se redujo significativamente en el grupo cisplatino en comparación con la de los grupos controles. El análisis al microscopio electrónico demostró el desprendimiento de pericitos de las células endoteliales, incluida la ruptura de la membrana basal compartida en los nervios ciáticos de ratas tratadas con cisplatino. Estos datos indican la pérdida de pericitos y el desprendimiento causado por el cisplatino. Se necesitan estudios futuros de los componentes y funciones del BHE después del tratamiento con cisplatino y serán esenciales para el desarrollo de tratamientos efectivos contra la neuropatía inducida por el cisplatino.


Assuntos
Animais , Masculino , Ratos , Cisplatino/toxicidade , Pericitos/efeitos dos fármacos , Doenças do Sistema Nervoso/patologia , Antineoplásicos/toxicidade , Peso Corporal/efeitos dos fármacos , Imuno-Histoquímica , Ratos Wistar , Pericitos/patologia , Microscopia Eletrônica de Transmissão , Doenças do Sistema Nervoso/induzido quimicamente
9.
Environ Res ; 175: 100-107, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31108353

RESUMO

BACKGROUND: The chemicals benzene, toluene, ethylbenzene, and xylenes (BTEX) are neuroactive. Exposures often co-occur because they share common sources. We examined neurologic effects of environmental BTEX exposure among U.S. Gulf coast residents taking into account concomitant exposures. METHODS: We measured blood concentrations of BTEX in 690 Gulf state residents. Neurologic symptoms were ascertained via telephone interview. We used log-binomial regression to estimate associations between blood BTEX levels and self-reported neurologic symptoms independently for the presence of any neurologic, central (CNS), or peripheral nervous system (PNS) symptoms. We estimated associations in single chemical models mutually adjusted for co-occurring BTEX and used weighted quantile sum regression to model associations between the combined BTEX mixture and neurologic symptoms. RESULTS: Half (49%) of participants reported at least one neurologic symptom. Each BTEX chemical was associated with increased CNS and PNS symptoms in single-chemical models comparing the highest to lowest quartile of exposure. After adjusting for coexposures, benzene was associated with CNS symptoms among all participants (PR = 2.13, 95% CI: 1.27, 3.57) and among nonsmokers (PR = 2.30, 95% CI: 1.35, 3.91). After adjusting for coexposures, associations with toluene were apparent only for reporting multiple PNS symptoms (PR = 2.00, 95% CI: 0.96, 4.16). In mixture analyses, a one-quartile increase in BTEX exposure was associated with neurologic symptoms (OR = 1.47, 95% CI: 1.11, 1.98). The weighted quantile sum index weighted benzene most heavily, which was consistent with single chemical analyses. CONCLUSIONS: Increasing blood benzene concentration was associated with increased prevalence of CNS symptoms. In this sample, BTEX-associated neurologic effects are likely driven by exposure to benzene and, to a lesser extent, toluene.


Assuntos
Exposição Ambiental , Hidrocarbonetos Aromáticos , Doenças do Sistema Nervoso , Poluição por Petróleo , Adulto , Benzeno/efeitos adversos , Benzeno/análise , Derivados de Benzeno/efeitos adversos , Derivados de Benzeno/sangue , Feminino , Humanos , Hidrocarbonetos Aromáticos/efeitos adversos , Hidrocarbonetos Aromáticos/sangue , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/epidemiologia , Fatores Socioeconômicos , Tolueno/efeitos adversos , Tolueno/sangue , Xilenos/efeitos adversos , Xilenos/sangue
10.
BMC Bioinformatics ; 20(Suppl 7): 199, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074377

RESUMO

BACKGROUND: Drug adverse events (AEs), or called adverse drug events (ADEs), are ranked one of the leading causes of mortality. The Ontology of Adverse Events (OAE) has been widely used for adverse event AE representation, standardization, and analysis. OAE-based ADE-specific ontologies, including ODNAE for drug-associated neuropathy-inducing AEs and OCVDAE for cardiovascular drug AEs, have also been developed and used. However, these ADE-specific ontologies do not consider the effects of other factors (e.g., age and drug-treated disease) on the outcomes of ADEs. With more ontological studies of ADEs, it is also critical to develop a general purpose ontology for representing ADEs for various types of drugs. RESULTS: Our survey of FDA drug package insert documents and other resources for 224 neuropathy-inducing drugs discovered that many drugs (e.g., sirolimus and linezolid) cause different AEs given patients' age or the diseases treated by the drugs. To logically represent the complex relations among drug, drug ingredient and mechanism of action, AE, age, disease, and other related factors, an ontology design pattern was developed and applied to generate a community-driven open-source Ontology of Drug Adverse Events (ODAE). The ODAE development follows the OBO Foundry ontology development principles (e.g., openness and collaboration). Built on a generalizable ODAE design pattern and extending the OAE and NDF-RT ontology, ODAE has represented various AEs associated with the over 200 neuropathy-inducing drugs given different age and disease conditions. ODAE is now deposited in the Ontobee for browsing and queries. As a demonstration of usage, a SPARQL query of the ODAE knowledge base was developed to identify all the drugs having the mechanisms of ion channel interactions, the diseases treated with the drugs, and AEs after the treatment in adult patients. AE-specific drug class effects were also explored using ODAE and SPARQL. CONCLUSION: ODAE provides a general representation of ADEs given different conditions and can be used for querying scientific questions. ODAE is also a robust knowledge base and platform for semantic and logic representation and study of ADEs of more drugs in the future.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Linezolida/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Preparações Farmacêuticas/administração & dosagem , Sirolimo/efeitos adversos , Software , Adulto , Fatores Etários , Antibacterianos/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Preparações Farmacêuticas/análise
11.
BMJ Case Rep ; 12(5)2019 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-31088820

RESUMO

A 35-year-old man presented to his optician with sudden onset diplopia and a 1-week history of headaches. He was noted to have sixth nerve palsy. The following day he was admitted to hospital with confusion and expressive dysphasia. He had been due to travel to Ghana on business and had received yellow fever (YF) vaccination 18 days prior to onset of headaches. His initial cerebrospinal fluid (CSF) revealed elevated protein, increased white cell count but was PCR negative for standard viral pathogens. Herpes simplex virus (HSV)-1 was detected by PCR in CSF at a very low level from a second lumbar puncture performed 6 days later, and the patient was treated for HSV meningoencephalitis. However, retrospective investigation for yellow fever vaccine-associated neurological disease revealed increasing titres of YF IgG in three serial CSF samples, and no evidence of HSV antibodies in CSF or plasma, ruling out HSV encephalitis.


Assuntos
Doenças do Sistema Nervoso/induzido quimicamente , Vacina contra Febre Amarela/efeitos adversos , Adulto , Herpesvirus Humano 1 , Humanos , Imunoglobulina G/sangue , Masculino , Doenças do Sistema Nervoso/virologia
12.
Sci Total Environ ; 678: 278-287, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31075594

RESUMO

Groundwater, the major source of drinking water in Bengal Delta Plain, is contaminated with geogenic arsenic (As) enrichment affecting millions of people. Children exposed to tubewell water containing As may be associated with thyroid dysfunction, which in turn may impact neurodevelopmental outcomes. However, data to support such relationship is sparse. The purpose of this study was to examine if chronic water As (WAs) from Holocene alluvial aquifers in this region was associated with serum thyroid hormone (TH) and if TH biomarkers were related to neurobehavioral (NB) performance in a group of adolescents. A sample of 32 healthy adolescents were randomly drawn from a child cohort in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh. Half of these participants were consistently exposed to low WAs (<10 µg/L) and the remaining half had high WAs exposure (≥10 µg/L) since birth. Measurements included serum total triiodothyronine (tT3), free thyroxine (fT4), thyrotropin (TSH) and thyroperoxidase antibodies (TPOAb); concurrent WAs and urinary arsenic (UAs); and adolescents' NB performance. WAs and UAs were positively and significantly correlated with TPOAb but were not correlated with TSH, tT3 and fT4. After accounting for covariates, both WAs and UAs demonstrated positive but non-significant relationships with TSH and TPOAb and negative but non-significant relationships with tT3 and fT4. TPOAb was significantly associated with reduced NB performance indicated by positive associations with latencies in simple reaction time (b = 82.58; p < 0.001) and symbol digit (b = 276.85; p = 0.005) tests. TSH was significantly and negatively associated with match-to-sample correct count (b = -0.95; p = 0.05). Overall, we did not observe significant associations between arsenic exposure and TH biomarkers although the relationships were in the expected directions. We observed TH biomarkers to be related to reduced NB performance as hypothesized. Our study indicated a possible mechanism of As-induced neurotoxicity, which requires further investigations for confirmatory findings.


Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Arsênico/efeitos adversos , Doenças do Sistema Nervoso/fisiopatologia , Hormônios Tireóideos/sangue , Poluentes Químicos da Água/efeitos adversos , Adolescente , Bangladesh , Estudos de Coortes , Exposição Ambiental , Feminino , Humanos , Estudos Longitudinais , Masculino , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/induzido quimicamente , Projetos Piloto
13.
Oxid Med Cell Longev ; 2019: 5452727, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001375

RESUMO

Ketamine is used in clinical practice as an anesthetic that pharmacologically modulates neurotransmission in postsynaptic receptors, such as NMDA receptors. However, widespread recreational use of ketamine in "party drug" worldwide since the 1990s quickly spread to the Asian orient region. Thus, this study aimed at investigating the behavioral and oxidative effects after immediate withdrawal of intermittent administration of ketamine in adolescent female rats. For this, twenty female Wistar rats were randomly divided into two groups: control and ketamine group (n = 10/group). Animals received ketamine (10 mg/kg/day) or saline intraperitoneally for three consecutive days. Three hours after the last administration, animals were submitted to open field, elevated plus-maze, forced swim tests, and inhibitory avoidance paradigm. Twenty-four hours after behavioral tests, the blood and hippocampus were collected for the biochemical analyses. Superoxide dismutase, catalase, nitrite, and lipid peroxidation (LPO) were measured in the blood samples. Nitrite and LPO were measured in the hippocampus. The present findings demonstrate that the early hours of ketamine withdrawal induced oxidative biochemistry unbalance in the blood samples, with elevated levels of nitrite and LPO. In addition, we showed for the first time that ketamine withdrawal induced depressive- and anxiety-like profile, as well as short-term memory impairment in adolescent rodents. The neurobehavioral deficits were accompanied by the hippocampal nitrite and LPO-elevated levels.


Assuntos
Ketamina/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Animais , Feminino , Ketamina/farmacologia , Ratos , Ratos Wistar
14.
Rev. neurol. (Ed. impr.) ; 68(7): 301-311, 1 abr., 2019. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-183315

RESUMO

Introducción. Los inhibidores de punto de control inmunológico han supuesto un nuevo paradigma en el tratamiento de diferentes tipos de neoplasias. Sin embargo, con el uso creciente de estos fármacos, se están observando diferentes efectos adversos. Entre ellos destacan los neurológicos, puesto que su frecuencia parece haberse infraestimado en los ensayos aprobatorios. Objetivo. Revisar la fisiopatología y la incidencia de los efectos adversos neurológicos por inhibidores de punto de control neurológicos, así como el abordaje basándose en diferentes guías clínicas. Desarrollo. Se revisan los casos que se han publicado desde la aprobación de los fármacos y añadimos la experiencia de nuestro centro. A su vez, se hace un resumen de las diferentes guías publicadas de forma reciente. Conclusiones. Las complicaciones derivadas del uso de los inhibidores de punto de control inmunológico son frecuentes. Incluyen múltiples cuadros de diferente gravedad, y pueden afectar a cualquier parte del sistema nervioso central y periférico. Además, en tumores del sistema nervioso, puede observarse un fenómeno de pseudoprogresión derivado de la inflamación asociada. Queda pendiente realizar nuevos estudios para conocer en detalle estos efectos adversos y desarrollar guías clínicas con las que optimizar el manejo


Introduction. Checkpoint inhibitors have dramatically transformed cancer treatment. However, due to the increasing number of tumors in which they are used, there is a high number of reported adverse effects. Among them, we highlight neurological side effects. In the approbatory clinical trials, they were thought to be sparse, but they may have been underestimated. Aim. To review the physiopathology and the incidence of neurological side effects due to the use of checkpoint inhibitors, as well as the clinical practice guidelines published in the last years. Development. To review the published case reports of neurological side effects since the approval of checkpoint inhibitors, and our own experience. Moreover, we summarize the main clinical practice guidelines. Conclusions. Checkpoint inhibitors neurological side effects are frequent. A wide variety of central or peripheral nervous system symptoms may develop. In the setting of brain tumors, inflammation due to immune system activation might lead to pseudoprogression. Further studies are needed to better describe these neurological side effects, and to implement clinical guidelines


Assuntos
Humanos , Doenças do Sistema Nervoso/induzido quimicamente , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológico
15.
Pediatrics ; 143(3)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819968

RESUMO

: media-1vid110.1542/5984244681001PEDS-VA_2018-2286Video Abstract BACKGROUND: Overuse of antibiotics can facilitate antibiotic resistance and is associated with adverse neonatal outcomes. We studied the association between duration of antibiotic therapy and short-term outcomes of very low birth weight (VLBW) (<1500 g) infants without culture-proven sepsis. METHODS: We included VLBW infants admitted to NICUs in the Canadian Neonatal Network between 2010-2016 who were exposed to antibiotics but did not have culture-proven sepsis in the first week. Antibiotic exposure was calculated as the number of days an infant received antibiotics in the first week of life. Composite primary outcome was defined as mortality or any major morbidity (severe neurologic injury, retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, or hospital-acquired infection). RESULTS: Of the 14 207 included infants, 21% (n = 2950), 38% (n = 5401), and 41% (n = 5856) received 0, 1 to 3, and 4 to 7 days of antibiotics, respectively. Antibiotic exposure for 4 to 7 days was associated with higher odds of the composite outcome (adjusted odds ratio 1.24; 95% confidence interval [CI] 1.09-1.41). Each additional day of antibiotic use was associated with 4.7% (95% CI 2.6%-6.8%) increased odds of composite outcome and 7.3% (95% CI 3.3%-11.4%) increased odds in VLBW infants at low risk of early-onset sepsis (born via cesarean delivery, without labor and without chorioamnionitis). CONCLUSIONS: Prolonged empirical antibiotic exposure within the first week after birth in VLBW infants is associated with increased odds of the composite outcome. This practice is a potential target for antimicrobial stewardship.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Pesquisa Empírica , Recém-Nascido de muito Baixo Peso/fisiologia , Terapia Intensiva Neonatal/tendências , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Recém-Nascido , Terapia Intensiva Neonatal/métodos , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/epidemiologia , Ontário/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
16.
BMJ ; 364: k4259, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833377

RESUMO

The studyA randomised trial of epinephrine in out-of-hospital cardiac arrestPerkins GD, Ji C, Deakin CD, Quinn T, Nolan JP, Scomparin C, Regan S, Long J, Slowther A, Pocock H, Black JJM, Moore F, Fothergill RT, Rees N, O'Shea L, Docherty M, Gunson I, Han K, Charlton K, Finn J, Petrou S, Stallard N, Gates S, Lall R for the PARAMEDIC2 CollaboratorsPublished on 18 July 2018 N Engl J Med 2018;379:711-21.This project was funded by the National Institute for Health Research HTA Programme (project number 12/127/126).To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000639/adrenaline-can-restart-the-heart-but-is-no-good-for-the-brain.


Assuntos
Epinefrina/administração & dosagem , Parada Cardíaca/tratamento farmacológico , Doenças do Sistema Nervoso/induzido quimicamente , Reanimação Cardiopulmonar/métodos , Epinefrina/efeitos adversos , Epinefrina/uso terapêutico , Parada Cardíaca/complicações , Humanos , Estudos Observacionais como Assunto , Taxa de Sobrevida , Simpatomiméticos/efeitos adversos , Simpatomiméticos/uso terapêutico , Reino Unido/epidemiologia
17.
Environ Res ; 172: 430-436, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826665

RESUMO

BACKGROUND: Quinolinic acid (QA), a neuroactive metabolite of the Kynurenine Pathway (KP), is an excitotoxin that is implicated in the pathogenesis of many neurological disorders. KP is the main tryptophan degradation pathway. Phthalates can structurally mimic tryptophan metabolites and diets containing phthalates in rats enhanced the production and excretion of QA. However, there are no human studies that have examined the association between phthalates and QA. OBJECTIVES: Taking advantage of different mesalamine formulations with/without dibutyl phthalate (DBP), we assessed whether DBP from mesalamine (>1000x background) altered the urinary concentrations of QA. METHODS: Men with inflammatory bowel disease participated in a prospective crossover pilot study. 15 Men were on non-DBP mesalamine (background) at baseline crossed-over for 4 months to high-DBP mesalamine (high) (B1H-Arm) and vice versa for 15 men who were on high-DBP mesalamine at baseline (H1B-Arm). Men provided 60 urine samples (2/man). We estimated crossover and cross-sectional changes in the creatinine normalized-QA using multivariable linear mixed effect models with random intercepts. RESULTS: At baseline, men who were on high-DBP mesalamine (H1B-Arm) had 72%, (95% confidence interval (CI): 18, 151) higher normalized-QA than men who were on background exposure and when high-DBP mesalamine was removed for four months, normalized-QA decreased with 32%, (95% CI: -45.0, -15.1). Consistently, when men in B1H-Arm were newly-exposed to high-DBP mesalamine, normalized-QA increased with 11%, (95% CI: -11, 38). CONCLUSIONS: High-DBP exposure from mesalamine increased the urinary concentrations of QA, which was largely reversed after removal of the high-DBP exposure for four months. This novel hypothesis should warrant new promising research considering the KP and QA concentrations as a plausible mediator for the neurotoxicity possibly linked with phthalate exposures.


Assuntos
Doenças do Sistema Nervoso , Ácidos Ftálicos , Ácido Quinolínico , Animais , Estudos Transversais , Humanos , Masculino , Doenças do Sistema Nervoso/induzido quimicamente , Ácidos Ftálicos/toxicidade , Projetos Piloto , Estudos Prospectivos , Ácido Quinolínico/urina , Ratos
18.
J Trace Elem Med Biol ; 52: 100-110, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30732869

RESUMO

The mercury-related central nervous system disorders have been extensively studied on animal models and human beings. However, clinical evidences of which neurological changes are in fact associated with mercury exposure remains controversial. This systematic review (Prospero registration under the number CRD42016041760) aimed to elucidate the association of methylmercury (MeHg) exposure with neurological alteration in populations living in MeHg-endemic risk area. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis criteria using available databases PubMed, LILACS, Scopus, Web of Science, The Cochrane Library, OpenGrey and Google Scholar. A search of the following terms: "methylmercury compounds", "organomercury compounds", "neurologic manifestations", "memory disorders", "neurobehavioral manifestations" and "communication disorders" were performed in a systematic way. Studies focusing on MeHg exposure and subsequent neurological alteration on humans (>13 years) were included. Evaluation of methodological quality and risk of bias as well as the level of evidence was performed. Our results have identified 470 studies and six articles were eligible for systematic review inclusion criteria. The studies suggested alterations related to the psychosensory, motor and coordination system, as well as motor speech, hearing, visual impairment, mood alterations and loss of intelligent quotient. Of all the six studies, two presented a high risk of bias, with methodological problems related to the confounding factors and all studies presented evidence level ranged from very low to low. In this way our results revealed that a definitive demonstration of an association of MeHg and neurological alterations in human beings is still a pending subject. Future studies in this topic should take into consideration more confident and reliable methods to answer this question.


Assuntos
Exposição Ambiental/efeitos adversos , Compostos de Metilmercúrio/efeitos adversos , Doenças do Sistema Nervoso/induzido quimicamente , Animais , Humanos , Atividade Motora/efeitos dos fármacos , Doenças do Sistema Nervoso/patologia
19.
Int Arch Occup Environ Health ; 92(3): 383-394, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30790043

RESUMO

PURPOSE: There is a lack of knowledge about neurobehavioral performance among patients with manganism and how their performance differs from that of idiopathic Parkinson disease patients (PD). This study was initiated with the aim to describe and compare neurobehavioral performance among patients diagnosed with manganism, PD and a group of referents. MATERIALS AND METHODS: Neurobehavioral performance was assessed in 34 patients diagnosed with manganism, 13 with PD, and 43 healthy workers (turners/fitters) who served as the reference group. Seventeen of the manganism patients had also been tested approximately 65 months previously. RESULTS: Manganism patients scored substantially more poorly than referents on tests for motor speed, manual dexterity and balance. They also performed more poorly than the PD patients on the postural sway test. In contrast, the PD patients had higher postural tremor intensity with narrower frequency dispersion than manganism patients. The pattern of neurobehavioral performance was more asymmetrical in PD compared to manganism patients, in particular when testing for tremor intestity, grooved pegboard and static steadiness, indicating lateralized impairment in the PD patients. The amount of bradykinesia was comparable between the patient groups. Neurobehavioral performance deteriorated slightly among 17 manganism patients followed for 65 months compared with the age-related decline among referents. CONCLUSIONS: Patients with manganism had severe bradykinesia and balance disturbances, but only slight postural tremor. In contrast, PD patients had significant postural tremor and bradykinesia, but only slight balance disturbances. Their neurobehavioral performance indicated lateralized impairment, more unilateral. Neurobehavioral performance deteriorated slightly in manganism patients during a 65-month follow-up.


Assuntos
Intoxicação por Manganês/patologia , Doença de Parkinson/patologia , Desempenho Psicomotor , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Lateralidade Funcional , Humanos , Hipocinesia , Masculino , Intoxicação por Manganês/fisiopatologia , Pessoa de Meia-Idade , Destreza Motora , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/patologia , Testes Neuropsicológicos , Exposição Ocupacional/efeitos adversos , Equilíbrio Postural , Federação Russa , Tremor
20.
Drug Saf ; 42(2): 315-334, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30649750

RESUMO

Adoptive T cell therapy (ACT) is a safe and effective personalized cancer immunotherapy that can comprise naturally occurring ex vivo expanded cells (e.g., tumor-infiltrating lymphocytes [TIL]) or T cells genetically engineered to confer antigen specificity (T-cell receptor [TCR] or chimeric antigen receptor [CAR] engineered T cells) to mediate cancer rejection. In recent years, some ACTs have produced unprecedented breakthrough responses: TIL therapy has moved from melanoma to solid tumor applications, TCR-engineered cells are developed for hematologic and solid tumors, and CAR-engineered T cells have received Food and Drug Administration (FDA) approval for the treatment of patients with certain B-cell malignancies. Although results are encouraging, to date, only a small percentage of patients with advanced malignancies can benefit from ACT. Besides ACT availability and accessibility, treatment-related toxicities represent a major hurdle in the widespread implementation of this therapeutic modality. The large variety of observed toxicities is caused by the infused cell product or as side effects of accompanying medication and chemotherapy. Toxicities can occur immediately or can be delayed. In order to render those highly promising therapeutic approaches safe enough for a wider pool of patients outside of clinical trials, an international consensus for toxicity management needs to be established.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia Adotiva/métodos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Ensaios Clínicos como Assunto/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Neoplasias/metabolismo , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo
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