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1.
Artigo em Inglês | MEDLINE | ID: mdl-32106530

RESUMO

The exposome provides a conceptual model for identifying and characterizing lifetime environmental exposures and resultant health effects. In this study, we applied key exposome concepts to look specifically at the neurodevelopmental pesticide exposome, which focuses on exposures to pesticides that have the potential to cause an adverse neurodevelopmental impact. Using household dust samples from a children's agricultural cohort located in the Yakima Valley of Washington state, we identified 87 individual pesticides using liquid chromatography-tandem mass spectrometry. A total of 47 of these have evidence of neurotoxicity included in the Environmental Protection Agency (EPA) (re)registration materials. We used a mixed effects model to model trends in pesticide exposure. Over the two study years (2005 and 2011), we demonstrate a significant decrease in the neurodevelopmental pesticide exposome across the cohort, but particularly among farmworker households. Additional analysis with a non-parametric binomial analysis that weighted the levels of potentially neurotoxic pesticides detected in household dust by their reference doses revealed that the decrease in potentially neurotoxic pesticides was largely a result of decreases in some of the most potent neurotoxicants. Overall, this study provides evidence that the neurodevelopmental pesticide exposome framework is a useful tool in assessing the effectiveness of specific interventions in reducing exposure as well as setting priorities for future targeted actions.


Assuntos
Expossoma , Praguicidas/efeitos adversos , Agricultura , Criança , Poeira , Fazendas , Humanos , Neurotoxinas/efeitos adversos , Washington
2.
World Neurosurg ; 136: 7-11, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917316

RESUMO

BACKGROUND: Cavernous angiomas (CAs) are vascular malformations that may result in stroke. CASE DESCRIPTION: Herein, we evaluate a CA patient with chronic migraine who experienced 2 documented symptomatic hemorrhages after receiving respective high doses of botulinum toxin (Btx). CONCLUSIONS: Recently, bacterial lipopolysaccharide has been reported to contribute to CA development through Toll-like receptor signaling, causing hemorrhagic angiogenic proliferation. Lipopolysaccharide and Btx share a common intracellular signaling pathway driving CA development and hemorrhage. Significance of these observations is demonstrated by previous works on plasma molecules showing prognostic associations with symptomatic hemorrhages in human CA, related to the same canonical pathways. Authors suggest careful tracking of the association of Btx and hemorrhage in CA patients.


Assuntos
Toxinas Botulínicas Tipo A/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Hemangioma Cavernoso/tratamento farmacológico , Hemorragias Intracranianas/etiologia , Neurotoxinas/efeitos adversos , Adulto , Toxinas Botulínicas Tipo A/administração & dosagem , Dor Crônica , Feminino , Humanos , MAP Quinase Quinase Quinase 3/metabolismo , Angiografia por Ressonância Magnética , Transtornos de Enxaqueca/etiologia , Neurotoxinas/administração & dosagem , Receptores Toll-Like/metabolismo
3.
Chem Biol Interact ; 315: 108884, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31678113

RESUMO

Quinolinic acid (QA) known as a neuro-active metabolite associated with the kynurenine pathway. At high concentrations, QA is often involved in the initiation and development of several human neurologic diseases, like Alzheimer's disease. Because of the QA action as the NMDA receptor, it is considered as a potent excitotoxin in vivo. Since it is probable that different mechanisms are employed by QA, activation of NMDA receptors cannot fully explain the revealed toxicity and it is even believed that there are multiple unknown mechanisms/targets leading to QA cytotoxicity. Herein we report accelerated amyloid oligomerization of 1N4R Tau under the effect of QA, in vitro, then the molecular structure, morphology and toxicity of the protein aggregate were documented by using various theoretical/experimental approaches. The possible mechanism of action of QA-induced Tau oligomerization has also been explored.


Assuntos
Amiloide/metabolismo , Neurotoxinas/efeitos adversos , Agregados Proteicos/efeitos dos fármacos , Piridinas/efeitos adversos , Ácido Quinolínico/efeitos adversos , Doença de Alzheimer/metabolismo , Humanos , Cinurenina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
4.
Int J Mol Sci ; 20(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671557

RESUMO

Parkinson's disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only symptomatic therapies are available. To achieve this goal, clarification of the pathology is required. Attempts have been made to emulate human PD and various animal models have been developed over the decades. Neurotoxin models have been commonly used for PD research. Recently, advances in transgenic technology have enabled the development of genetic models that help to identify new approaches in PD research. However, PD animal model trends have not been investigated. Revealing the trends for PD research will be valuable for increasing our understanding of the positive and negative aspects of each model. In this article, we clarified the trends for animal models that were used to research PD in the 2000s, and we discussed each model based on these trends.


Assuntos
Neurotoxinas/efeitos adversos , Doença de Parkinson/patologia , Animais , Modelos Animais de Doenças , Humanos , Doença de Parkinson/etiologia
5.
Mar Drugs ; 17(10)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590222

RESUMO

Currently, animal experiments in rodents are the gold standard for developmental neurotoxicity (DNT) investigations; however, testing guidelines for these experiments are insufficient in terms of animal use, time, and costs. Thus, alternative reliable approaches are needed for predicting DNT. We chose rat neural stem cells (rNSC) as a model system, and used a well-known neurotoxin, domoic acid (DA), as a model test chemical to validate the assay. This assay was used to investigate the potential neurotoxic effects of Ochratoxin A (OTA), of which the main target organ is the kidney. However, limited information is available regarding its neurotoxic effects. The effects of DA and OTA on the cytotoxicity and on the degree of differentiation of rat rNSC into astrocytes, neurons, and oligodendrocytes were monitored using cell-specific immunofluorescence staining for undifferentiated rNSC (nestin), neurospheres (nestin and A2B5), neurons (MAP2 clone M13, MAP2 clone AP18, and Doublecortin), astrocytes (GFAP), and oligodendrocytes (A2B5 and mGalc). In the absence of any chemical exposure, approximately 46% of rNSC differentiated into astrocytes and neurons, while 40.0% of the rNSC differentiated into oligodendrocytes. Both non-cytotoxic and cytotoxic concentrations of DA and OTA reduced the differentiation of rNSC into astrocytes, neurons, and oligodendrocytes. Furthermore, a non-cytotoxic nanomolar (0.05 µM) concentration of DA and 0.2 µM of OTA reduced the percentage differentiation of rNSC into astrocytes and neurons. Morphometric analysis showed that the highest concentrations (10 µM) of DA reduced axonal length. These indicate that low, non-cytotoxic concentrations of DA and OTA can interfere with the differentiation of rNSC.


Assuntos
Ácido Caínico/análogos & derivados , Células-Tronco Neurais/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Neurotoxinas/efeitos adversos , Ocratoxinas/efeitos adversos , Animais , Astrócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Ácido Caínico/efeitos adversos , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
6.
Ecotoxicology ; 28(8): 964-972, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31414340

RESUMO

Polyaromatic hydrocarbons are a group of chemical pollutants which cause a significant threat to the living organisms in estuaries and marine ecosystems. We report the effect of chrysene, a major PAH pollutant found in Cochin Estuary along the southwest coast of India, on the neuroendocrine and immune gene expression of the post larvae (PL-25) of Penaeus monodon. The PL- 25 of P. monodon were administered with feed coated with increasing concentrations of chrysene (1, 2 and 3 µg/g) for 10 days and the gene expression was studied on 7th, 11th and 15th day. The PL exposed to chrysene showed moulting stress and changes in the levels of moult-inhibiting hormone I (MIH I) indicated by irregular moulting in the experimental tanks. At the molecular level, the higher concentration of chrysene induced two-fold upregulation of neuroendocrine (MIH I) and downregulation of immune (ProPO and crustin) gene on the 7th day of exposure. The expression of MIH I gene reduced on withdrawing the experimental feed (on 11th day), while continued downregulation of ProPO and crustin were observed on the 11th day. The results of the present study indicate that the microgram levels of PAH can impinge the neuroendocrine and immune system of the P. monodon, which may induce morbidity and mortality to the larvae in polluted coastal ecosystems. Therefore, more attention may be given to avoid PAH pollution in the estuaries to maintain a healthy ecosystem and to protect the animals from extinction.


Assuntos
Crisenos/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Imunotoxinas/efeitos adversos , Neurotoxinas/efeitos adversos , Penaeidae/efeitos dos fármacos , Poluentes Químicos da Água/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Sistema Imunitário/efeitos dos fármacos , Índia , Sistemas Neurossecretores/efeitos dos fármacos , Penaeidae/crescimento & desenvolvimento , Penaeidae/imunologia , Penaeidae/fisiologia
7.
J Steroid Biochem Mol Biol ; 192: 105384, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31175966

RESUMO

Insulin-like growth factor-1 (IGF-1), an endogenous peptide, exerts important role in brain development, neurogenesis and neuroprotection. There are accumulating evidence for the interaction of IGF-1 and 17ß-estradiol systems. IGF-1/IGF-1 receptor (IGF-1R) signaling has been reported to regulate G-protein estrogen receptor (GPER) expression in cancer cells. Whether GPER is involved in the neuroprotective effect of IGF-1 against MPTP/MPP+-induced dopaminergic neuronal injury remains unclear. We showed that IGF-1 could improve MPTP-induced motor deficits and ameliorate the decreased contents of DA and its metabolites in striatum as well as the loss of TH-IR neurons in the substantia nigra (SN). IGF-1 pretreatment also reversed the changes of Bcl-2 and Bax protein expressions in SN in MPTP mice. These effects were abolished by IGF-1 receptor (IGF-1R) antagonist JB-1 or GPER antagonist G15 except the inhibitory effect of G15 on Bax protein expression. Moreover, IGF-1 pretreatment enhanced cell survival against MPP+-induced neurotoxicity in SH-SY5Y cells. IGF-1 exerted anti-apoptotic effects by restoring MPP+-induced changes of Bcl-2 and Bax protein expressions as well as mitochondria membrane potential. Co-treatment with JB-1 or G15 could block these effects. Furthermore, IGF-1 regulated the protein expression of GPER through activation of phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) signaling pathways. Overall, we show for the first time that GPER may contribute to the neuroprotective effects of IGF-1 against MPTP/MPP+-induced dopaminergic neuronal injury.


Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Neurônios Dopaminérgicos/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/farmacologia , Neuroblastoma/prevenção & controle , Doença de Parkinson/prevenção & controle , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuroblastoma/etiologia , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/efeitos adversos , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Receptores Estrogênicos/genética , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas
8.
Cornea ; 38(8): 1040-1042, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30950895

RESUMO

PURPOSE: To describe the development and resolution of corneal edema in 3 patients who were exposed to compounds that stimulate dopaminergic pathways. METHODS: We conducted a review of the literature on bilateral corneal edema secondary to amantadine use and report a case series of corneal edema seen in an outpatient ophthalmology specialty clinic, shortly after exposure to agents that enhance dopamine transmission. RESULTS: Cases 1 and 2 report a 25-year-old man with attention-deficit hyperactivity disorder and a 73-year-old man with Parkinson disease who were placed on dopaminergic medications to treat their conditions. The former was administered methylphenidate and the latter patient was administered ropinirole. Both patients developed corneal edema soon afterward. Case 3 is a 67-year-old man with a recent exposure to resin from Euphorbia resinifera, a cactus in his garden. After cessation of the offending medications and treatment for exposure to resiniferatoxin, the corneal edema progressively resolved and visual acuity returned to baseline in all 3 cases. CONCLUSIONS: Methylphenidate, ropinirole, and resiniferatoxin have different mechanisms of actions but have a common end point leading to increased dopamine. We believe that these agents are linked with the reversible corneal edema seen in our 3 patients. This strongly correlates with previous studies that have linked amantadine, a drug that blocks dopamine reuptake, to reversible corneal edema.


Assuntos
Edema da Córnea/induzido quimicamente , Dopaminérgicos/efeitos adversos , Adulto , Idoso , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Edema da Córnea/diagnóstico , Edema da Córnea/fisiopatologia , Diterpenos/efeitos adversos , Dopamina/metabolismo , Humanos , Indóis/efeitos adversos , Masculino , Metilfenidato/efeitos adversos , Neurotoxinas/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
9.
Eur Ann Otorhinolaryngol Head Neck Dis ; 136(4): 313-316, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30910364

RESUMO

BACKGROUND: Iatrogenic cervical spondylodiscitis is rare, but may occur after various medical interventions. METHODS: We report a case of a diabetic 70-years-old female with C5-C6 spondylodiscitis and symptomatic epidural abscess with neck pain and upper limb paresis after endoscopic botulinum toxin injection for the treatment of dysphagia. Treatment included antibiotic therapy with amoxicillin and later on benzylpenicillin for the next ten weeks and corporectomy with spondylodesis. RESULT: The patient made an excellent recovery, with complete resolution of paresis and only minor residual hypoesthesia at one year after operation. CONCLUSION: Cervical spondylodiscitis should be considered early, in patients with neck pain after endoscopic cricopharyngeal injection, as timely diagnosis and treatment can prevent serious and irreversible neurological deficit.


Assuntos
Toxinas Botulínicas/efeitos adversos , Vértebras Cervicais , Discite/etiologia , Doença Iatrogênica , Neurotoxinas/efeitos adversos , Idoso , Toxinas Botulínicas/administração & dosagem , Transtornos de Deglutição/tratamento farmacológico , Discite/microbiologia , Abscesso Epidural/microbiologia , Esfíncter Esofágico Superior , Feminino , Humanos , Injeções Intramusculares/efeitos adversos , Cervicalgia/etiologia , Neurotoxinas/administração & dosagem , Paresia/etiologia , Compressão da Medula Espinal/etiologia , Infecções Estreptocócicas/diagnóstico
10.
Ann Otol Rhinol Laryngol ; 128(4): 316-322, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30614248

RESUMO

OBJECTIVES:: To determine the impact of socioeconomic status (SES) on voice outcomes for spasmodic dysphonia (SD) patients treated with botulinum toxin injections. METHODS:: This was a prospective cross-sectional study in a tertiary care, academic voice clinic in Canada. Adult SD patients returning to the voice clinic for their botulinum toxin injections were recruited from October 2017 to April 2018. Patients completed a questionnaire on demographic data, the Hollingshead Four-Factor Index for socioeconomic status (validated instrument based on education, occupation, gender, and marital status), and the Voice-Handicap Index 10 (VHI-10) (validated instrument on self-reported vocal handicap). Primary outcome was the association between VHI-10 and Hollingshead Index. Secondary variables were median household income by postal code, duration of disease, gender, age, and professional voice user. Descriptive statistics and multiple linear regression were conducted. RESULTS:: One hundred and one patients (age = 62.8 ± 13.7 years, 20.8% male) were recruited with VHI-10 of 22.1 ± 8.1 (out of 40) and Hollingshead Index of 46.3 ± 11.7 (range, 8-66). Median household income was $75 875 ± $16 393, which was above the Canadian average of $70 336. About 91.1% were Caucasian, 54.4% had university degree, 86.1% spoke English, and 43.5% were employed. In multiple linear regression, there was mild to moderate negative correlation (r = -.292, P = .004) between VHI-10 and Hollingshead Index when controlling for disease duration, age, gender, and professional voice use. CONCLUSION:: SD patients treated with botulinum toxin were mostly affluent, Caucasian, well educated, and English speakers. Lower self-perceived vocal handicap was associated with higher socioeconomic status.


Assuntos
Toxinas Botulínicas , Disfonia , Classe Social , Qualidade da Voz , Idoso , Atitude Frente a Saúde , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/efeitos adversos , Canadá/epidemiologia , Estudos Transversais , Avaliação da Deficiência , Disfonia/epidemiologia , Disfonia/fisiopatologia , Disfonia/psicologia , Disfonia/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurotoxinas/administração & dosagem , Neurotoxinas/efeitos adversos , Estudos Prospectivos , Autorrelato/estatística & dados numéricos
11.
Mar Drugs ; 17(1)2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30621279

RESUMO

Tetrodotoxin (TTX) is a potent marine neurotoxin with bacterial origin. To date, around 28 analogs of TTX are known, but only 12 were detected in marine organisms, namely TTX, 11-oxoTTX, 11-deoxyTTX, 11-norTTX-6(R)-ol, 11-norTTX-6(S)-ol, 4-epiTTX, 4,9-anhydroTTX, 5,6,11-trideoxyTTX, 4-CysTTX, 5-deoxyTTX, 5,11-dideoxyTTX, and 6,11-dideoxyTTX. TTX and its derivatives are involved in many cases of seafood poisoning in many parts of the world due to their occurrence in different marine species of human consumption such as fish, gastropods, and bivalves. Currently, this neurotoxin group is not monitored in many parts of the world including in the Indian Ocean area, even with reported outbreaks of seafood poisoning involving puffer fish, which is one of the principal TTX vectors know since Egyptian times. Thus, the main objective of this review was to assess the incidence of TTXs in seafood and associated seafood poisonings in the Indian Ocean and the Red Sea. Most reported data in this geographical area are associated with seafood poisoning caused by different species of puffer fish through the recognition of TTX poisoning symptoms and not by TTX detection techniques. This scenario shows the need of data regarding TTX prevalence, geographical distribution, and its vectors in this area to better assess human health risk and build effective monitoring programs to protect the health of consumers in Indian Ocean area.


Assuntos
Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/etiologia , Neurotoxinas/efeitos adversos , Alimentos Marinhos/efeitos adversos , Tetrodotoxina/efeitos adversos , Animais , Humanos , Incidência , Oceano Índico
12.
Ann Thorac Surg ; 107(2): 567-572, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30071236

RESUMO

BACKGROUND: Industrial chemicals are increasingly recognized as potential developmental neurotoxicants. Di(2-ethylhexyl) phthalate (DEHP), used to impart flexibility and temperature tolerance to polyvinylchloride, and bisphenol A (BPA), used to manufacture polycarbonate, are commonly present in medical devices. The magnitude of exposure in neonates during hospitalization for cardiac operations is unknown. METHODS: We quantified urinary concentrations of DEHP metabolites and BPA preoperatively and postoperatively in neonates undergoing cardiac operations and their mothers. Urinary concentrations of these biomarkers reflect recent exposures (half-lives are approximately 6 to 24 hours). Biomarker concentrations in mothers' and infants' preoperative and postoperative samples were compared. RESULTS: Operations were performed in 18 infants (mean age, 5 ± 4 [SD] days). The maternal sample was obtained on postpartum day 4 ± 4. The preoperative urine sample was obtained on day-of-life 4 ± 2 and the postoperative sample on day-of-life 6 ± 4. Mean maternal concentrations for DEHP metabolites and BPA were at the 50th percentile for females in the United States general population. Infant preoperative concentrations of 1 DEHP metabolite and BPA were significantly higher than maternal concentrations. Postoperative concentrations for all DEHP metabolites were significantly greater than preoperative concentrations. CONCLUSIONS: There is considerable perioperative exposure to DEHP and BPA for neonates undergoing cardiac operations. Infant concentrations for both BPA and DEHP metabolites were significantly higher than maternal concentrations, consistent with the infant's exposure to medical devices. Further study is needed to determine the potential role of these suspect neurotoxicants in the etiology of neurodevelopmental disability after cardiac operations.


Assuntos
Compostos Benzidrílicos/efeitos adversos , Dietilexilftalato/efeitos adversos , Exposição Ambiental/efeitos adversos , Equipamentos e Provisões/efeitos adversos , Cardiopatias Congênitas/cirurgia , Neurotoxinas/efeitos adversos , Fenóis/efeitos adversos , Compostos Benzidrílicos/urina , Biomarcadores/urina , Dietilexilftalato/urina , Feminino , Seguimentos , Cardiopatias Congênitas/urina , Humanos , Recém-Nascido , Masculino , Neurotoxinas/urina , Fenóis/urina , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco
13.
Biochim Biophys Acta Gen Subj ; 1863(12): 129243, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30385391

RESUMO

All chemical forms of Hg can affect neurodevelopment; however, low levels of organic Hg (methylmercury-MeHg and ethylmercury-EtHg in Thimerosal-containing vaccines, hereafter 'TCV') exposures during early life (pregnancy and lactation) co-occur with other environmental neurotoxic substances. These neurotoxicants may act in parallel, synergistically, or antagonistically to Hg. Nevertheless, the risks of neurotoxicity associated with multiple neuro-toxicants depend on type, time, combinations of exposure, and environmental and/or genetic-associated factors. Neurological developmental disorders, delays in cognition and behavioral outcomes associated with multiple exposures (which include Hg) may show transient or lasting outcomes depending on constitutional and/or environmental factors that can interact to neutralize, aggravate or attenuate these effects; often these studies are challenging to interpret. During pregnancy and lactation, fish-MeHg exposure is frequently confounded with the opposing effects of neuroactive nutrients (in fish) that lead to positive, negative, or no effects on neurobehavioral tests. In infancy, exposures to acute binary mixtures (TCV- EtHg and Al-adjuvants in infant immunizations) are associated with increased risks of tics and other developmental disorders. Despite the certitude that promulgates single environmental neurotoxicants, empirical comparisons of combined exposures indicate that Hg-related outcome is uneven. Hg in combination with other neurotoxic mixtures may elevate risks of neurotoxicity, but these risks arise in circumstances that are not yet predictable. Therefore, to achieve the goals of the Minamata treaty and to safeguard the health of children, low levels of mercury exposure (in any chemical form) needs to be further reduced whether the source is environmental (air- and food-borne) or iatrogenic (pediatric TCVs).


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/etiologia , Feto/efeitos dos fármacos , Mercúrio/efeitos adversos , Sistema Nervoso/efeitos dos fármacos , Neurotoxinas/efeitos adversos , Vacinas/efeitos adversos , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Gravidez
14.
Neuropharmacology ; 144: 219-232, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30366005

RESUMO

Methoxetamine (MXE) is a novel psychoactive substance that can induce several short-term effects on emotional states and behavior. However, little is known about the persistent emotional and behavioral effects of MXE. Moreover, neurotoxic effects of MXE have been hypothesized, but never demonstrated in vivo. To clarify these issues, rats received repeated treatment with MXE every other day (0.1-0.5 mg/kg, i.p., × 5), and 7 days later they were challenged with MXE (0.1-0.5 mg/kg, i.p.). Behavioral effects of MXE were first evaluated by measuring emission of ultrasonic vocalizations and locomotor activity after each administration. Thereafter, persistent behavioral effects of MXE were evaluated, starting 8 days after challenge, through elevated plus maze, spontaneous alternation, novel object recognition, and marble burying tests. After completion of behavioral analysis, neurotoxic effects of MXE were evaluated by measuring densities of dopamine transporter, tyrosine hydroxylase, and serotonin transporter in various brain regions. Repeated treatment and challenge with MXE affected neither calling behavior nor locomotor activity of rats. Conversely, rats previously treated with MXE exhibited behavioral alterations in the elevated plus maze, marble burying and novel object recognition tests, suggestive of increased anxiety and impaired non-spatial memory. Noteworthy, the same rats displayed dopaminergic damage in the medial prefrontal cortex, nucleus accumbens, caudate-putamen, substantia nigra pars compacta, and ventral tegmental area, along with accumbal serotonergic damage. Our findings show for the first time that repeated administration of MXE induces persistent behavioral abnormalities and neurotoxicity in rats, which can help elucidating the risks associated with human MXE consumption.


Assuntos
Comportamento Animal/efeitos dos fármacos , Cicloexanonas/efeitos adversos , Cicloexilaminas/efeitos adversos , Síndromes Neurotóxicas , Neurotoxinas/efeitos adversos , Psicotrópicos/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Relação Dose-Resposta a Droga , Emoções/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , Proteínas de Ligação a RNA/metabolismo , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo
15.
Chemosphere ; 214: 623-632, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30290362

RESUMO

The non-proteinogenic amino acid ß-N-methylamino-l-alanine (BMAA) is associated with the development of neurodegenerative diseases such as Alzheimer's disease, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS-PDC) and amyotrophic lateral sclerosis. BMAA is known to induce neurotoxic effects leading to neurodegeneration via multiple mechanisms including misfolded protein accumulation, glutamate induced excitotoxicity, calcium dyshomeostasis, endoplasmic reticulum stress and oxidative stress. In the present study, for the first time, genotoxic activity of BMAA (2.5, 5, 10 and 20 µg/mL) was studied in human peripheral blood cells (HPBCs) using the comet and cytokinesis-block micronucleus cytome assays. In addition, the influence of BMAA on the oxidative stress was assessed. At non-cytotoxic concentrations BMAA did not induce formation of DNA strand breaks in HPBCs after 4 and 24 h exposure; however, it significantly increased the number of micronuclei after 24 and 48 h at 20 µg/mL and nucleoplasmic bridges after 48 h at 20 µg/mL. The frequency of nuclear buds was slightly though non-significantly increased after 48 h. Altogether, this indicates that in HPBCs BMAA is clastogenic and induces complex genomic alterations including structural chromosomal rearrangements and gene amplification. No influence on oxidative stress markers was noticed. These findings provide new evidence that environmental neurotoxin BMAA, in addition to targeting common pathways involved in neurodegeneration, can also induce genomic instability in non-target HPBCs suggesting that it might be involved in cancer development. Therefore, these data are important in advancing our current knowledge and opening new questions in the understanding of the mechanisms of BMAA toxicity, particularly in the context of genotoxicity.


Assuntos
Diamino Aminoácidos/efeitos adversos , Biomarcadores/metabolismo , Células Sanguíneas/patologia , Neurotoxinas/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Adulto , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Dano ao DNA , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Agonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Humanos
16.
J Cosmet Dermatol ; 18(1): 55-58, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29569830

RESUMO

BACKGROUND: Abobotulinum- toxin A is used extensively for the treatment of frown (glabellar) lines. AIMS: The aim of this study was to evaluate the efficacy and complications of a new injection technique and to assess the amount of satisfaction in patients with the frown lines. METHODS: This cross-sectional study was conducted in 104 patients with moderate-to-severe glabellar lines. In the new technique by reassessing the responsible anatomic muscles of wrinkles, we tried to modify the injection technique of Abobotulinum-toxin A to yield more favorable results. The range and severity of frown lines were assessed by a 4-score test and a photograph taken before and 2 weeks after the injection. Patients were followed up to 180 days after injection. RESULTS: The response time of 87.5% of patients was within the first 48 hours and the remaining 12.5% showed the symptoms within the first week after injection. At 30 days after injection, the frown lines had disappeared in 88.5% of patients in static mode and 85.6% in mechanic mode. Maximum injection durability in the first 3, 4, and 6 months after injection was 82%, 52%, and 38%, respectively. The amount of complete satisfaction after 3 months was reported to be 86.5%. CONCLUSIONS: This study indicated that the new injection technique of Abobotulinum-toxin A could be beneficial in the treatment of frown lines with more satisfactory results, especially in those patients who were not contented with the present conventional method.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Técnicas Cosméticas , Neurotoxinas/administração & dosagem , Envelhecimento da Pele , Adulto , Toxinas Botulínicas Tipo A/efeitos adversos , Estudos Transversais , Expressão Facial , Músculos Faciais/efeitos dos fármacos , Feminino , Testa , Humanos , Injeções Intramusculares/métodos , Masculino , Pessoa de Meia-Idade , Neurotoxinas/efeitos adversos , Satisfação do Paciente , Fotografação
17.
Clin. biomed. res ; 39(2): 161-170, 2019.
Artigo em Português | LILACS | ID: biblio-1023105

RESUMO

O botulismo é uma doença resultante da ação de uma toxina produzida pelo Clostridium botulinum. Devido à sua gravidade e alta mortalidade é considerado um problema de saúde pública. Nesta revisão apresentamos os principais fatores de riscos associados à intoxicação alimentar provocada pelo Clostridium botulinum, bem como realizamos um levantamento epidemiológico sobre o botulismo alimentar e infantil. A busca bibliográfica considerou as bases de dados Scielo, Medline, Lilacs e PubMed. Foram selecionados artigos originais e relatos de caso publicados em inglês, espanhol e português, incluindo publicações dos últimos dez anos. A partir das análises dos títulos, resumos e artigos, um total de 26 artigos foram incluídos nesta revisão. Verificou-se predomínio de 54% dos casos referentes ao botulismo alimentar, dos quais aproximadamente 58% confirmaram a ocorrência da toxina tipo A; e 35% referente ao botulismo infantil. Na literatura consultada os principais sintomas, relacionados ao botulismo alimentar, identificados foram: visão turva, vômito, paralisia flácida, náuseas, tontura, diplopia, dificuldade respiratória, disatria, disfagia, fraqueza muscular, boca seca, ptose e cefaleia. Dentre as principais fontes de contaminação, 65% das publicações selecionadas identificaram as conservas como principal causa do botulismo alimentar. Embora o mel (42%) seja a única fonte registrada de alimento veiculador do agente causador do botulismo infantil, alguns relatos na literatura (25%) associaram à doença com a inalação de poeira contendo esporos do Clostridium botulinum, bem como o uso de plantas medicinais (25%). Os sintomas mais comuns observados na literatura foram: constipação dificuldade respiratória e dificuldade de sucção. Apesar de vários relatos na literatura acerca das duas doenças, o botulismo ainda é muito subnotificado dado ao diagnóstico muitas vezes equivocado, ressaltando-se a importância do diagnóstico precoce no tratamento da doença pelos profissionais de saúde, bem como a disponibilidade de informações relevantes para a investigação epidemiológica de doenças de notificação compulsória. Os dados apresentados também demonstram a importância de sensibilizar a população dos principais riscos e medidas de prevenção, já que a maioria dos casos relatados está relacionada a práticas inadequadas de preparo dos alimentos. (AU)


Botulism is a disease resulting from the action of a toxin produced by Clostridium botulinum. Because of its severity and high mortality, it is considered a public health problem. In this review, we present the main risk factors associated with food poisoning caused by Clostridium botulinum, as well as an epidemiological survey on foodborne and infant botulism. A bibliographic search was conducted in SciELO, MEDLINE, LILACS and PubMed databases. Original articles and case reports published in English, Spanish and Portuguese in the past ten years were selected. After analyzing titles, abstracts and articles, 26 articles were used in this review. In total, 54% of the cases were related to foodborne botulism, of which approximately 58% had confirmed type A botulism, and 35% were related to infant botulism. In the literature consulted, the main symptoms related to foodborne botulism were blurred vision, vomiting, flaccid paralysis, nausea, dizziness, diplopia, respiratory distress, dysarthria, dysphagia, muscle weakness, dry mouth, ptosis and headache. Among the sources of contamination, 65% of the published studies reported home-canned foods as the main cause of foodborne botulism. Although honey (42%) is the only reported food source for the agent causing infant botulism, some reports in the literature (25%) associated the disease with inhalation of dust containing Clostridium botulinum spores, as well as use of medicinal plants (25%). The most common symptoms observed in the literature were constipation, difficulty breathing and difficulty suckling. Although several reports on the two forms of the disease exist, botulism remains under-reported because of often incorrect diagnosis. Thus, early diagnosis is important for an adequate treatment provided by health professionals, as well as availability of relevant information for the epidemiological investigation of notifiable diseases. The data presented in this study also demonstrate the importance of raising people's awareness to main risks and prevention measures, as most reported cases were related to inadequate food preparation practices. (AU)


Assuntos
Humanos , Lactente , Botulismo/epidemiologia , Neurotoxinas/efeitos adversos , Esporos Bacterianos , Clostridium botulinum/fisiologia , Lactente
18.
J Toxicol Sci ; 43(11): 671-684, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405000

RESUMO

Thalidomide was originally developed to treat primary neurological and psychiatric diseases. There are reports of anticonvulsant effects of thalidomide in rats and antiepileptic effects in patients. Hence, thalidomide (100, 200 and 400 mg/kg) was herein administered to mice to evaluate possible protection against seizures induced by the systemic administration of neurotoxins: 10 mg/kg of 4-aminopyridine (4-AP), 90 mg/kg of pentylenetetrazol (PTZ), or 380 mg/kg of pilocarpine. The effect of an NO and COX inhibitor (7-NI and ibuprofen, respectively) was also examined. The results show that thalidomide (1) induces the typical sedative effects, (2) has no anticonvulsant effect in mice treated with 4-AP, and (3) has anticonvulsant effect (400 mg/kg) in mice treated with PTZ and pilocarpine. It was found that 7-NI has an anticonvulsant effect in the pilocarpine model and that thalidomide's effect is not enhanced by its presence. However, thalidomide (200 mg/kg) plus 7-NI or ibuprofen tend to have a toxic effect in PTZ model. On the other hand, the combination of thalidomide and 7-NI or ibuprofen protects against pilocarpine-induced seizures. In conclusion, thalidomide did not exert an anticonvulsant effect for clonic-tonic type convulsions (4-AP), but it did so for seizures induced by PTZ and pilocarpine (representing absence seizures and status epilepticus, respectively). NO and prostaglandins were involved in the convulsive process elicited by pilocarpine.


Assuntos
Anticonvulsivantes , Neurotoxinas/efeitos adversos , Pentilenotetrazol/efeitos adversos , Pilocarpina/efeitos adversos , Convulsões/prevenção & controle , Talidomida/administração & dosagem , Talidomida/farmacologia , 4-Aminopiridina/efeitos adversos , Doença Aguda , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Ibuprofeno/administração & dosagem , Indazóis/administração & dosagem , Masculino , Camundongos Endogâmicos , Óxido Nítrico , Convulsões/induzido quimicamente
19.
J Am Acad Dermatol ; 79(3): 407-419, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30119865

RESUMO

Cosmetic dermatologic surgery has evolved to be a minimally invasive field that addresses patient concerns with a multimodal approach while minimizing adverse events and downtime. Within the armamentarium of dermatologic surgery, injections of soft tissue augmentation materials and neuromodulators are key tools for recontouring the aging face. Treatment of the individual patient is preceded by a comprehensive consultation that elicits patient concerns and preferences. A treatment plan is collaboratively developed to correct relevant deficits and retreat as appropriate to maintain the correction. The goal of volumization with fillers is to recreate atrophic subcutis and dermis, thereby filling the deflated face and returning it to a more youthful contour. Neurotoxins can help minimize the emergence of static wrinkles and selectively recontour the face. Treatment techniques for both filler and neurotoxin injections are customized for particular patient needs and are based on the type of deficit and the anatomic location.


Assuntos
Técnicas Cosméticas , Preenchedores Dérmicos/administração & dosagem , Dermatologia/métodos , Injeções Subcutâneas/métodos , Neurotoxinas/administração & dosagem , Envelhecimento da Pele , Preenchedores Dérmicos/efeitos adversos , Humanos , Injeções Subcutâneas/instrumentação , Neurotoxinas/efeitos adversos , Planejamento de Assistência ao Paciente , Educação de Pacientes como Assunto , Seleção de Pacientes
20.
J Am Acad Dermatol ; 79(3): 423-435, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30119866

RESUMO

Injectable fillers and neuromodulators are used for a range of indications pertaining to the correction of facial aging and disfigurement. Fillers can correct soft tissue loss, depressed scars, and atrophy or asymmetry induced by systemic or local disease. Neuromodulators correct muscle-mediated skin creases, reshape the face, and address right-left functional asymmetry. Among the prepackaged injectable fillers approved by the US Food and Drug administration are hyaluronic acid derivatives, calcium hydroxylapatite, and poly-L-lactic acid; neuromodulators include three types of botulinum toxin type A and one type of type B. Adverse events associated with injections are typically mild, easily managed injection pain, followed by redness, swelling, and bruising. Asymmetry, nodules, ptosis, and intravascular occlusion are less common. Filler and toxin injections are part of a complete treatment plan. Reinjection is typically required to maintain the clinical effect, and combination treatment with laser and energy devices can enhance the aggregate effect.


Assuntos
Cicatriz/tratamento farmacológico , Preenchedores Dérmicos/administração & dosagem , Dermatologia/métodos , Neurotoxinas/administração & dosagem , Envelhecimento da Pele , Pele/patologia , Atrofia/tratamento farmacológico , Técnicas Cosméticas , Preenchedores Dérmicos/efeitos adversos , Esquema de Medicação , Humanos , Neurotoxinas/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Dor/etiologia , Dor/prevenção & controle , Manejo da Dor/métodos , Seleção de Pacientes
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