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1.
BMC Neurol ; 22(1): 181, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578314

RESUMO

BACKGROUND: Bromine compounds are used in several drugs, including over-the-counter drugs. They sometimes cause intoxication known as bromism. Although the acute neurological symptoms and sequelae of bromism vary, few reports have mentioned acute encephalopathy. CASE PRESENTATION: We report two cases of bromisoval-induced bromism with status epilepticus. Presence of pseudohyperchloremia and history of over-the-counter medication use guided the diagnosis. In the acute phase, our patients showed bilateral medial thalamic lesions on magnetic resonance imaging. The imaging findings were similar to those of Wernicke's encephalopathy. Although these findings improved in the chronic phase, neuropsychiatric sequelae, such as confabulation and amnesia, occurred. CONCLUSION: Bromism can cause acute encephalopathy, and it is important to differentiate it from Wernicke-Korsakoff syndrome.


Assuntos
Bromisoval , Síndrome de Korsakoff , Estado Epiléptico , Encefalopatia de Wernicke , Humanos , Síndrome de Korsakoff/complicações , Transtornos da Memória/etiologia , Estado Epiléptico/complicações , Estado Epiléptico/diagnóstico , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/etiologia , Encefalopatia de Wernicke/patologia
2.
Neurobiol Aging ; 105: 137-147, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34062489

RESUMO

Alzheimer's disease (AD) is the prevailing form of dementia. Protein degradation and antioxidant pathways have a critical role in preventing the accumulation of protein aggregation; thus, failure of proteostasis in neurons along with redox imbalance mark AD. Herein, we exploited an AD Drosophila model expressing human amyloid precursor (hAPP) and beta-secretase 1 (hBACE1) proteins, to better understand the role of proteostatic or antioxidant pathways in AD. Ubiquitous expression of hAPP, hBACE1 in flies caused more severe degenerative phenotypes versus neuronal targeted expression; it also, suppressed proteasome activity, increased oxidative stress and significantly enhanced stress-sensitivity. Overexpression of Prosß5 proteasomal subunit or Nrf2 transcription factor in AD Drosophila flies partially restored proteasomal activity but did not rescue hAPP, hBACE1 induced neurodegeneration. On the other hand, expression of autophagy-related Atg8a in AD flies decelerated neurodegeneration, increased stress-resistance, and improved flies' health-/lifespan. Overall, our data suggest that the noxious effects of amyloid-beta aggregates can be alleviated by enhanced autophagy, thus dietary or pharmacological interventions that target autophagy should be considered in AD therapeutic approaches.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/terapia , Autofagia/genética , Autofagia/fisiologia , Drosophila , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/efeitos adversos , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Bromisoval , Modelos Animais de Doenças , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Combinação de Medicamentos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Degeneração Neural/genética , Degeneração Neural/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo
3.
Rinsho Shinkeigaku ; 60(11): 795-798, 2020 Nov 27.
Artigo em Japonês | MEDLINE | ID: mdl-33115996

RESUMO

A 37-year-old man who had been on bromvalerylurea (BU) medication for 11 years at a maximum dose of 2,400 mg per day for headache therapy was admitted to our hospital due to gait disturbance. He had weight loss and exanthema all over his body. Cognitive dysfunction, intellectual deterioration, attention disturbance, decreased muscle strength, and decreased vibratory sense in the lower limbs were observed. Brain MRI showed diffuse brain atrophy, and a peripheral nerve conduction examination revealed decreased nerve conduction velocity and action potential amplitude in the extremities. We diagnosed him with chronic BU intoxication based on pseudohyperchloremia, BU detected in the blood, and bromide elevation. By discontinuing BU and performing intravenous infusion, neurological symptoms and exanthema were improved, and peripheral nerve conduction examination findings also improved. There are few reports of peripheral neuropathy cases of chronic BU intoxication; herein we report one such case along with previously reported cases.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Bromisoval/envenenamento , Hipnóticos e Sedativos/envenenamento , Polineuropatias/diagnóstico , Polineuropatias/etiologia , Adulto , Atrofia/diagnóstico por imagem , Atrofia/etiologia , Doença Crônica , Extremidades/inervação , Hidratação , Transtornos Neurológicos da Marcha/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Polineuropatias/terapia , Tomografia Computadorizada de Emissão de Fóton Único
4.
Glia ; 66(10): 2158-2173, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30194744

RESUMO

Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1ß (IL-1ß), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor ß1 (TGFß1), interleukin-6 (IL-6), and tumor necrosis factor α at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGFß1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Lesões Encefálicas Traumáticas/fisiopatologia , Bromisoval/farmacologia , Hipnóticos e Sedativos/farmacologia , Macrófagos/fisiologia , Microglia/fisiologia , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Células Cultivadas , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Macrófagos/efeitos dos fármacos , Masculino , Microglia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/lesões , Prosencéfalo/patologia , Prosencéfalo/fisiopatologia , RNA Mensageiro/metabolismo , Ratos Wistar , Ferimentos Perfurantes/tratamento farmacológico , Ferimentos Perfurantes/patologia , Ferimentos Perfurantes/fisiopatologia
5.
J Pharmacol Sci ; 134(2): 116-123, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28645489

RESUMO

An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level.


Assuntos
Anti-Inflamatórios/farmacologia , Bromisoval/farmacologia , Hipnóticos e Sedativos/farmacologia , Microglia/efeitos dos fármacos , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Trifosfato de Adenosina/metabolismo , Animais , Linhagem Celular , Citocinas/metabolismo , Complexo II de Transporte de Elétrons/antagonistas & inibidores , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/genética , Janus Quinase 1/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Fosforilação , Ratos Wistar , Rotenona/farmacologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo
6.
J Health Soc Behav ; 58(2): 147-165, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28661778

RESUMO

In this study, I examine how parents' cultural knowledge shapes experiences navigating the healthcare system after a child is diagnosed with cancer and the extent to which differential styles of health-related advocacy contribute to inequalities in healthcare experiences. I combine data from parents' perspectives, physicians' perspectives, and direct observation of clinical interactions and find three overarching styles of health-related advocacy. Findings show that cultural dispositions and competencies shape parents' abilities to effectively navigate the healthcare system, and physicians differentially reward each style of health-related advocacy. Parents' styles of advocacy shape relationships with clinicians, physicians' perceptions of families, and physicians' strategies for interacting with families. These findings refine understanding of the mechanisms through which social class manifests in clinical interactions, shapes patient-physician relationships, and contributes to unequal healthcare experiences.


Assuntos
Cultura , Acesso aos Serviços de Saúde , Disparidades nos Níveis de Saúde , Relações Profissional-Família , Relações Profissional-Paciente , Bromisoval , Catecóis , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Inositol , Masculino , Classe Social , Fatores Socioeconômicos , Inquéritos e Questionários
7.
Neurochem Int ; 99: 158-168, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27392596

RESUMO

The low molecular weight organic compound bromovalerylurea (BU) has long been used as a hypnotic/sedative. In the present study, we found that BU suppressed mRNA expression of proinflammatory factors and nitric oxide release in lipopolysaccharide (LPS)-treated rat primary microglial cell cultures. BU prevented neuronal degeneration in LPS-treated neuron-microglia cocultures. The anti-inflammatory effects of BU were as strong as those of a synthetic glucocorticoid, dexamethasone. A rat hemi-Parkinsonian model was prepared by injecting 6-hydroxydopamine into the right striatum. BU was orally administered to these rats for 7 days, which ameliorated the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and alleviated motor deficits. BU suppressed the expression of mRNAs for interferon regulatory factors (IRFs) 1, 7 and 8 in the right (lesioned) ventral midbrain as well as those for proinflammatory mediators. BU increased mRNA expression of various neuroprotective factors, including platelet-derived growth factor and hepatocyte growth factor, but it did not increase expression of alternative activation (M2) markers. In microglial culture, BU suppressed the LPS-induced increase in expression of IRFs 1 and 8, and it reduced LPS-induced phosphorylation of JAK1 and STATs 1 and 3. Knockdown of IRFs 1 and 8 suppressed LPS-induced NO release by microglial cells. These results suggest that suppression of microglial IRF expression by BU prevents neuronal cell death in the injured brain region, where microglial activation occurs. Because many Parkinsonian patients suffer from sleep disorders, BU administration before sleep may effectively ameliorate neurological symptoms and alleviate sleep dysfunction.


Assuntos
Bromisoval/farmacologia , Neurônios Dopaminérgicos/metabolismo , Hipnóticos e Sedativos/farmacologia , Fatores Reguladores de Interferon/biossíntese , Microglia/metabolismo , Oxidopamina/toxicidade , Animais , Células Cultivadas , Técnicas de Cocultura , Neurônios Dopaminérgicos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/genética , Masculino , Microglia/efeitos dos fármacos , Ratos , Ratos Wistar
10.
J Dermatol ; 43(5): 564-6, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26507105

RESUMO

Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides.


Assuntos
Brometos/efeitos adversos , Bromisoval/efeitos adversos , Erupção por Droga/patologia , Hipnóticos e Sedativos/efeitos adversos , Medicamentos sem Prescrição/efeitos adversos , Pioderma Gangrenoso/patologia , Doenças Raras/patologia , Equilíbrio Ácido-Base , Adulto , Anorexia Nervosa/tratamento farmacológico , Biópsia , Brometos/administração & dosagem , Brometos/sangue , Bromisoval/sangue , Bromisoval/uso terapêutico , Cloretos/sangue , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Erupção por Droga/sangue , Erupção por Droga/etiologia , Eritema/induzido quimicamente , Eritema/tratamento farmacológico , Eritema/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/uso terapêutico , Medicamentos sem Prescrição/análise , Prednisolona/uso terapêutico , Pioderma Gangrenoso/tratamento farmacológico , Doenças Raras/sangue , Doenças Raras/induzido quimicamente , Convulsões/etiologia , Síncope/etiologia , Suspensão de Tratamento
11.
Biochem Biophys Res Commun ; 459(2): 319-326, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25732089

RESUMO

Sepsis is a severe pathologic event, frequently causing death in critically ill patients. However, there are no approved drugs to treat sepsis, despite clinical trials of many agents that have distinct targets. Therefore, a novel effective treatment should be developed based on the pathogenesis of sepsis. We recently observed that an old hypnotic drug, bromvalerylurea (BU) suppressed expression of many kinds of pro- and anti-inflammatory mediators in LPS- or interferon-γ activated alveolar and peritoneal macrophages (AMs and PMs). Taken the anti-inflammatory effects of BU on macrophages, we challenged it to septic rats that had been subjected to cecum-ligation and puncture (CLP). BU was subcutaneously administered to septic rats twice per day. Seven days after CLP treatment, 85% of septic rats administrated vehicle had died, whereas administration of BU reduce the rate to 50%. Septic rats showed symptoms of multi-organ failure; respiratory, circulatory and renal system failures as revealed by histopathological analyses, blood gas test and others. BU ameliorated these symptoms. BU also prevented elevated serum-IL-6 level as well as IL-6 mRNA expression in septic rats. Collectively, BU might be a novel agent to ameliorate sepsis by preventing the onset of MOF.


Assuntos
Bromisoval/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Sepse/tratamento farmacológico , Animais , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Proteínas I-kappa B/metabolismo , Interferon gama/metabolismo , Interleucina-6/sangue , Interleucina-6/genética , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Insuficiência de Múltiplos Órgãos/patologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , Sepse/etiologia , Sepse/fisiopatologia
12.
Yakushigaku Zasshi ; 50(2): 143-58, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-27149780

RESUMO

Soam discovered the drug Bromovalerylurea (or less BV) in 1907. After that, BV was imported in Japan in the latter part of the Meiji period as Western medicine. Under the influence of the First World War, in Japan, BV was domestic production. And BV are listed in JP V (1932), it is continued listing until the current JP X VI (2011). As a foreign pharmacopoeia which listed the BV, only in addition to the JP, there was a German Pharmacopoeia (DAB). During this time, the JP and DAB, the standards and test methods of BV, it was amended as shown in Table 1 and Table 2. The discrimination test and analysis test was defined based on the chemical properties of urea and isovaleric acid and bromine. Therefore, consistency was seen in the chemical criteria for test. From this it is understood that BV is Bromoisovalerateureido synthesized based on urea and isovaleric acid and bromine. This isovaleric acid is the active ingredient of Japanese Valerian and Valerian roots. BV is an organic synthetic urea derivative that was effectively improved organic synthesis isovaleric acid with respect to quality and efficacy surface. For this reason at the time that BV have been developed, it is an ideal new drug, it was described as a good medicine have no side effects. But to BV, there is a nature that it has tolerance, addictive, a dependency. In Japan after the Second World War, there was a lack of awareness about the nature of such BV. That it had become a system that masses can easily purchase the BV. Revision of the Pharmaceutical Affairs Law of 1960 against in this, selling regulation of BV is provided. However, for analgesic formulated with BV of dose observed in the Pharmaceutical Affairs Law, as generic drugs, selling is permitted, it is continuing until today. For this reason in recent years, long-term use of BV by self-judgment of the masses is frequent. And chronic bromine poisoning BV by this it have been a problem. Therefore regard to BV, always for their safety, including the overseas situation, I think it is important to seize the new knowledge and information.


Assuntos
Bromisoval/história , Farmacopeias como Assunto/história , Psicotrópicos/história , Bromisoval/análise , Alemanha , História do Século XX , História do Século XXI , Japão
19.
Leg Med (Tokyo) ; 11 Suppl 1: S411-2, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19251460

RESUMO

We applied here energy dispersive X-ray fluorescent spectrometry (EDXRF) to two medico-legal autopsy cases of bromvalerylurea ingestion. Rapid elemental analysis using EDXRF identified bromide in blood, urine and stomach contents of victims during autopsy. The present cases indicate that screening with EDXRF, an instrument suitable for non-destructive, rapid elemental analysis, provides useful information for identification of drugs.


Assuntos
Brometos/análise , Bromisoval/envenenamento , Hipnóticos e Sedativos/envenenamento , Espectrometria por Raios X , Adulto , Feminino , Toxicologia Forense , Conteúdo Gastrointestinal/química , Humanos , Masculino , Detecção do Abuso de Substâncias/métodos
20.
Clin Toxicol (Phila) ; 46(9): 861-3, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18668386

RESUMO

BACKGROUND: Bromides are still sold as sedatives, antitussives, and anticonvulsants in many countries. Bromovalerylurea is a bromide-containing sedative-hypnotic that is occasionally combined with non-steroidal anti-inflammatory drugs in over-the-counter products. Chronic intake of excessive bromovalerylurea can produce bromide intoxication, but acute bromovalerylurea intoxication presenting with myoclonic jerks has never been described. CASE REPORT: A 23-year-old woman was brought to our emergency department with unusual drowsiness. Her physical examination was normal except for frequent myoclonic jerks in all extremities that could be triggered by moving the patient or by noxious stimuli. Initial blood tests results were normal; the serum bromide concentration was 81.0 mg/L (reference <10 mg/L). Treatment with intravenous normal saline and furosemide resulted in gradual improvement in her drowsiness and myoclonic jerks. By the second hospital day, she was normal. A brain magnetic resonance imaging (MRI) was normal. At a 2-month follow-up visit, the patient had no neurological sequelae. DISCUSSION: Chronic bromide intoxication caused by long-term abuse of bromovalerylurea may present as psychiatric or neurologic abnormalities. Our case of acute bromovalerylurea intoxication presented with severe myoclonic jerks and lethargy. The serum bromide concentration was similar to the reported concentrations in acute bromide intoxications. Treatment with normal saline and diuretics results in increased clearance of bromide and an improvement in clinical effects. CONCLUSION: Myoclonic jerks may be one of the major presentations of acute bromovalerylurea intoxication. Physicians should consider bromide intoxication in the differential diagnosis of the causes of myoclonic jerks.


Assuntos
Bromisoval/envenenamento , Hipnóticos e Sedativos/envenenamento , Mioclonia/induzido quimicamente , Bromo/sangue , Diuréticos/uso terapêutico , Feminino , Seguimentos , Furosemida/uso terapêutico , Humanos , Cloreto de Sódio/uso terapêutico , Tentativa de Suicídio , Adulto Jovem
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