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1.
Curr Pain Headache Rep ; 23(1): 6, 2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30673879

RESUMO

PURPOSE OF REVIEW: Non-steroid anti-inflammatory drugs (NSAIDs) constitute a vital class of medications in today's headache regimen. However, up until the nineteenth century, they were largely unknown to most of the medical community. The purpose of this review is to explore the evolution of NSAIDs in the treatment of headaches spurred on by the Industrial Revolution in the USA. RECENT FINDINGS: The currently available data on the impact of NSAIDs reflects their significant contribution to headache treatment. The emergence of mass production spurred on by the Industrial Revolution, lead to widespread use of antipyrine, salicylic acid, and acetanilide. However, along with it came the growing awareness of consumer safety, leading to their ultimate downfall, and the subsequent birth of the Food and Drug Act.


Assuntos
Acetanilidas/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antipirina/uso terapêutico , Cefaleia/tratamento farmacológico , Padrões de Prática Médica/história , Ácido Salicílico/uso terapêutico , Acetanilidas/história , Anti-Inflamatórios não Esteroides/história , Antipirina/história , Cefaleia/história , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Ácido Salicílico/história , Resultado do Tratamento , Estados Unidos/epidemiologia
2.
Cochrane Database Syst Rev ; 7: CD012171, 2018 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-30043448

RESUMO

BACKGROUND: Ear wax (cerumen) is a normal bodily secretion that can become a problem when it obstructs the ear canal. Symptoms attributed to wax (such as deafness and pain) are among the commonest reasons for patients to present to primary care with ear trouble.Wax is part of the ear's self-cleaning mechanism and is usually naturally expelled from the ear canal without causing problems. When this mechanism fails, wax is retained in the canal and may become impacted; interventions to encourage its removal may then be needed. Application of ear drops is one of these methods. Liquids used to remove and soften wax are of several kinds: oil-based compounds (e.g. olive or almond oil); water-based compounds (e.g. sodium bicarbonate or water itself); a combination of the above or non-water, non-oil-based solutions, such as carbamide peroxide (a hydrogen peroxide-urea compound) and glycerol. OBJECTIVES: To assess the effects of ear drops (or sprays) to remove or aid the removal of ear wax in adults and children. SEARCH METHODS: We searched the Cochrane ENT Trials Register; Cochrane Register of Studies; PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the most recent search was 23 March 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which a 'cerumenolytic' was compared with no treatment, water or saline, an alternative liquid treatment (oil or almond oil) or another 'cerumenolytic' in adults or children with obstructing or impacted ear wax. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were 1) the proportion of patients (or ears) with complete clearance of ear wax and 2) adverse effects (discomfort, irritation or pain). Secondary outcomes were: extent of wax clearance; proportion of people (or ears) with relief of symptoms due to wax; proportion of people (or ears) requiring further intervention to remove wax; success of mechanical removal of residual wax following treatment; any other adverse effects recorded and cost. We used GRADE to assess the quality of the evidence for each outcome; this is indicated in italics. MAIN RESULTS: We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old.The overall risk of bias across the 10 included studies was low or unclear. PRIMARY OUTCOME: proportion of patients (or ears) with complete clearance of ear waxSix studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses.Active treatment versus no treatmentOnly one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence).Active treatment versus water or salineWe found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result.Water or saline versus no treatmentThis comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence).Active treatment A versus active treatment BSeveral single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other.Subgroup analysis of oil-based active treatments versus non-oil based active treatmentsWe found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments. PRIMARY OUTCOME: adverse effects: discomfort, irritation or painOnly seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence).Secondary outcomesThree studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies.There was very limited or no information available on our remaining secondary outcomes. AUTHORS' CONCLUSIONS: Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain.A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments.There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.


Assuntos
Cerume , Meato Acústico Externo , Higiene , Tensoativos/uso terapêutico , Adulto , Antipirina/uso terapêutico , Benzocaína/uso terapêutico , Peróxido de Carbamida , Carbonatos/uso terapêutico , Criança , Clorobutanol/uso terapêutico , Colina/análogos & derivados , Colina/uso terapêutico , Ácido Dioctil Sulfossuccínico/uso terapêutico , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Humanos , Peróxidos/uso terapêutico , Soluções Farmacêuticas/uso terapêutico , Óleos Vegetais/uso terapêutico , Potássio/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Salicilatos/uso terapêutico , Cloreto de Sódio/uso terapêutico , Ureia/análogos & derivados , Ureia/uso terapêutico , Água
3.
Drugs Today (Barc) ; 54(6): 349-360, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29998226

RESUMO

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a fatal motor neuron degenerative disorder leading to paralysis and eventual death. At present, we do not have any specific cure for this deadly disorder. Current drug therapy can only reduce morbidity in ALS patients. In 1995, riluzole was the first drug approved by the U.S. Food and Drug Administration (FDA) for ALS. After a long gap of 22 years, Mitsubishi Tanabe Pharma America got U.S. FDA approval for edaravone (Radicava) in May 2017 for the management of ALS. Edaravone, a novel neuroprotective agent, is indicated to slow down progression of ALS. In 2015, Mitsubishi Tanabe Pharma launched edaravone (Radicut) for the treatment of stroke and ALS in Japan. The U.S. FDA approved edaravone following clinical evidence from three clinical trials conducted in 368 ALS patients in Japan. Edaravone is awaiting approval by the European Medicines Agency (EMA) in Europe. Edaravone (60 mg) is administered by very slow intravenous infusion (60 minutes) in 28-day cycles. It has been shown to slow down the loss of physical function in ALS patients by 33% as compared to placebo. Edaravone is a strong antioxidant that prevents oxidative stress from inducing motor neuron death in ALS patients. Being a potent free radical scavenger, it has been shown to inhibit nitration of tyrosine residues in the cerebrospinal fluid and improve motor functions in mouse models of ALS. The product has been patented and the FDA has not approved any generic version of edaravone. This article discusses the preclinical pharmacology, pharmacokinetics, safety profile, clinical studies and drug interactions of edaravone (Radicava) in ALS.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Antipirina/análogos & derivados , Depuradores de Radicais Livres/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Antipirina/efeitos adversos , Antipirina/farmacocinética , Antipirina/farmacologia , Antipirina/uso terapêutico , Edaravone , Humanos
4.
Cochrane Database Syst Rev ; 7: CD011492, 2018 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-29987845

RESUMO

BACKGROUND: Brain radionecrosis (tissue death caused by radiation) can occur following high-dose radiotherapy to brain tissue and can have a significant impact on a person's quality of life (QoL) and function. The underlying pathophysiological mechanism remains unclear for this condition, which makes establishing effective treatments challenging. OBJECTIVES: To assess the effectiveness of interventions used for the treatment of brain radionecrosis in adults over 18 years old. SEARCH METHODS: In October 2017, we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, Embase and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) for eligible studies. We also searched unpublished data through Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials for ongoing trials and handsearched relevant conference material. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any intervention directed to treat brain radionecrosis in adults over 18 years old previously treated with radiation therapy to the brain. We anticipated a limited number of RCTs, so we also planned to include all comparative prospective intervention trials and quasi-randomised trials of interventions for brain radionecrosis in adults as long as these studies had a comparison group that reflects the standard of care (i.e. placebo or corticosteroids). Selection bias was likely to be an issue in all the included non-randomised studies therefore results are interpreted with caution. DATA COLLECTION AND ANALYSIS: Two review authors (CC, PB) independently extracted data from selected studies and completed a 'Risk of bias' assessment. For dichotomous outcomes, the odds ratio (OR) for the outcome of interest was reported. For continuous outcomes, treatment effect was reported as mean difference (MD) between treatment arms with 95% confidence intervals (CIs). MAIN RESULTS: Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria.A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed.An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision).In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms.One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases.None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements.A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints. AUTHORS' CONCLUSIONS: There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.


Assuntos
Corticosteroides/uso terapêutico , Antipirina/análogos & derivados , Bevacizumab/uso terapêutico , Encéfalo/efeitos da radiação , Lesões por Radiação/terapia , Adulto , Antipirina/uso terapêutico , Bevacizumab/efeitos adversos , Encéfalo/diagnóstico por imagem , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Quimioterapia Combinada , Edaravone , Gadolínio , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radioterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
J Stroke Cerebrovasc Dis ; 27(9): e221-e223, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29861128

RESUMO

Conjugate eye deviation (CED) is defined as a sustained shift in horizontal gaze toward 1 side, together with gaze failure to the other side, caused by lesions in the brainstem, basal ganglia, or cortical frontal eye fields. To date, very few reports have described CED in patients with medullary infarction. A 76-year-old woman presented with sudden onset of vertigo and right hemiparesis, accompanied by CED to the right with gaze palsy to the left. Her brain magnetic resonance imaging showed left upper medial medullary infarction involving the left nucleus prepositus hypoglossi (NPH) and adjacent to the left inferior olivary nucleus (ION). After treatments with 200 mg of aspirin and 60 mg of edaravone daily, symptoms gradually improved. The NPH and ION constitute NPH-ION-floccus-vestibular nucleus loop and contribute to the inhibitory mechanisms for horizontal eye movements. In addition, NPH projects excitatory neurons to the contralateral vestibular nucleus. In our case, disorders of the NPH and ION might have dysregulated inhibitory and excitatory projections, and thereby cause CED to the right with gaze palsy to the left. This represents a rare case showing CED to the contralesional side in upper medial medullary infarction.


Assuntos
Infartos do Tronco Encefálico/complicações , Movimentos Oculares , Fixação Ocular , Bulbo/irrigação sanguínea , Transtornos da Motilidade Ocular/etiologia , Idoso , Antipirina/análogos & derivados , Antipirina/uso terapêutico , Aspirina/uso terapêutico , Infartos do Tronco Encefálico/diagnóstico por imagem , Infartos do Tronco Encefálico/tratamento farmacológico , Infartos do Tronco Encefálico/fisiopatologia , Angiografia Cerebral/métodos , Imagem de Difusão por Ressonância Magnética , Edaravone , Movimentos Oculares/efeitos dos fármacos , Feminino , Fixação Ocular/efeitos dos fármacos , Depuradores de Radicais Livres/uso terapêutico , Humanos , Angiografia por Ressonância Magnética , Bulbo/diagnóstico por imagem , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/tratamento farmacológico , Transtornos da Motilidade Ocular/fisiopatologia , Recuperação de Função Fisiológica , Resultado do Tratamento
6.
Oxid Med Cell Longev ; 2018: 5216383, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29765498

RESUMO

Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP) with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp.) before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg), after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.


Assuntos
Antipirina/análogos & derivados , Depuradores de Radicais Livres/uso terapêutico , Heme Oxigenase-1/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Sepse/tratamento farmacológico , 2-Metoxiestradiol , Animais , Antipirina/farmacologia , Antipirina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Catalase/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Edaravone , Estradiol/análogos & derivados , Estradiol/farmacologia , Depuradores de Radicais Livres/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Interleucina-1beta/análise , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sepse/mortalidade , Sepse/patologia , Taxa de Sobrevida
7.
J Stroke Cerebrovasc Dis ; 27(5): 1302-1310, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29373227

RESUMO

BACKGROUND: We investigated how diabetes mellitus (DM) affects the outcome of acute ischemic stroke (AIS), comparing with the outcomes in those who had hypertension (HT) and atrial fibrillation (AF). METHODS: This study was a sub-analysis of PROTECT4.5, which was previously performed as a large-scale, prospective observational study of edaravone with approximately 10,000 patients with AIS in Japan. The study patients treated with edaravone alone or edaravone + alteplase (recombinant tissue plasminogen activator [tPA]) were analyzed for their outcomes and explored for the risk factors of poor outcome, after being divided into 8 groups according to their affected complications of DM, HT, or AF in the groups treated with edaravone alone or edaravone + tPA. RESULTS: Among patients treated with edaravone alone and edaravone + tPA, the mean reduction in the National Institutes of Health Stroke Scale from baseline to 3 months after the onset was 2.0 and 4.4 in DM groups, respectively. The reduction was smaller in these groups compared with other groups (3.3-4.3 and 6.0-7.7, respectively). The logistic regression model revealed that DM was an independent risk factor for highly unfavorable outcome of modified Rankin Scale score 3-6 at 3 months after the onset, among both patients treated with edaravone alone and those treated with edaravone + tPA (odds ratio [OR]: 2.23, 95% confidential interval [CI]: 1.42-3.50 and OR: 2.05, 95% CI: 1.33-3.14, respectively). CONCLUSIONS: DM is suggested to adversely affect the outcome of AIS in Japanese patients.


Assuntos
Antipirina/análogos & derivados , Isquemia Encefálica/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Fibrinolíticos/administração & dosagem , Depuradores de Radicais Livres/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antipirina/efeitos adversos , Antipirina/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidade , Avaliação da Deficiência , Progressão da Doença , Edaravone , Feminino , Fibrinolíticos/efeitos adversos , Depuradores de Radicais Livres/efeitos adversos , Humanos , Incidência , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Vigilância de Produtos Comercializados , Estudos Prospectivos , Recuperação de Função Fisiológica , Sistema de Registros , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
8.
J Stroke Cerebrovasc Dis ; 27(5): 1425-1430, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29373230

RESUMO

BACKGROUND: Cerebral vasospasm is an uncontrollable and sometimes fatal complication occurring after subarachnoid hemorrhage. However, cerebral hyperperfusion syndrome is a rare complication after subarachnoid hemorrhage. Although plain computed tomography of cerebral hyperperfusion syndrome looks similar to cerebral infarction induced by cerebral vasospasm, they should be distinguished from each other because they require completely different treatments. CASE DESCRIPTION: A 65-year-old man complained of severe headache and vomiting. A computed tomography scan of his head showed subarachnoid hemorrhage with acute hydrocephalus caused by intraventricular hematoma and aneurysm of the left middle cerebral artery. After endoscopic irrigation of the ventricular hematoma to decrease the intracranial pressure, we performed neck clipping for the ruptured aneurysm. We used a temporary clip to the proximal M1 segment twice for a total of 15 minutes. Five days after the clipping, a computed tomography scan of the patient's head showed a large low-density area in the left cerebral hemisphere. Although cerebral infarction caused by cerebral vasospasm was suspected, his perfusion computed tomography demonstrated a state of hyperperfusion corresponding to the low-density area. We started treatment to prevent vasodilation and excessive cerebral blood flow instead of treatment for cerebral vasospasm. After changing the treatment, the patient's symptoms gradually improved, and his perfusion computed tomography (8 days after surgery) showed no excessive increased blood flow. CONCLUSIONS: We present a case of cerebral hyperperfusion syndrome and its successful treatment, distinct from that of cerebral vasospasm, after ruptured aneurysm clipping. In addition, we discuss the mechanism of this rare syndrome based on previous reports.


Assuntos
Aneurisma Roto/cirurgia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/etiologia , Hematoma/cirurgia , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Hemorragia Subaracnóidea/cirurgia , Idoso , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/fisiopatologia , Angiografia Digital , Antipirina/análogos & derivados , Antipirina/uso terapêutico , Angiografia Cerebral/métodos , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/fisiopatologia , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Edaravone , Endoscopia , Glicerol/uso terapêutico , Hematoma/diagnóstico por imagem , Hematoma/fisiopatologia , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/fisiopatologia , Ligadura , Masculino , Procedimentos Neurocirúrgicos/métodos , Imagem de Perfusão/métodos , Recuperação de Função Fisiológica , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/fisiopatologia , Irrigação Terapêutica/métodos , Resultado do Tratamento
9.
Artigo em Inglês | MEDLINE | ID: mdl-29334251

RESUMO

The recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life. Respect for our patients' autonomy is critical when discussing these issues, but we should always be guided by the ethical principles of beneficence and non-maleficence.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Antipirina/análogos & derivados , Ensaios Clínicos como Assunto/ética , Ética Clínica , Depuradores de Radicais Livres/uso terapêutico , Esclerose Amiotrófica Lateral/psicologia , Antipirina/efeitos adversos , Antipirina/economia , Antipirina/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Análise Custo-Benefício , Edaravone , Depuradores de Radicais Livres/efeitos adversos , Depuradores de Radicais Livres/economia , Humanos , Relações Profissional-Paciente , Qualidade de Vida , Estados Unidos
10.
Brain Res ; 1682: 24-35, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29294349

RESUMO

We used a multimodal approach to evaluate the effects of edaravone in a rat model of spinal cord injury (SCI). SCI was induced by extradural compression of thoracic spinal cord. In experiment 1, 30 min prior to compression, rats received a 3 mg/kg intravenous bolus of edaravone followed by a maintenance infusion of 1 (low-dose), 3 (moderate-dose), or 10 (high-dose) mg/kg/h edaravone. Although both moderate- and high-dose edaravone regimens promoted recovery of spinal motor-evoked potentials (MEPs) at 2 h post-SCI, the effect of the moderate dose was more pronounced. In experiment 2, moderate-dose edaravone was administered 30 min prior to compression, at the start of compression, or 10 min after decompression. Although both preemptive and coincident administration resulted in significantly improved spinal MEPs at 2 h post-SCI, the effect of preemptive administration was more pronounced. A moderate dose of edaravone resulted in significant attenuation of lipid peroxidation, as evidenced by lower concentrations of the free radical malonyldialdehyde in the spinal cord 3 h post-SCI. Malonyldialdehyde levels in the high-dose edaravone group were not reduced. Both moderate- and high-dose edaravone resulted in significant functional improvements, evidenced by better Basso-Beattie-Bresnahan (BBB) scores and better performance on an inclined plane during an 8 week period post-SCI. Both moderate- and high-dose edaravone significantly attenuated neuronal loss in the spinal cord at 8 weeks post-SCI, as evidenced by quantitative immunohistochemical analysis of NeuN-positive cells. In conclusion, early administration of a moderate dose of edaravone minimized the negative consequences of SCI and facilitated functional recovery.


Assuntos
Antipirina/análogos & derivados , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , 3,4-Metilenodioxianfetamina/metabolismo , Análise de Variância , Animais , Antipirina/uso terapêutico , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edaravone , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Índice de Gravidade de Doença , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiopatologia , Fatores de Tempo
12.
Neurol Res ; 40(1): 1-10, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29125058

RESUMO

Objectives The potential protective effects and mechanisms of edaravone have not been well elucidated in vascular dementia (VaD) induced by chronic cerebral hypoperfusion (CCH). The aim of this study was to investigate whether edaravone could improve cognitive damage in rats induced by CCH, and whether the effects of edaravone were associated with ERK/Nrf2/HO-1 signaling pathway. Methods CCH was induced by bilateral common carotid arteries occlusion (BCCAO). Sprague-Dawley (SD) rats were randomly divided into four groups: sham (sham-operated) group, vehicle (BCCAO + normal saline) group, edaravone3.0 group and edaravone6.0 group. The edaravone3.0 and edaravone6.0 group rats were provided 3.0 mg/kg and 6.0 mg/kg of edaravone, respectively, intraperitoneal (i.p.) injection twice daily following the first day after BCCAO. In this experiment, the spatial learning and memory were assessed using the Morris water maze. The malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the hippocampus were measured biochemically. And, the levels of total ERK1/2 (t-ERK1/2), Phospho-ERK1/2 (p-ERK1/2), total Nrf2 (t-Nrf2), nuclear Nrf2 (n-Nrf2), and HO-1 were assessed by western blot. Results The results showed that the treatment with edaravone significantly improved CCH-induced cognitive damage, and boosted endogenous antioxidants SOD activity and HO-1 level, decreased MDA contents in the hippocampus by activating Nrf2 signaling pathway which was related to ERK1/2. We also found that the neuronal morphology of the hippocampal CA1 area significantly improved and the number of Nrf2 positive cells markedly increased in the edaravone treatment groups. Conclusion Our results demonstrated a neuroprotective effect of edaravone on hippocampus against oxidative stress and cognitive deficit induced by CCH. The mechanism may be related to the enhancement of antioxidant defense system by activating ERK/Nrf2/HO-1 signaling pathway.


Assuntos
Antipirina/análogos & derivados , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Depuradores de Radicais Livres/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antipirina/química , Antipirina/uso terapêutico , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edaravone , Depuradores de Radicais Livres/química , Heme Oxigenase-1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Superóxido Dismutase/metabolismo
13.
Pediatr Int ; 60(3): 270-275, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29280262

RESUMO

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.


Assuntos
Encefalopatia Aguda Febril/diagnóstico , Encefalopatia Aguda Febril/tratamento farmacológico , Adolescente , Anticonvulsivantes/uso terapêutico , Antipirina/análogos & derivados , Antipirina/uso terapêutico , Criança , Pré-Escolar , Edaravone , Feminino , Depuradores de Radicais Livres/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Lactente , Japão , Masculino , Prognóstico , Estudos Retrospectivos
14.
Oxid Med Cell Longev ; 2017: 6873281, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259732

RESUMO

The combination of alteplase, a recombinant tissue plasminogen activator, and edaravone, an antioxidant, reportedly enhances recanalization after acute ischemic stroke. We examined the influence of edaravone on the thrombolytic efficacy of alteplase by measuring thrombolysis using a newly developed microchip-based flow-chamber assay. Rat models of embolic cerebral ischemia were treated with either alteplase or alteplase-edaravone combination therapy. The combination therapy significantly reduced the infarct volume and improved neurological deficits. Human blood samples from healthy volunteers were exposed to edaravone, alteplase, or a combination of alteplase and edaravone or hydrogen peroxide. Whole blood was perfused over a collagen- and thromboplastin-coated microchip; capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 69.9% lower in the edaravone-alteplase- than alteplase-treated group. The thrombolytic effect of alteplase was significantly attenuated in the presence of hydrogen peroxide, suggesting that oxidative stress might hinder thrombolysis. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, edaravone significantly inhibited the decrease. Edaravone enhances alteplase-mediated thrombolysis, likely by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.


Assuntos
Antipirina/análogos & derivados , Depuradores de Radicais Livres/uso terapêutico , Terapia Trombolítica/métodos , Adulto , Animais , Antipirina/farmacologia , Antipirina/uso terapêutico , Edaravone , Depuradores de Radicais Livres/farmacologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
15.
Cell ; 171(4): 725, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29100067

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive, adult onset neurodegenerative disease that is always fatal. The history of ALS drug discovery is fraught with many stops and starts. It took 22 years after the FDA approval of the anti-excitotoxic drug Riluzole before another drug was found to be effective in altering ALS progression: the anti-oxidant Edaravone.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Antipirina/análogos & derivados , Aprovação de Drogas , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Antipirina/uso terapêutico , Edaravone , Humanos , Riluzol/uso terapêutico
17.
Int Immunopharmacol ; 53: 1-10, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29028547

RESUMO

Compound edaravone injection (C.EDA), a compound preparation composed of edaravone (EDA) and (+)-Borneol with the mass ratio of 4: 1, displays a better anti-inflammatory activity than EDA. However, its precise mechanism remains to be further studied. In this work, we investigated whether (+)-Borneol could improve the efficacy of EDA against DSS-induced colitis. We found that C.EDA at 7.5 and 15mg/kg could significantly relieve the disease activity index (DAI) and reduce the loss of body weight and colon length in a dose-dependent manner, while EDA or (+)-Borneol alone only had moderate effects even at the highest dose. Additionally, ELISA revealed that C.EDA could more dramatically decrease the protein levels of inflammatory cytokines and increase the levels of anti-inflammatory cytokine than EDA or (+)-Borneol alone both in colon tissues and serum. H&E staining and IHC assay also indicated that C.EDA exhibited more prominent effects on increasing the population of M2 macrophages, decreasing M1 macrophages infiltration and protecting intestinal barrier integrity. Furthermore, in vitro studied demonstrated that C.EDA, EDA or (+)-Borneol failed in inhibiting M1 macrophages activation but could specifically induce the activation of M2 macrophages in a STAT3-dependent manner. Knockdown the expression of STAT3 successfully abolished the effect of C.EDA and EDA on promoting M2 macrophages activation. Consistent with in vivo study, C.EDA exhibited a more efficient ability of inducing M2 macrophages polarization and STAT3 activation than EDA or (+)-Borneol alone in vitro. In conclusion, we confirmed that (+)-Borneol improved the efficacy of EDA against DSS-induced colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway.


Assuntos
Antipirina/análogos & derivados , Canfanos/uso terapêutico , Colite/tratamento farmacológico , Colo/patologia , Inflamação/tratamento farmacológico , Macrófagos/imunologia , Animais , Antipirina/uso terapêutico , Diferenciação Celular , Células Cultivadas , Colite/induzido quimicamente , Citocinas/metabolismo , Sulfato de Dextrana , Combinação de Medicamentos , Edaravone , Feminino , Janus Quinase 2/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Células Th2/imunologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-28872907

RESUMO

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone suggest that it may possess broad free radical scavenging activity and protect neurons, glia, and vascular endothelial cells against oxidative stress. During the 1980s and 1990s, edaravone was developed for the treatment of acute ischemic stroke. In 2001, a clinical program in ALS was initiated and five clinical studies were conducted in Japan. Phase III studies were designed to rapidly evaluate (within a 24-week double-blind study window) functional changes using the Revised ALS Functional Rating Scale (ALSFRS-R) as a primary endpoint. The study populations were selected according to these considerations and were further refined as the studies proceeded. Although the first phase III study did not meet its primary endpoint, post-hoc analyses showed an apparent effect of edaravone, when additional patient inclusion criteria defined by ALSFRS-R score, pulmonary function, certainty of ALS diagnosis, and duration of disease were applied. This population was hypothesized not only to have retained broad functionality and normal respiratory function at study baseline but also to be likely to show measurable disease progression over 24 weeks. A second confirmatory phase III study applying these refinements in patient selection was prospectively designed and successfully documented a statistically significant difference between the edaravone and placebo groups in the ALSFRS-R primary endpoint. This paper describes and reviews data pertinent to the potential mechanism of action of edaravone, and reviews the development history of edaravone for the treatment of ALS.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Esclerose Amiotrófica Lateral/metabolismo , Antipirina/análogos & derivados , Depuradores de Radicais Livres/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Esclerose Amiotrófica Lateral/diagnóstico , Antipirina/farmacologia , Antipirina/uso terapêutico , Ensaios Clínicos como Assunto/métodos , Edaravone , Depuradores de Radicais Livres/farmacologia , Humanos , Estresse Oxidativo/fisiologia
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