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1.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1145-1154, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31326872

RESUMO

Survivin (IAP proteins) is considered as a significant target for anticancer drug research owing to its upregulation in tumor cells to mediate resistance to apoptotic stimulus. The current study aimed to investigate phytochemicals as inhibitors of survivin with caspases to reactivate the functioning of caspases through molecular docking. The compounds namely 2(R), 4(R)-dihydroxypyrrolidine, 4-hydroxy-2-(4-methoxyphenyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide, 2,3-Diketo-L-gulonic acid, (3-hydroxy-2-octadeca-9,12-dienoyloxypropyl) octadecanoate, 2-[[4-[[4-[(4-formamido-1-methylimidazole-2-carbonyl)amino]-1-methylimidazole-2-carbonyl]amino]-1-methylimidazole-2-carbonyl]amino]ethyl-dimethylazanium, Picolinic acid and (2-Hydroxy-5-nitrophenyl) dihydrogen phosphate successfully bind inside the pocket of survivin. ADMETsar was used to evaluate the anticancer potential of selected compounds. These compounds can be proposed as effective inhibitors, disrupting the survivin-caspases interaction and reactivating the caspases function of apoptosis. The study might facilitate the development of cost-effective and natural drugs against cancer. However, further validation is essential for confirmation of its drug efficacy and bio-compatibility.

2.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1145-1154, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303583

RESUMO

Survivin (IAP proteins) is considered as a significant target for anticancer drug research owing to its upregulation in tumor cells to mediate resistance to apoptotic stimulus. The current study aimed to investigate phytochemicals as inhibitors of survivin with caspases to reactivate the functioning of caspases through molecular docking. The compounds namely 2(R), 4(R)-dihydroxypyrrolidine, 4-hydroxy-2-(4-methoxyphenyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide, 2,3-Diketo-L-gulonic acid, (3-hydroxy-2-octadeca-9,12-dienoyloxypropyl) octadecanoate, 2-[[4-[[4-[(4-formamido-1-methylimidazole-2-carbonyl)amino]-1-methylimidazole-2-carbonyl]amino]-1-methylimidazole-2-carbonyl]amino]ethyl-dimethylazanium, Picolinic acid and (2-Hydroxy-5-nitrophenyl) dihydrogen phosphate successfully bind inside the pocket of survivin. ADMETsar was used to evaluate the anticancer potential of selected compounds. These compounds can be proposed as effective inhibitors, disrupting the survivin-caspases interaction and reactivating the caspases function of apoptosis. The study might facilitate the development of cost-effective and natural drugs against cancer. However, further validation is essential for confirmation of its drug efficacy and bio-compatibility.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Compostos Fitoquímicos/farmacologia , Survivina/antagonistas & inibidores , Survivina/química , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/toxicidade , Caspases/metabolismo , Simulação por Computador , Humanos , Simulação de Acoplamento Molecular , Terapia de Alvo Molecular , Compostos Fitoquímicos/farmacocinética , Compostos Fitoquímicos/toxicidade , Conformação Proteica , Survivina/metabolismo , Distribuição Tecidual
3.
Cochrane Database Syst Rev ; 4: CD009412, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29634083

RESUMO

BACKGROUND: Aggressive, agitated or violent behaviour due to psychosis constitutes an emergency psychiatric treatment where fast-acting interventions are required. Risperidone is a widely accessible antipsychotic that can be used to manage psychosis-induced aggression or agitation. OBJECTIVES: To examine whether oral risperidone alone is an effective treatment for psychosis-induced aggression or agitation. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (up to April 2017); this register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings. There are no language, date, document type, or publication status limitations for inclusion of records into the register. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing rapid use of risperidone and other drugs, combinations of drugs or placebo for people exhibiting aggression or agitation (or both) thought to be due to psychosis. DATA COLLECTION AND ANALYSIS: We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR) and for continuous data we calculated mean difference (MD), all with 95% confidence intervals (CI) and used a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce a 'Summary of findings' tables. MAIN RESULTS: The review now contains data from nine trials (total n = 582) reporting on five comparisons. Due to risk of bias, small size of trials, indirectness of outcome measures and a paucity of investigated and reported 'pragmatic' outcomes, evidence was graded as very-low quality. None of the included studies provided useable data on our primary outcome 'tranquillisation or asleep' by 30 minutes, repeated need for tranquillisation or any economic outcomes. Data were available for our other main outcomes of agitation or aggression, needing restraint, and incidence of adverse effects.Risperidone versus haloperidol (up to 24 hours follow-up)For the outcome, specific behaviour - agitation, no clear difference was found between risperidone and haloperidol in terms of efficacy, measured as at least 50% reduction in the Positive and Negative Syndrome Scale - Psychotic Agitation Sub-score (PANSS-PAS) (RR 1.04, 95% CI 0.86 to 1.26; participants = 124; studies = 1; very low-quality evidence) and no effect was observed for need to use restraints (RR 2.00, 95% CI 0.43 to 9.21; participants = 28; studies = 1; very low-quality evidence). Incidence of adverse effects was similar between treatment groups (RR 0.94, 95% CI 0.54 to 1.66; participants = 124; studies = 1; very low-quality evidence).Risperidone versus olanzapineOne small trial (n = 29) reported useable data for the comparison risperidone versus olanzapine. No effect was observed for agitation measured as PANSS-PAS endpoint score at two hours (MD 2.50, 95% CI -2.46 to 7.46; very low-quality evidence); need to use restraints at four days (RR 1.43, 95% CI 0.39 to 5.28; very-low quality evidence); specific movement disorders measured as Behavioural Activity Rating Scale (BARS) endpoint score at four days (MD 0.20, 95% CI -0.43 to 0.83; very low-quality evidence).Risperidone versus quetiapineOne trial reported (n = 40) useable data for the comparison risperidone versus quetiapine. Aggression was measured using the Modified Overt Aggression Scale (MOAS) endpoint score at two weeks. A clear difference, favouring quetiapine was observed (MD 1.80, 95% CI 0.20 to 3.40; very-low quality evidence). No evidence of a difference between treatment groups could be observed for incidence of akathisia after 24 hours (RR 1.67, 95% CI 0.46 to 6.06; very low-quality evidence). Two participants allocated to risperidone and one allocated to quetiapine experienced myocardial ischaemia during the trial.Risperidone versus risperidone + oxcarbazepineOne trial (n = 68) measured agitation using the Positive and Negative Syndrome Scale - Excited Component.(PANSS-EC) endpoint score and found a clear difference, favouring the combination treatment at one week (MD 2.70, 95% CI 0.42 to 4.98; very low-quality evidence), but no effect was observed for global state using Clinical Global Impression - Improvement (CGI-I) endpoint score at one week (MD -0.20, 95% CI -0.61 to 0.21; very-low quality evidence). Incidence of extrapyramidal symptoms after 24 hours was similar between treatment groups (RR 1.59, 95% CI 0.49 to 5.14; very-low quality evidence).Risperidone versus risperidone + valproic acidTwo trials compared risperidone with a combination of risperidone plus valproic acid. No clear differences between the treatment groups were observed for aggression (MOAS endpoint score at three days: MD 1.07, 95% CI -0.20 to 2.34; participants = 54; studies = 1; very low-quality evidence) or incidence of akathisia after 24 hours: RR 0.75, 95% CI 0.28 to 2.03; participants = 122; studies = 2; very low-quality evidence). AUTHORS' CONCLUSIONS: Overall, results for the main outcomes show no real effect for risperidone. The only data available for use in this review are from nine under-sampled trials and the evidence available is of very low quality. This casts uncertainty on the role of risperidone in rapid tranquillisation for people with psychosis-induced aggression. High-quality pragmatic RCTs are feasible and are needed before clear recommendations can be drawn on the use of risperidone for psychosis-induced aggression or agitation.


Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Agitação Psicomotora/tratamento farmacológico , Transtornos Psicóticos/complicações , Risperidona/uso terapêutico , Administração Oral , Agressão/psicologia , Antipsicóticos/efeitos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Humanos , Oxcarbazepina , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/psicologia , Fumarato de Quetiapina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risperidona/efeitos adversos , Tranquilizantes/uso terapêutico , Ácido Valproico/uso terapêutico
4.
J Stroke Cerebrovasc Dis ; 27(5): 1403-1411, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29398533

RESUMO

BACKGROUND AND PURPOSE: Intravenous alteplase (rt-PA) increases the risk of hemorrhagic transformation of acute ischemic stroke. The objective of our study was to evaluate clinical, laboratory, and imaging predictors on forecasting the risk of hemorrhagic transformation following treatment with rt-PA. We also evaluated the factors associated with cerebral microbleeds that increase the risk of hemorrhagic transformation. METHODS: Consecutive patients with acute ischemic stroke admitted between January 1, 2009 and December 31, 2013 were included in the study if they received IV rt-PA, had magnetic resonance imaging (MRI) of the brain on admission, and computed tomography or MRI of the brain at 24 (18-36) hours later to evaluate for the presence of hemorrhagic transformation. The clinical data, lipid levels, platelet count, MRI, and computed tomography images were retrospectively reviewed. RESULTS: The study included 366 patients, with mean age 67 ± 15 years; 46% were women and 88% were white. The median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range 3-15). Hemorrhagic transformation was observed in 87 (23.8%) patients and cerebral microbleeds were noted in 95 (25.9%). Patients with hemorrhagic transformation tended to be older, nonwhite, have atrial fibrillation, higher baseline NIHSS score, lower cholesterol and triglyceride levels, and cerebral microbleeds and nonlacunar infarcts. Patients with cerebral microbleeds were more likely to be older, have hypertension, hyperlipidemia, previous history of stroke, and prior use of antithrombotics. On multivariate analysis race, NIHSS score, nonlacunar infarct, and presence of cerebral microbleeds were independently associated with hemorrhagic transformation following treatment with rt-PA. CONCLUSIONS: Presence of cerebral microbleeds is an independent predictor of hemorrhagic transformation of acute ischemic stroke following treatment with rt-PA.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/efeitos adversos , Hemorragias Intracranianas/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Distribuição de Qui-Quadrado , Imagem de Difusão por Ressonância Magnética , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
5.
World Neurosurg ; 111: e465-e470, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29277596

RESUMO

BACKGROUND: Smartphones and their apps are used ubiquitously in medical practice. However, in some cases their use can be at odds with current patient data safety regulations such as Canada's Personal Health Information Protection Act of 2004. To assess current practices and inform mobile application development, we sought to better understand mobile device usage patterns among Canadian neurosurgery residents. METHODS: Through the Canadian Neurosurgery Research Collaborative, an online survey characterizing smartphone ownership and usage patterns was developed and sent to all Canadian neurosurgery resident in April of 2016. Questionnaires were collected and completed surveys analyzed. RESULTS: Of 146 eligible residents, 76 returned completed surveys (52% response rate). Of these 99% of respondents owned a smartphone, with 79% running on Apple's iOS. Four general mobile uses were identified: 1) communication between members of the medical team, 2) decision support, 3) medical reference, and 4) documentation through medical photography. Communication and photography were areas where the most obvious breaches in the Canadian Personal Health Information Protection Act were noted, with 89% of respondents taking pictures of patients' radiologic studies and 75% exchanging them with Short Message System. Hospital policies had no impact on user behaviors. CONCLUSIONS: Smartphones are used daily by most neurosurgery residents. Identified usage patterns are associated with perceived gains in efficacy and challenges in privacy and data reliability. We believe creating and improving workflows that address these usage patterns has a greater potential to improve privacy than changing policies and enforcing regulations.


Assuntos
Neurocirurgiões/estatística & dados numéricos , Smartphone/estatística & dados numéricos , Canadá , Estudos Transversais , Feminino , Humanos , Internato e Residência , Masculino , Neurocirurgia , Inquéritos e Questionários
6.
Spinal Cord Ser Cases ; 3: 17024, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28690870

RESUMO

INTRODUCTION: Spinal dural arteriovenous fistulae (sdAVF) are rare lesions. Patients typically present with slowly progressive myelopathy that is often mistaken for degenerative cervical or lumbar stenosis. On spinal magnetic resonance imaging (MRI), multisegmental T2 hyperintensities along with associated flow voids are pathognomonic of sdAVF. However, diagnosis can be difficult. Definitive diagnosis and localization is achieved with complete spinal angiography. Treatment options include open surgical ligation, endovascular embolization or multimodality treatment. The purpose of this study is to present a series of cases to aid in the assessment, diagnosis and treatment of this unusual pathology. CASE PRESENTATION: We present 10 cases of sdAVF treated at our center over an 8-year period. Seventy percent of patients were male. The mean age of presentation was 62.6 years. The most common lesion was a dorsal dural AVF with single feeder. All patients underwent open surgical ligation, six having preoperative coil embolization of the radicular artery to allow for intraoperative localization of the fistula. Eight patients showed improvement following treatment as graded by the Nurick system. Two patients failed to improve. None of the patients worsened. One patient had a radiation burn from the spinal angiogram requiring secondary closure and one patient had a pseudomeningocele at the site of surgery that resolved. DISCUSSION: The successful treatment of sdAVF requires a detailed understanding of clinical presentation and imaging findings to allow for precise treatment. Owing to the rarity of the condition, clinicians must continue to share their experiences to advance our knowledge.

7.
J Neurointerv Surg ; 9(9): 849-853, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27543629

RESUMO

INTRODUCTION: Stents reduce the rate of angiographic recurrence of intracranial aneurysms. The newest stent for intracranial use is the Low-profile Visible Intraluminal Support device (LVIS Jr). OBJECTIVE: To assess the efficacy of the new stent in a multicenter retrospective registry. MATERIALS AND METHOD: Centers across Canada using LVIS Jr were contacted and asked to participate in a retrospective registry of consecutive patients treated with LVIS Jr for intracranial aneurysms between January 2013 and July 2015. RESULTS: A total of 102 patients, with saccular aneurysms in 100 patients (72 women; age range 21-78 years; mean 56.0 years; median 57.5 years) were treated with a LVIS Jr stent. The mean maximum diameter of the dome and neck of the aneurysm and dome to neck ratios were 8.3 mm±7.7 mm, 4.4 mm±1.9 mm, and 1.86±1.22, respectively. Angiographic complications arose in 23 patients, clinical complications in 9 patients, and only 3% of permanent neurological deficits occurred. Death occurred in 1 patient, unrelated to the stent. The ruptured status of the aneurysms (OR=3.29; p=0.046) and use of LVIS Jr for bailout (OR=2.54; p=0.053) showed a trend towards significant association with higher angiographic complications. At the last available follow-up, 68 class I, 20 class II, and 12 class III results were seen. CONCLUSIONS: The LVIS Jr stent is a safe and effective device for stent-assisted coiling, with 3% permanent neurological complications. Stent-assisted coiling continues to be technically challenging in cases of ruptured aneurysms and bailout situations.


Assuntos
Aneurisma Roto/epidemiologia , Aneurisma Roto/cirurgia , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Sistema de Registros , Stents/normas , Adulto , Idoso , Aneurisma Roto/diagnóstico por imagem , Canadá/epidemiologia , Angiografia Cerebral/métodos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Int Psychiatry ; 8(4): 92-94, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508101

RESUMO

Despite the growing importance of mental health in international and national policies, the contribution to the psychiatric evidence base from non-Western countries is sparse. Such a gap in research output between high- and low-income countries constrains improvements in public health and mental health policy and practice in developing countries, where there is perhaps the greatest unmet need. If research is to inform local mental health policy and practice, it must reflect the diverse realities of local health systems and cultural factors.

10.
Cochrane Database Syst Rev ; (4): CD007445, 2010 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-20393959

RESUMO

BACKGROUND: Agitated or violent behaviour constitutes 10% of all emergency psychiatric treatment. Some guidelines do not recommend the use of chlorpromazine for rapid tranquillisation but it is still often used for this purpose. OBJECTIVES: To examine the effects of oral or intramuscular chlorpromazine for psychosis induced agitation or aggression. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (up to July 2009) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: Randomised control trials or double blind trials (implying randomisation) comparing chlorpromazine with another drug or placebo for people who are thought to be acutely aggressive or agitated due to psychotic illness. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effects model. MAIN RESULTS: One study (total n=30) met the inclusion criteria. When compared with haloperidol (Man 1973) (1 RCT, n=30) people allocated chlorpromazine were no more likely to have one additional injection than those allocated haloperidol (RR 3.00 CI 0.13 to 68.26). This remained true for 2-4 injections (RR 0.90 CI 0.52 to 1.55) and for 5 or more injections (RR 0.75 CI 0.20 to 2.79). Two people allocated chlorpromazine had sudden, serious hypotension while no one allocated haloperidol had such an effect (RR 5.00 CI 0.26 to 96.13). No extrapyramidal symptoms were observed. One person allocated chlorpromazine developed status epilepticus (RR 3.00 CI 0.13 to 68.26). AUTHORS' CONCLUSIONS: Overall the quality of evidence is limited, poor and dated. Where drugs that have been better evaluated are available, it may be best to avoid use of chlorpromazine. Where chlorpromazine is used for acute aggression or where choices are limited, relevant trials are possible and urgently needed.


Assuntos
Agressão/efeitos dos fármacos , Antipsicóticos/administração & dosagem , Clorpromazina/administração & dosagem , Agitação Psicomotora/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Administração Oral , Agressão/psicologia , Haloperidol/administração & dosagem , Humanos , Injeções Intramusculares , Transtornos Psicóticos/psicologia
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