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2.
Acta Paediatr ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475192

RESUMO

AIM: The main objective is to review the available evidence in the literature for developmental origins of neuropsychiatric diseases and their underlying mechanisms. We also probe emerging cutting-edge prenatal MR imaging tools and their future role in advancing our understanding the prenatal footprints of neuropsychiatric disorders. OBSERVATIONS: Both human and animal studies support early intrauterine origins of neuropsychiatric disease, particularly autism spectrum disorders (ASD), attention and hyperactivity disorders, schizophrenia, depression, anxiety and mood disorders. Specific mechanisms of intrauterine injury include infection, inflammation, hypoxia, hypoperfusion, ischaemia polysubstance use/abuse, maternal mental health and placental dysfunction. CONCLUSIONS AND RELEVANCE: There is ample evidence to suggest developmental vulnerability of the foetal brain to intrauterine exposures that increases and individual's risk for neuropsychiatric disease, especially the risk of ASD, depression and anxiety. Elucidating the exact timing and mechanisms of injury can be difficult and require novel, non-invasive approaches to the study emerging structural and functional brain development of the foetus. Clinical care should both emphasise maternal health during pregnancy, as well as close, continued monitoring for at risk offspring throughout young adulthood for the early identification and treatment of neuropsychiatric diseases.

3.
Best Pract Res Clin Anaesthesiol ; 34(3): 355-368, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004153

RESUMO

Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine's high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options have allowed physician and physician extenders such as physician assistants and nurse practitioners to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.

6.
Neurol Ther ; 9(2): 301-315, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32785879

RESUMO

Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000-10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

7.
J Thromb Haemost ; 18(8): 1813-1838, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32356929

RESUMO

Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are point-of-care viscoelastic devices that use whole blood samples to assess coagulation and fibrinolysis. These devices have been studied extensively in cardiac surgery, but there is limited robust evidence supporting its use in obstetrics. The hesitancy toward its routine use in obstetrics may be due to the current lack of randomized controlled trials and large observational studies. The study aims to systematically review studies that investigated TEG/ROTEM use in pregnancy or peripartum, and to provide recommendations for future studies to fill current research gaps. We performed a systematic review of studies on viscoelastic testing in obstetrics. Included studies were original research, used TEG or ROTEM during pregnancy or peripartum, and published in English. Ninety-three studies, spanning 31 years from 1989 to 2020 and with a total of 32,817 participants, were included. Sixty-two (66.7%) of the studies used TEG and 31 (33.3%) used ROTEM. To date, there are a total of two randomized controlled trials on TEG/ROTEM use in obstetrics. ROTEM may be used to guide transfusion therapy for postpartum hemorrhage. TEG and ROTEM can detect the hypercoagulable changes associated with pregnancy. Variability between study protocols and results suggests the need for future large prospective high-quality studies with standardized protocols to investigate the utility of TEG/ROTEM in assessing risk for thrombosis and hemorrhage as well as in guiding prophylaxis and treatment in obstetric patients. This review identifies the gaps and provides concrete recommendations for future studies to fill those gaps.

9.
Platelets ; 31(6): 740-745, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32456506

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/sangue , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Trombocitopenia/etiologia , Trombocitose/etiologia , Contagem de Células Sanguíneas , Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea , Infecções por Coronavirus/complicações , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Humanos , Inflamação/sangue , Inflamação/etiologia , Pneumonia Viral/complicações , Tromboelastografia , Trombocitopenia/sangue , Trombocitose/sangue , Trombofilia/sangue , Trombofilia/etiologia
11.
Pain Ther ; 9(1): 195-215, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222952

RESUMO

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

12.
J Neurosci ; 35(20): 7927-37, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25995477

RESUMO

An imbalance in molecular signaling cascades and transcriptional regulation in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine D1 versus D2 receptors, is implicated in the behavioral responses to psychostimulants. To provide further insight into the molecular mechanisms occurring in MSN subtypes by cocaine, we examined the transcription factor early growth response 3 (Egr3). We evaluated Egr3 because it is a target of critical cocaine-mediated signaling pathways and because Egr3-binding sites are found on promoters of key cocaine-associated molecules. We first used a RiboTag approach to obtain ribosome-associated transcriptomes from each MSN subtype and found that repeated cocaine administration induced Egr3 ribosome-associated mRNA in NAc D1-MSNs while reducing Egr3 in D2-MSNs. Using Cre-inducible adeno-associated viruses combined with D1-Cre and D2-Cre mouse lines, we observed that Egr3 overexpression in D1-MSNs enhances rewarding and locomotor responses to cocaine, whereas overexpression in D2-MSNs blunts these behaviors. miRNA knock-down of Egr3 in MSN subtypes produced opposite behavioral responses from those observed with overexpression. Finally, we found that repeated cocaine administration altered Egr3 binding to promoters of genes that are important for cocaine-mediated cellular and behavioral plasticity. Genes with increased Egr3 binding to promoters, Camk2α, CREB, FosB, Nr4a2, and Sirt1, displayed increased mRNA in D1-MSNs and, in some cases, a reduction in D2-MSNs. Histone and the DNA methylation enzymes G9a and Dnmt3a displayed reduced Egr3 binding to their promoters and reduced mRNA in D1-MSNs. Our study provides novel insight into an opposing role of Egr3 in select NAc MSN subtypes in cocaine action.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Proteína 3 de Resposta de Crescimento Precoce/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Sequência de Aminoácidos , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , DNA (Citosina-5-)-Metiltransferases , Proteína 3 de Resposta de Crescimento Precoce/genética , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Neurônios/classificação , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Núcleo Accumbens/citologia , Especificidade de Órgãos , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
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