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1.
Horm Behav ; 127: 104878, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33148500

RESUMO

Dominance status in hamsters is driven by interactions between arginine-vasopressin V1a, oxytocin (OT), and serotonin 1A (5-HT1A) receptors. Activation of V1a and OT receptors in the anterior hypothalamus (AH) increases aggression in males, while decreasing aggression in females. In contrast, activation of 5-HT1A receptors in the AH decreases aggression in males and increases aggression in females. The mechanism underlying these differences is not known. The purpose of this study was to determine if dominance status and sex interact to regulate V1a, OT, and 5-HT1A receptor binding. Same-sex hamsters (N = 47) were paired 12 times across six days in five min sessions. Brains from paired and unpaired (non-social control) hamsters were collected immediately after the last interaction and processed for receptor binding using autoradiography. Differences in V1a, OT, and 5-HT1A receptor binding densities were observed in several brain regions as a function of social status and sex. For example, in the AH, there was an interaction between sex and social status, such that V1a binding in subordinate males was lower than in subordinate females and V1a receptor density in dominant males was higher than in dominant females. There was also an interaction in 5-HT1A receptor binding, such that social pairing increased 5-HT1A binding in the AH of males but decreased 5-HT1A binding in females compared with unpaired controls. These results indicate that dominance status and sex play important roles in shaping the binding profiles of key receptor subtypes across the neural circuitry that regulates social behavior.


Assuntos
Agressão/fisiologia , Hierarquia Social , Mesocricetus/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Arginina/metabolismo , Arginina Vasopressina/metabolismo , Cricetinae , Feminino , Hipotálamo Anterior/metabolismo , Masculino , Mesocricetus/metabolismo , Mesocricetus/psicologia , Ocitocina/metabolismo , Ligação Proteica , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de Ocitocina/metabolismo , Receptores de Vasopressinas/metabolismo , Serotonina/metabolismo , Caracteres Sexuais , Comportamento Social
2.
Mol Psychiatry ; 23(2): 467-475, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27752079

RESUMO

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/ß-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/ß-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/ß-catenin pathway.


Assuntos
Espinhas Dendríticas/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Animais , Ansiedade , Transtornos de Ansiedade , Espinhas Dendríticas/metabolismo , Depressão , Transtorno Depressivo , Proteínas de Transporte de Glutamato da Membrana Plasmática/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Transtornos Mentais/genética , Camundongos , Camundongos Knockout , Polimorfismo de Nucleotídeo Único/genética , Células Piramidais/fisiologia , Comportamento Social , Sinapses/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo
3.
Int J Clin Pract ; 65(8): 887-95, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21679286

RESUMO

Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral treatment approved by the US Food and Drug Administration for the treatment of relapsing forms of multiple sclerosis (MS). The aim of this review was to provide a concise, comprehensive overview of the clinically relevant mechanism of action, efficacy and safety information available for fingolimod. Key data were derived from two international, Phase III, double-blind, randomised trials (TRANSFORMS and FREEDOMS) performed over 12 and 24 months, respectively, which evaluated fingolimod 0.5 and 1.25 mg daily in 1703 patients with relapsing forms of MS. In TRANSFORMS, there was a 52% reduction in the annualised relapse rate (ARR) with fingolimod 0.5 mg vs. 30 µg intramuscular interferon beta-1a (0.16 vs. 0.33; p < 0.001) at 1 year. In FREEDOMS, there was a 55% decrease in ARR at 2 years with fingolimod 0.5 mg vs. placebo (0.18 vs. 0.40; p < 0.001). Risk of disability progression, confirmed at 3 months, was also reduced by 30% over the 2-year study period with fingolimod vs. placebo (p = 0.02). Significantly fewer new or enlarged lesions on T(2) -weighted images were seen in both studies (TRANSFORMS, p = 0.002 vs. interferon beta-1a at 1 year; FREEDOMS, p < 0.001 vs. placebo at 2 years). Overall, fingolimod 0.5 mg was well tolerated by patients. Transient, generally asymptomatic bradycardia and infrequent atrioventricular block were seen with the administration of the first dose. Macular oedema and serious infections occurred infrequently. Reversible, asymptomatic elevations of liver enzymes could also occur. As the first approved oral disease-modifying treatment, fingolimod offers patients a convenient alternative to regular self-injection for the treatment of relapsing forms of MS. In addition to high efficacy with a relatively acceptable safety profile, fingolimod provides a therapy with a new mechanism of action.


Assuntos
Imunossupressores/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Propilenoglicóis/administração & dosagem , Esfingosina/análogos & derivados , Administração Oral , Adulto , Ensaios Clínicos Fase III como Assunto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Cloridrato de Fingolimode , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/farmacocinética , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Propilenoglicóis/efeitos adversos , Propilenoglicóis/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Lisoesfingolipídeo/efeitos dos fármacos , Fatores de Risco , Prevenção Secundária , Esfingosina/administração & dosagem , Esfingosina/efeitos adversos , Esfingosina/farmacocinética , Resultado do Tratamento , Adulto Jovem
4.
Neurobiol Learn Mem ; 92(3): 410-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19500683

RESUMO

Over the past three decades there has been a substantial increase in the amount of fructose consumed by North Americans. Recent evidence from rodents indicates that hippocampal insulin signaling facilitates memory and excessive fructose consumption produces hippocampal insulin resistance. Based on this evidence, the present study tested the hypothesis that a high fructose diet would impair hippocampal-dependent memory. Adult male Sprague-Dawley rats (postnatal day 61) were fed either a control (0% fructose) or high fructose diet (60% of calories). Food intake and body mass were measured regularly. After 19 weeks, the rats were given 3 days of training (8 trials/day) in a spatial version of the water maze task, and retention performance was probed 48 h later. The high fructose diet did not affect acquisition of the task, but did impair performance on the retention test. Specifically, rats fed a high fructose diet displayed significantly longer latencies to reach the area where the platform had been located, made significantly fewer approaches to that area, and spent significantly less time in the target quadrant than did control diet rats. There was no difference in swim speed between the two groups. The retention deficits correlated significantly with fructose-induced elevations of plasma triglyceride concentrations. Consequently, the impaired spatial water maze retention performance seen with the high fructose diet may have been attributable, at least in part, to fructose-induced increases in plasma triglycerides.


Assuntos
Dieta , Carboidratos da Dieta/administração & dosagem , Frutose/administração & dosagem , Transtornos da Memória/fisiopatologia , Percepção Espacial/fisiologia , Edulcorantes/administração & dosagem , Animais , Peso Corporal , Ingestão de Alimentos , Hepatomegalia/fisiopatologia , Fígado/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Natação/fisiologia , Fatores de Tempo , Triglicerídeos/sangue
5.
J Clin Pathol ; 20(2): 124-7, 1967 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-5628852

RESUMO

A case is reported of an English woman who presented with a mass in the breast which was locally excised. Histological studies revealed a giant-cell granulomatous inflammation involving the duct system and a fungus showing brown pigmentation was demonstrated in the lesions. This was not grown in culture but the morphological appearance suggested classification in the genus Cladosporium. The relation of this to the more usual forms of cutaneous chromoblastomycosis is discussed.


Assuntos
Doenças Mamárias/microbiologia , Cromoblastomicose/microbiologia , Doenças Mamárias/patologia , Cromoblastomicose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Fungos Mitospóricos/isolamento & purificação
6.
Ann R Coll Surg Engl ; 65(1): 8-10, 1983 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6824311

RESUMO

The traditional methods of follow-up of patients after curative surgery for large-bowel carcinoma have been shown to be time-consuming but largely ineffectual. A new approach is proposed which utilises laboratory investigations. A plea is made for controlled trials of cytotoxic regimens in patients with proven recurrent disease.


Assuntos
Neoplasias Intestinais/cirurgia , Intestino Grosso , Recidiva Local de Neoplasia/diagnóstico , Antineoplásicos/uso terapêutico , Antígeno Carcinoembrionário/análise , Seguimentos , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/imunologia , Intestino Grosso/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Complicações Pós-Operatórias/diagnóstico
7.
Ann R Coll Surg Engl ; 57(6): 326-8, 1975 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1211793

RESUMO

A survey of 260 adult male patients who had undergone inguinal hernia repair was carried out to see how long they stayed off work after operation. There was no evidence that a prolonged convalescent period reduced the subsequent hernia recurrence rate. Evidence from the North American literature suggests that patients can resume their usual physical activity without ill effect much sooner after operation than is the current practice in the United Kingdom. General practitioners should be informed of the advice that has been given to their patients about the resumption of physical activities after operation.


Assuntos
Hérnia Inguinal/cirurgia , Convalescença , Humanos , Masculino , Pessoa de Meia-Idade , Ocupações , Esforço Físico , Complicações Pós-Operatórias , Recidiva , Fatores de Tempo
8.
Nurs Clin North Am ; 28(4): 829-38, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8265422

RESUMO

The client receiving immunosuppressive therapy for demyelinating disorders faces many challenges. The nurse should be involved in the constant assessment of the client for potential complications of the therapy as well as changes in the underlying disease process. Many of the nursing interventions focus on comfort and symptom management as well as providing information for the client and family to use in understanding the therapy and minimizing the effects of immunosuppression. Involving the family in client management will only strengthen the overall plan and outcomes for client care.


Assuntos
Doenças Desmielinizantes/enfermagem , Terapia de Imunossupressão/enfermagem , Humanos , Hospedeiro Imunocomprometido , Fatores Imunológicos/uso terapêutico , Terapia de Imunossupressão/métodos , Esclerose Múltipla/enfermagem , Polirradiculoneuropatia/enfermagem
9.
Nurs Clin North Am ; 34(3): 725-42, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10433655

RESUMO

Neurologic degenerative disorders pose challenges to patients, their families, and health care professionals who care for them. In recent years there have been many advances in the diagnosis and management of neurologic degenerative diseases. Multiple sclerosis, myasthenia gravis, Parkinson's disease, and amyotrophic lateral sclerosis are discussed.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/terapia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Esclerose Lateral Amiotrófica/classificação , Esclerose Lateral Amiotrófica/fisiopatologia , Humanos , Esclerose Múltipla/classificação , Esclerose Múltipla/fisiopatologia , Miastenia Gravis/fisiopatologia , Doença de Parkinson/fisiopatologia , Instituições Filantrópicas de Saúde
10.
Obesity (Silver Spring) ; 21(5): 910-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23784893

RESUMO

OBJECTIVE: In rodents, diets exceeding nutritional requirements (i.e., high-energy diets; HED) impair hippocampal-dependent memory. Our research suggests that the effects likely involve HED-induced increases in liver lipids. In this experiment, rats were provided with diet choices to test whether voluntary consumption of a HED impairs spatial memory, whether differences in initial weight gain predict memory deficits, and whether increases in liver lipids are associated with the memory deficits. DESIGN AND METHODS: Adult male Sprague-Dawley rats were given a control diet or cafeteria-style HED for 8 weeks. Weight gain during the first 5 days on the diet was used to divide rats into a HED-Lean group and a HED-Obese group. Spatial water maze memory was tested 8 weeks later and postmortem liver lipid concentrations were quantified. RESULTS: Compared with the HED-Lean and control rats, the HED-Obese rats had impaired spatial memory and met the human diagnostic criterion of non-alcoholic fatty liver disease (>5% liver lipids relative to liver weight). Moreover, liver lipids were correlated with memory deficits. CONCLUSIONS: These findings show that voluntary consumption of a HED impairs memory, that initial weight gain predicts fatty liver and memory deficits, and that fatty liver may contribute to the memory-impairing effects of obesity.


Assuntos
Ingestão de Energia , Fígado Gorduroso/etiologia , Hipocampo , Metabolismo dos Lipídeos , Transtornos da Memória/etiologia , Memória , Obesidade , Animais , Dieta , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/metabolismo , Hepatopatia Gordurosa não Alcoólica , Obesidade/metabolismo , Obesidade/psicologia , Ratos , Ratos Sprague-Dawley , Aumento de Peso/fisiologia
11.
Physiol Behav ; 106(2): 133-41, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22280920

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a disorder observed in children and adults characterized by an accumulation of liver fat (>5% wet weight) in the absence of excessive alcohol intake. NAFLD affects 10 to 30% of the American population and is the most common cause of liver disease in the United States. NAFLD leads to serious disturbances in cardiovascular and hormonal function; however, possible effects on brain function have been overlooked. The aims of the present study were to test whether diet-induced NAFLD impairs hippocampal-dependent memory and to determine whether any observed deficits are associated with changes in hippocampal insulin signaling or concentrations of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). Post-weanling male Sprague-Dawley rats were fed a high fructose (60% of calories) or control diet for 12 weeks and then trained and tested in a spatial water maze. NAFLD was confirmed with postmortem measures of liver mass and liver lipid concentrations. NAFLD did not affect acquisition of the spatial water maze, but did impair retention tested 48 h later. Specifically, both groups demonstrated similar decreases in latency to swim to the escape platform over training trials, but on the memory test NAFLD rats took longer to reach the platform and made fewer visits to the platform location than control diet rats. There were no differences between the groups in terms of insulin-stimulated phosphorylation of insulin receptor ß subunit (IR-ß) and protein kinase B (PKB/AKT) in hippocampal slices or hippocampal BDNF or IGF-1 concentrations. Thus, these data indicate that NAFLD impairs hippocampal-dependent memory function and that the deficit does not appear attributable to alterations in hippocampal insulin signaling or hippocampal BDNF or IGF-1 concentrations.


Assuntos
Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/psicologia , Hipocampo/fisiopatologia , Transtornos da Memória/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/complicações , Frutose/efeitos adversos , Hipocampo/metabolismo , Insulina/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/complicações , Hepatopatia Gordurosa não Alcoólica , Tamanho do Órgão/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor de Insulina/metabolismo
14.
Ann R Coll Surg Engl ; 64(3): 200, 1982 May.
Artigo em Inglês | MEDLINE | ID: mdl-19310807
19.
BMJ ; 304(6823): 385, 1992 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-1623336
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