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1.
Rev Med Suisse ; 15(667): 1882-1886, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617977

RESUMO

The association of an angiotensin II receptor antagonist and a neprilysin inhibitor (ARNI or Angiotensin Receptor-Neprilysin Inhibitor) is a new actor in the management of heart failure with reduced left ventricular ejection fraction (LVEF). The PARADIGM-HF trial performed in outpatients with a LVEF ≤ 35-40 % demonstrated that sacubitril-valsartan was superior to enalapril in reducing cardiovascular mortality and heart failure hospitalizations. Precautions in the initiation of sacubitril-valsartan, its use as well as its place in the drug management strategy for chronic heart failure are described in the present review. Additional data in patients hospitalized with reduced LVEF, in patients with LVEF > 45 % as well as the effects on blood pressure, renal or cognitive functions are presented.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Enalapril/farmacologia , Enalapril/uso terapêutico , Insuficiência Cardíaca/metabolismo , Humanos , Rim/efeitos dos fármacos , Neprilisina/metabolismo , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do Tratamento
2.
Klin Padiatr ; 231(5): 262-268, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31505693

RESUMO

OBJECTIVE: The consumption of illegal substances during pregnancy is an increasing social and medical issue. Main substances of prenatal drug exposure are beside tehtrahydrocannabinol (THC), opioids and methamphetamine. The effect of these substances on the long-term development of children remains uncertain. METHODS: Since 2012 newborn infants born at the university hospital of children at Leipzig which were prenatal exposed to drugs were followed long-term at the out-patient clinic for child protection. For 42 children with prenatal opioid or methamphetamine exposure the developmentent was analysed using the Bayley Scales (BSID III) at the age of 2-3 years. The children were compared with 84 unexposed control children. One case matched to 2 controls, adapted by age, gender, gestational age and birth weight. RESULTS: Motoric development between prenatal methylamphetamine, opioid exposed children and the control group showed no significant difference. Methylamphetamine exposed children (n=23) At 2 exposure show significantly lower scores in cognition and language (79,1 compared 95,9 of the control group), opioid exposed children have a slight cognitive deficits with a medium score of 91,7 (n=19). 56% of the methamphetamine group were developmentally retarded at the measurement date. Additionally, children had significant lower Bayley Scores which had single parent and/ or low educational and professional qualifications of their caregiver. Both substances increased the risk of postnatal complications to 46-53% despite of similar gestational ages in all groups. CONCLUSION: Children with prenatal methamphetamine or opioid exposure seem to have cognition and language deficits at 2 and 3 years of age. Methamphetamine might have a higher negative effect than opioids. The psychosocial risk factors associated with parental drug abuse are important for achieving age-appropriate development.


Assuntos
Analgésicos Opioides/toxicidade , Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metanfetamina/toxicidade , Atividade Motora/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Comportamento do Lactente/efeitos dos fármacos , Comportamento do Lactente/psicologia , Recém-Nascido , Linguagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 529-535, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484617

RESUMO

To investigate the effect of N-acetylcysteine(NAC)on cognitive function and nuclear factor erythroid 2 related factor 2/ heme oxygenase-1(Nrf2/HO-1)pathway in mouse models of postoperative cognitive dysfunction. Methods Fifty-four male C57BL/6J mice(3-4 months old)were randomly divided into control group,surgery group,and surgery+NAC group by block randomization.The intramedullary fixation for left tibial fracture surgery was performed to establish postoperative cognitive dysfunction models.NAC(150 mg/kg)was administered intraperitoneally in group surgery+NAC 30 minutes before and 3 hours,6 hours after surgery,while saline was given in control group and surgery group.Six mice in each group were selected randomly underwent Morris water maze test on the third day after surgery.Animals were sacrificed at the first and third postoperative days,and the hippocampus was harvested.Enzyme-linked immunosorbent assay was used to quantify the levels of interleukin-6(IL-6)and malondialdehyde(MDA)in hippocampus.Western blot and real-time polymerase chain reaction were used to measure the expressions of Nrf2 and HO-1 in hippocampus. Results There was no significant difference in swimming speed among three groups(F=2.135,P=0.114).Compared with control group and surgery+NAC group,the surgery group had prolonged escape latency(P<0.01),reduced platform crossing times(P<0.01),and shortened time spent in the target quadrant(P<0.01).Compared with the control group,the surgery group and the surgery+NAC group had significantly increased levels of IL-6 and MDA in hippocampus at the first postoperative day(all P=0.000).On the third postoperative day,there was no significant difference in the levels of IL-6(P=0.251)and MDA(P=0.103)between control group and surgery+NAC group.The protein expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group(all P=0.000).The mRNA expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group (all P=0.000). Conclusions NAC pretreatment may reduce oxidative stress and inflammatory response in hippocampus and improve cognitive function.Such effect may be relate to the activation of Nrf2/HO-1 pathway.


Assuntos
Acetilcisteína/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Disfunção Cognitiva/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias , Distribuição Aleatória
4.
Medicine (Baltimore) ; 98(34): e16931, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441882

RESUMO

Several studies have shown that statin users have a lower risk of new-onset dementia (NOD) compared nonusers. However, other studies have shown opposite results. In this study, we investigated the association between the use of statins and the development of NOD.This was a longitudinal cohort study using data from claim forms submitted to the Taiwanese Bureau of National Health Insurance. The study included patients with NOD and non-NOD subjects from January 2002 to December 2013. We estimated the hazard ratios (HRs) of NOD associated with statin use, whereas nonuser subjects were used as a reference group.A total of 19,522 NOD cases were identified in 100,610 hyperlipidemic patients during the study period. The risk of NOD, after adjusting for sex, age, comorbidities, and concurrent medication, was lower among statin users than nonusers (HR 0.95, 95% CI [confidence interval] 0.94-0.96; P < .001). The adjusted HRs for NOD were 1.53 (95% CI, 1.45-1.62), 0.63 (95% CI, 0.57-0.71), and 0.34 (95% CI, 0.30-0.38) when the cumulative defined daily doses ranged from 28 to 365, 366 to 730, and more than 730 relative to nonusers, respectively.We concluded that statin use is associated with a decreased NOD risk. The protective effect of statins for NOD seemed to be related to high exposure to statins. This study also highlights that high exposure to statins has a dose-response effect on lowering NOD risk.


Assuntos
Cognição/efeitos dos fármacos , Demência/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Demência/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologia
5.
Medicine (Baltimore) ; 98(34): e16966, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441902

RESUMO

The importance of optimal blood pressure control for preventing or reducing the impairment of vascular and cognitive functions is well known. However, the reversibility of early alterations in vascular and cognitive functions through antihypertensive agents is under-investigated. In this study, we evaluated the influence of 3 months of angiotensin-converting enzyme (ACE) inhibition treatment on the morphological and functional arterial wall and cognitive performance changes in 30 newly diagnosed primary hypertensive patients.Common carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) were detected by ultrasonography. Arterial stiffness indicated by augmentation index (AIx) and pulse wave velocity (PWV) was assessed by arteriography. Cognitive functions were assessed by neuropsychological examination.The executive function overall score was significantly higher at 3-month follow-up than at baseline (median, 0.233 (IQR, 0.447) vs -0.038 (0.936); P = .001). Three-month ACE inhibition did not produce significant improvement in IMT, FMD, AIx and PWV values. Significant negative associations were revealed between IMT and complex attention (r = -0.598, P = .0008), executive function (r = -0.617, P = .0005), and immediate memory (r = -0.420, P = .026) overall scores at follow-up. AIx had significant negative correlations with complex attention (r = -0.568, P = .001), executive function (r = -0.374, P = .046), and immediate memory (r = -0.507, P = .005). PWV correlated significantly and negatively with complex attention (r = -0.490, P = .007).Timely and effective antihypertensive therapy with ACE inhibitors has significant beneficial effects on cognitive performance in as few as 3 months. Early ACE inhibition may have an important role in the reversal of initial impairments of cognitive function associated with hypertension-induced vascular alterations.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Cognição/efeitos dos fármacos , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Artéria Braquial/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Expert Opin Drug Saf ; 18(10): 915-923, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373245

RESUMO

Introduction: Muscarinic receptor antagonists, 5α-reductase inhibitors and α1-adrenoceptor antagonists are frequently used drug classes for the treatment of lower urinary tract symptoms including those of overactive bladder syndrome and benign prostatic enlargement/benign prostatic obstruction. Areas covered: The authors review the evidence for adverse effects of these drug classes on cognitive function, mood and other functions of the central nervous system and discuss such effects against the evidence for mechanistic plausibility. Expert opinion: Muscarinic antagonists carry a risk for impaired cognition and other brain functions that differs quantitatively between compounds, being highest with oral formulations of oxybutynin. 5□-Reductase inhibitors can cause depressive symptoms even at low doses and starting several months after discontinuation of treatment. The evidence for α1-adrenoceptor antagonists and specifically tamsulosin to cause dementia is controversial and lacks mechanistic plausibility. We recommend that physicians treating patients with lower urinary tract symptoms carefully monitor mental status prior to prescribing and periodically thereafter.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Antagonistas Muscarínicos/efeitos adversos , Inibidores de 5-alfa Redutase/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Afeto/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Masculino , Antagonistas Muscarínicos/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/efeitos adversos , Tansulosina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico
7.
Life Sci ; 234: 116739, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400352

RESUMO

AIM: This study aimed to investigate the effect of icariin (referred as ICA) on Alzheimer's disease (AD) model through endoplasmic reticulum (ER) stress pathway. MAIN METHODS: Nine months male APP/PS1 and wild-type (WT) mice were randomly divided into four groups: APP/PS1 control, APP/PS1 + ICA, WT control and WT + ICA groups. The treated mice were given ICA 60 mg/kg/d and control mice were received the same volume distilled water for consecutive 3 months. The Morris water maze and Novel object recognition were used to detect animals' behavior. Nissl staining was used to observe the neuronal morphology in hippocampus area. Aß deposition in hippocampal region was observed by immunofluorescence staining. TUNEL staining was used to observe apoptosis. Detection of expression of ER stress related factors by Western blot and real time RT-PCR. KEY FINDINGS: Chronically administrated with ICA compared with APP/PS1 control mice significantly improved the behavior performance, reduced neuronal apoptosis, as well as suppressing the ER stress signaling pathway, including that decreased the level of glucose-regulated protein 78, phosphorylated ER-regulated kinase and phosphorylated eukaryotic initiation factor α, as well activating transcription factor-4, C/EBP homologous protein, DNA damage inducible protein 34 and tribbles homologous protein 3. SIGNIFICANCE: Our data indicated that ICA suppressed the ER stress signaling to protect against AD animal model, these findings suggest that a potential point for researching the effect of ICA on neurodegeneration.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Precursor de Proteína beta-Amiloide/metabolismo , Cognição/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Flavonoides/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Memória/efeitos dos fármacos , Camundongos
8.
J Agric Food Chem ; 67(36): 10048-10058, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31422666

RESUMO

Ginseng, the roots and rhizomes of Panax ginseng C. A. Meyer, is used not only as a herbal medicine but also as a functional food to support body functions. Ginsenoside Rg3 (GRg3) is a major bioactive component in ginseng. In this study, the beneficial effects of GRg3 on rats with Alzheimer's disease (AD) were evaluated via the behavioral experiment and antioxidant capacity. Moreover, metabolomic analysis based on UPLC-QTOF-MS/MS and apoptosis analysis was used to obtain the change between AD and GRg3-administrated rats to assess the underlying mechanisms on improving mitochondrial dysfunction. Results showed that GRg3 could prevent the cognitive impairment of AD rats by improving the mitochondrial dysfunction. The potential mechanisms were related to regulate the abnormality of energy metabolism, electron transport chain, amino acid metabolism, purine metabolism, and antiapoptosis. These findings support the exploitation of GRg3 as an effective complementary and functional food to prevent and delay AD.


Assuntos
Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Ginsenosídeos/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Doença de Alzheimer/fisiopatologia , Aminoácidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Humanos , Masculino , Mitocôndrias/metabolismo , Panax/química , Ratos , Ratos Wistar
10.
Medicine (Baltimore) ; 98(27): e16091, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277107

RESUMO

BACKGROUND: Cognitive impairment is a principal manifestation of Alzheimer disease (AD). To provide a clinical reference for the treatment of AD, a network meta-analysis (NMA) was performed to evaluate the effects of different anti-dementia drugs on the cognitive impairment exhibited by patients with AD. METHODS: Relevant randomized controlled trials are found through the Pubmed database, Web of Science, Clinical Trials, Embase, Cohranne library, Chinese National Knowledge Infrastructure database, CBM databases, and Wanfang among others. A total of 33 articles were collected, with the earliest document collected having been published in February 2017. The included reports were screened for quality of papers by using strict inclusion and exclusion criteria. All analyses were based on previously published studies reporting de-identified data; thus, no ethical approval or patient consent were required. The Mini-Mental State Examination scores informed the classification of the 33 articles into a mild subgroup, which featured 11 articles, and 12 drugs (besides a placebo); a moderate subgroup, which featured 17 articles and 15 drugs (besides a placebo); and a severe subgroup, which featured 5 articles and 3 drugs (besides a placebo). RESULTS: While donepezil, galanthamine, and huperzine demonstrated the highest efficacy in the mild cognitive dysfunction subgroup (mean difference = 5.2, 2.5, and 2.4, respectively). Donepezil, huperzine A, and rivastigmine achieved the most significant effects in the moderate cognitive dysfunction subgroup (MD = 3.8, 2.9, and 3.0 respectively). In the severe subgroup, donepezil was demonstrably superior to memantine. Donepezil was thus found to effectively address cognitive impairment in patients with AD regardless of the degrees of cognitive decline. CONCLUSIONS: Evaluation of the clinically common anti-dementia drugs using NMA affirmed the utility of cholinesterase inhibitors, especially donepezil, in alleviating cognitive dysfunction of patients with AD. This study may therefore help to inform the clinical selection of pharmacotherapeutic interventions addressing cognitive dysfunction in patients with AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Nootrópicos/uso terapêutico , Teorema de Bayes , Humanos , Testes de Estado Mental e Demência , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Life Sci ; 233: 116698, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356906

RESUMO

AIM: Type 1 diabetes (T1DM) is a common chronic disease in childhood. Increasing insulin resistance in puberty gives rise to higher doses of insulin usage in treatment. Of this reason new approaches in treatment are needed. Noopept researches suggest it to have anti-diabetic properties. We tried to determine the effects of noopept on pubertal diabetes. MAIN METHOD: The research was made with 60 prepubertal, 28 day-old, male, Sprague Dawley rats. The rats were divided into randomised 6 groups (n = 10/group). i) Control, ii) Diabetes Control, iii) Noopept Control, iv) Diabetes + Noopept, v) Diabetes + Insulin, vi) Diabetes + Insulin + Noopept. T1DM model was induced by streptozotocin on postnatal 28th day. 0.5 mg/kg noopept and 1 IU insulin were administered intraperitoneally for 14 days. Blood glucose and body weight measurements, puberty follow-up and MWM tests were performed. Hippocampus, hypothalamus and testis were evaluated histologically. Hypothalamic GnRH and kisspeptin were studied immunohistochemically. Serum LH, FSH and insulin, hippocampal homogenate NGF and BDNF levels were determined by ELISA. KEY FINDINGS: Delayed puberty was normalized by noopept (p < 0.05). Blood glucose levels were lower in noopept-administered diabetic groups (p < 0.05). Noopept decreased HOMA-IR in insulin administered diabetic group (p < 0.05). Number of degenerated cells in hippocampus and testis were higher in diabetes control group when compared with other groups (p < 0.05). GnRH immunoreactivity in Diabetes + Noopept group was increased when compared to insulin + noopept group (p = 0.018). There was no difference in kisspeptin, serum LH, FSH, hippocampal NGF-BDNF levels and spatial learning assessment among groups (p > 0.05). SIGNIFICANCE: Noopept may have positive effect in treatment of pubertal diabetes.


Assuntos
Cognição/fisiologia , Diabetes Mellitus Experimental/tratamento farmacológico , Dipeptídeos/farmacologia , Resistência à Insulina , Fármacos Neuroprotetores/farmacologia , Puberdade/fisiologia , Animais , Glicemia/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Insulina/metabolismo , Masculino , Fator de Crescimento Neural/metabolismo , Puberdade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
12.
Psychopharmacology (Berl) ; 236(8): 2501-2512, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31302719

RESUMO

RATIONALE: Although methylphenidate and other stimulants have been demonstrated to improve task performance across a variety of domains, a computationally rigorous account of how these drugs alter cognitive processing remains elusive. Recent applications of mathematical models of cognitive processing and electrophysiological methods to this question have suggested that stimulants improve the integrity of evidence accumulation processes for relevant choices, potentially through catecholaminergic modulation of neural signal-to-noise ratios. However, this nascent line of work has thus far been limited to simple perceptual tasks and has largely omitted more complex conflict paradigms that contain experimental manipulations of specific top-down interference resolution processes. OBJECTIVES AND METHODS: To address this gap, this study applied the conflict linear ballistic accumulator (LBA), a newly proposed model designed for conflict tasks, to data from healthy adults who performed the Multi-Source Interference Task (MSIT) after acute methylphenidate or placebo challenge. RESULTS: Model-based analyses revealed that methylphenidate improved performance by reducing individuals' response thresholds and by enhancing evidence accumulation processes across all task conditions, either by improving the quality of evidence or by reducing variability in accumulation processes. In contrast, the drug did not reduce bottom-up interference or selectively facilitate top-down interference resolution processes probed by the experimental conflict manipulation. CONCLUSIONS: Enhancement of evidence accumulation is a biologically plausible and task-general mechanism of stimulant effects on cognition. Moreover, the assumption that methylphenidate's effects on behavior are only visible with complex executive tasks may be misguided.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Simulação por Computador , Conflito (Psicologia) , Metilfenidato/farmacologia , Modelos Psicológicos , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Adulto , Cognição/efeitos dos fármacos , Cognição/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Adulto Jovem
13.
Psychopharmacology (Berl) ; 236(8): 2337-2358, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31324936

RESUMO

RATIONALE: Disorders of compulsivity such as stimulant use disorder (SUD) and obsessive-compulsive disorder (OCD) are characterised by deficits in behavioural flexibility, some of which have been captured using probabilistic reversal learning (PRL) paradigms. OBJECTIVES: This study used computational modelling to characterise the reinforcement learning processes underlying patterns of PRL behaviour observed in SUD and OCD and to show how the dopamine D2/3 receptor agonist pramipexole and the D2/3 antagonist amisulpride affected these responses. METHODS: We applied a hierarchical Bayesian method to PRL data across three groups: individuals with SUD, OCD, and healthy controls. Participants completed three sessions where they received placebo, pramipexole, and amisulpride, in a double-blind placebo-controlled, randomised design. We compared seven models using a bridge sampling estimate of the marginal likelihood. RESULTS: Stimulus-bound perseveration, a measure of the degree to which participants responded to the same stimulus as before irrespective of outcome, was significantly increased in SUD, but decreased in OCD, compared to controls (on placebo). Individuals with SUD also exhibited reduced reward-driven learning, whilst both the SUD and OCD groups showed increased learning from punishment (nonreward). Pramipexole and amisulpride had similar effects on the control and OCD groups; both increased punishment-driven learning. These D2/3-modulating drugs affected the SUD group differently, remediating reward-driven learning and reducing aspects of perseverative behaviour, amongst other effects. CONCLUSIONS: We provide a parsimonious computational account of how perseverative tendencies and reward- and punishment-driven learning differentially contribute to PRL in SUD and OCD. D2/3 agents modulated these processes and remediated deficits in SUD in particular, which may inform therapeutic effects.


Assuntos
Transtorno Obsessivo-Compulsivo/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Reforço (Psicologia) , Reversão de Aprendizagem/fisiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Adulto , Estimulantes do Sistema Nervoso Central/uso terapêutico , Cognição/efeitos dos fármacos , Cognição/fisiologia , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Antagonistas de Dopamina/farmacologia , Antagonistas de Dopamina/uso terapêutico , Antagonistas dos Receptores de Dopamina D2/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Transtorno Obsessivo-Compulsivo/psicologia , Receptores de Dopamina D2/agonistas , Receptores de Dopamina D3/agonistas , Receptores de Dopamina D3/antagonistas & inibidores , Reversão de Aprendizagem/efeitos dos fármacos , Recompensa , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto Jovem
15.
Dev Neuropsychol ; 44(5): 409-416, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31223031

RESUMO

Tobacco use is a prevalent problem in the general population as well as among military veterans. Despite the fact that tobacco users are at an increased risk of many medical and psychiatric comorbidities, the risk of cognitive impairment in younger active tobacco users is less studied. Military veterans from the conflicts in Iraq and Afghanistan (n = 113) were administered a neuropsychological protocol. Even after controlling for the severity of PTSD symptoms, tobacco use was negatively related to performance on measures of processing speed, memory, and executive functioning. The current findings have implications for the neuropsychological evaluation of tobacco users.


Assuntos
Cognição/efeitos dos fármacos , Função Executiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Uso de Tabaco/efeitos adversos , Veteranos/psicologia , Adulto , Campanha Afegã de 2001- , Afeganistão , Comorbidade , Feminino , Humanos , Iraque , Guerra do Iraque 2003-2011 , Masculino , Pessoa de Meia-Idade , Militares/psicologia , Testes Neuropsicológicos , Prevalência , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/estatística & dados numéricos
16.
Bull Cancer ; 106(9): 805-811, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31171345

RESUMO

Testicular cancers are the most frequent and the most curable cancers in young men. Treatments of these cancers represent a great success with cure rate over to 95 %. However, chemotherapy side effects may occur during or after several years post-treatment. This review aimed to highlight complications and physical and psychological side effects occurring mainly after chemotherapy treatment for testicular cancer, and to propose a personalized post-cancer plan specific for patients treated for testicular cancer. Treatments of these cancers can cause short-term complications (asthenia, nausea, vomiting, alopecia..). These side effects disappear within a few months after the end of the treatments. Late complications may occur several years post-treatment. Cardiovascular disease, metabolic syndrome and secondary neoplasia represent the most severe late effects among patients treated for testicular cancer. Given the increased incidence of these chemotherapy-induced side effects, it is indispensable to establish a specific follow up which must include a particular vigilance on the risk of occurrence of second cancer, a follow-up of the cardio-vascular risk factors, pulmonary and auditory follow-up, and early detection of psychosocial disorders.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Testiculares/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Cognição/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Síndrome de Fadiga Crônica/induzido quimicamente , Fertilidade/efeitos dos fármacos , Seguimentos , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/prevenção & controle , Pneumopatias/induzido quimicamente , Masculino , Síndrome Metabólica/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Neoplasias Testiculares/psicologia , Fatores de Tempo
17.
Life Sci ; 231: 116566, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201846

RESUMO

AIMS: Diabetes mellitus can cause cognitive impairments, a state between normal aging and dementia. Effective clinical interventions are urgently needed to prevent or treat this complication. Liraglutide as a glucagon-like peptide 1 analog has been shown to exert memory-enhancing and neuroprotective effects on neurodegenerative diseases. This study aims to investigate the neuroprotective effects of liraglutide in streptozotocin (STZ)-induced diabetic mice with cognitive deficits. METHODS: Male C57BL/6J mice were intraperitoneal injected with STZ (65 mg/kg body weight daily for 5 days) to induce type 1 diabetes model. Then the mice were treated with liraglutide (250 mg/kg/day, for 6 weeks) or saline. Weekly changes of body weight and fasting blood glucose were measured. Cognitive performance was evaluated by Morris water maze test. The ultrastructure of hippocampus was observed by transmission electron microscope. The superoxide dismutase activities and malondialdehyde levels in the hippocampus were detected by biochemistry assay. Apoptosis-related proteins and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) signaling were detected by Western blotting. KEY FINDINGS: We found that STZ-induced diabetic mice exhibited impaired learning and memory, ultrastructure damage of hippocampal neurons and synapses, exacerbated oxidative stress and neuronal apoptosis, as compared to the control mice. These effects were attenuated by the treatment with liraglutide. Furthermore, liraglutide reversed diabetes-induced alterations in PI3K/Akt signaling pathway that plays an essential role in modulating neuronal survival, apoptosis and plasticity. SIGNIFICANCE: These data suggest that the neuroprotective effects of liraglutide on diabetes-induced cognitive impairments are associated with the improvements of hippocampal synapses and inhibition of neuronal apoptosis.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Liraglutida/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipoglicemiantes/farmacologia , Liraglutida/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/efeitos adversos , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
18.
Life Sci ; 231: 116584, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31220527

RESUMO

Taurine is a key functional amino acid with many functions in the nervous system. The effects of taurine on cognitive function have aroused increasing attention. First, the fluctuations of taurine and its transporters are associated with cognitive impairments in physiology and pathology. This may help diagnose and treat cognitive impairment though mechanisms are not fully uncovered in existing studies. Then, taurine supplements in cognitive impairment of different physiologies, pathologies and toxicologies have been demonstrated to significantly improve and restore cognition in most cases. However, elevated taurine level in cerebrospinal fluid (CSF) by exogenous administration causes cognition retardations only in physiologically sensitive period between the perinatal to early postnatal period. In this review, taurine levels are summarized in different types of cognitive impairments. Subsequently, the effects of taurine supplements on cognitions in physiology, different pathologies and toxication of cognitive impairments (e.g. aging, Alzheimer' disease, streptozotocin (STZ)-induced brain damage, ischemia model, mental disorder, genetic diseases and cognitive injuries of pharmaceuticals and toxins) are analyzed. These data suggest that taurine can improve cognition function through multiple potential mechanisms (e.g. restoring functions of taurine transporters and γ-aminobutyric acid (GABA) A receptors subunit; mitigating neuroinflammation; up-regulating Nrf2 expression and antioxidant capacities; activating Akt/CREB/PGC1α pathway, and further enhancing mitochondria biogenesis, synaptic function and reducing oxidative stress; increasing neurogenesis and synaptic function by pERK; activating PKA pathway). However, more mechanisms still need explorations.


Assuntos
Cognição/efeitos dos fármacos , Taurina/metabolismo , Taurina/farmacologia , Doença de Alzheimer/fisiopatologia , Animais , Antioxidantes/farmacologia , Cognição/fisiologia , Disfunção Cognitiva/fisiopatologia , Suplementos Nutricionais , Feminino , Humanos , Masculino , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Receptores de GABA , Receptores de GABA-A/efeitos dos fármacos , Estreptozocina/farmacologia , Taurina/fisiologia
19.
Sheng Li Xue Bao ; 71(3): 463-470, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31218337

RESUMO

Anabolic-androgenic steroid (AAS) is responsible for muscle building and masculinizing. Using AAS can enhance muscle development and strength, and improve athletic performance. AAS abuse is not only seen in sport. Research has shown that there is an increasing number of adolescent AAS abusers. Adolescents are at a critical period of physical and mental development. Sex hormones are one of the important physiological factors affecting the development of their bodies and brains. Long-term or high-dose AAS treatment is likely to cause irreversible damage to their nervous system and psychological behavior, and these effects are easily overlooked. The article reviewed the long-term adverse effects of AAS on psychological behavior, emotion, cognitive functions and the nervous system of adolescents.


Assuntos
Anabolizantes/farmacologia , Cognição/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Esteroides/farmacologia , Adolescente , Humanos , Transtornos Relacionados ao Uso de Substâncias
20.
Support Care Cancer ; 27(10): 3717-3727, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250183

RESUMO

BACKGROUND: Cognitive impairment is recognized as a common symptom experienced by cancer survivors which impacts on quality of life (QoL) and day-to-day activities. One of the treatment options is the use of psychostimulants but the evidence supporting its use remains unclear. OBJECTIVES: To identify the level of evidence of psychostimulants' effect on the management of cognitive impairment in adult cancer survivors. METHODS: Electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) and reference lists of relevant reviews were searched from inception to December 2017, with no language restrictions applied. Randomized controlled trials (RCTs), evaluating the effect of psychostimulants on cognitive impairment among cancer patients with no primary or secondary brain tumor or brain radiation, were included. The primary outcome was cognitive function changes, whereas secondary outcomes were adverse events (AEs) and QoL. RESULTS: Six RCTs were included: three studies investigating methylphenidate and three modafinil, with a total of 244 and 146 patients, respectively. Due to important differences in methodologies between studies, a meta-analysis was assumed inappropriate for the primary outcome. A narrative synthesis was performed. One study using methylphenidate and two using modafinil demonstrated improvements in some cognitive functions as measured by objective cognitive assessment tests. Psychostimulants did not improve QoL and were not associated with more AEs. CONCLUSION: To date, limited evidence is available to estimate the usefulness (or lack) of psychostimulants on cognitive function in this population.


Assuntos
Sobreviventes de Câncer/psicologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Qualidade de Vida/psicologia , Adulto , Cognição/efeitos dos fármacos , Humanos , Metilfenidato/uso terapêutico , Modafinila/uso terapêutico , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
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