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1.
Alcohol Clin Exp Res ; 45(5): 922-933, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33682145

RESUMO

BACKGROUND: Alcohol use disorders (AUDs) are associated with altered regulation of physiological processes in the brain. Acetate, a metabolite of ethanol, has been implicated in several processes that are disrupted in AUDs including transcriptional regulation, metabolism, inflammation, and neurotransmission. To further understand the effects of acetate on brain function in AUDs, we investigated the effects of acetate on cerebral blood flow (CBF), systemic inflammatory cytokines, and behavior in AUD. METHODS: Sixteen participants with AUD were recruited from a nonmedical, clinically managed detoxification center. Each participant received acetate and placebo in a randomly assigned order of infusion and underwent 3T MR scanning using quantitative pseudo-continuous arterial spin labeling. Participants and the study team were blinded to the infusion. CBF values (ml/100 g/min) extracted from thalamus were compared between placebo and acetate using a mixed effect linear regression model accounting for infusion order. Voxel-wise CBF comparisons were set at threshold of p < 0.05 cluster-corrected for multiple comparisons, voxel-level p < 0.0001. Plasma cytokine levels and behavior were also assessed between infusions. RESULTS: Fifteen men and 1 woman were enrolled with Alcohol Use Disorders Identification Test (AUDIT) scores between 13 and 38 with a mean of 28.3 ± 9.1. Compared to placebo, acetate administration increased CBF in the thalamus bilaterally (Left: 51.2 vs. 68.8, p < 0.001; Right: 53.7 vs. 69.6, p = 0.001), as well as the cerebellum, brainstem, and cortex. Older age and higher AUDIT scores were associated with increases in acetate-induced thalamic blood flow. Cytokine levels and behavioral measures did not differ between placebo and acetate infusions. CONCLUSIONS: This pilot study in AUD suggests that during the first week of abstinence from alcohol, the brain's response to acetate differs by brain region and this response may be associated with the severity of alcohol dependence.


Assuntos
Acetatos/farmacologia , Alcoolismo/metabolismo , Comportamento/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Inflamação/metabolismo , Tálamo/irrigação sanguínea , Adulto , Fatores Etários , Abstinência de Álcool , Alcoolismo/fisiopatologia , Encéfalo/irrigação sanguínea , Citocinas/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Distribuição Aleatória
2.
Bull Entomol Res ; 111(2): 190-199, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32778187

RESUMO

The Colorado potato beetle, Leptinotarsa decemlineata (Say), is one of the most destructive pest species to have developed resistance to most chemical insecticides. We determined the composition and evaluated the potential of Tanacetum parthenium L. and Tanacetum vulgare L. (Asteraceae family) essential oil (EO) application as an alternative eco-friendly control strategy against L. decemlineata. We assessed the antifeedant activity for L. decemlineata larvae and adults by estimating the damage to potato leaves treated with three concentrations of EOs dissolved in ethanol (0.125, 0.25 and 0.5%). Results showed that T. parthenium EO was more effective against larvae, and T. vulgare was more effective against adults. In an olfactometer assay, the time required to choose an untreated leaf disc did not depend on the Tanacetum species, or life stage examined. However, the concentration of EO exhibited a significant effect on the behaviour of both developmental stages. At higher EO concentrations, both third instar larvae and adults require less time to choose an untreated leaf disc. Additionally, T. parthenium EO provoked more rapid movement away from the treated leaf disc than T. vulgare, especially at the highest concentration. Successful modification of L. decemlineata behaviour by the two Tanacetum oils suggests that they possess the potential for use in potato protection.


Assuntos
Besouros/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tanacetum parthenium/química , Animais , Comportamento/efeitos dos fármacos , Repelentes de Insetos/farmacologia , Larva/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Tanacetum/química
3.
Biomed Res Int ; 2020: 8823038, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33376745

RESUMO

Dementia and related conditions disturb the ability to perform routine life activities prohibiting a person from making appropriate decisions. Seeds of Cucumis melo and Citrullus lanatus have been investigated extensively for various pharmacological properties; hence, considering the presence of bioactive compounds, it was assumed that these seed extracts may support the functioning of the central nervous system. Thus, the present study was designed to investigate the short-term and long-term memory-enhancing effects of C. melo and C. lanatus seed extracts in mice by the Morris water maze (spatial learning and memory), stationary rod test, and passive avoidance tests (fear-motivated tests). Ethanol extract of both seeds were prepared by standard procedure and given to animals in the doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. The results were compared to standard drugs diazepam and imipramine given in the doses of 3 mg/kg and 30 mg/kg, respectively. Extracts of both the seeds were found to possess significant memory and cognition-enhancing effects in mice when tested by passive avoidance, stationary rod, and water maze tests. Results demonstrate memory and cognition-enhancing effects of these extracts which may be due to the presence of bioactive compounds in these seeds.


Assuntos
Citrullus/química , Cucumis/química , Memória/efeitos dos fármacos , Nootrópicos/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Animais , Comportamento/efeitos dos fármacos , Cognição , Demência/tratamento farmacológico , Medo , Humanos , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos BALB C
4.
Nature ; 586(7827): 87-94, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32939091

RESUMO

Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states1-12. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use13,14, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1-3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed-including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.


Assuntos
Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiologia , Transtornos Dissociativos/fisiopatologia , Potenciais de Ação/efeitos dos fármacos , Animais , Comportamento/efeitos dos fármacos , Ondas Encefálicas/efeitos dos fármacos , Córtex Cerebral/citologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Transtornos Dissociativos/diagnóstico por imagem , Eletrofisiologia , Feminino , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Ketamina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Optogenética , Autorrelato , Tálamo/citologia , Tálamo/diagnóstico por imagem , Tálamo/efeitos dos fármacos , Tálamo/fisiologia
5.
OMICS ; 24(7): 394-403, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32486962

RESUMO

Neurodegeneration is one of the greatest threats to global public health. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are among the major causes of chronic neurological conditions in the elderly populations. Hence, neuroprotection is at the epicenter of the current 21st-century research agenda in biomedicine. Yet, novel molecular targets are limited and solely needed for neuroprotection. Marked person-to-person variations in outcomes require a deeper understanding of drug targets in neurology and clinical neurosciences. In this context, traditional medicines offer untapped potentials for discovery and translation of novel molecular targets to human neurodegenerative disease research and clinical neurology. This expert review offers a synthesis of the prospects and challenges of harnessing new molecular targets from traditional medicines, with a view to applications for neuroprotection in human neurodegenerative diseases.


Assuntos
Biomarcadores , Suscetibilidade a Doenças , Medicina Tradicional , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo , Neuroproteção , Animais , Comportamento/efeitos dos fármacos , Genômica/métodos , Humanos , Medicina Tradicional/métodos , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/terapia , Neuroproteção/efeitos dos fármacos , Testes Neuropsicológicos , Proteômica/métodos
6.
J Psychoactive Drugs ; 52(2): 130-137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31570056

RESUMO

Ayahuasca, a plant-based hallucinogen that serves as a spiritual medicine in South America, has improved depression in at least one placebo-controlled clinical trial. Case studies suggest that dramatic behavioral changes often follow the Ayahuasca ceremony, but most explanations of antidepressant effects focus on changes in mindfulness. This study investigated whether both mindfulness and behavioral activation might contribute to these anti-depressant effects. We surveyed individuals (N = 152) about their changes in depressive symptoms, behavioral activation, and mindfulness after an Ayahuasca experience. Mindfulness was strongly associated with reduced depression severity (r = - .670, p < .001), while behavioral activation was moderately linked (r = - .474, p < .001). Changes in depressive symptoms (Center for Epidemiological Sciences Depression Short Form [CES-D-10]) covaried with subscales from the Five Facet Mindfulness Questionnaire [FFMQ] and Experiences Questionnaire [EQ], confirming previous findings (ß = -.57, 95% CI -5.70, -3.25), p < .001). In addition, a modification of the Behavioral Activation for Depression Scale-Short Form [BADS-SF] accounted for significant unique variance in the improvements in depression (ß = - .16, 95% CI -6.32, -0.08), p < .05). Changes in behavioral activation likely serve as a mechanism underlying Ayahuasca's antidepressant effects. Future clinical trials could benefit from tracking behavioral activation.


Assuntos
Antidepressivos/farmacologia , Banisteriopsis , Comportamento/efeitos dos fármacos , Depressão/tratamento farmacológico , Objetivos , Alucinógenos/farmacologia , Atenção Plena , Preparações de Plantas/farmacologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
J Agric Food Chem ; 67(45): 12441-12451, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31674783

RESUMO

Sesamin, a lignan from sesame seed, has been reported to attenuate chronic mild stress-induced depressive-like behaviors. Gut microbiota play pivotal roles in mediating psychological behaviors by regulating gut barrier integrity and systemic inflammatory responses. Here, we found that oral sesamin administration (50 mg/kg·bodyweight/day) significantly attenuated depressive, aversive, repetitive, and anxiety-like behaviors in a long-term multiple nonsocial stress-treated mice model. Sesamin inhibited stress-induced gut barrier integrity damage, reduced circulating lipopolysaccharide (LPS) levels, and suppressed neuroinflammatory responses. Moreover, sesamin treatment also restructured the gut microbiome by enhancing the relative abundances of Bacteroidales and S24-7. The correlation analysis indicated that the microbiota composition changes were strongly correlated with behavioral disorders, serotonin, norepinephrine, and LPS levels. In conclusion, sesamin has preventive effects on stress-induced behavioral and psychological disorders, which might be highly related to the reshaped microbiota composition. This study provides a clue for understanding the systemic mechanism of anti-depression effects of sesamin.


Assuntos
Depressão/tratamento farmacológico , Suplementos Nutricionais/análise , Dioxóis/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Lignanas/administração & dosagem , Extratos Vegetais/administração & dosagem , Sesamum/química , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Comportamento/efeitos dos fármacos , Depressão/microbiologia , Depressão/psicologia , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Sementes/química , Estresse Psicológico
8.
J Nutr ; 149(4): 687-697, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30926992

RESUMO

BACKGROUND: Evidence suggests that iron deficiency (ID) affects cognitive performance, as measured in behavior. Although such effects must be mediated by changes in the brain, very few studies have included measures of brain activity to assess this relation. OBJECTIVE: We tested the hypothesis that provision of iron-biofortified beans would result in improvements in measures of iron status, brain dynamics, and behavior. METHODS: A double-blind, randomized, intervention study was conducted in 55 women aged 18-27 y with low iron status (serum ferritin <20 µg/L). Women were randomly assigned to consume iron-biofortified (86.1 ppm iron) or comparison beans (50.1 ppm iron) daily for 18 wk. Iron status was assessed by hemoglobin, ferritin, transferrin receptor, and body iron; cognitive performance with 5 computerized tasks; and brain dynamics by concurrent electroencephalography (EEG). All measures were taken at baseline and endline. RESULTS: The groups did not differ on any measures at baseline. Intention-to-treat analyses revealed significant (all P < 0.05) improvements in hemoglobin (partial effect size attributable to the independent variable, η2 = 0.16), ferritin (η2 = 0.17), and body iron (η2 = 0.10), speed of responding in attentional and mnemonic tasks (η2 = 0.04-0.29), sensitivity and efficiency of memory retrieval (η2 = 0.12-0.55), and measures of EEG amplitude and spectral power (η2 = 0.08 to 0.49). Mediation models provided evidence in support of the hypothesis that changes in iron status produce changes in behavior by way of changes in brain activity. CONCLUSIONS: Behavioral performance and brain activity, as measured by EEG, are sensitive to iron status, and the consumption of iron-biofortified beans for 18 wk resulted in improvements in measures of both, relative to what was obtained with a comparison bean, in a sample of female university students. Furthermore, the results support the conclusion that changes in brain activity resulting from consumption of biofortified beans mediate the relations between changes in iron biomarkers and changes in cognition. Clinical trial registry: ClinicalTrials.gov Reg No. NCT01594359.


Assuntos
Comportamento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Fabaceae , Alimentos Fortificados , Ferro/sangue , Adolescente , Adulto , Comportamento/fisiologia , Cognição/fisiologia , Método Duplo-Cego , Feminino , Humanos , Ferro/administração & dosagem , Ruanda/epidemiologia , Adulto Jovem
10.
J Altern Complement Med ; 25(3): 326-335, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30383388

RESUMO

OBJECTIVES: There is a rapidly evolving legal and medical culture around cannabis, with corresponding changes in the demographics of users. For instance, the percentage of the aging population accessing cannabis is growing substantially, outpacing other age groups. The goals of this study were to describe the acute effects of cannabis, subjective experiences of withdrawal, and beliefs around the addictiveness of cannabis, as well as to determine whether these effects differ as a function of age or reason for use (medical vs. recreational use). It was hypothesized that medical users and younger users would report fewer adverse effects. SUBJECTS: Survey responses from 2905 cannabis users were analyzed. RESULTS: Hierarchical logistic regression analyses were used to compare group percentages after statistically controlling for confounding differences in their demographic and cannabis use characteristics. The most commonly endorsed acute effects were improved sleep, more calm/peaceful, desire to eat, more creative, and dry mouth; while the most commonly endorsed withdrawal symptoms were irritability, insomnia, and anxiety. Relative to recreational users, medical users were less likely to report undesirable acute effects but were more likely to report undesirable withdrawal symptoms. Older (50+) individuals reported fewer undesirable acute effects and withdrawal symptoms compared with younger users (18-29). Only 17% of the total sample reported believing that cannabis is addictive, and this did not vary as a function of reason for use. CONCLUSIONS: Older people and medical users appear to experience acute and withdrawal effects of cannabis differently than recreational and younger users, perhaps because these groups benefit more from the medicinal properties of cannabis. These data can provide descriptive information to help inform health care providers and potential consumers about effects of cannabis use.


Assuntos
Comportamento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Uso da Maconha/epidemiologia , Maconha Medicinal/farmacologia , Síndrome de Abstinência a Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cannabis , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/farmacologia , Adulto Jovem
11.
J Psychopharmacol ; 32(1): 49-69, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29020861

RESUMO

Psilocybin can occasion mystical-type experiences with participant-attributed increases in well-being. However, little research has examined enduring changes in traits. This study administered psilocybin to participants who undertook a program of meditation/spiritual practices. Healthy participants were randomized to three groups (25 each): (1) very low-dose (1 mg/70 kg on sessions 1 and 2) with moderate-level ("standard") support for spiritual-practice (LD-SS); (2) high-dose (20 and 30 mg/70 kg on sessions 1 and 2, respectively) with standard support (HD-SS); and (3) high-dose (20 and 30 mg/70kg on sessions 1 and 2, respectively) with high support for spiritual practice (HD-HS). Psilocybin was administered double-blind and instructions to participants/staff minimized expectancy confounds. Psilocybin was administered 1 and 2 months after spiritual-practice initiation. Outcomes at 6 months included rates of spiritual practice and persisting effects of psilocybin. Compared with low-dose, high-dose psilocybin produced greater acute and persisting effects. At 6 months, compared with LD-SS, both high-dose groups showed large significant positive changes on longitudinal measures of interpersonal closeness, gratitude, life meaning/purpose, forgiveness, death transcendence, daily spiritual experiences, religious faith and coping, and community observer ratings. Determinants of enduring effects were psilocybin-occasioned mystical-type experience and rates of meditation/spiritual practices. Psilocybin can occasion enduring trait-level increases in prosocial attitudes/behaviors and in healthy psychological functioning. Trial Registration ClinicalTrials.gov Identifier NCT00802282.


Assuntos
Comportamento/efeitos dos fármacos , Meditação/psicologia , Misticismo/psicologia , Psilocibina/uso terapêutico , Adulto , Idoso , Atitude , Método Duplo-Cego , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
J Psychopharmacol ; 31(2): 169-183, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27899689

RESUMO

Management of the behavioural and psychological symptoms of dementia remains a challenge worldwide. Herbal medicines may play a role in the development of new interventions. To determine effects of herbal medicines for management of the behavioural and psychological symptoms of dementia, meta-analysis was conducted of 31 controlled trials (3613 participants). Frequently tested herbal medicines were the Ginkgo biloba leaf extract EGb 761 (seven studies) and the multi-ingredient formula Yokukansan (eight studies). Sixteen studies tested other herbal medicines. Improvements were detected in Neuropsychiatric Inventory scores in EGb 761 groups compared to placebo (MD -3.46 [-5.94, -0.98]; I2 = 93%; n = 1757) and Yokukansan groups compared to no treatment (SMD -0.53 [-0.86, -0.21]; I2 = 0%; n = 150). Cognitive scores were improved in EGb 761 groups while Yokukansan did not appear to affect cognitive function. Of the other herbal medicines, there were improvements in the behavioural and psychological symptoms of dementia and cognitive outcomes in two of four placebo-controlled studies. EGb 761 and Yokukansan appeared safe and well tolerated. Adverse effects and dropouts were not reported consistently for the other herbal medicines. Weaknesses of these included short durations, small sample sizes, lack of blinding and other risks of bias. Well-designed studies are needed to further investigate the reported effects of these interventions on the behavioural and psychological symptoms of dementia.


Assuntos
Comportamento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Demência/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Medicina Herbária/métodos , Humanos , Testes Neuropsicológicos , Fitoterapia/métodos
13.
Immunotherapy ; 9(11): 929-941, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-29338610

RESUMO

Following cancer treatment, patients often report behavioral and cognitive changes. Novel cancer immunotherapeutics have the potential to produce sustained cancer survivorship, meaning patients will live longer with the side effects of treatment. Given the role of inflammatory pathways in mediating behavioral and cognitive impairments seen in cancer, we aim in this review to discuss emerging evidence for the contribution of immune checkpoint blockade to exacerbate these CNS effects. We discuss ongoing studies regarding the ability of immune checkpoint inhibitors to reach the brain and how treatment responses to checkpoint inhibitors may be modulated by genetic factors. We further consider the use of preclinical tumor-models to study the role of tumor status in CNS effects of immune checkpoint inhibitors and multimodality therapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Sistema Nervoso Central/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Terapia de Alvo Molecular/efeitos adversos , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Animais , Comportamento/efeitos dos fármacos , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/fisiopatologia , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/psicologia , Fenótipo , Medição de Risco , Fatores de Risco
14.
Biol Pharm Bull ; 39(9): 1468-74, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27582327

RESUMO

The concomitant use of herb and prescription medications is increasing globally. Herb-drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug-metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7±2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6ß-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug-metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.


Assuntos
Arilamina N-Acetiltransferase/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Xantina Oxidase/metabolismo , Adulto , Comportamento/efeitos dos fármacos , Cafeína/farmacocinética , Cafeína/urina , Demência/tratamento farmacológico , Dextrometorfano/farmacocinética , Dextrometorfano/urina , Interações Medicamentosas , Medicamentos de Ervas Chinesas/uso terapêutico , Voluntários Saudáveis , Humanos , Hidrocortisona/urina , Masculino , Pessoa de Meia-Idade
15.
Adv Clin Chem ; 73: 127-68, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26975972

RESUMO

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Elevated blood lipids may be a major risk factor for CVD. Due to consistent and robust association of higher low-density lipoprotein (LDL)-cholesterol levels with CVD across experimental and epidemiologic studies, therapeutic strategies to decrease risk have focused on LDL-cholesterol reduction as the primary goal. Current medication options for lipid-lowering therapy include statins, bile acid sequestrants, a cholesterol-absorption inhibitor, fibrates, nicotinic acid, and omega-3 fatty acids, which all have various mechanisms of action and pharmacokinetic properties. The most widely prescribed lipid-lowering agents are the HMG-CoA reductase inhibitors, or statins. Since their introduction in the 1980s, statins have emerged as the one of the best-selling medication classes to date, with numerous trials demonstrating powerful efficacy in preventing cardiovascular outcomes (Kapur and Musunuru, 2008 [1]). The statins are commonly used in the treatment of hypercholesterolemia and mixed hyperlipidemia. This chapter focuses on the biochemistry of statins including their structures, pharmacokinetics, and mechanism of actions as well as the potential adverse reactions linked to their clinical uses.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Comportamento/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Cognição/efeitos dos fármacos , Diabetes Mellitus/induzido quimicamente , Interações Medicamentosas , Dislipidemias/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Nefropatias/induzido quimicamente , Estrutura Molecular , Doenças Musculares/induzido quimicamente
16.
Toxicology ; 337: 58-71, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26277741

RESUMO

The brain is a target of environmental toxic pollutants that impair cerebral functions. Uranium is present in the environment as a result of natural deposits and release by human applications. The first part of this review describes the passage of uranium into the brain, and its effects on neurological functions and cognitive abilities. Very few human studies have looked at its cognitive effects. Experimental studies show that after exposure, uranium can reach the brain and lead to neurobehavioral impairments, including increased locomotor activity, perturbation of the sleep-wake cycle, decreased memory, and increased anxiety. The mechanisms underlying these neurobehavioral disturbances are not clearly understood. It is evident that there must be more than one toxic mechanism and that it might include different targets in the brain. In the second part, we therefore review the principal mechanisms that have been investigated in experimental models: imbalance of the anti/pro-oxidant system and neurochemical and neurophysiological pathways. Uranium effects are clearly specific according to brain area, dose, and time. Nonetheless, this review demonstrates the paucity of data about its effects on developmental processes and the need for more attention to the consequences of exposure during development.


Assuntos
Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , Compostos de Urânio/toxicidade , Urânio/toxicidade , Animais , Comportamento/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Urânio/farmacocinética , Compostos de Urânio/farmacocinética
17.
J Integr Med ; 13(4): 231-40, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26165367

RESUMO

BACKGROUND: Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. OBJECTIVE: The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes. SEARCH STRATEGY: Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. INCLUSION CRITERIA: Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. DATA EXTRACTION AND ANALYSIS: The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). RESULTS: Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. CONCLUSION: Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.


Assuntos
Comportamento/efeitos dos fármacos , Crocus , Transtorno Depressivo Maior/tratamento farmacológico , Fitoterapia/métodos , Preparações de Plantas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtorno Depressivo Maior/psicologia , Humanos
18.
Eur J Pharmacol ; 750: 82-9, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25592319

RESUMO

Drug testing with traditional behavioral assays constitutes a major bottleneck in the development of novel therapies. PsychoGenics developed three comprehensive high-throughput systems, SmartCube(®), NeuroCube(®) and PhenoCube(®) systems, to increase the efficiency of the drug screening and phenotyping in rodents. These three systems capture different domains of behavior, namely, cognitive, motor, circadian, social, anxiety-like, gait and others, using custom-built computer vision software and machine learning algorithms for analysis. This review exemplifies the use of the three systems and explains how they can advance drug screening with their applications to phenotyping of disease models, drug screening, selection of lead candidates, behavior-driven lead optimization, and drug repurposing.


Assuntos
Comportamento/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Ensaios de Triagem em Larga Escala/métodos , Animais , Progressão da Doença , Avaliação Pré-Clínica de Medicamentos/instrumentação , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Fenótipo
19.
J Ethnopharmacol ; 161: 108-15, 2015 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-25527314

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Few studies have reported on the utilization of traditional Chinese medicine (TCM) among dementia patients. The aim of the present study is to analyze factors associated with TCM users in the dementia populations and to investigate the medical conditions related to TCM visits. MATERIALS AND METHODS: A total of 18,141 dementia patients were screened from the one million sample of the National Health Insurance Research Database. The dementia patients were then divided into TCM users and non-TCM users according to their medical records between 1997 and 2008. Demographic characteristics included gender, age, insured amount, and geographic location and medical conditions including comorbidity diseases, behavioral and psychological symptoms, and anti-dementia medication were also investigated. Their tendency of TCM usage was investigated using a multivariate logistic regression. RESULTS: In Taiwan, 43.3% dementia patients had sought TCM treatments. The inclination of TCM usage was inversely proportional to age; the younger and early-onset dementia (age less than 55 years) patients constituted the high usage group. Female, living in central Taiwan, and higher insured amount were also associated with higher tendency of TCM use. Multilevel Poisson regression analysis showed that the Adjust odds ratios (OR) of TCM use were 1.80 (95% CI=1.68-1.94), 2.52 (95% CI=2.30-2.76), and 3.41 (95% CI=3.01-3.86) for those with one, two, three or more behavioral and psychological symptoms of dementia (BPSD), respectively compared with dementia sufferers without BPSD. In addition, polypharmacy led to higher utilization of TCM (one type: Adjust OR=1.41, 95% CI=1.28-1.56, two types: Adjust OR=1.97, 95% CI=1.63-2.00; three or more types: Adjust OR=2.95, 95% CI=2.27-2.78). More than 70% TCM visits were treated with Chinese herbal remedies, while others used acupuncture and manipulative therapies. Qi-Ju-Di-Huang-Wan (9.7%) was the most frequently prescribed formula, followed by Jia-Wei-Xiao-Yao-San and Ban-Xia-Bai-Zhu-Tian-Ma-Tang. CONCLUSION: More than 40% of the dementia patients in Taiwan used TCM. Young-onset dementia, higher number of BPSD, multiple chronic diseases, and polypharmacy were independent predictors for dementia patients seeking TCM medical advice. On the basis of the current findings, additional clinical or epidemiologic study on the prescription patterns of TCM in dementia treatment, or the herb-drug interaction and safety issue can be conducted.


Assuntos
Demência/tratamento farmacológico , Medicina Tradicional Chinesa/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Comportamento/efeitos dos fármacos , Doença Crônica , Bases de Dados Factuais , Demência/epidemiologia , Demência/psicologia , Feminino , Humanos , Cobertura do Seguro , Masculino , Pessoa de Meia-Idade , Polimedicação , Taiwan/epidemiologia
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