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1.
Int J Mol Sci ; 25(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39125857

RESUMO

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/ßCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/ßCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/ßCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1ß, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/ßCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/ßCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1ß levels. The effects of the NEO/ßCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.


Assuntos
Antidepressivos , Depressão , Estresse Psicológico , beta-Ciclodextrinas , Animais , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/química , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Masculino , Estresse Psicológico/tratamento farmacológico , Depressão/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Ansiedade/tratamento farmacológico , Ansiolíticos/farmacologia , Natação , Administração Oral
2.
Mol Pharmacol ; 106(3): 107-116, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39079719

RESUMO

Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine secreted by the pineal gland during the dark phase of the photoperiod. Its main function is the synchronization of different body rhythms with the dark-light cycle. Research on melatonin has significantly advanced since its discovery and we now know that it has considerable significance in various physiological processes, including immunity, aging, and reproduction. Moreover, in recent years evidence of the pharmacological possibilities of melatonin has increased. Indoleamine, on the other hand, has antidepressant-like effects in rodents, which may be mediated by the activation of calcium-calmodulin-dependent kinase II (CaMKII) and are also related to the regulation of neuroplasticity processes, including neurogenesis, synaptic maintenance, and long-term potentiation. Remarkably, patients with major depression show decreased levels of circulating melatonin in plasma. This review presents evidence of the antidepressant-like effects of melatonin in preclinical models and the participation of CaMKII in these actions. CaMKII's role in cognition and memory processes, which are altered in depressive states, are part of the review, and the effects of melatonin in these processes are also reviewed. Furthermore, participation of CaMKII on structural and synaptic plasticity and the effects of melatonin are also described. Finally, the advantages of using melatonin in combination with other antidepressants such as ketamine for neuroplasticity are described. Evidence supports that CaMKII is activated by melatonin and downstream melatonin receptors and may be the common effector in the synergistic effects of melatonin with other antidepressants. SIGNIFICANCE STATEMENT: This review compiled evidence supporting that melatonin causes antidepressant-like effects in mice through calmodulin kinase II stimulation of downstream melatonin receptors as well as the participation of this enzyme in neuroplasticity, memory, and cognition. Finally, we describe evidence about the effectiveness of antidepressant-like effects of melatonin in combination with ketamine.


Assuntos
Antidepressivos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Melatonina , Plasticidade Neuronal , Melatonina/farmacologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/metabolismo
3.
Mol Pharmacol ; 106(1): 3-12, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38811168

RESUMO

Melatonin N-acetyl-5-methoxytriptamine is an ancient molecule which synchronizes the internal biologic activity with the environmental photoperiod. It is synthesized by the pineal gland during the night and released to the general circulation, where it reaches nanomolar concentrations. The indolamine acts through melatonin receptors and binds to different proteins such as calmodulin: a phylogenetically conserved protein which is the main transductor of the calcium signaling. In this review, we will describe evidence supporting that melatonin binds to calmodulin in presence of calcium, and we discuss the effects of this indolamine on the activity of calmodulin kinase II as an inhibitor and as stimulator of calmodulin-dependent protein kinase II activity. We also provide a literature review supporting the relevance of melatonin binding to calmodulin in the regulation of circadian rhythms in unicellular organisms, as well as in neuronal development in mammals as an ancient, conserved mechanism. Finally, we highlight the importance of antioxidant effects of melatonin on calmodulin preservation. SIGNIFICANCE STATEMENT: This review compiled evidence supporting that melatonin binds to calmodulin. We discuss the dual effect of melatonin on the activity of calmodulin kinase II, the possible mechanisms involved, and the relevance on regulation of circadian rhythms and neurodevelopment. Finally, we describe evidence supporting that the binding of melatonin to calmodulin hydrophobic pockets may prevent the oxidation of methionine species with a shielding effect that preserves the functionality of calmodulin.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Calmodulina , Ritmo Circadiano , Melatonina , Melatonina/metabolismo , Calmodulina/metabolismo , Humanos , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Ritmo Circadiano/fisiologia , Cálcio/metabolismo , Ligação Proteica
4.
J Racial Ethn Health Disparities ; 10(1): 395-409, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35118609

RESUMO

BACKGROUND: Communities of color have been disproportionately impacted by COVID-19. We explored barriers and facilitators to COVID-19 vaccine uptake among African American, Latinx, and African immigrant communities in Washington, DC. METHODS: A total of 76 individuals participated in qualitative interviews and focus groups, and 208 individuals from communities of color participated in an online crowdsourcing contest. RESULTS: Findings documented a lack of sufficient, accurate information about COVID-19 vaccines and questions about the science. African American and African immigrant participants spoke about the deeply rooted historical underpinnings to their community's vaccine hesitancy, citing the prior and ongoing mistreatment of people of color by the medical community. Latinx and African immigrant participants highlighted how limited accessibility played an important role in the slow uptake of COVID-19 vaccines in their communities. Connectedness and solidarity were found to be key assets that can be drawn upon through community-driven responses to address social-structural challenges to COVID-19 related vaccine uptake. CONCLUSIONS: The historic and ongoing socio-economic context and realities of communities of color must be understood and respected to inform community-based health communication messaging to support vaccine equity for COVID-19 and other infectious diseases.


Assuntos
COVID-19 , Comunicação em Saúde , Humanos , Vacinas contra COVID-19 , District of Columbia , COVID-19/prevenção & controle , Saúde Pública
5.
Molecules ; 27(23)2022 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-36500599

RESUMO

Citrus paradisi species belong to the Rutaceae family, and it is commonly known as grapefruit. Grapefruit consumption involves a large amount of waste that goes to landfills and produces significant pollution affecting the human health. To examine this phenomenon, we designed an efficient chemical method that recovers naringin-rich flavonoid extracts from the fresh waste of grapefruits, by using the solvent impregnation resin method (SIR) with XAD-4 amberlite and either methanol or water as elution systems. Additionally, we focused on evaluating these extracts' anxiolytic- and antidepressant-like effects in behavioral predictive paradigms in mice. According to direct Principal Component Analysis (PCA) by NMR, and Direct Injection Electrospray Ionization-Mass Spectrometry (DIESI-MS), methanol extracts obtained after resin treatment were free of coumarin compounds and evinced had a high content of naringin. Poncirin, phenylalanine, chrysin 5,7-dimethyl ether, 5,7-dimethoxy-4'-hydroxyflavanone, 2,3-dihydro-2-(4-hydroxyphenyl)-5,6,7,8-tetramethoxy-4H-1-benzopyran-4-one, tetrahydrocurcumin, corchoionoside C, 6'-coumaroyl-1'-O-[2-(3,4-dihydroxyphenyl) ethyl]-ß-D-glucopyranoside were also detected. Naringin-rich methanol extract caused a clear anxiolytic-like effect in the Elevated Plus Maze (EPM) and the Hole-Board (HBT) Tests, increasing oral doses of this extract did not produce a sedative effect. A single oral dose caused an antidepressant-like effect in the Tail Suspension Test (TST), while repeated administrations of the methanol extract elicited a robust antidepressant effect in the Forced Swimming Test (FST) in mice. Our evidence highlights the importance of bioprospecting studies of organic waste with therapeutic potentials, such as anxiety and depression disorders.


Assuntos
Ansiolíticos , Humanos , Animais , Camundongos , Ansiolíticos/química , Metanol/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico
6.
Molecules ; 27(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36431847

RESUMO

Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina's exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin's role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.


Assuntos
Melatonina , Glândula Pineal , Melatonina/farmacologia , Melatonina/metabolismo , Glândula Pineal/metabolismo , Fatores de Crescimento Neural/metabolismo , Núcleo Supraquiasmático/metabolismo , Sono/fisiologia , Fator de Crescimento Transformador beta/metabolismo
7.
Molecules ; 27(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36080418

RESUMO

Melatonin (MEL), an indolamine with diverse functions in the brain, has been shown to produce antidepressant-like effects, presumably through stimulating neurogenesis. We recently showed that the combination of MEL with ketamine (KET), an NMDA receptor antagonist, has robust antidepressant-like effects in mice, at doses that, by themselves, are non-effective and have no adverse effects. Here, we show that the KET/MEL combination increases neurogenesis in a clone derived from human olfactory neuronal precursors, a translational pre-clinical model for effects in the human CNS. Neurogenesis was assessed by the formation of cell clusters > 50 µm in diameter, positively stained for nestin, doublecortin, BrdU and Ki67, markers of progenitor cells, neurogenesis, and proliferation. FGF, EGF and BDNF growth factors increased the number of cell clusters in cultured, cloned ONPs. Similarly, KET or MEL increased the number of clusters in a dose-dependent manner. The KET/MEL combination further increased the formation of clusters, with a maximal effect obtained after a triple administration schedule. Our results show that the combination of KET/MEL, at subeffective doses that do not produce adverse effects, stimulate neurogenesis in human neuronal precursors. Moreover, the mechanism by which the combination elicits neurogenesis is meditated by melatonin receptors, CaM Kinase II and CaM antagonism. This could have clinical advantages for the fast treatment of depression.


Assuntos
Ketamina , Melatonina , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Hipocampo/metabolismo , Humanos , Ketamina/metabolismo , Ketamina/farmacologia , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Neurogênese , Neurônios
8.
Int J Mol Sci ; 23(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35269623

RESUMO

Melatonin (MEL) is a pleiotropic indolamine that reaches multiple intracellular targets. Among these, MEL binds to calmodulin (CaM) with high affinity. In presence of Ca2+, CaM binds to CaM-dependent kinase II (CaMKII). The Ca2+-CaM/CaMKII pathway regulates a myriad of brain functions in different cellular compartments. Evidence showing the regulation of this cellular pathway by MEL is scarce. Thus, our main objective was to study the interaction of MEL with CaM and its effects on CaMKII activity in two microenvironments (aqueous and lipidic) naturally occurring within the cell. In addition, colocalization of MEL with CaM in vivo was explored in mice brain hippocampus. In vitro CaM-MEL interaction and the structural conformations of CaM in the presence of this indoleamine were assessed through electrophoretic mobility and isoelectric point. The functional consequence of this interaction was evaluated by measuring CaMKII activity. Ca2+-CaM-MEL increased the activity of CaMKII in aqueous buffer but reduced the kinase activity in lipid buffer. Importantly, MEL colocalizes in vivo with Ca2+-CaM in the hippocampus. Our evidence suggests that MEL regulates the key cellular Ca2+-CaM/CaMKII pathway and might explain why physiological MEL concentrations reduce CaMKII activity in some experimental conditions, while in others it drives biological processes through activation of this kinase.


Assuntos
Calmodulina , Melatonina , Animais , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Calmodulina/metabolismo , Melatonina/farmacologia , Camundongos , Fosforilação
9.
Nat Prod Res ; 36(23): 6170-6176, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35357257

RESUMO

This study evaluated the antidepressant-like effects of a methanol extract of Leonotis nepetifolia in behavioural tests in mice. Our results showed that a single administration of the extract significantly reduced immobility behaviour in the tail suspension test, while three administrations were necessary to diminish immobility behaviour in the forced swimming test. A daily dose of the extract for 28 days improved body weight gain and significantly reduced corticosterone levels of mice exposed to chronic unpredictable mild stress. Metabolic profiling of the extract revealed that nepetaefolin, methoxynepataefolin, and 7-O-ß-glucoside luteolin were the main products. Acute and repeated administration of the extract produced antidepressant-like effects in animals subjected to chronic stress. Our results suggest the hypothalamus-hypophysis-adrenal axis participates in the antidepressant actions of the extract. These results show that alterations in behaviour elicited by stress can be prevented with L. nepetifolia treatment.


Assuntos
Lamiaceae , Metanol , Animais , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Elevação dos Membros Posteriores , Natação , Extratos Vegetais/farmacologia , Depressão/tratamento farmacológico
10.
J Comp Neurol ; 530(7): 1020-1048, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34617601

RESUMO

Corticothalamic interactions between associative cortices and higher order thalamic nuclei are involved in high-cognitive functions such as decision-making and working memory. Corticothalamic neurons (CTn) in the prefrontal cortex and other associative areas have been much less studied than their counterparts in the primary sensory areas. The availability of characterized transgenic tools to study CTn in associative areas will facilitate their study and contribute to overcome the scarcity of data about their properties, network dynamics, and contribution to cognitive functions. Here, we characterized the Syt6-Cre (KI148Gsat/Mmud) transgenic mouse line, by tracking expression of a Cre-mediated reporter. In this line, Cre-reporter is strongly expressed in the prefrontal, motor, cingulate, and retrosplenial cortices, as well as in other brain areas including the cerebellum and the olfactory tubercle. Cortical expression starts embryonically and reaches the adult expression pattern by postnatal day 15. In the cortex, Cre-reporter is expressed by layer 6-CTn and by layer 5-CTn to a lesser extent. We quantified Syt6-Cre+ CTn axon varicosities to estimate the distribution and density of putative corticothalamic driver and modulator inputs to thalamic nuclei in the medial, midline, intralaminar, anterior, and motor groups. Also, we characterized the effect of optogenetic stimulation of Syt6-Cre+ neurons in the activity of the prefrontal cortex. CTn stimulation in the prefrontal cortex induces an oscillatory activity in the local field potential that resembles the cortical downstates typically observed during slow-wave sleep or quiet wake.


Assuntos
Córtex Cerebral , Integrases , Animais , Córtex Cerebral/fisiologia , Integrases/genética , Camundongos , Camundongos Transgênicos , Vias Neurais/fisiologia , Neurônios
11.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502152

RESUMO

Major depressive disorder is a disabling disease with the number of affected individuals increasing each year. Current antidepressant treatments take between three to six weeks to be effective with forty percent of patients being resistant to treatment, making it necessary to search for new antidepressant treatments. Ketamine, a phencyclidine hydrochloride derivative, given intravenously, induces a rapid antidepressant effect in humans. In mice, it causes increased neurogenesis and antidepressant-like effects. However, it also produces psychomimetic effects in humans and in rodents increases the locomotor activity. In contrast, melatonin, a hormone secreted by the pineal gland and synthesized in extrapineal sites, increases new neuron formation and causes antidepressant-like effects in adult rodents with no collateral effects. Here, we assessed the effects of a non-effective dose of ketamine in combination with melatonin (KET/MEL), both on neurogenesis as well as on the antidepressant-like effect in mice. Our results showed that KET/MEL combination increased neurogenesis and produced antidepressant-like effects without altering locomotor activity after both single and triple administration protocols. Our data strongly suggest that KET/MEL combination could be used to simultaneously promote neurogenesis, reverting neuronal atrophy and inducing antidepressant-like effects.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Ketamina/uso terapêutico , Melatonina/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Melatonina/administração & dosagem , Melatonina/farmacologia , Camundongos , Neurogênese/efeitos dos fármacos
12.
Rev. cuba. enferm ; 37(2): e3596, 2021. tab, graf
Artigo em Espanhol | LILACS, BDENF - Enfermagem, CUMED | ID: biblio-1347410

RESUMO

Introducción: El clima organizacional en salud es un factor que trasciende en el desempeño profesional; asimismo un ambiente laboral y cultura de seguridad en adecuadas condiciones repercutirían en mejores prácticas sanitarias. Objetivo: Evaluar la relación y características de las variables clima organizacional y cultura de seguridad. Métodos: Investigación descriptiva, transversal, correlacional, no experimental, ejecutada entre marzo y diciembre del 2019, en el servicio de Cuidados Intermedios Neonatales del Instituto Nacional Materno Perinatal, Perú. La población fue 53 enfermeros. Se emplearon los instrumentos: En Clima Organizacional, se aplicó el cuestionario del Ministerio de Salud peruano y En cultura de seguridad, se aplicó la encuesta Hospital Survey on Patient Safety Culture de la Agency for Healthcare Research and Quality. La información fue analizada mediante la prueba de normalidad Kolmogorov-Smirnov y coeficiente correlacional Rho de Spearman. Resultados: Existe un coeficiente correlacional de 0,43 entre variables. La motivación, toma de decisiones, innovación, remuneración, liderazgo, identidad y comunicación organizacional del clima organizacional están significativamente relacionadas (p ≤ 0,05) con la cultura de seguridad. El 70 por ciento de profesionales percibe un clima organizacional no saludable; reflejado en cuatro dimensiones en proceso de avance y cuatro con bajos índices de respuesta, el 56,35 por ciento refirió una cultura de seguridad positiva con dos dimensiones en fortalezas y tres en oportunidad de mejora. Conclusiones: El clima organizacional y siete de sus dimensiones están relacionados con la cultura de seguridad en Cuidados Intermedios Neonatales. La evaluación de características supone que, pese a las debilidades del clima organizacional, entorno a la remuneración, recompensa, liderazgo e innovación, estas son compensadas por una apropiada cultura de seguridad, con un favorable aprendizaje organizacional y trabajo en equipo(AU)


Introduction: Organizational climate in health is a factor transcending professional performance. Likewise, a work environment and safety culture in adequate conditions would have repercussions in better sanitary practices. Objective: To assess the relationship and characteristics of the variables organizational climate and safety culture. Methods: Descriptive, cross-sectional, correlational and non-experimental research carried out, between March and December 2019, in the neonatal intermediate care service of the National Maternal-Perinatal Institute, Peru. The population was 53 nurses. The following instruments were used: Organizational Climate, from the Peruvian Ministry of Health, as well as the Hospital Survey on Patient Safety Culture. The information was analyzed using the Kolmogorov-Smirnov normality test and Spearman's Rho correlation coefficient. Results: There is a correlational coefficient of 0.43 between variables. Motivation, decision making, innovation, remuneration, leadership, identity and organizational communication of the organizational climate are significantly related (p ≤ 0.05) with safety culture. 70 percent of the professionals perceive an unhealthy organizational climate, reflected in four dimensions in progress and other four with low response rates. 56.35 percent reported a positive safety culture with two dimensions in strengths and three in opportunity for improvement. Conclusions: Organizational climate and seven of its dimensions are related to safety culture in neonatal intermediate care. The assessment of characteristics presupposes that, despite the weaknesses of organizational climate, around remuneration, reward, leadership and innovation, these are compensated by an appropriate safety culture, with favorable organizational learning and teamwork(AU)


Assuntos
Humanos , Cultura Organizacional , Unidades de Terapia Intensiva Neonatal , Tomada de Decisões , Segurança do Paciente , Epidemiologia Descritiva , Estudos Transversais , Guias de Prática Clínica como Assunto
13.
FEBS Open Bio ; 11(1): 48-60, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33410599

RESUMO

Acute myeloid leukaemia (AML) is a clonal disorder that affects hematopoietic stem cells or myeloid progenitors. One of the most common mutations that results in AML occurs in the gene encoding fms-like tyrosine kinase 3 (FLT3). Previous studies have demonstrated that AML cells expressing FLT3-internal tandem duplication (ITD) are more sensitive to the proteasome inhibitor bortezomib (Bz) than FLT3 wild-type cells, with this cytotoxicity being mediated by autophagy (Atg). Here, we show that proteasome inhibition with Bz results in modest but consistent proteaphagy in MOLM-14 leukemic cells expressing the FLT3-ITD mutation, but not in OCI-AML3 leukemic cells with wild-type FLT3. Chemical inhibition of Atg with bafilomycin A simultaneously blocked proteaphagy and resulted in the accumulation of the p62 Atg receptor in Bz-treated MOLM-14 cells. The use of ubiquitin traps revealed that ubiquitin plays an important role in proteasome-Atg cross-talk. The p62 inhibitor verteporfin blocked proteaphagy and, importantly, resulted in accumulation of high molecular weight forms of p62 and FLT3-ITD in Bz-treated MOLM-14 cells. Both Atg inhibitors enhanced Bz-induced apoptosis in FLT3-ITD-driven leukemic cells, highlighting the therapeutic potential of these treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Tirosina Quinase 3 Semelhante a fms/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Macroautofagia/efeitos dos fármacos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Mutação , Inibidores de Proteassoma/uso terapêutico , Verteporfina/farmacologia , Verteporfina/uso terapêutico
14.
J Ethnopharmacol ; 265: 113316, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32866569

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Calea zacatechichi is a plant with an extensive popular and ritual use in Mexico. In healthy volunteers, it induces well-being and tranquility senses, and facilitates superficial stages of sleep. However, anxiolytic, and antidepressant-like effects and changes on the sleep-waking stages have not been explored. AIM: To determine anxiolytic and antidepressant-like effects of an aqueous extract of C. zacatechichi (CZ) in rodents and to analyze their effects on hippocampal activity in the rat sleep-waking cycle. MATERIAL AND METHODS: CZ anxiolytic- and antidepressant-like effects were evaluated in several mice and rat behavioral paradigms. CZ effects on temporal distribution of sleep were described, and hippocampus EEG frequency patterns were analyzed during the sleep-waking cycle; absolute and relative powers were analyzed during Rapid Eye Movements (REM) and non-REM sleep stages. CZ chemical analysis was performed by UPLC-ESI-MS. RESULTS: CZ produced specific and robust anxiolytic- and antidepressant-like effects in mice and rats, similar to those of prototypical drugs, at doses ranging from 0.5 to 50 mg/kg. CZ at 100 mg/kg produced visible mild sedative effects in rats, associated with a significant increase in Slow Wave Sleep episodes during a 6 h recording, and enhanced fast frequencies of hippocampus (gamma-band:31-50 Hz) during REM sleep. CONCLUSION: Results could support the well-being and tranquility senses reported by healthy consumers, and to explain the oneiric content during dreams and some improvements in cognitive processes described by consumers. Anxiolytic- and antidepressant-like effects of this species, reported for first time in this study could improve some aspects of mental health.


Assuntos
Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Asteraceae/química , Extratos Vegetais/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/isolamento & purificação , Antidepressivos/administração & dosagem , Antidepressivos/isolamento & purificação , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , México , Camundongos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Sono/efeitos dos fármacos , Sono REM/efeitos dos fármacos
15.
Polymers (Basel) ; 12(9)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872115

RESUMO

Plant cuticles have attracted attention because they can be used to produce hydrophobic films as models for novel biopolymers. Usually, cuticles are obtained from agroresidual waste. To find new renewable natural sources to design green and commercially available bioplastics, fruits of S. aculeatissimum and S. myriacanthum were analyzed. These fruits are not used for human or animal consumption, mainly because the fruit is composed of seeds. Fruit peels were object of enzymatic and chemical methods to get thick cutins in good yields (approximately 77% from dry weight), and they were studied by solid-state resonance techniques (CPMAS 13C NMR), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM) and direct injection electrospray ionization mass spectrometry (DIESI-MS) analytical methods. The main component of S. aculeatissimum cutin is 10,16-dihydroxypalmitic acid (10,16-DHPA, 69.84%), while S. myriacanthum cutin besides of 10,16-DHPA (44.02%); another two C18 monomers: 9,10,18-trihydroxy-octadecanoic acid (24.03%) and 18-hydroxy-9S,10R-epoxy-octadecanoic acid (9.36%) are present. The hydrolyzed cutins were used to produce films demonstrating that both cutins could be a potential raw material for different biopolymers.

16.
In. Hernández Rodríguez, Alberto Inocente; Orta Hernández, Santa Deybis. Consideraciones sobre ensayos clínicos. Experiencias en Cuba. La Habana, Editorial Ciencias Médicas, 2020. , tab.
Monografia em Espanhol | CUMED | ID: cum-76387
17.
Enferm. clín. (Ed. impr.) ; 29(4): 216-224, jul.-ago. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182915

RESUMO

Objetivos: Comprender el universo emocional de mujeres cordobesas afectadas por hepatitis C. Método: Estudio cualitativo hermenéutico. Las participantes cumplían los criterios de inclusión de ser mujer mayor de edad, diagnosticada en la actualidad de hepatitis C y pertenecer a la Plataforma de Afectad@s por la Hepatitis C de Córdoba. El muestreo intencional fue de intensidad y nominado. La recogida de datos se realizó a través de entrevistas en profundidad. El análisis siguió 3niveles: explicación, comprensión superficial y comprensión en profundidad. En el segundo nivel, se incorporó la metáfora «universo de emociones», una taxonomía que organiza las emociones en conjuntos de galaxias para facilitar la comprensión de los fenómenos afectivos. Resultados: Se incluyó a 4 participantes. Los 7 temas resultado recorren las distintas galaxias del universo emocional de las mujeres. «Enfermedad maldita» explora su asco, tristeza y vergüenza. «Afectos íntimos» se detiene tanto en la felicidad y el amor como en la tristeza. «Plataforma amistad» profundiza en la comprensión, bienestar y afecto. «Médicos» se ocupa de la desconfianza y decepción con respecto al nuevo tratamiento; «cura», de la tristeza, miedo, ansiedad y esperanza. «Estado de malestar» se ocupa de la ansiedad. Y «acceso universal ya» explora su ira. Conclusiones: A pesar de la presencia del amor, en el complejo universo emocional de las mujeres con hepatitis C destacan la ira, tristeza y ansiedad. Una hermenéutica de sus emociones facilita la humanización tanto de los cuidados de enfermería que reciben como de la investigación de la que son objeto


Objectives: Understanding the emotional universe of women from Cordoba affected by hepatitis C. Method: Hermeneutic qualitative study. Participants met the criteria of being adult women with a current diagnosis of hepatitis C and belonging to the Plataforma de Afectad@s por la Hepatitis C of Cordoba. The intentional sampling was nominated and followed a criterion of intensity. Data collection was conducted through in-depth interviews. The analysis took place in 3levels: Explanation, naïve understanding and in-depth understanding. In the second level, the metaphor universe of emotions was incorporated, which is a taxonomy that organizes emotions into clusters of galaxies to facilitate understanding of affective phenomena. Results: Four participants were included. Seven themes roam the galaxies in the emotional universe of women. «Damned disease» explores their disgust, sadness and shame. «Intimate affections» focuses on happiness and love as well as sadness. «Friendship-platform» focuses on understanding, welfare and affection. «Physicians» deal with distrust and disappointment regarding new treatment, and with «curing» sadness, fear, anxiety and hope. «State of ill-being» focuses on anxiety. And «universal access now» explores anger. Conclusions: Despite the presence of love in the complex emotional universe of women with hepatitis C, anger, sadness and anxiety are highlighted. Hermeneutics of their emotions facilitates nursing care and nursing research humanization


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Hepatite C/epidemiologia , Mulheres/psicologia , Cuidados de Enfermagem/psicologia , Apoio Social , Hepatite C/psicologia , 25783 , Hermenêutica , Pesquisa Qualitativa
18.
J Ethnopharmacol ; 231: 453-463, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30545804

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Piper auritum Kunth is employed as an aphrodisiac in the traditional medicine, but corroborative evidence for such effect is scarce. AIM OF THE STUDY: The pro-sexual effect of an aqueous extract of P. auritum and its possible mechanisms were analyzed in two paradigms of male sexual function. MATERIAL AND METHODS: Effects of an aqueous extract of P. auritum (PA, single administration) were investigated in the fictive ejaculation, and copulatory behavior paradigms in sexually sluggish male rats. WAY 100635 (antagonist of 5-HT1A receptors), atosiban (antagonist of oxytocinergic receptors), L-NAME (inhibitor of the nitric oxide synthase) and baclofen (antagonist of GABAB receptors) were used as pre-treatments in order to investigate the role of different neurotransmitter systems in PA actions. Chemical profile of PA was determined by Gases Chromatography and Ultra Performance Chromatography-Electrospray Ionization-Masses Spectrometry (UPLC-ESI-MS). RESULTS: In males with retarded ejaculation, PA stimulated ejaculatory behavior and recovered electromyographic activity of pelvic musculature participating in seminal emission and ejaculation. All pre-treatments blocked stimulating effects of PA on the fictive ejaculation; additionally WAY 100635 interfered with PA actions on ejaculatory behavior. Safrol, apigenin dimethylether, myristicin, vaccihein A, sakuranin and sakuranetin flavonoids, were main constituents of PA, with possible participation in its pro-sexual effects. CONCLUSIONS: Pro-sexual effects of P. auritum elicited at level of ejaculation were mediated by several neurotransmitter systems, among which serotonin and its 5-HT1A receptors play an important role. Present findings support P. auritum reputation as an aphrodisiac, with potential use in delayed ejaculation disorder.


Assuntos
Afrodisíacos/farmacologia , Piper , Extratos Vegetais/farmacologia , Comportamento Sexual/efeitos dos fármacos , Animais , Afrodisíacos/química , Comportamento Animal/efeitos dos fármacos , Ejaculação/efeitos dos fármacos , Feminino , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Piper/química , Piperazinas/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Piridinas/farmacologia , Ratos Wistar , Receptor 5-HT1A de Serotonina/fisiologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia
19.
Enferm Clin (Engl Ed) ; 29(4): 216-224, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30459051

RESUMO

OBJECTIVES: Understanding the emotional universe of women from Cordoba affected by hepatitis C. METHOD: Hermeneutic qualitative study. Participants met the criteria of being adult women with a current diagnosis of hepatitis C and belonging to the Plataforma de Afectad@s por la Hepatitis C of Cordoba. The intentional sampling was nominated and followed a criterion of intensity. Data collection was conducted through in-depth interviews. The analysis took place in 3levels: Explanation, naïve understanding and in-depth understanding. In the second level, the metaphor universe of emotions was incorporated, which is a taxonomy that organizes emotions into clusters of galaxies to facilitate understanding of affective phenomena. RESULTS: Four participants were included. Seven themes roam the galaxies in the emotional universe of women. «Damned disease¼ explores their disgust, sadness and shame. «Intimate affections¼ focuses on happiness and love as well as sadness. «Friendship-platform¼ focuses on understanding, welfare and affection. «Physicians¼ deal with distrust and disappointment regarding new treatment, and with «curing¼ sadness, fear, anxiety and hope. «State of ill-being¼ focuses on anxiety. And «universal access now¼ explores anger. CONCLUSIONS: Despite the presence of love in the complex emotional universe of women with hepatitis C, anger, sadness and anxiety are highlighted. Hermeneutics of their emotions facilitates nursing care and nursing research humanization.


Assuntos
Emoções , Hepatite C/psicologia , Idoso , Feminino , Hermenêutica , Humanos , Pessoa de Meia-Idade
20.
Nat Prod Res ; 33(17): 2526-2530, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29527955

RESUMO

In this study, we investigated the antidepressant-like effects of the hexane (HCP), ethyl acetate (ECP) and methanol (MCP) extracts of the roots of Casimiroa pubescens Ramírez (Rutaceae) using the forced swim test (FST). In an initial experiment, each extract was orally administered to mice only once 60 min before to the FST. In a second experiment, doses were administered 24, 7 and 1 h before testing. Our results showed that the triple administration of the extracts provided a stronger effect than single administration. However, the combination of HCP at 7.5 mg/kg and imipramine (IMI) at 12.5 mg/kg showed the greatest effect. The coumarins 3-(1',1', dimethyl allyl)-herniarin, auraptene, 8-geranyl-oxy psoralen, isopimpinellin and the flavonoid zapotin were isolated from the extracts. The hexane extract of C. pubescens showed an antidepressant-like activity, which may inspire further studies on developing new antidepressant agents.


Assuntos
Antidepressivos/farmacologia , Casimiroa/química , Extratos Vegetais/farmacologia , Animais , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Depressão/prevenção & controle , Camundongos , Raízes de Plantas/química , Solventes/farmacologia , Natação , Fatores de Tempo
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