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1.
Arch Sex Behav ; 53(2): 689-701, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37735277

RESUMO

This study seeks to build on previous research about how pornography use is associated with relationship outcomes. Using the 3AM model (Wright, 2011) as a theoretical guide, sexual behaviors were tested as a possible mediator of the association between pornography use and relationship well-being. Using a national data set of individuals in heterosexual relationships (n = 2519), associations between different types of pornography use (alone use vs. joint use), sexual behaviors, and relationship outcomes were analyzed. Results showed that pornography use with a partner is a distinct activity when compared to pornography use alone. Additionally, significant indirect relationships between pornography use and relationship outcomes were found through sexual behaviors. Both vaginal sex and oral sex had positive effects, while anal sex had a unique, negative effect (use of sex toys was not significantly related). Future research should continue to examine the context of pornography use and how it is related to behaviors and outcomes in relationships.


Assuntos
Literatura Erótica , Heterossexualidade , Feminino , Humanos , Comportamento Sexual , Inquéritos e Questionários , Jogos e Brinquedos
2.
Arch Sex Behav ; 53(9): 3461-3474, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39134735

RESUMO

Pornography viewers often report being addicted to pornography even if their behavior does not indicate such addiction. In this study with 1099 participants (52% male), we explored how the specific belief in being addicted to pornography could predict both individual and relational outcomes beyond actual pornography use and reported compulsive pornography use (i.e., considering one's use to be out of control). Using a structural equation model, our results showed that higher agreement with the pornography addiction label, without accounting for compulsivity, was associated with higher depression, suicide ideation, communication discomfort about pornography, and higher odds of having a relationship end solely because of pornography. After accounting for compulsivity, higher agreement with the pornography addiction label was only associated with higher communication discomfort about pornography and higher odds of having a relationship end solely because of pornography. This study highlights that identifying as addicted to pornography may include a stigma that is particularly detrimental to relationship outcomes.


Assuntos
Comportamento Aditivo , Literatura Erótica , Humanos , Literatura Erótica/psicologia , Masculino , Feminino , Adulto , Comportamento Aditivo/psicologia , Depressão/psicologia , Adulto Jovem , Ideação Suicida , Autoimagem , Adolescente , Estigma Social
3.
J Gen Intern Med ; 37(11): 2661-2668, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35233708

RESUMO

INTRODUCTION: COVID-19 disrupted access to critical healthcare and resources for many, especially affecting patients at safety-net hospitals who rely on regular care for multiple complex conditions. Students realized they could support patients from the sidelines by helping navigate abrupt healthcare changes and proactively addressing needs at home. AIM: To comprehensively identify and meet the clinical and social needs of Atlanta, Georgia's patients at highest risk, left without their usual access to healthcare, through proactive telephonic outreach. SETTING AND PATIENTS: Medical and Physician's Assistant students from Emory and Morehouse Schools of Medicine partnered with Grady Health System, Atlanta's safety-net hospital. Artificial intelligence prioritized over 15,000 patients by risk of morbidity and mortality from COVID-19. PROGRAM DESCRIPTION: In this novel program, students performed telephonic outreach to thousands of patients at highest risk of poor outcomes from COVID-19. Students used a custom REDCap form that served as both a call script and data collection tool. It provided step-by-step guidance to (1) screen for COVID-19 and educate on prevention; (2) help patients navigate health system changes to fill gaps in care; and (3) identify and address social needs. Based on patients' responses, the form prompted tailored reminders for next steps and connections to medical and social resources. PROGRAM EVALUATION: In the program's first 16 months, students made 7,988 calls, of which 3,354 were answered. Over half (53%) of patients had at least one need requiring action: 48% health and 16% social. DISCUSSION: This proactive, novel initiative identified substantial clinical and social need among patients at highest risk for poor outcomes and filled a pressing health system gap exacerbated by COVID-19. Simultaneously, interprofessional students gained applied exposure to health systems sciences. This program can serve as a model for rapid, cost-effective, high-yield outreach to promote patient health at home both during and beyond the pandemic.


Assuntos
COVID-19 , Inteligência Artificial , COVID-19/epidemiologia , Atenção à Saúde , Humanos , Pandemias/prevenção & controle , Estudantes
4.
Mol Psychiatry ; 23(4): 824-832, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28397841

RESUMO

The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [11C]ABP688 positron emission tomography (PET) scans on the same day-before and during intravenous ketamine administration-and a third scan 1 day later. At baseline, significantly lower [11C]ABP688 binding was detected in the MDD as compared with the control group. We observed a significant ketamine-induced reduction in mGluR5 availability (that is, [11C]ABP688 binding) in both MDD and control subjects (average of 14±9% and 19±22%, respectively; P<0.01 for both), which persisted 24 h later. There were no differences in ketamine-induced changes between MDD and control groups at either time point (P=0.8). A significant reduction in depressive symptoms was observed following ketamine administration in the MDD group (P<0.001), which was associated with the change in binding (P<0.04) immediately after ketamine. We hypothesize that glutamate released after ketamine administration moderates mGluR5 availability; this change appears to be related to antidepressant efficacy. The sustained decrease in binding may reflect prolonged mGluR5 internalization in response to the glutamate surge.


Assuntos
Depressão/diagnóstico por imagem , Ketamina/metabolismo , Receptor de Glutamato Metabotrópico 5/efeitos dos fármacos , Adulto , Antidepressivos/farmacologia , Encéfalo/metabolismo , Radioisótopos de Carbono , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/metabolismo , Humanos , Ketamina/farmacologia , Masculino , Tomografia por Emissão de Pósitrons/métodos , Receptor de Glutamato Metabotrópico 5/metabolismo
5.
Exp Brain Res ; 237(4): 1077-1092, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30758515

RESUMO

Transfer, in which capability acquired in one situation influences performance in another is considered, along with retention, as demonstrative of effectual learning. In this regard, interlimb transfer of functional capacity has commanded particular attention as a means of gauging the generalisation of acquired capability. Both theoretical treatments and prior empirical studies suggest that the successful accomplishment of a physical training regime is required to bring about generalised changes that extend to the untrained limb. In the present study, we pose the following question: Does interlimb transfer occur if and only if the training movements are executed? We report findings from JG-an individual recruited to a larger scale trial, who presented with (unilateral) deficits of motor control. We examined whether changes in the performance of the untrained right limb arose following practice undertaken by the impaired left limb, wherein the majority of JG's attempts to execute the training task were unsuccessful. Comparison was made with a group of "control" participants drawn from the main trial, who did not practice the task. For JG, substantial gains in the performance of the untrained limb (registered 3 days, 10 days and 1 year following training) indicated that effective learning had occurred. Learning was, however, expressed principally when the unimpaired (i.e. untrained) limb was utilised to perform the task. When the impaired limb was used, marked deficiencies in movement execution remained prominent throughout.


Assuntos
Generalização Psicológica/fisiologia , Atividade Motora/fisiologia , Transtornos dos Movimentos/fisiopatologia , Desempenho Psicomotor/fisiologia , Transferência de Experiência/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Adulto Jovem
6.
Mol Psychiatry ; 22(12): 1759-1766, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28242869

RESUMO

Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol-dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [11C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol-dependent subjects. Alcohol-dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink. Linear mixed modeling of partial-volume-corrected [11C]PBR28 data revealed a main effect of alcohol dependence (P=0.034), corresponding to 10% lower TSPO levels in alcohol-dependent subjects. Within this group, exploratory analyses found a negative association of TSPO levels in the hippocampus and striatum with alcohol dependence severity (P<0.035). Peripheral immune response was assessed in a subset of subjects by measuring cytokine expression from monocytes cultured both in the presence and absence of lipopolysaccharide. Peripheral monocyte response to lipopolysaccharide stimulation was lower in alcohol-dependent subjects compared with controls for the proinflammatory cytokines interleukin-6 and interleukin-8. Thus, alcohol-dependent individuals exhibited less activated microglia in the brain and a blunted peripheral proinflammatory response compared with controls. These findings suggest a role for pharmaceuticals tuning the neuroimmune system as therapeutics for alcohol dependence.


Assuntos
Alcoolismo/metabolismo , Encéfalo/metabolismo , Inflamação/metabolismo , Microglia/metabolismo , Receptores de GABA/metabolismo , Acetamidas , Adulto , Alcoolismo/diagnóstico por imagem , Alcoolismo/genética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Radioisótopos de Carbono , Células Cultivadas , Citocinas/metabolismo , Feminino , Humanos , Inflamação/diagnóstico por imagem , Inflamação/genética , Lipopolissacarídeos , Masculino , Monócitos/imunologia , Neuroimagem , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Piridinas , Compostos Radiofarmacêuticos , Receptores de GABA/genética , Índice de Gravidade de Doença
7.
J Phys Chem A ; 122(30): 6321-6327, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-29993251

RESUMO

Microwave-millimeter/submillimeter wave double-resonance spectroscopy has been developed with the use of technology typically employed in chirped pulse Fourier transform microwave spectroscopy and fast-sweep direct absorption (sub)millimeter-wave spectroscopy. This technique offers the high sensitivity provided by millimeter/submillimeter fast-sweep techniques with the rapid data acquisition offered by chirped pulse Fourier transform microwave spectrometers. Rather than detecting the movement of population as is observed in a traditional double-resonance experiment, instead we detected the splitting of spectral lines arising from the AC Stark effect. This new technique will prove invaluable when assigning complicated rotational spectra of complex molecules. The experimental design is presented along with the results from the double-resonance spectra of methanol as a proof-of-concept for this technique.

8.
J Neuroeng Rehabil ; 14(1): 74, 2017 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-28705227

RESUMO

Here we provide an overview of findings and viewpoints on the mechanisms of sensorimotor learning presented at the 2016 Biomechanics and Neural Control of Movement (BANCOM) conference in Deer Creek, OH. This field has shown substantial growth in the past couple of decades. For example it is now well accepted that neural systems outside of primary motor pathways play a role in learning. Frontoparietal and anterior cingulate networks contribute to sensorimotor adaptation, reflecting strategic aspects of exploration and learning. Longer term training results in functional and morphological changes in primary motor and somatosensory cortices. Interestingly, re-engagement of strategic processes once a skill has become well learned may disrupt performance. Efforts to predict individual differences in learning rate have enhanced our understanding of the neural, behavioral, and genetic factors underlying skilled human performance. Access to genomic analyses has dramatically increased over the past several years. This has enhanced our understanding of cellular processes underlying the expression of human behavior, including involvement of various neurotransmitters, receptors, and enzymes. Surprisingly our field has been slow to adopt such approaches in studying neural control, although this work does require much larger sample sizes than are typically used to investigate skill learning. We advocate that individual differences approaches can lead to new insights into human sensorimotor performance. Moreover, a greater understanding of the factors underlying the wide range of performance capabilities seen across individuals can promote personalized medicine and refinement of rehabilitation strategies, which stand to be more effective than "one size fits all" treatments.


Assuntos
Cognição/fisiologia , Aprendizagem/fisiologia , Destreza Motora , Adaptação Psicológica , Humanos , Individualidade
9.
J Proteome Res ; 15(8): 2466-78, 2016 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-27378148

RESUMO

Prostate cancer metastasis to bone is terminal; thus, novel therapies are required to prevent end-stage disease. Kallikrein-related peptidase 4 (KLK4) is a serine protease that is overproduced in localized prostate cancer and is abundant in prostate cancer bone metastases. In vitro, KLK4 induces tumor-promoting phenotypes; however, the underlying proteolytic mechanism is undefined. The protein topography and migration analysis platform (PROTOMAP) was used for high-depth identification of KLK4 substrates secreted by prostate cancer bone metastasis-derived PC-3 cells to delineate the mechanism of KLK4 action in advanced prostate cancer. Thirty-six putative novel substrates were determined from the PROTOMAP analysis. In addition, KLK4 cleaved the established substrate, urokinase-type plasminogen activator, thus validating the approach. KLK4 activated matrix metalloproteinase-1 (MMP1), a protease that promotes prostate tumor growth and metastasis. MMP1 was produced in the tumor compartment of prostate cancer bone metastases, highlighting its accessibility to KLK4 at this site. KLK4 further liberated an N-terminal product, with purported angiogenic activity, from thrombospondin-1 (TSP1) and cleaved TSP1 in an osteoblast-derived matrix. This is the most comprehensive analysis of the proteolytic action of KLK4 in an advanced prostate cancer model to date, highlighting KLK4 as a potential multifunctional regulator of prostate cancer progression.


Assuntos
Calicreínas/fisiologia , Metaloproteinase 1 da Matriz/metabolismo , Neoplasias da Próstata/patologia , Trombospondina 1/metabolismo , Neoplasias Ósseas/química , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/secundário , Progressão da Doença , Humanos , Masculino , Neoplasias da Próstata/química , Proteólise
10.
Neuroimage ; 141: 71-80, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27426839

RESUMO

The positron emission tomography (PET) radioligand (-)-[(18)F]flubatine is specific to α4ß2(⁎) nicotinic acetylcholine receptors (nAChRs) and has promise for future investigation of the acetylcholine system in neuropathologies such as Alzheimer's disease, schizophrenia, and substance use disorders. The two goals of this work were to develop a simplified method for α4ß2(⁎) nAChR quantification with bolus plus constant infusion (B/I) (-)-[(18)F]flubatine administration, and to assess the radioligand's sensitivity to acetylcholine fluctuations in humans. Healthy human subjects were imaged following either bolus injection (n=8) or B/I (n=4) administration of (-)-[(18)F]flubatine. The metabolite-corrected input function in arterial blood was measured. Free-fraction corrected distribution volumes (VT/fP) were estimated with modeling and graphical analysis techniques. Next, sensitivity to acetylcholine was assessed in two ways: 1. A bolus injection paradigm with two scans (n=6), baseline (scan 1) and physostigmine challenge (scan 2; 1.5mg over 60min beginning 5min prior to radiotracer injection); 2. A single scan B/I paradigm (n=7) lasting up to 240min with 1.5mg physostigmine administered over 60min beginning at 125min of radiotracer infusion. Changes in VT/fP were measured. Baseline VT/fP values were 33.8±3.3mL/cm(3) in thalamus, 12.9±1.6mL/cm(3) in cerebellum, and ranged from 9.8 to 12.5mL/cm(3) in other gray matter regions. The B/I paradigm with equilibrium analysis at 120min yielded comparable VT/fP values with compartment modeling analysis of bolus data in extrathalamic gray matter regions (regional means <4% different). Changes in VT/fP following physostigmine administration were small and most pronounced in cortical regions, ranging from 0.8 to 4.6% in the two-scan paradigm and 2.8 to 6.5% with the B/I paradigm. These results demonstrate the use of B/I administration for accurate quantification of (-)-[(18)F]flubatine VT/fP in 120min, and suggest possible sensitivity of (-)-[(18)F]flubatine binding to physostigmine-induced changes in acetylcholine levels.


Assuntos
Acetilcolina/metabolismo , Benzamidas/farmacocinética , Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Receptores Nicotínicos/metabolismo , Adulto , Benzamidas/administração & dosagem , Encéfalo/diagnóstico por imagem , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Simulação por Computador , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Infusões Intraventriculares , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Neurológicos , Neurotransmissores/metabolismo , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual , Adulto Jovem
11.
Biol Chem ; 397(12): 1299-1305, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27533117

RESUMO

Kallikrein-related peptidase (KLK) 14 is a serine protease linked to several pathologies including prostate cancer. We show that KLK14 has biphasic effects in vitro on activating and inhibiting components of the prostate cancer associated hepatocyte growth factor (HGF)/Met system. At 5-10 nm, KLK14 converts pro-HGF to the two-chain heterodimer required for Met activation, while higher concentrations degrade the HGF α-chain. HGF activator-inhibitor (HAI)-1A and HAI-1B, which inhibit pro-HGF activators, are degraded by KLK14 when protease:inhibitor stoichiometry is 1:1 or the protease is in excess. When inhibitors are in excess, KLK14 generates HAI-1A and HAI-1B fragments known to inhibit pro-HGF activating serine proteases. These in vitro data suggest that increased KLK14 activity could contribute at multiple levels to HGF/Met-mediated processes in prostate and other cancers.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Células Sf9 , Spodoptera
12.
Exp Cell Res ; 333(1): 105-15, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25724901

RESUMO

The EphB4 receptor tyrosine kinase is over-expressed in a variety of different epithelial cancers including prostate where it has been shown to be involved in survival, migration and angiogenesis. We report here that EphB4 also resides in the nucleus of prostate cancer cell lines. We used in silico methods to identify a bipartite nuclear localisation signal (NLS) in the extracellular domain and a monopartite NLS sequence in the intracellular kinase domain of EphB4. To determine whether both putative NLS sequences were functional, fragments of the EphB4 sequence containing each NLS were cloned to create EphB4NLS-GFP fusion proteins. Localisation of both NLS-GFP proteins to the nuclei of transfected cells was observed, demonstrating that EphB4 contains two functional NLS sequences. Mutation of the key amino residues in both NLS sequences resulted in diminished nuclear accumulation. As nuclear translocation is often dependent on importins we confirmed that EphB4 and importin-α can interact. To assess if nuclear EphB4 could be implicated in gene regulatory functions potential EphB4-binding genomic loci were identified using chromatin immunoprecipitation and Lef1 was confirmed as a potential target of EphB4-mediated gene regulation. These novel findings add further complexity to the biology of this important cancer-associated receptor.


Assuntos
Núcleo Celular/metabolismo , Receptor EphB4/metabolismo , Transporte Ativo do Núcleo Celular , Sequência de Aminoácidos , Linhagem Celular Tumoral , DNA/metabolismo , Expressão Gênica , Humanos , Fator 1 de Ligação ao Facilitador Linfoide/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Masculino , Dados de Sequência Molecular , Sinais de Localização Nuclear , Neoplasias da Próstata , Ligação Proteica , Receptor EphB4/química , alfa Carioferinas/metabolismo
13.
Neuroimage ; 86: 164-71, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-23933039

RESUMO

BACKGROUND: Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [(11)C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [(11)C]MRB (a NET ligand) and [(11)C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys. METHODS: Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01-0.12mg/kg/h and 0.045-1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated. RESULTS: ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0-1.8mg/kg, approx. 300-600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates. CONCLUSION: Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.


Assuntos
Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Propilaminas/administração & dosagem , Propilaminas/farmacocinética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/farmacocinética , Animais , Cloridrato de Atomoxetina , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Depressão/metabolismo , Relação Dose-Resposta a Droga , Macaca mulatta , Tomografia por Emissão de Pósitrons/métodos , Distribuição Tecidual
14.
Int J Neuropsychopharmacol ; 18(2)2014 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-25522383

RESUMO

BACKGROUND: Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters. METHODS: We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. RESULTS: TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC50 of 11.7 ng/mL and 50.8 ng/mL, respectively, consistent with modest selectivity for NET in vivo. Accounting for species differences in protein binding, the projected human NET and SERT plasma EC50 values were 5.5 ng/mL and 23.9 ng/mL, respectively. A single-dose, open-label PET study (4-20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [(11)C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [(11)C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30-40 h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC50 for NET was estimated to be 1.21 ng/mL, and at doses of greater than 4 mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35 ng/mL. CONCLUSIONS: These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.


Assuntos
Inibidores da Captação de Neurotransmissores/farmacologia , Inibidores da Captação de Neurotransmissores/farmacocinética , Éteres Fenílicos/farmacologia , Éteres Fenílicos/farmacocinética , Piperidinas/farmacologia , Piperidinas/farmacocinética , Adulto , Compostos de Anilina , Animais , Análise Química do Sangue , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Meia-Vida , Humanos , Imageamento por Ressonância Magnética , Masculino , Modelos Biológicos , Morfolinas , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Ratos Sprague-Dawley , Reboxetina , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Sulfetos
15.
Mol Psychiatry ; 18(9): 1034-40, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23670490

RESUMO

Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [(11)C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [(11)C]OMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [(11)C]OMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively--OMAR VT, anandamide and cortisol--correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Transtornos de Estresse Pós-Traumáticos/patologia , Adulto , Amidas , Análise de Variância , Ácidos Araquidônicos/sangue , Ácidos Araquidônicos/metabolismo , Endocanabinoides/sangue , Endocanabinoides/metabolismo , Etanolaminas/metabolismo , Feminino , Glicerídeos/sangue , Humanos , Hidrocortisona/metabolismo , Imidazóis/metabolismo , Modelos Logísticos , Masculino , Ácidos Palmíticos/metabolismo , Piperidinas/farmacocinética , Alcamidas Poli-Insaturadas/metabolismo , Pirazóis/farmacocinética , Cintilografia , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Adulto Jovem
16.
Ophthalmic Plast Reconstr Surg ; 30(1): e15-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23511999

RESUMO

A 68-year-old woman was referred to the Oculofacial Plastic and Reconstructive Surgery service for evaluation of a left upper eyelid lesion that was worrisome for carcinoma. The mass measured 8 × 8 mm; it was well-circumscribed, pink, and firm with distortion of the eyelid margin, central ulceration, and loss of the lashes. The patient denied previous surgery or trauma in this area, but she had a history of blepharopigmentation (tattoo eyeliner) of all 4 eyelids approximately 7 years prior. Incisional biopsy revealed inflammatory changes consistent with a localized reaction to the tattoo pigment granules. Local kenalog injection was attempted with improvement of the overall appearance but with persistent deformity including irregularity of the margin and loss of lashes. The persistent abnormal appearance was worrisome for an underlying carcinoma missed on the initial incisional biopsy and prompted a full-thickness wedge resection and reconstruction of the abnormal area. The results of biopsy of the excised tissue confirmed absence of malignant neoplasm and showed changes consistent with tattoo granuloma. Tattoo granuloma of the eyelid should be considered in the differential diagnosis of eyelid lesions worrisome for carcinoma in patients with a history of blepharopigmentation.


Assuntos
Corantes/efeitos adversos , Doenças Palpebrais/diagnóstico , Neoplasias Palpebrais/diagnóstico , Granuloma de Corpo Estranho/diagnóstico , Neoplasias Cutâneas/diagnóstico , Tatuagem/efeitos adversos , Idoso , Diagnóstico Diferencial , Doenças Palpebrais/tratamento farmacológico , Doenças Palpebrais/etiologia , Feminino , Glucocorticoides/uso terapêutico , Granuloma de Corpo Estranho/tratamento farmacológico , Granuloma de Corpo Estranho/etiologia , Humanos , Injeções Intralesionais , Triancinolona Acetonida/uso terapêutico
17.
J Sex Res ; : 1-10, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207084

RESUMO

Pornography use has become a normative sexual behavior. Despite this, little is known about how romantic couples navigate, discuss, or create boundaries and rules about pornography use in their relationship. Using short-answer qualitative responses from 3385 individuals in heterosexual romantic relationships, this study examined common themes in the rules and boundaries created by couples about pornography use. Results from a content analysis of all responses suggested that most individuals reported no specific rules or a lack of discussion of rules centered on pornography in their relationship. When individuals did report rules, these rules tended to focus on restrictions on pornography use based on the context and content of pornography itself or specific contexts of the relationship that would allow or disallow pornography use to occur. In general, results suggested that many couples lacked frequent communication and discussion about rules and boundaries centered on pornography use in their relationship, despite how common this behavior is. Implications for relationship quality and well-being are discussed.

18.
Pacing Clin Electrophysiol ; 36(3): e87-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22882363

RESUMO

Flecainide is a Vaughan Williams Class Ic antidysrhythmic associated with PR, QRS, and QTc prolongation on the electrocardiogram and development of life-threatening cardiac toxicity in overdose. The cornerstone of treatment is fluid resuscitation and the administration of magnesium and sodium bicarbonate. We report a case of flecainide overdose associated with life-threatening hemodynamic compromise successfully treated with intravenous fat emulsion (IFE) therapy. IFE should be considered as a novel adjunctive therapy in patients with life-threatening toxicity following flecainide overdose.


Assuntos
Antiarrítmicos/intoxicação , Overdose de Drogas/terapia , Emulsões Gordurosas Intravenosas/uso terapêutico , Flecainida/intoxicação , Tratamento de Emergência , Humanos , Masculino , Pessoa de Meia-Idade
19.
J Emerg Med ; 44(2): 360-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22989695

RESUMO

BACKGROUND: Synthetic cannabinoid receptor agonists are becoming increasingly popular with adolescents as an abused substance. Chronic use of these drugs can lead to addiction syndrome and withdrawal symptoms similar to cannabis abuse. Due to their potential health risk, several countries have banned these substances. OBJECTIVES: To report the clinical presentation and legislation status of synthetic cannabinoids in "Spice" products and alert the health care community about the identification and risk assessment problems of these compounds. CASE REPORTS: We retrospectively reviewed cases presenting to our Emergency Department (ED) during a 3-month period with chief complaints of Spice drug use before arrival. Six cases presented to our ED after using Spice drugs. Two patients were admitted after reporting seizures. All but one presented with tachycardia. Two patients had hallucinations. The average length of ED observation was 2.8 h. No patient with seizures had recurrent episodes. CONCLUSION: Spice drugs can cause potentially serious health care conditions that necessitate ED evaluation. Most cases can be discharged from the ED after a period of observation. Legal issues surrounding these drugs are yet to be finalized in the United States.


Assuntos
Canabinoides/efeitos adversos , Drogas Desenhadas/efeitos adversos , Alucinações/induzido quimicamente , Convulsões/induzido quimicamente , Transtornos Relacionados ao Uso de Substâncias/complicações , Taquicardia/induzido quimicamente , Adolescente , Agonistas de Receptores de Canabinoides/efeitos adversos , Agonistas de Receptores de Canabinoides/química , Canabinoides/química , Drogas Desenhadas/química , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
20.
Am J Emerg Med ; 30(6): 950-3, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21802878

RESUMO

Quetiapine overdose is a clinical entity commonly encountered in emergency departments. Quetiapine is a drug with many mechanisms, including antimuscarinic effects. Traditionally, treatment of quetiapine toxicity has been primarily supportive care. Case reports exist documenting improvement in mental status in these patients after administration of physostigmine, a carbamate capable of reversing antimuscarinic toxicity. In this descriptive case series, 3 patients with quetiapine toxicity treated with physostigmine are reported. In each case, the patient had significant altered mental status that was rapidly reversed with administration of physostigmine. In all 3 cases, patient disposition was changed to a lower level of care, requiring less invasive monitoring. In 1 case, intubation was prevented. Because quetiapine toxicity is commonly encountered and the use of physostigmine in this setting is a potentially practice-altering treatment, emergency physicians should be aware of this phenomenon.


Assuntos
Antipsicóticos/efeitos adversos , Inibidores da Colinesterase/uso terapêutico , Transtornos da Consciência/induzido quimicamente , Dibenzotiazepinas/efeitos adversos , Fisostigmina/uso terapêutico , Adulto , Antipsicóticos/antagonistas & inibidores , Transtornos da Consciência/tratamento farmacológico , Dibenzotiazepinas/antagonistas & inibidores , Overdose de Drogas/tratamento farmacológico , Serviço Hospitalar de Emergência , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Fumarato de Quetiapina , Adulto Jovem
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