RESUMO
The oceanographic ecology of pelagic Sargassum, and the means by which these floating macroalgae thrive in the nutrient-poor waters of the open ocean, have been studied for decades. Beginning in 2011, the Great Atlantic Sargassum Belt (GASB) emerged, with Sargassum proliferating in the tropical Atlantic and Caribbean where it had not previously been abundant. Here we show that the nutritional status of Sargassum in the GASB is distinct, with higher nitrogen and phosphorus content than populations residing in its Sargasso Sea habitat. Moreover, we find that variations in arsenic content of Sargassum reflect phosphorus limitation, following a hyperbolic relationship predicted from Michaelis-Menten nutrient uptake kinetics. Although the sources of nutrients fueling the GASB are not yet clear, our results suggest that nitrogen and phosphorus content of Sargassum, together with its isotopic composition, can be used to identify those sources, whether they be atmospheric, oceanic, or riverine in origin.
Assuntos
Arsênio , Sargassum , Nitrogênio , Nutrientes , Fósforo , Oceano AtlânticoRESUMO
The aim of the present study was to examine a potential mechanism of action of gabapentin to manage cannabis-use disorders by determining the interoceptive effects of gabapentin in cannabis users discriminating [INCREMENT]-tetrahydrocannabinol ([INCREMENT]-THC) using a pharmacologically selective drug-discrimination procedure. Eight cannabis users learned to discriminate 30 mg oral [INCREMENT]-THC from placebo and then received gabapentin (600 and 1200 mg), [INCREMENT]-THC (5, 15, and 30 mg), and placebo alone and in combination. Self-report, task performance, and physiological measures were also collected. [INCREMENT]-THC served as a discriminative stimulus, produced positive subjective effects, elevated heart rate, and impaired psychomotor performance. Both doses of gabapentin substituted for the [INCREMENT]-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of [INCREMENT]-THC when administered alone. When administered concurrently, gabapentin shifted the discriminative-stimulus effects of [INCREMENT]-THC leftward/upward, and combinations of [INCREMENT]-THC and gabapentin generally produced larger effects on cannabinoid-sensitive outcomes relative to [INCREMENT]-THC alone. These results suggest that one mechanism by which gabapentin might facilitate cannabis abstinence is by producing effects that overlap with those of cannabinoids.
Assuntos
Aminas/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Aprendizagem por Discriminação/efeitos dos fármacos , Dronabinol/uso terapêutico , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Abuso de Maconha/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Combinação de Medicamentos , Feminino , Gabapentina , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Desempenho Psicomotor/efeitos dos fármacos , Inquéritos e Questionários , Escala Visual AnalógicaRESUMO
The monetary incentive delay (MID) task is a widely used probe for isolating neural circuitry in the human brain associated with incentive motivation. In the present functional magnetic resonance imaging (fMRI) study, 82 young adults, characterized along dimensions of impulsive sensation seeking, completed a MID task. fMRI and behavioral incentive functions were decomposed into incentive valence and magnitude parameters, which were used as predictors in linear regression to determine whether mesolimbic response is associated with problem drinking and recent alcohol use. Alcohol use was best explained by higher fMRI response to anticipation of losses and feedback on high gains in the thalamus. In contrast, problem drinking was best explained by reduced sensitivity to large incentive values in mesolimbic regions in the anticipation phase and increased sensitivity to small incentive values in the dorsal caudate nucleus in the feedback phase. Altered fMRI responses to monetary incentives in mesolimbic circuitry, particularly those alterations associated with problem drinking, may serve as potential early indicators of substance abuse trajectories.
Assuntos
Afeto/fisiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Encéfalo/fisiologia , Comportamento Impulsivo/fisiologia , Motivação/fisiologia , Adulto , Mapeamento Encefálico , Corpo Estriado/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tálamo/fisiologia , Adulto JovemRESUMO
The University of California San Diego Community Women's Health Program (CWHP) has emerged as a successful and sustainable coexistence model of women's healthcare. The cornerstone of this midwifery practice is California's only in-hospital birth center. Located within the medical center, this unique and physically separate birth center has been the site for more than 4000 births. With 10% cesarean delivery and 98% breast-feeding rates, it is an exceptional example of low-intervention care. Integrating this previously freestanding birth center into an academic center has brought trials of mistrust and ineffectual communication. Education, consistent leadership, and development of multidisciplinary guidelines aided in overcoming these challenges. This collaborative model provides a structure in which residents learn to be respectful consultants and appreciate differences in medical practice. The CWHP and its Birth Center illustrates that through persistence and flexibility a collaborative model of maternity services can flourish and not only positively influence new families but also future generations of providers.
Assuntos
Salas de Parto/estatística & dados numéricos , Tocologia , Assistência Perinatal , Padrões de Prática em Enfermagem/estatística & dados numéricos , Centros Médicos Acadêmicos , California , Comportamento Cooperativo , Educação , Feminino , Humanos , Recém-Nascido , Tocologia/métodos , Tocologia/organização & administração , Modelos Organizacionais , Parto , Equipe de Assistência ao Paciente , Assistência Perinatal/métodos , Assistência Perinatal/organização & administração , Guias de Prática Clínica como Assunto , Gravidez , Resultado da GravidezRESUMO
Epidemiological studies find that psychiatric disorders, including mental disorders and substance use disorders, are common among adults and highly comorbid. Integrated treatment refers to the focus of treatment on two or more conditions and to the use of multiple treatments such as the combination of psychotherapy and pharmacotherapy. Integrated treatment for comorbidity has been found to be consistently superior compared to treatment of individual disorders with separate treatment plans. This article focuses on a review of the risks for developing comorbid disorders and the combinations of treatments that appear to be most effective for clients with particular comorbid disorders.
Assuntos
Prestação Integrada de Cuidados de Saúde/métodos , Transtornos Mentais/terapia , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Terapia Combinada , Humanos , PsicoterapiaRESUMO
Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.
Assuntos
Mirtilos Azuis (Planta) , Dieta , Insulina/sangue , Neoplasias Mamárias Animais/prevenção & controle , Fitoterapia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Proteína Wnt1/fisiologia , Animais , Western Blotting , Feminino , Humanos , Técnicas Imunoenzimáticas , Lactação , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Transgênicos , Gravidez , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de SinaisRESUMO
BACKGROUND: Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABA(B) receptor subtype by assessing the separate and combined effects of the GABA(B)-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures. METHODS: Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50mg), Δ9-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. RESULTS: Δ9-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone. CONCLUSIONS: These results suggest that the GABA(B) receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABA(B) receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABA(A)) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans.
Assuntos
Baclofeno/farmacologia , Discriminação Psicológica/efeitos dos fármacos , Dronabinol/farmacologia , Agonistas GABAérgicos/uso terapêutico , Alucinógenos/farmacologia , Receptores de GABA-B/efeitos dos fármacos , Adolescente , Adulto , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/efeitos dos fármacos , Demografia , Interações Medicamentosas , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Abuso de Maconha/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inquéritos e Questionários , Percepção do Tempo/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To update clinicians on the latest in evidence-based treatments for substance use disorders (SUD) and non-substance use disorders among adults and suggest how these treatments can be combined into an evidence-based process that enhances treatment effectiveness in comorbid patients. METHOD: Articles were extracted from Pubmed using the search terms "dual diagnosis," "comorbidity" and "co-occurring" and were reviewed for evidence of effectiveness for pharmacologic and psychotherapeutic treatments of comorbidity. RESULTS: Twenty-four research reviews and 43 research trials were reviewed. The preponderance of the evidence suggests that antidepressants prescribed to improve substance-related symptoms among patients with mood and anxiety disorders are either not highly effective or involve risk due to high side-effect profiles or toxicity. Second generation antipsychotics are more effective for treatment of schizophrenia and comorbid substance abuse and current evidence suggests clozapine, olanzapine and risperidone are among the best. Clozapine appears to be the most effective of the antipsychotics for reducing alcohol, cocaine and cannabis abuse among patients with schizophrenia. Motivational interviewing has robust support as a highly effective psychotherapy for establishing a therapeutic alliance. This finding is critical since retention in treatment is essential for maintaining effectiveness. Highly structured therapy programs that integrate intensive outpatient treatments, case management services and behavioral therapies such as Contingency Management (CM) are most effective for treatment of severe comorbid conditions. CONCLUSIONS: Creative combinations of psychotherapies, behavioral and pharmacological interventions offer the most effective treatment for comorbidity. Intensity of treatment must be increased for severe comorbid conditions such as the schizophrenia/cannabis dependence comorbidity due to the limitations of pharmacological treatments.
Assuntos
Tratamento Farmacológico/métodos , Entrevistas como Assunto , Transtornos Mentais/terapia , Motivação , Psicoterapia/métodos , Transtornos Relacionados ao Uso de Substâncias/terapia , Terapia Combinada , Comorbidade , Diagnóstico Duplo (Psiquiatria) , Medicina Baseada em Evidências , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Pacientes , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVE: The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence. METHOD: Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use. Patients were started on open-label divalproex. After stabilization on divalproex sodium, weekly assessments were undertaken for 8weeks. Subjects also attended dual recovery counseling. RESULTS: The results revealed significant improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use severity index, % alcohol abstinent days, drinks per drinking day, marijuana use and cigarettes smoking. They also had significant improvement on manic, depressive, and sleep symptoms and on functioning. There were no reported adverse events or increases in liver function tests. CONCLUSION: The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence. Double-blind, placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted.
Assuntos
Antimaníacos/uso terapêutico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/complicações , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Adulto , Idoso , Aconselhamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Grupos de Autoajuda , Resultado do TratamentoRESUMO
In preclinical safety studies, drug-induced vascular injury can negatively impact candidate-drug selection because there are no obvious diagnostic markers for monitoring this pathology preclinically or clinically. Furthermore, our current understanding of the pathogenesis of this lesion is limited. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary target cells, smooth muscle (SMC) and endothelial cell (EC), are unknown. Evaluation of potential novel markers for clinical monitoring with a mechanistic underpinning would add value in risk assessment and risk management. This mini review focuses on the efforts and progress to identify diagnostic markers as well as understanding the mechanism of action in nonrodent drug-induced vascular injury.
Assuntos
Biomarcadores/metabolismo , Drogas em Investigação/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Doenças Vasculares/induzido quimicamente , Doenças Vasculares/metabolismo , Animais , Biomarcadores/análise , Cães , Avaliação Pré-Clínica de Medicamentos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Doenças Vasculares/patologia , Fator de von Willebrand/análise , Fator de von Willebrand/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: We developed a new approach that enhances selective photothermolysis of tumor through laser activation of synergistic phenomena around nanoclusters, which are self-assembled into cancer cells. STUDY DESIGN/MATERIALS AND METHODS: In vitro verification of this approach was performed by laser pulse irradiation (420-570 nm and 1064 nm; 8-12 nanosecond; 0.1-10 J/cm2) of MDA-MB-231 breast cancer cells targeted with primary antibodies to which 40-nm gold nanoparticles were selectively attached by means of secondary antibodies. Photothermal (PT) radiometry, thermolens techniques, electron microscopy, atomic force microscopy, silver and gold enhancing kits, and viability test (Annexin V-propidium iodide) were employed to study nanoparticle spatial organization, the dynamics of microbubble formation, and cell damage. RESULTS: The assembly of gold nanoclusters on the cell membrane was accompanied by increased local absorption and red-shifting as compared to cells that did not have nanoclusters. These effects were amplified by a silver-enhancing kit and pre-irradiation of cells with low laser-pulse energy. Finally, a significant increase in laser-induced bubble formation and cancer cell killing was observed using near-IR lasers (1064 nm). A cancer cell antigens was used to provide target specificity for nanoclusters formation making the cancer cells sensitive to laser activation. CONCLUSION: The described approach uses relatively small and simple gold nanoparticles offering more effective delivery to target. In addition, the further self-assembling of these nanoparticles into nanoclusters on live cells provides significant enhancement of laser-induced cell damage. These nanoclusters (gold "nanobombs") can be activated in cancer cells only by confining near-IR laser pulse energy within the critical mass of the nanoparticles in the nanoclusters.
Assuntos
Adenocarcinoma/terapia , Anticorpos Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Terapia com Luz de Baixa Intensidade/métodos , Nanoestruturas/efeitos da radiação , Adenocarcinoma/imunologia , Anticorpos Antineoplásicos/efeitos da radiação , Neoplasias da Mama/imunologia , Linhagem Celular Tumoral , Feminino , Ouro/efeitos da radiação , Ouro/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Metais/efeitos da radiação , Metais/uso terapêutico , Fototerapia/métodosRESUMO
OBJECTIVE: Marijuana abuse, primarily a disorder of adolescents and young adults, is highly prevalent among patients with severely ill psychiatric population, especially those with bipolar disorder. Additional marijuana abuse may impact on the clinical presentation of bipolar illness and may potentially act as mediator of treatment response in this population. However, the characterization of bipolar disorder patients with additional marijuana abuse and the impact of such abuse on treatment outcome has been rarely examined. The aim of this study was to characterize bipolar alcoholic patients with comorbid marijuana abuse and test the impact of marijuana abuse on alcohol and mood outcome of patients with bipolar disorder and comorbid alcohol dependence. METHOD: We conducted secondary analyses of a randomized, double blind, placebo-controlled trial testing valproate in 52 bipolar alcoholics. Subjects had a comprehensive assessment at baseline using structured diagnostic assessments, and they were then assessed every 2 weeks for 24 weeks. RESULTS: Twenty-five subjects (48%) reported marijuana abuse. Those with co-occurring marijuana abuse were younger, had fewer years of education, and had significantly higher number of additional psychiatric comorbidity. They also had more severe alcohol and other drug use and were significantly more likely to present in the manic phase. The mixed model indicated that the placebo-treated marijuana abuse group had the worst alcohol use outcome. CONCLUSIONS: Marijuana abuse among patients with bipolar disorder and alcohol dependence is associated with higher degree of severity of alcohol and other drugs of abuse and may negatively impact on alcohol treatment outcome.