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1.
Sci Rep ; 14(1): 9653, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671018

RESUMO

Due to population growth, climate change, and the urban heat island effect, heat exposure is becoming an important issue faced by urban built environments. Heat exposure assessment is a prerequisite for mitigation measures to reduce the impact of heat exposure. However, there is limited research on urban heat exposure assessment approaches that provides fine-scale spatiotemporal heat exposure information, integrated with meteorological status and human collective exposure as they move about in cities, to enable proactive heat exposure mitigation measures. Smart city digital twins (SCDTs) provide a new potential avenue for addressing this gap, enabling fine spatiotemporal scales, human-infrastructure interaction modeling, and predictive and decision support capabilities. This study aims to develop and test an SCDT for collective urban heat exposure assessment and forecasting. Meteorological sensors and computer vision techniques were implemented in Columbus, Georgia, to acquire temperature, humidity, and passersby count data. These data were then integrated into a collective temperature humidity index. A time-series prediction model and a crowd simulation were employed to predict future short-term heat exposures based on the data accumulated by this SCDT and to support heat exposure mitigation efforts. The results demonstrate the potential of SCDT to enhance public safety by providing city officials with a tool for discovering, predicting, and, ultimately, mitigating community exposure to extreme heat.

2.
Sci Rep ; 12(1): 22092, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543830

RESUMO

Human-Building Interaction (HBI) is a convergent field that represents the growing complexities of the dynamic interplay between human experience and intelligence within built environments. This paper provides core definitions, research dimensions, and an overall vision for the future of HBI as developed through consensus among 25 interdisciplinary experts in a series of facilitated workshops. Three primary areas contribute to and require attention in HBI research: humans (human experiences, performance, and well-being), buildings (building design and operations), and technologies (sensing, inference, and awareness). Three critical interdisciplinary research domains intersect these areas: control systems and decision making, trust and collaboration, and modeling and simulation. Finally, at the core, it is vital for HBI research to center on and support equity, privacy, and sustainability. Compelling research questions are posed for each primary area, research domain, and core principle. State-of-the-art methods used in HBI studies are discussed, and examples of original research are offered to illustrate opportunities for the advancement of HBI research.


Assuntos
Ambiente Construído , Humanos , Consenso , Previsões
3.
Environ Pollut ; 292(Pt B): 118369, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740737

RESUMO

The Sars-CoV-2 disease (known as COVID-19) has become a global public health emergency. Researchers have been unveiling the transmission mechanisms and disclosing possible contributing factors. Studies have theorized plausible linkage mechanisms between air pollution exposure and COVID-19 infection and have divided the air pollution exposure into two types: long-term exposure and short-term exposure. However, present studies on impacts of short-term exposure have not reached a conclusive result and are mostly focusing on Asian and European countries. In this study, we conduct a nationwide analysis to examine the association between short-term air pollution exposure and COVID-19 infection in the United States. Daily confirmed cases, air pollution information, and meteorological factors at the county level were collected between March 1st and June 30th, 2020. A total of 806 (out of 3143) counties were included in this study, with 554 counties for PM2.5 and 670 counties for ozone (O3), which account for around 2.1 million cumulative confirmed cases, i.e., about 80% of all confirmed cases in the U.S. over the study period. A generalized additive model was applied to investigate the relationship between short-term exposure to PM2.5/O3 and COVID-19 confirmed cases. The statistically significant results indicate that, with every 10 µg/m3 increase in mean pollutant concentration, the number of daily confirmed cases increases by 9.41% (CI: 8.77%-10.04%) for PM2.5 and by 2.42% (CI: 1.56%-3.28%) for O3. The relative risks associated with short-term PM2.5 exposure remain positive after isolating the impacts of long-term exposure. The results of this study suggest that short-term exposure to air pollution, especially to PM2.5, may contribute to the spread and course of the pandemic. This finding has important implications for policymakers and the public to take preventive measures such as staying at home on polluted days while improving ventilation indoors to lower the probability of infection.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental , Humanos , Material Particulado/análise , SARS-CoV-2 , Estados Unidos/epidemiologia
4.
Sci Total Environ ; 811: 152284, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-34902421

RESUMO

Urbanization introduces the threat of increased epidemic disease transmission resulting from crowding on mass transit. The coronavirus disease 2019 (COVID-19) pandemic, which has directly led to over 600,000 deaths in the US as of July 2021, triggered mass social distancing policies to be enacted as a key deterrent of widespread infections. Social distancing can be challenging in confined spaces required for transportation such as mass transit systems. Little is published regarding the degree to which mass transit system adoption effects impacted the rise of the COVID-19 pandemic in urban centers. Taking an ecological approach where areal data are the unit of observation, this national-scale study aims to measure the association between the adoption of mass transit and COVID-19 spread through confirmed cases in US metropolitan areas. National survey-based transit adoption measures are entered in negative binomial regression models to evaluate differences between areas. The model results demonstrate that mass transit adoption in US metropolitan areas was associated with the magnitude of outbreaks. Higher incidence of COVID-19 early in the pandemic was associated with survey results conveying higher transit use. Increasing weekly bus transit usage in metropolitan statistical areas by one scaled unit was associated with a 1.38 [95% CI: (1.25, 1.90)] times increase in incidence rate of COVID-19; a one scaled unit increase in weekly train transit usage was associated with an increase in incidence rate of 1.54 [95% CI: (1.42, 2.07)] times. These conclusions should inform early action practices in urban centers with busy transit systems in the event of future infectious disease outbreaks. Deeper understanding of these observed associations may also benefit modeling efforts by allowing researchers to include mathematical adjustments or better explain caveats to results when communicating with decision makers and the public in the crucial early stages of an epidemic.


Assuntos
COVID-19 , Pandemias , Surtos de Doenças , Humanos , Incidência , SARS-CoV-2
6.
Sci Rep ; 9(1): 20247, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882711

RESUMO

Recent advances in energy technologies, policies, and practices have accelerated the global rate of improvements in energy efficiency, bringing the energy targets identified in the 2030 United Nations (UN) Sustainable Development Agenda within reach. However, Target 7.3 requires this rate to double by 2030, demanding a more substantial response to energy interventions. At present, energy interventions are failing to reach optimal levels of adoption in buildings, which are the largest urban energy consumers. This is due to a combination of direct and indirect effects generally referred to as the energy efficiency gap. Here, we compare over 18.8 million positional records of individuals against Greater London's buildings energy consumption records over the course of one year. We demonstrate that indirect (i.e., spillover) effects, arising from recurrent mobility, govern the diffusion of urban buildings' energy efficiency, far outpacing direct effects. This has been understood as a consequence of underlying spatiotemporal dependencies at the intersection of energy use and social interactions. We add to this the critical role of recurrent mobility (i.e., the mobility of those urban populations who repeatedly visit certain locations, such as home and work) as a diffusion conduit. These findings suggest that in order to improve the current levels of adoption, interventions must target times and locations that function as dense hubs of energy consumption and social interactions. Recurrent mobility thus provides a viable complement to existing targeted intervention approaches aimed at improving energy efficiency, supporting efforts to meet the UN's 2030 energy targets.

7.
PLoS One ; 12(12): e0188734, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29216236

RESUMO

Increasing frequency of extreme winter storms has resulted in costly damages and a disruptive impact on the northeastern United States. It is important to understand human mobility patterns during such storms for disaster preparation and relief operations. We investigated the effects of severe winter storms on human mobility during a 2015 blizzard using 2.69 million Twitter geolocations. We found that displacements of different trip distances and radii of gyration of individuals' mobility were perturbed significantly. We further explored the characteristics of perturbed mobility during the storm, and demonstrated that individuals' recurrent mobility does not have a higher degree of similarity with their perturbed mobility, when comparing with its similarity to non-perturbed mobility. These empirical findings on human mobility impacted by severe winter storms have potential long-term implications on emergency response planning and the development of strategies to improve resilience in severe winter storms.


Assuntos
Temperatura Baixa , Movimento , Estações do Ano , Pesquisa Empírica , Humanos , New England , Mídias Sociais
8.
PLoS One ; 11(10): e0164476, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27736912

RESUMO

Online social networks are today's fastest growing communications channel and a popular source of information for many, so understanding their contribution to building awareness and shaping public perceptions of climate change is of utmost importance. Today's online social networks are composed of complex combinations of entities and communication channels and it is not clear which communicators are the most influential, what the patterns of communication flow are, or even whether the widely accepted two-step flow of communication model applies in this new arena. This study examines the diffusion of energy saving practices in a large online social network across organizations, opinion leaders, and the public by tracking 108,771 communications on energy saving practices among 1,084 communicators, then analyzing the flow of information and influence over a 28 day period. Our findings suggest that diffusion networks of messages advocating energy saving practices are predominantly led by the activities of dedicated organizations but their attempts do not result in substantial public awareness, as most of these communications are effectively trapped in organizational loops in which messages are simply shared between organizations. Despite their comparably significant influential values, opinion leaders played a weak role in diffusing energy saving practices to a wider audience. Thus, the two-step flow of communication model does not appear to describe the sharing of energy conservation practices in large online heterogeneous networks. These results shed new light on the underlying mechanisms driving the diffusion of important societal issues such as energy efficiency, particularly in the context of large online social media outlets.


Assuntos
Conservação de Recursos Energéticos , Mídias Sociais , Comunicação
9.
PLoS One ; 11(1): e0147299, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26820404

RESUMO

Natural disasters pose serious threats to large urban areas, therefore understanding and predicting human movements is critical for evaluating a population's vulnerability and resilience and developing plans for disaster evacuation, response and relief. However, only limited research has been conducted into the effect of natural disasters on human mobility. This study examines how natural disasters influence human mobility patterns in urban populations using individuals' movement data collected from Twitter. We selected fifteen destructive cases across five types of natural disaster and analyzed the human movement data before, during, and after each event, comparing the perturbed and steady state movement data. The results suggest that the power-law can describe human mobility in most cases and that human mobility patterns observed in steady states are often correlated with those in perturbed states, highlighting their inherent resilience. However, the quantitative analysis shows that this resilience has its limits and can fail in more powerful natural disasters. The findings from this study will deepen our understanding of the interaction between urban dwellers and civil infrastructure, improve our ability to predict human movement patterns during natural disasters, and facilitate contingency planning by policymakers.


Assuntos
Planejamento em Desastres , Defesa Civil , Humanos , População Urbana
10.
PLoS One ; 9(11): e112608, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25409009

RESUMO

Human mobility is influenced by environmental change and natural disasters. Researchers have used trip distance distribution, radius of gyration of movements, and individuals' visited locations to understand and capture human mobility patterns and trajectories. However, our knowledge of human movements during natural disasters is limited owing to both a lack of empirical data and the low precision of available data. Here, we studied human mobility using high-resolution movement data from individuals in New York City during and for several days after Hurricane Sandy in 2012. We found the human movements followed truncated power-law distributions during and after Hurricane Sandy, although the ß value was noticeably larger during the first 24 hours after the storm struck. Also, we examined two parameters: the center of mass and the radius of gyration of each individual's movements. We found that their values during perturbation states and steady states are highly correlated, suggesting human mobility data obtained in steady states can possibly predict the perturbation state. Our results demonstrate that human movement trajectories experienced significant perturbations during hurricanes, but also exhibited high resilience. We expect the study will stimulate future research on the perturbation and inherent resilience of human mobility under the influence of hurricanes. For example, mobility patterns in coastal urban areas could be examined as hurricanes approach, gain or dissipate in strength, and as the path of the storm changes. Understanding nuances of human mobility under the influence of such disasters will enable more effective evacuation, emergency response planning and development of strategies and policies to reduce fatality, injury, and economic loss.


Assuntos
Tempestades Ciclônicas , Desastres , Migração Humana/estatística & dados numéricos , Humanos , Cidade de Nova Iorque
11.
Adolesc Med State Art Rev ; 20(1): 188-202, x-xi, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19492698

RESUMO

Anxiety is a common component of visits to the doctor's office by adolescents; however, it is often overlooked as a possible causative agent of the presenting complaint. With a high index of suspicion and proper questioning, a clinician can analyze the contribution that anxiety plays in the life of an adolescent patient. Behavioral and pharmacologic interventions exist for this group of disorders, and with proper diagnosis and treatment the symptoms of these disorders can possibly be ameliorated. This article provides a concise guide to the diagnosis and treatment of anxiety and anxiety-related disorders including hyperventilation syndrome, syncope, sleep disorders, panic disorder, and obsessive compulsive disorder.


Assuntos
Transtornos de Ansiedade , Adolescente , Ansiedade/diagnóstico , Ansiedade/terapia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , Humanos , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/terapia , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/terapia , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Distúrbios do Início e da Manutenção do Sono/terapia , Síncope/diagnóstico , Síncope/terapia
14.
Int J Cardiol ; 137(3): 267-75, 2009 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-18723230

RESUMO

BACKGROUND: Ghrelin, was observed to have treatment-potential for severe chronic heart failure (CHF) and cardiac cachexia based on anti-cachectic and cardio-protective effects. METHODS: We performed two studies to assess the effects of human ghrelin on food intake, body weight and body composition, as well as heart function in a rat model of CHF. Study-1 (50 or 500 nmole/kg/d ghrelin by pump infusion) was focused on food intake and body composition, study-2 (50 or 100 nmole/kg/d ghrelin by subcutaneous injection (3-times daily) was focused on heart function due to a lack of cardiac effects observed in study-1. In both studies, myocardial infarction was induced by LAD ligation. On day 28 after surgery, rats were randomized and treated with ghrelin or placebo for 4 weeks. Food intake (study-1), body composition (NMR) cardiac function (echocardiography and invasive hemodynamics (study-2 only) were assessed. RESULTS: In study-1, CHF rats treated with high dose ghrelin showed an increase in body weight (+25%, p<0.001), lean mass (+16%, p<0.01) and fat mass (+17%, p=0.001) vs placebo. In study-2, CHF rats treated with both low- and high dose ghrelin showed an increase in body weight (both +18%, p

Assuntos
Composição Corporal/efeitos dos fármacos , Ingestão de Alimentos , Grelina/farmacologia , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Ecocardiografia , Grelina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Injeções Subcutâneas , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
15.
Endocr Relat Cancer ; 15(2): 583-96, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18509006

RESUMO

Dopamine D2 and somatostatin receptors (sstrs) were reported to affect non-functioning pituitary adenoma (NFPA) proliferation in vitro. However, the reported results differ according to the experimental conditions used. We established an experimental protocol allowing reproducible evaluation of NFPA cell proliferation in vitro, to test and compare the antiproliferative effects of dopamine and somatostatin analogs (alone or in combination) with the activity of the dopamine-somatostatin chimeric molecule BIM-23A760. The protocol was utilized by four independent laboratories, studying 38 fibroblast-deprived NFPA cell cultures. Cells were characterized for GH, POMC, sstr1-sstr5, total dopamine D2 receptor (D2R) (in all cases), and D2 receptor long and short isoforms (in 15 out of 38 cases) mRNA expression and for alpha-subunit, LH, and FSH release. D2R, sstr3, and sstr2 mRNAs were consistently observed, with the dominant expression of D2R (2.9+/-2.6 copy/copy beta-glucuronidase; mean+/-s.e.m.), when compared with sstr3 and sstr2 (0.6+/-1.0 and 0.3+/-0.6 respectively). BIM-23A760, a molecule with high affinity for D2R and sstr2, significantly inhibited [3H]thymidine incorporation in 23 out of 38 (60%) NFPA cultures (EC50=1.2 pM and Emax=-33.6+/-3.7%). BIM-23A760 effects were similar to those induced by the selective D2R agonist cabergoline that showed a statistically significant inhibition in 18 out of 27 tumors (compared with a significant inhibition obtained in 17 out of 27 tumors using BIM-23A760, in the same subgroup of adenomas analyzed), while octreotide was effective in 13 out of 27 cases. In conclusion, superimposable data generated in four independent laboratories using a standardized protocol demonstrate that, in vitro, chimeric dopamine/sstr agonists are effective in inhibiting cell proliferation in two-thirds of NFPAs.


Assuntos
Adenoma/tratamento farmacológico , Adenoma/patologia , Dopamina/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/patologia , Somatostatina/análogos & derivados , Adulto , Idoso , Antineoplásicos Hormonais/farmacologia , Cabergolina , Divisão Celular/efeitos dos fármacos , Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Ergolinas/farmacologia , Feminino , Fibroblastos/citologia , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/farmacologia , RNA Mensageiro/metabolismo , Receptores de Dopamina D2/genética , Receptores de Somatostatina/genética , Somatostatina/farmacologia , Sulpirida/farmacologia , Timidina/metabolismo , Trítio , Células Tumorais Cultivadas
16.
AANA J ; 76(1): 47-52, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18323320

RESUMO

The purpose of our study was to investigate the anxiolytic effects of linalool and its potential interaction with the GABAA receptor in Sprague-Dawley rats. Lavender has been used traditionally as an herbal remedy in the treatment of many medical conditions, including anxiety. Linalool is a major component of the essential oil of lavender. Forty-four rats were divided into 4 groups: control, linalool, midazolam (positive control), and flumazenil and linalool. The behavioral and the neurohormonal/physiological components of anxiety were evaluated. The behavioral component was examined by using the elevated plus maze (open arm time/total time) and the neurohormonal/physiological component by measuring serum catecholamine and corticosterone levels. Data analysis was performed using a 2-tailed Multivariate Analysis of Variance and Sheffe post-hoc test. Our data suggest that linalool does not produce anxiolysis by modulation of the GABAA receptor; however, linalool may modulate motor movements and locomotion.


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Lavandula , Monoterpenos/uso terapêutico , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Monoterpenos Acíclicos , Animais , Ansiolíticos/farmacologia , Antídotos/uso terapêutico , Ansiedade/sangue , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Epinefrina/sangue , Flumazenil/uso terapêutico , Moduladores GABAérgicos/uso terapêutico , Locomoção/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Midazolam/uso terapêutico , Monoterpenos/farmacologia , Destreza Motora/efeitos dos fármacos , Análise Multivariada , Norepinefrina/sangue , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/efeitos dos fármacos
17.
Endocrinology ; 149(2): 827-35, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18039782

RESUMO

Chronic kidney disease (CKD) is associated with an increase in inflammatory cytokines and can result in cachexia with loss of muscle and fat stores. We previously demonstrated the efficacy of treating a model of cancer cachexia with ghrelin and a ghrelin receptor agonist. Currently, we examine a surgical model of CKD in rats, resulting in uremia and decreased accrual of lean body mass. Treatment with ghrelin and two ghrelin receptor agonists (BIM-28125 and BIM-28131) resulted in increased food intake and an improvement in lean body mass accrual that was related in part to a decrease in muscle protein degradation as assessed by muscle levels of the 14-kDa actin fragment resulting from cleaved actomyosin. Additionally, there was a decrease in circulating inflammatory cytokines in nephrectomized animals treated with ghrelin relative to saline treatment. Ghrelin-treated animals also had a decrease in the expression of IL-1 receptor in the brainstem and a decrease in expression of prohormone convertase-2, an enzyme involved in the processing of proopiomelanocortin to the anorexigenic peptide alpha-MSH. We conclude that ghrelin treatment in uremia results in improved lean mass accrual in part due to suppressed muscle proteolysis and possibly related to antiinflammatory effects.


Assuntos
Peso Corporal/efeitos dos fármacos , Caquexia/tratamento farmacológico , Citocinas/sangue , Grelina/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Absorciometria de Fóton , Animais , Caquexia/etiologia , Caquexia/imunologia , Citocinas/genética , Dactinomicina/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/sangue , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/etiologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Nefrectomia , Neuropeptídeos/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Receptores de Grelina/agonistas , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/imunologia
18.
Pituitary ; 10(3): 267-74, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17587180

RESUMO

Glucocorticoids are important immunosuppressive hormones; these steroids also inhibit somatic growth by decreased growth hormone (GH) secretion and induced protein catabolism. The ability of ghrelin, the endogenous ligand for the GHS-1a receptor, to increase body weight is attributed to a combination of enhanced food intake, increased gastric emptying and increased food assimilation, coupled with potent GH releasing activity. The aim of the present study was to evaluate the ability of a full-length, metabolically stabilized ghrelin agonist, BIM-28125, to reverse the dexamethasone-induced decrease of growth rate of prepubertal Sprague-Dawley male rats. Twenty-one days old rats were randomly assigned to two treatment groups. Beginning on day 23 of age, 16 animals were treated ip either with saline or DEX (40 microg/kg/day). On day 33 after birth, these two groups were further subdivided and treated sc with either vehicle or BIM-28125 (80 nmol/kg, t.i.d.). On day 47 after birth, rats were killed and trunk blood was collected for hormone determinations. DEX significantly reduced final body weight and nose-anal length; BIM-28125 increased linear growth in saline-treated rats and reversed growth inhibition in DEX-treated rats. The inhibitory effects of DEX on somatic growth was paralleled by decreased 24 h food intake (FI), decreased food efficiency (FE) and lower plasma IGF-1 levels versus vehicle-treated rats. BIM-28125 induced an increase of FI, FE and plasma IGF-1 in saline-treated rats, and reversed the inhibitory effects of DEX. These preclinical results leads to the conclusion that BIM-28125 may represent a good tool to reverse the catabolic effects induced by glucocorticoids.


Assuntos
Grelina/análogos & derivados , Glucocorticoides/antagonistas & inibidores , Glucocorticoides/farmacologia , Crescimento/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/crescimento & desenvolvimento , Animais , Glicemia/metabolismo , Células CHO , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Epididimo/efeitos dos fármacos , Epididimo/crescimento & desenvolvimento , Grelina/farmacologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Obesidade/induzido quimicamente , Obesidade/patologia , Fosfatidilinositóis/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores da Somatotropina/efeitos dos fármacos , Proteínas Recombinantes/farmacologia
19.
Endocrinology ; 148(6): 3004-12, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17347304

RESUMO

Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.


Assuntos
Composição Corporal/efeitos dos fármacos , Caquexia/etiologia , Caquexia/patologia , Ingestão de Alimentos/efeitos dos fármacos , Neoplasias/complicações , Hormônios Peptídicos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Grelina , Hormônio do Crescimento/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Neoplasias/patologia , Ratos , Ratos Endogâmicos F344 , Carga Tumoral/efeitos dos fármacos
20.
J Clin Endocrinol Metab ; 91(6): 2257-63, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16595604

RESUMO

CONTEXT: Cortistatin (CST) is a neuropeptide that shares high homology with somatostatin and binds with high affinity to all somatostatin receptor (SSTR) subtypes. Many of its endocrine and biological activities overlap with those of somatostatin. OBJECTIVE/DESIGN: The objective of the study was to assess the direct in vitro effects of CST on human pituitary hormone secretion. SETTING: This study was performed in the endocrine laboratory of a tertiary academic medical center. MATERIALS: Primary cell cultures of human fetal (21-25 wk gestation) pituitary tissues and cultured hormone-secreting adenoma cells were used in this study. INTERVENTIONS: Cell cultures were incubated with CST-14 or CST-17, somatostatin, GHRH, SSTR analogs, and ghrelin analogs, and hormone secretion was analyzed. OUTCOME MEASURES: GH and prolactin (PRL) medium concentrations were tested by hormone assay, and SSTR mRNA was tested by RT-PCR. RESULTS: CST-14 (10 nm) inhibited GH secretion by up to 65% in all fetal pituitary specimens after 4-h incubation (P < 0.05). CST-14 or CST-17 (10 nm) inhibited basal GH secretion in six of the 13 GH-cell adenomas and two of the three GH-PRL mixed adenomas. CST-17 (100 nm) suppressed the GH response to GHRH and ghrelin analog (10 nm each) by 30-50% in adenomas (P < 0.05). Three PRL-adenomas treated with CST-17 (10 nm) showed a 20-40% inhibition of PRL release (P < 0.05), whereas in three others no suppression or mild response was achieved at this concentration. A comparable inhibition of PRL secretion was obtained with SSTR5-selective analog but significantly less with SSTR2-preferential compounds. RT-PCR revealed the expression of both SSTR2 and SSTR5 in all GH-cell and mixed adenomas studied and all PRL-secreting adenomas studied, except for two of the CST-resistant prolactinomas, in which SSTR5 was absent. CONCLUSIONS: This is the first report of in vitro CST suppression of human GH and PRL in cultured pituitary tissues. The regulation of PRL release from cultured adenomas appears to be primarily mediated by SSTR5.


Assuntos
Adenoma/metabolismo , Feto/metabolismo , Hormônio do Crescimento Humano/metabolismo , Neuropeptídeos/farmacologia , Hipófise/efeitos dos fármacos , Neoplasias Hipofisárias/metabolismo , Prolactina/metabolismo , Prolactinoma/metabolismo , Humanos , Hipófise/metabolismo , Células Tumorais Cultivadas
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