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1.
Nat Commun ; 11(1): 1014, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094337

RESUMO

The Interior Exploration using Seismic Investigations, Geodesy and Heat Transport (InSight) spacecraft landed successfully on Mars and imaged the surface to characterize the surficial geology. Here we report on the geology and subsurface structure of the landing site to aid in situ geophysical investigations. InSight landed in a degraded impact crater in Elysium Planitia on a smooth sandy, granule- and pebble-rich surface with few rocks. Superposed impact craters are common and eolian bedforms are sparse. During landing, pulsed retrorockets modified the surface to reveal a near surface stratigraphy of surficial dust, over thin unconsolidated sand, underlain by a variable thickness duricrust, with poorly sorted, unconsolidated sand with rocks beneath. Impact, eolian, and mass wasting processes have dominantly modified the surface. Surface observations are consistent with expectations made from remote sensing data prior to landing indicating a surface composed of an impact-fragmented regolith overlying basaltic lava flows.

2.
Environ Sci Process Impacts ; 18(12): 1477-1483, 2016 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-27892563

RESUMO

The quality of data generated for the analysis of environmental samples is critical to State and Federal regulatory agencies to ensure that decisions based upon the amounts of contaminants in environmental samples are truly protective of public health. The quality and validation of these measurements using the approved analytical methodology could be significantly enhanced by incorporating certified reference materials as part of the quality control protocols, yet this has not been widely implemented. Data from certified reference materials can provide critical information that can impact assessments regarding data use that is unavailable by other means. Using the analysis of Cr(vi) in soil extracts as the test case, some of the issues surrounding the use of certified reference materials for environmental applications are discussed in this paper, including the relative cost, and the availability and applicability regarding element coverage and content.


Assuntos
Monitoramento Ambiental/normas , Controle de Qualidade , Poluentes do Solo/análise , Poluentes do Solo/normas , Solo/química , Humanos , Padrões de Referência , Estados Unidos , United States Environmental Protection Agency
3.
Science ; 350(6257): aac7575, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26450214

RESUMO

The landforms of northern Gale crater on Mars expose thick sequences of sedimentary rocks. Based on images obtained by the Curiosity rover, we interpret these outcrops as evidence for past fluvial, deltaic, and lacustrine environments. Degradation of the crater wall and rim probably supplied these sediments, which advanced inward from the wall, infilling both the crater and an internal lake basin to a thickness of at least 75 meters. This intracrater lake system probably existed intermittently for thousands to millions of years, implying a relatively wet climate that supplied moisture to the crater rim and transported sediment via streams into the lake basin. The deposits in Gale crater were then exhumed, probably by wind-driven erosion, creating Aeolis Mons (Mount Sharp).


Assuntos
Lagos , Marte , Clima , Exumação , Paleontologia
4.
An Acad Bras Cienc ; 87(3): 1763-70, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26312428

RESUMO

The representatives of the genus Hylesia Hübner, [1820] are significant among the medically important Lepidoptera. Adult females use abdominal setae to wrap and protect the eggs that remain for months in nature. These setae, in contact with human skin, may cause allergic reactions including swelling, itching and local erythema, known as lepidopterism. The morphology of the abdominal scales and setae from the female H. oratex Dyar, 1913 is herein described and aspects related to their medical significance are discussed. Portions of each abdominal segment were examined through a scanning electron microscope. Two types of scales without medical importance, and two types of setae with medical importance, classified as "true setae" and "modified setae" were found. The true setae, which are slightly fusiform and have radially arranged lateral projections, are responsible for the allergic reactions caused by skin penetration. The modified setae, which are larger, curved, with the median enlarged and serrated margins, can be responsible for the release of chemical substances. This information provides a better understanding of the structure of the urticating setae, which are responsible for lepidopterism outbreaks in humans, and contributes towards the identification of the moth species involved.


Assuntos
Abdome/anatomia & histologia , Mariposas/ultraestrutura , Receptores Notch/ultraestrutura , Animais , Feminino , Microscopia Eletrônica de Varredura , Mariposas/classificação
5.
Int J Obes (Lond) ; 37(3): 350-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22508335

RESUMO

BACKGROUND: North American (NA) ginseng (Panax quinquefolius) is a popular natural health product (NHP) that has been demonstrated to regulate immune function, inflammatory processes and response to stress and fatigue. Recent evidence suggests that various extracts of NA ginseng may have different bioactivities because of distinct profiles of ginsenosides and polysaccharides. To date, the bioactive role of ginseng on adipocytes remains relatively unexplored. OBJECTIVE: The goal of this work was to study the extract-specific bioactivity of NA ginseng on differentiated preadipocyte gene expression and adipocytokine secretion. METHODS: In vitro differentiated 3T3-L1 preadipocytes were treated with 25 and 50 µg ml of either crude ethanol (EtOH) or aqueous (AQ) NA ginseng extracts, or polysaccharide and ginsenoside extracts isolated from the AQ extract. Global gene expression was studied with microarrays and the resulting data were analyzed with functional pathway analysis. Adipocytokine secretion was also measured in media. RESULTS: Pathway analysis indicated that the AQ extract, and in particular the polysaccharide extract, triggered a global inflammomodulatory response in differentiated preadipocytes. Specifically, the expression of Il-6 (interleukin 6), Ccl5 (chemokine (C-C motif) ligand 5), Nfκb (nuclear factor-kappaB) and Tnfα (tumor necrosis factor alpha) was increased. These effects were also reflected at the protein level through the increased secretion of IL-6 and CCL5. No effect was seen with the EtOH extract or ginsenoside extract. Using a specific toll-like receptor 4 (TLR4) inhibitor reduced the upregulation of inflammatory gene expression, indicating the relevance of this pathway for the signaling capacity of NA ginseng polysaccharides. CONCLUSION: This work emphasizes the distinct bioactivities of different ginseng extracts on differentiated preadipocyte signaling pathways, and highlights the importance of TLR4 for mediating the inflammomodulatory role of ginseng polysaccharides.


Assuntos
Adipócitos/metabolismo , Etanol/farmacologia , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Células 3T3-L1/efeitos dos fármacos , Células 3T3-L1/metabolismo , Adipócitos/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Quimiocinas/efeitos dos fármacos , Quimiocinas/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Camundongos , Subunidade p50 de NF-kappa B/efeitos dos fármacos , Subunidade p50 de NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
6.
Transl Psychiatry ; 2: e80, 2012 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-22832817

RESUMO

Individuals who abuse methamphetamine (MA) exhibit heightened aggression, but the neurobiological underpinnings are poorly understood. As variability in the serotonin transporter (SERT) gene can influence aggression, this study assessed possible contributions of this gene to MA-related aggression. In all, 53 MA-dependent and 47 control participants provided self-reports of aggression, and underwent functional magnetic resonance imaging while viewing pictures of faces. Participants were genotyped at two functional polymorphic loci in the SERT gene: the SERT-linked polymorphic region (SERT-LPR) and the intron 2 variable number tandem repeat polymorphism (STin2 VNTR); participants were then classified as having high or low risk for aggression according to individual SERT risk allele combinations. Comparison of SERT risk allele loads between groups showed no difference between MA-dependent and control participants. Comparison of self-report scores showed greater aggression in MA-dependent than control participants, and in high genetic risk than low-risk participants. Signal change in the amygdala was lower in high genetic risk than low-risk participants, but showed no main effect of MA abuse; however, signal change correlated negatively with MA use measures. Whole-brain differences in activation were observed between MA-dependent and control groups in the occipital and prefrontal cortex, and between genetic high- and low-risk groups in the occipital, fusiform, supramarginal and prefrontal cortex, with effects overlapping in a small region in the right ventrolateral prefrontal cortex. The findings suggest that the investigated SERT risk allele loads are comparable between MA-dependent and healthy individuals, and that MA and genetic risk influence aggression independently, with minimal overlap in associated neural substrates.


Assuntos
Agressão/fisiologia , Alelos , Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/fisiopatologia , Encéfalo/fisiopatologia , Estimulantes do Sistema Nervoso Central , Emoções/fisiologia , Predisposição Genética para Doença/genética , Variação Genética/genética , Genótipo , Metanfetamina , Rede Nervosa/fisiopatologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Tonsila do Cerebelo/fisiopatologia , Mapeamento Encefálico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Expressão Facial , Feminino , Lobo Frontal/fisiopatologia , Humanos , Íntrons/genética , Imageamento por Ressonância Magnética , Masculino , Metanfetamina/efeitos adversos , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Lobo Occipital/fisiopatologia , Reconhecimento Visual de Modelos/fisiologia , Córtex Pré-Frontal/fisiopatologia , Síndrome de Abstinência a Substâncias/genética , Síndrome de Abstinência a Substâncias/fisiopatologia , Inquéritos e Questionários
7.
Anal Bioanal Chem ; 387(7): 2401-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17265084

RESUMO

During the past seven years, several states within the US have enacted regulations that limit the amounts of selected non-nutritive elements in fertilizers. Internationally, several countries, including Japan, China, and Australia, and the European Union also limit the amount of selected elements in fertilizers. The elements of interest include As, Cd, Co, Cr, Cu, Hg, Mo, Ni, Pb, Se, and Zn. Fertilizer manufacturers and state regulatory authorities, faced with meeting and verifying these limits, need to develop analytical methods for determination of the elements of concern and to validate results obtained using these methods. Until now, there were no certified reference materials available with certified mass fraction values for all elements of interest in a blended, multi-nutrient fertilizer matrix. A new standard reference material (SRM) 695 trace elements in multi-nutrient fertilizer, has been developed to help meet these needs. SRM 695 has recently been issued with certified mass fraction values for seventeen elements, reference values for an additional five elements, and information values for two elements. The certificate of analysis includes an addendum listing percentage recovery for eight of these elements, determined using an acid-extraction inductively-coupled plasma optical-emission spectrometry (ICP-OES) method recently developed and tested by members of the Association of American Plant Food Control Officials.


Assuntos
Técnicas de Química Analítica/métodos , Técnicas de Química Analítica/normas , Fertilizantes/análise , Oligoelementos/análise , Espectrometria de Massas/métodos , Padrões de Referência , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Atômica/métodos
8.
Int Nurs Rev ; 53(1): 28-33, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16430757

RESUMO

PURPOSE: This study contributes to the ongoing efforts of the International Classification for Nursing Practice (ICNP) to describe the phenomenon of dignified dying, to describe nursing actions used to promote dignified dying, and to evaluate the validity of a dignified dying scale among practising nurses in India. DESIGN AND SAMPLE: This descriptive study surveyed 229 nurses who had cared for dying patients and were currently practising in government and private hospitals in India. METHODS: Nurses were recruited to complete a survey in either Hindi or English. The survey included demographic, open-ended questions, and a dignified dying scale of Likert-like items. Nurses also identified nursing interventions used in practice to promote dignified dying. FINDINGS: The descriptions of dignified dying phenomenon fit within the three major areas of the Dignity-Conserving Model of Care. A variety of interventions were reported, with more focusing on spiritual than physical factors. The 14 items selected reliably measured dignified dying, with a Cronbach's alpha of 0.79. Factor analysis yielded a 4-factor solution, with 11 items accounting for 56% of the variance. CONCLUSIONS: Nurses in India endorsed spirituality as an essential aspect of the phenomenon of dignified dying. Nursing actions to promote dignified dying supported finding spiritual comfort at end of life. These results contribute to an understanding of nursing phenomena and actions worldwide.


Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Morte , Papel do Profissional de Enfermagem , Recursos Humanos de Enfermagem Hospitalar , Assistência Terminal , Análise de Variância , Atitude do Pessoal de Saúde/etnologia , Atitude Frente a Morte/etnologia , Estudos Transversais , Dispneia/prevenção & controle , Análise Fatorial , Promoção da Saúde , Saúde Holística , Hospitais Privados , Hospitais Públicos , Humanos , Índia , Modelos de Enfermagem , Papel do Profissional de Enfermagem/psicologia , Relações Enfermeiro-Paciente , Pesquisa Metodológica em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Recursos Humanos de Enfermagem Hospitalar/psicologia , Dor/prevenção & controle , Pesquisa Qualitativa , Direito a Morrer , Espiritualidade , Inquéritos e Questionários , Assistência Terminal/organização & administração , Assistência Terminal/psicologia , Vocabulário Controlado
9.
Clin Neurophysiol ; 114(8): 1477-88, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12888031

RESUMO

OBJECTIVE: To determine if transient anaesthetic deafferentation of the radial nerve would lead to alterations in processing of early somatosensory evoked potentials (SEPs) from the median nerve or alter cortico-motor output to the median nerve innervated abductor pollicis brevis (APB) muscle. METHODS: Spinal, brainstem, and cortical SEPs to median nerve stimulation were recorded before, during and after ipsilateral radial nerve block with local anaesthesia. Motor evoked potentials (MEPs) and motor cortex output maps were recorded from the APB muscle. RESULTS: There were no significant changes to most early SEP peaks. The N30 peak, however, showed a significant increase in amplitude, which remained elevated throughout the anaesthetic period, returning to baseline once the anaesthetic had completely worn off. MEP amplitude of the median nerve innervated APB muscle was significantly decreased during the radial nerve blockade. There was also a significant alteration in the APB optimal site location, and a small but significant decrease in the silent period during the radial nerve blockade. CONCLUSIONS: Transient anaesthetic deafferentation of the radial nerve at the elbow leads to a rapid modulation of cortical processing of median nerve input and output. These changes suggest an overall decrease in motor cortex output to a median nerve innervated muscle not affected by the radial nerve block, occurring concomitantly with an increased amplitude of the median nerve generated N30 SEP peak, thought to represent processing in the supplementary motor area (SMA). Independent subcortical connections to the SMA are thought to contribute to the N30 response observed in this study. Unmasking of pre-existing but latent cortico-cortical and/or thalamo-cortical connections may be the mechanism underlying the cortical SEP increases observed following radial nerve deafferentation. SIGNIFICANCE: Transient deafferentation of the radial nerve, which supplies wrist and hand extensor muscles, has been shown to alter sensory processing from and motor output to the median nerve innervated thenar muscles.


Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Nervo Mediano/fisiologia , Bloqueio Nervoso/métodos , Nervo Radial/fisiologia , Córtex Somatossensorial/fisiologia , Adulto , Vias Aferentes/fisiologia , Mapeamento Encefálico , Tronco Encefálico/fisiologia , Estimulação Elétrica , Eletroencefalografia , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Magnetismo , Masculino , Córtex Motor/fisiologia , Contração Muscular , Medula Espinal/fisiologia , Fatores de Tempo
10.
Clin Neurophysiol ; 114(8): 1531-7, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12888037

RESUMO

OBJECTIVE: Numerous somatosensory evoked potential (SEP) studies have provided clear evidence that during repetitive voluntary movement, the transmission of somatosensory afferent information is attenuated. The objective of this work was to determine if this gating phenomenon could persist beyond the period of repetitive movement. METHODS: We recorded spinal, brainstem, and cortical SEPs to median nerve stimulation before and immediately after a modified 20 min repetitive typing task that did not involve the thenar muscles. RESULTS: There were significant decreases in pre-central cortical and subcortical SEP amplitudes for several minutes following task cessation. CONCLUSIONS: These results demonstrate the persistence of the gating phenomenon beyond the cessation of the actual repetitive movement. They also indicate that plastic changes do occur in cortical and subcortical components of the somatosensory system, following voluntary repetitive contractions. SIGNIFICANCE: The persistence of changes in somatosensory processing beyond the period of repetitive activity may be relevant to the initiation of overuse injuries.


Assuntos
Vias Aferentes/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Mediano/fisiologia , Inibição Neural , Córtex Somatossensorial/fisiologia , Adulto , Análise de Variância , Mapeamento Encefálico , Tronco Encefálico/fisiologia , Estimulação Elétrica , Eletroencefalografia , Eletromiografia , Feminino , Humanos , Masculino , Movimento , Condução Nervosa , Tempo de Reação , Medula Espinal/fisiologia , Fatores de Tempo
11.
EMBO J ; 20(20): 5769-78, 2001 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11598019

RESUMO

The role of herpes simplex virus ICP27 protein in mRNA export is investigated by microinjection into Xenopus laevis oocytes. ICP27 dramatically stimulates the export of intronless viral mRNAs, but has no effect on the export of cellular mRNAs, U snRNAs or tRNA. Use of inhibitors shows, in contrast to previous suggestions, that ICP27 neither shuttles nor exports viral mRNA via the CRM1 pathway. Instead, ICP27-mediated viral RNA export requires REF and TAP/NXF1, factors involved in cellular mRNA export. ICP27 binds directly to REF and complexes containing ICP27, REF and TAP are found in vitro and in virally infected cells. A mutant ICP27 that does not interact with REF is inactive in viral mRNA export. We propose that ICP27 associates with viral mRNAs and recruits TAP/NXF1 via its interaction with REF proteins, allowing the otherwise inefficiently exported viral mRNAs to access the TAP-mediated export pathway. This represents a novel mechanism for export of viral mRNAs.


Assuntos
Proteínas Imediatamente Precoces/fisiologia , Proteínas de Transporte Nucleocitoplasmático , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Proteínas de Saccharomyces cerevisiae , Simplexvirus/fisiologia , Animais , Transporte Biológico , Feminino , Proteínas Fúngicas/metabolismo , Regulação Viral da Expressão Gênica , Células HeLa , Humanos , Substâncias Macromoleculares , Microinjeções , Proteínas Nucleares/metabolismo , Oócitos , Ligação Proteica , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Simplexvirus/genética , Xenopus laevis
12.
J Fam Pract ; 50(8): 703, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11509165

RESUMO

OBJECTIVE: Immunization rates for influenza and pneumococcal vaccines among the elderly (especially minority elderly) are below desired levels. We sought to answer 4 questions: (1) What factors explain most missed immunizations? (2) How are patient beliefs and practices regarding adult immunization affected by racial or cultural factors? (3) How are immunizations and patient beliefs affected by physician, organizational, and operational factors? and (4) Based on the relationships identified, can typologies be created that foster the tailoring of interventions to improve immunization rates? STUDY DESIGN: A multidisciplinary team chose the PRECEDE-PROCEED framework, the Awareness-to-Adherence model of clinician response to guidelines, and the Triandis model of consumer decision making as the best models to assess barriers to and facilitators of immunization. Our data collection methods included focus groups, face-to-face and telephone interviews, self-administered surveys, site visits, participant observation, and medical record review. POPULATION: To encounter a broad spectrum of patients, facilities, systems, and interventions, we sampled from 4 strata: inner-city neighborhood health centers, clinics in Veterans Administration facilities, rural practices in a network, and urban/suburban practices in a network. In stage 1, a stratified random cluster sample of 60 primary care clinicians was selected, 15 in each of the strata. In stage 2, a random sample of 15 patients was selected from each clinician's list of patients, aiming for 900 total interviews. CONCLUSIONS: This multicomponent approach is well suited to identifying barriers to and facilitators of adult immunizations among a variety of populations, including the disadvantaged.


Assuntos
Medicina de Família e Comunidade/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde/organização & administração , Imunização/psicologia , Imunização/estatística & dados numéricos , Vacinas contra Influenza , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Vacinas Pneumocócicas , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Feminino , Grupos Focais , Fidelidade a Diretrizes/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Grupos Minoritários/educação , Grupos Minoritários/psicologia , Modelos Psicológicos , Cultura Organizacional , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pennsylvania , Guias de Prática Clínica como Assunto , Análise de Regressão , Inquéritos e Questionários
13.
J Assoc Nurses AIDS Care ; 12(3): 95-7, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11387809

RESUMO

Of the recently approved antiretroviral agents, efavirenz has become a popular medication for the treatment of HIV infection. The efficacy of an efavirenz-based regimen has allowed the use of a combination of this medication with other antiretroviral agents in all levels of HIV disease, resulting in decreased viral replication and positive clinical results. Efavirenz is also proposed as an acceptable agent to switch to from a protease inhibitor-based regimen to reduce the risk of metabolic complications. In addition, the favorable side-effect profile, diminished pill burden for clients, and daily dosing have contributed to its popularity. Primary care practitioners should be cognizant of the possible side-effect profile of antiretroviral therapy combinations and enter into a collaborative relationship with the infectious disease clinician to ensure safe and effective patient care.


Assuntos
Infecções por HIV/tratamento farmacológico , Hipertrigliceridemia/epidemiologia , Oxazinas/efeitos adversos , Inibidores da Transcriptase Reversa/efeitos adversos , Alcinos , Benzoxazinas , Ciclopropanos , Delaware/epidemiologia , Feminino , Infecções por HIV/enfermagem , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/induzido quimicamente , Masculino , Prontuários Médicos , Estudos Retrospectivos , Triglicerídeos/sangue
16.
Epidemiol Infect ; 124(3): 489-95, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10982073

RESUMO

We examined clinical and epidemiological features of 575 laboratory-confirmed cases of vibrio gastroenteritis in Alabama, Florida, Louisiana, and Texas from 1988 to 1997 (the US Gulf of Mexico Regional Vibrio Surveillance System). Illnesses occurred year round, with peaks in spring and autumn. Illnesses lasted a median of 7 days and included fever in half of patients and bloody stools in 25% of patients with relevant information. Seventy-two percent of patients reported no underlying illnesses. In the week before onset, 236 (53%) of 445 patients for whom data were available ate raw oysters, generally at a restaurant or bar. Educational efforts should address the risk of vibrio gastroenteritis for raw oyster consumers, including healthy individuals. Further studies should examine environmental conditions affecting vibrio counts on seafood and processing technologies to enhance the safety of raw oysters.


Assuntos
Contaminação de Alimentos , Gastroenterite/virologia , Ostreidae/virologia , Frutos do Mar/virologia , Vibrioses/epidemiologia , Adulto , Animais , Educação , Feminino , Gastroenterite/etiologia , Gastroenterite/patologia , Humanos , Masculino , Fatores de Risco , Estações do Ano , Sudeste dos Estados Unidos/epidemiologia , Vibrioses/etiologia , Vibrioses/patologia
17.
J Med Chem ; 43(10): 1940-8, 2000 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-10821706

RESUMO

Examination of the gastrointestinal (GI) tract has been performed for decades using barium sulfate. Although this agent has many recognized limitations including extreme radiopacity, poor intrinsic affinity for the GI mucosa, and very high density, no alternative contrast agents have emerged which produce comparable or better contrast visualization. In fact, the various techniques of the GI radiologic examination (i.e., single contrast, double contrast, biphasic) were developed to compensate for its limitations. Each of these techniques requires complex patient manipulation to achieve adequate mucosal coating or compression to overcome the marked radiopacity of barium sulfate in order to obtain a diagnostically useful examination. A series of novel radiopaque oils, the 1,3, 5-trialkyl-2,4,6-triiodobenzenes, was designed to improve the efficacy, stability, and safety of barium formulations. These substances were prepared in two steps from 1,3,5-trichlorobenzene. Compound 17 (1,3,5-tri-n-hexyl-2,4,6-triiodobenzene), formulated as an oil-in-water emulsion, was found to be well-tolerated in rodents (mice, hamsters, rats) following acute oral and/or intraperitoneal administrations at 4 times the anticipated human clinical dose. No metabolism of 17 was detected in rat, hamster, dog, monkey, or human hepatic microsomes, suggesting the lack of oral toxicity was a consequence of poor absorption. In imaging experiments in dogs, emulsions of 17 have demonstrated excellent mucosal coating and improved radiodensity relative to barium sulfate suspensions. On the basis of the preliminary imaging and toxicity data, compound 17 was selected as a potential development candidate.


Assuntos
Meios de Contraste/síntese química , Sistema Digestório/diagnóstico por imagem , Iodobenzenos/síntese química , Absorção , Animais , Fenômenos Químicos , Físico-Química , Cricetinae , Cães , Desenho de Fármacos , Emulsões , Humanos , Técnicas In Vitro , Iodobenzenos/metabolismo , Iodobenzenos/toxicidade , Cinética , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos ICR , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Radiografia , Ratos , Ratos Sprague-Dawley , Doenças da Glândula Tireoide/induzido quimicamente
18.
Protein Eng ; 13(2): 129-32, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10708652

RESUMO

The AmiC protein in Pseudomonas aeruginosa is the negative regulator and ligand receptor for an amide-inducible aliphatic amidase operon. In the wild-type PAC1 strain, amidase expression is induced by acetamide or lactamide, but not by butyramide. A mutant strain of P. aeruginosa, PAC181, was selected for its sensitivity to induction by butyramide. The molecular basis for the butyramide inducible phenotype of P.aeruginosa PAC181 has now been determined, and results from a Thr-->Asn mutation at position 106 in PAC181-AmiC. In the wild-type PAC1-AmiC protein this residue forms part of the side wall of the amide-binding pocket but does not interact with the acetamide ligand directly. In the crystal structure of PAC181-AmiC complexed with butyramide, the Thr-->Asn mutation increases the size of the ligand binding site such that the mutant protein is able to close into its 'on' configuration even in the presence of butyramide. Although the mutation allows butyramide to be recognized as an inducer of amidase expression, the mutation is structurally sub-optimal, and produces a significant decrease in the stability of the mutant protein.


Assuntos
Adaptação Biológica/genética , Proteínas de Bactérias/genética , Proteínas Periplásmicas de Ligação , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/genética , Seleção Genética , Amidas/metabolismo , Amidas/farmacologia , Amidoidrolases/genética , Amidoidrolases/metabolismo , Substituição de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , Dicroísmo Circular , Cristalografia por Raios X , Genes Reguladores , Temperatura Alta , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Mutação de Sentido Incorreto , Fenótipo , Ligação Proteica , Desnaturação Proteica , Engenharia de Proteínas , Estrutura Terciária de Proteína , Proteínas Repressoras/química , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
19.
J Appl Physiol (1985) ; 88(2): 467-72, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10658012

RESUMO

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1. 0 +/- 0.1 degrees C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereas L-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion of L-NAME resulted in a significant decrease in CVC (37 +/- 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.


Assuntos
Atropina/farmacologia , Temperatura Corporal/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Pele/irrigação sanguínea , Adulto , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiologia , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Recém-Nascido , Bombas de Infusão , Masculino , Microdiálise , Parassimpatolíticos/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Sudorese/fisiologia , Fatores de Tempo , Resistência Vascular/efeitos dos fármacos
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