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1.
Adv Exp Med Biol ; 1131: 27-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646506

RESUMO

Ca2+, Na+ and K+- permeable ion channels as well as GPCRs linked to Ca2+ release are important drug targets. Accordingly, high-throughput fluorescence plate reader assays have contributed substantially to drug discovery efforts and pharmacological characterization of these receptors and ion channels. This chapter describes some of the basic properties of the fluorescent dyes facilitating these assay approaches as well as general methods for establishment and optimisation of fluorescence assays for ion channels and Gq-coupled GPCRs.


Assuntos
Bioensaio , Canais Iônicos , Receptores Acoplados a Proteínas-G , Animais , Bioensaio/tendências , Descoberta de Drogas , Corantes Fluorescentes/metabolismo , Humanos , Canais Iônicos/análise , Receptores Acoplados a Proteínas-G/análise
2.
Cell Calcium ; 72: 39-50, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29748132

RESUMO

Alterations in Ca2+ signaling can regulate key cancer hallmarks such as proliferation, invasiveness and resistance to cell death. Changes in the regulation of intracellular Ca2+ and specific components of Ca2+ influx are a feature of several cancers and/or cancer subtypes, including the basal-like breast cancer subtype, which has a poor prognosis. The development of genetically encoded calcium indicators, such as GCaMP6, represents an opportunity to measure changes in intracellular free Ca2+ during processes relevant to breast cancer progression that occur over long periods (e.g. hours), such as cell death. This study describes the development of a MDA-MB-231 breast cancer cell line stably expressing GCaMP6m. The cell line retained the key features of this aggressive basal-like breast cancer cell line. Using this model, we defined alterations in relative cytosolic free Ca2+ ([Ca2+]CYT) when the cells were treated with C2-ceramide. Cell death was measured simultaneously via assessment of propidium iodide permeability. Treatment with ceramide produced delayed and heterogeneous sustained increases in [Ca2+]CYT. Where cell death occurred, [Ca2+]CYT increases preceded cell death. The sustained increases in [Ca2+]CYT were not related to the rapid morphological changes induced by ceramide. Silencing of the plasma membrane Ca2+ ATPase isoform 1 (PMCA1) was associated with an augmentation in ceramide-induced increases in [Ca2+]CYT and also cell death. This work demonstrates the utility of GCaMP6 Ca2+ indicators for investigating [Ca2+]CYT changes in breast cancer cells during events relevant to tumor progression, which occur over hours rather than minutes.

3.
Adv Pharmacol ; 79: 141-171, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28528667

RESUMO

The calcium ion (Ca2+) is an important signaling molecule implicated in many cellular processes, and the remodeling of Ca2+ homeostasis is a feature of a variety of pathologies. Typical methods to assess Ca2+ signaling in cells often employ small molecule fluorescent dyes, which are sometimes poorly suited to certain applications such as assessment of cellular processes, which occur over long periods (hours or days) or in vivo experiments. Genetically encoded calcium indicators are a set of tools available for the measurement of Ca2+ changes in the cytosol and subcellular compartments, which circumvent some of the inherent limitations of small molecule Ca2+ probes. Recent advances in genetically encoded calcium sensors have greatly increased their ability to provide reliable monitoring of Ca2+ changes in mammalian cells. New genetically encoded calcium indicators have diverse options in terms of targeting, Ca2+ affinity and fluorescence spectra, and this will further enhance their potential use in high-throughput drug discovery and other assays. This review will outline the methods available for Ca2+ measurement in cells, with a focus on genetically encoded calcium sensors. How these sensors will improve our understanding of the deregulation of Ca2+ handling in disease and their application to high-throughput identification of drug leads will also be discussed.


Assuntos
Canais de Cálcio/metabolismo , Cálcio/metabolismo , Descoberta de Drogas/métodos , Animais , Corantes Fluorescentes/administração & dosagem , Humanos , Transdução de Sinais
4.
Arch Dis Child ; 102(11): 1019-1029, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28468868

RESUMO

BACKGROUND: Inborn errors of metabolism (IEMs) underlie a substantial proportion of paediatric disease burden but their genetic diagnosis can be challenging using the traditional approaches. METHODS: We designed and validated a next-generation sequencing (NGS) panel of 226 IEM genes, created six overlapping phenotype-based subpanels and tested 102 individuals, who presented clinically with suspected childhood-onset IEMs. RESULTS: In 51/102 individuals, NGS fully or partially established the molecular cause or identified other actionable diagnoses. Causal mutations were identified significantly more frequently when the biochemical phenotype suggested a specific IEM or a group of IEMs (p<0.0001), demonstrating the pivotal role of prior biochemical testing in guiding NGS analysis. The NGS panel helped to avoid further invasive, hazardous, lengthy or expensive investigations in 69% individuals (p<0.0001). Additional functional testing due to novel or unexpected findings had to be undertaken in only 3% of subjects, demonstrating that the use of NGS does not significantly increase the burden of subsequent follow-up testing. Even where a molecular diagnosis could not be achieved, NGS-based approach assisted in the management and counselling by reducing the likelihood of a high-penetrant genetic cause. CONCLUSION: NGS has significant clinical utility for the diagnosis of IEMs. Biochemical testing and NGS analysis play complementary roles in the diagnosis of IEMs. Incorporating NGS into the diagnostic algorithm of IEMs can improve the accuracy of diagnosis.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Erros Inatos do Metabolismo/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Erros Inatos do Metabolismo/genética , Adulto Jovem
5.
J Clin Endocrinol Metab ; 102(6): 2069-2074, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28323957

RESUMO

Context: The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. Objective: To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Design: Retrospective analysis. Setting: International collaboration. Patients: Included were 13 A883F carriers. Intervention: The intervention was thyroidectomy. Main Outcome Measures: Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. Results: One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. Conclusions: MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Carcinoma Neuroendócrino/genética , Neoplasia Endócrina Múltipla Tipo 2b/genética , Feocromocitoma/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/etiologia , Adulto , Carcinoma Neuroendócrino/etiologia , Carcinoma Neuroendócrino/cirurgia , Criança , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Masculino , Neoplasia Endócrina Múltipla Tipo 2b/complicações , Mutação , Penetrância , Feocromocitoma/etiologia , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
6.
Clin Dysmorphol ; 25(2): 54-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26636501

RESUMO

Myhre syndrome is a rare autosomal dominant genetic condition characterized by short stature, distinctive facial dysmorphisms, generalized muscle hypertrophy, skeletal abnormalities, decreased joint motility, developmental delay, deafness and cardiac defects. Myhre syndrome and the allelic laryngeal stenosis, arthropathy, prognathism and short stature syndrome are caused by a missense mutation of SMAD4, resulting in altered expression of transforming growth factor ß and bone morphogenic protein, affecting cell growth and differentiation. Here, we report on the case of a 7-year-old girl showing symptoms of Myhre syndrome and with a known SMAD4 mutation presenting with the novel symptom of severe constipation.


Assuntos
Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Criptorquidismo/complicações , Criptorquidismo/diagnóstico , Transtornos do Crescimento/complicações , Transtornos do Crescimento/diagnóstico , Deformidades Congênitas da Mão/complicações , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Constipação Intestinal/tratamento farmacológico , Criptorquidismo/genética , Facies , Feminino , Transtornos do Crescimento/genética , Deformidades Congênitas da Mão/genética , Humanos , Lactente , Deficiência Intelectual/genética , Mutação , Fenótipo , Proteína Smad4/genética , Resultado do Tratamento
8.
Dig Dis Sci ; 58(8): 2253-60, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23824407

RESUMO

BACKGROUND: The mainstay of medical therapy for Barrett's esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown. AIM: The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS: Patients with GEJSIM and Barrett's esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated. RESULTS: A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526). CONCLUSIONS: The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett's mucosa.


Assuntos
Antiulcerosos/uso terapêutico , Esôfago de Barrett/tratamento farmacológico , Junção Esofagogástrica/patologia , Omeprazol/uso terapêutico , Antiulcerosos/administração & dosagem , Esôfago de Barrett/patologia , Relação Dose-Resposta a Droga , Determinação da Acidez Gástrica , Humanos , Concentração de Íons de Hidrogênio , Metaplasia , Omeprazol/administração & dosagem
9.
J Rheumatol ; 38(12): 2635-42, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22045843

RESUMO

OBJECTIVE: Our study uses the entire proteomes of serum and synovial fluid (SF) to characterize the avenues of microvascular egress of plasma proteins, and quantifies that traffic in normal and diseased human knees. METHODS: Paired aliquots of serum and SF were collected from 17 knees of 11 subjects who died without evident joint disease and 16 patients with clinical effusions, fractionated by gel filtration chromatography and analyzed as continuous plots of the SF/serum concentration ratio versus molecular radius from 1 to 12 nanometers (nm). Curve-stripping methodology, a 3-pore model, and known protein kinetics were then applied to estimate the dimensions of and the net outflow through fenestral, "small," and "large" apertures in the microvascular endothelium. RESULTS: The 3-pore model correlated highly with the observed data (r = 0.992 in normal and 0.980 in arthritis), yielding the following mean values: for the fenestra, the normal radius (nm) was 1.75 and the effused 3.5, and the normal flow (µl/min) was 1.74 and the arthritic 22.0; for the small pore, the normal radius was 8.6 and the effused 8.5, and the normal flow was 1.5 and the arthritic flow 9.1; for the large pore, the normal radius was 40 and the effused 36, and the normal flow was 0.24 and the arthritic flow 15.5. CONCLUSION: These findings provide the first functional definition of synovial, endothelial fenestrae; reveal that the "increased vascular permeability" of inflammation is not limited to interendothelial gaps; present evidence suggesting that glycocalyceal damage and aquaporin upregulation may affect permeability in arthritic synovium; and define a straightforward methodology for interpretation of biomarker concentrations in arthritic SF.


Assuntos
Permeabilidade Capilar/fisiologia , Endotélio Vascular/metabolismo , Artropatias , Articulação do Joelho , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Animais , Proteínas Sanguíneas/análise , Endotélio Vascular/patologia , Endotélio Vascular/ultraestrutura , Humanos , Artropatias/metabolismo , Artropatias/patologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Modelos Biológicos , Porosidade , Líquido Sinovial/química , Membrana Sinovial/ultraestrutura
10.
Dig Dis Sci ; 56(12): 3488-91, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21710227

RESUMO

INTRODUCTION: The ultimate purpose of measuring quality of care is to discriminate between healthcare providers in order to motivate improvement. Recently, a set of evidence-based indicators has been proposed for measurement of processes of care for patients with cirrhosis, for example early endoscopy for variceal bleeding. The objective of this study was to determine whether these indicators can be measured in a reliable and automated fashion in routine practice. MATERIALS AND METHODS: We applied the top five indicators, based on agreement of a panel of experts, to hospitalized adults at our institution over a 3-year period. RESULTS: Only two of the indicators could be reliably measured on the basis of the published wording, and these two still required physician chart review. After applying some assumptions, the indicators were met in 46-100% of cases. None of the indicators was linked to a single physician or institution in all cases, and none occurred with sufficient frequency to discriminate quality between providers. CONCLUSION: Measuring quality of care in cirrhosis is a laudable objective, but current indicators are not yet ready for administrative use.


Assuntos
Pessoal de Saúde/normas , Cirrose Hepática/terapia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Indicadores de Qualidade em Assistência à Saúde , Adulto , Seguimentos , Humanos , Cirrose Hepática/diagnóstico , Estudos Retrospectivos , Inquéritos e Questionários , Estados Unidos
11.
Dig Dis Sci ; 56(5): 1427-31, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21416245

RESUMO

BACKGROUND: An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. AIMS: The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. METHODS: A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (<30 mmHg) or non-propagating contractions. Ineffective esophageal motility (IEM) was categorized as mild (30-40% ineffective swallows), moderate (50-60% ineffective swallows), and severe (≥70% ineffective swallows). Dysphagia was graded on a 0-3 scale for frequency and severity. RESULTS: Seventy-five tracings from EoE patients were reviewed (85% male, mean age 41 ± 12 years). IEM was identified in 25 patients and categorized as mild (n = 13), moderate (n = 6), and severe (n = 6). Nutcracker esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). CONCLUSIONS: In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.


Assuntos
Transtornos da Motilidade Esofágica/fisiopatologia , Esofagite/fisiopatologia , Adulto , Estudos de Coortes , Monitoramento do pH Esofágico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Eur J Appl Physiol ; 111(5): 797-807, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21046139

RESUMO

To evaluate the effect of hydration and carbohydrate (CHO) status on plasma sodium, fluid balance, and regulatory factors (IL-6 & ADH) during and after exercise; 10 males completed the following conditions: low CHO, euhydrated (fluid intake = sweat loss) (LCEH); low CHO, dehydrated (no fluid) (LCDH); high CHO, euhydrated (HCEH); and high CHO, dehydrated (HCDH). Each trial consisted of 90-min cycling at 60% VO(2) max in a 35°C environment followed by 3-h rehydration (RH). During RH, subjects received either 150% of sweat loss (LCDH & HCDH) or an additional 50% of sweat loss (LCEH and HCEH). Blood was analyzed for glucose, IL-6, ADH, and Na(+). Post-exercise Na(+) was greater (p < 0.001) for LCDH and HCDH (141.7 + 0.72 and 141.6 + 0.4 mM) versus LCEH and HCEH (136.4 + 0.6 and 135.9 + 0.3 mM). Post-exercise IL-6 was similar in all conditions, and post-exercise ADH was greater (p = 0.01) in dehydrated versus euhydrated conditions. The rate of urine production was greater in HCEH (7.59 + 3.0 mL/min) compared to all other conditions (3.86 + 2.2, 5.29 + 3.1, and 2.96 + 1.1 mL/min for LCDH, LCEH, and HCDH, respectively). Despite CHO and hydration manipulations, no regulatory effects of IL-6 and ADH on plasma [Na(+)] were observed. With euhydration during exercise and additional fluid consumed during recovery, a high-CHO status increased urinary output during recovery, and it decreased the frequency of hyponatremia (Na(+) < 135 mM). Therefore, a high-CHO status may provide some protection against exercise-associated hyponatremia.


Assuntos
Carboidratos da Dieta/administração & dosagem , Exercício/fisiologia , Hiponatremia/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Adulto , Humanos , Masculino , Sódio/sangue
14.
J Acoust Soc Am ; 123(6): 4272-82, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18537378

RESUMO

Opera performance conveys both visual and auditory information to an audience, and so opera theaters should be evaluated in both domains. This study investigates the effect of static visual and auditory cues on seat preference in an opera theater. Acoustical parameters were measured and visibility was analyzed for nine seats. Subjective assessments for visual-only, auditory-only, and auditory-visual preferences for these seat positions were made through paired-comparison tests. In the cases of visual-only and auditory-only subjective evaluations, preference judgment tests on a rating scale were also employed. Visual stimuli were based on still photographs, and auditory stimuli were based on binaural impulse responses convolved with a solo tenor recording. For the visual-only experiment, preference is predicted well by measurements taken related to the angle of seats from the theater midline at the center of the stage, the size of the photographed stage view, the visual obstruction, and the distance from the stage. Sound pressure level was the dominant predictor of auditory preference in the auditory-only experiment. In the cross-modal experiments, both auditory and visual preferences were shown to contribute to overall impression, but auditory cues were more influential than the static visual cues. The results show that both a positive visual-only or a positive auditory-only evaluations positively contribute to the assessments of seat quality.


Assuntos
Percepção Auditiva , Sinais (Psicologia) , Música , Percepção Visual , Estimulação Acústica , Atenção , Dança , Humanos , Orientação , Estimulação Luminosa , Tempo de Reação , Localização de Som
15.
Abdom Imaging ; 33(5): 598-600, 2008 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18446401

RESUMO

CT colonography has become a potential alternative technique to optical colonoscopy for the detection of colorectal polyps and cancer. While considered safer than optical colonoscopy, CT colonography is not without risk. We report a case of colonic perforation during CT colonography using automated CO(2) insufflation and present procedural changes to help minimize the adverse effects of perforation when it occurs.


Assuntos
Colonografia Tomográfica Computadorizada/efeitos adversos , Perfuração Intestinal/etiologia , Idoso , Dióxido de Carbono , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Insuflação/efeitos adversos , Masculino
16.
Expert Opin Pharmacother ; 9(7): 1129-43, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18422471

RESUMO

BACKGROUND: Irritable bowel syndrome is a common disorder that is associated with a significant impact on both affected individuals and society. While the pathophysiology of irritable bowel syndrome remains unknown, knowledge regarding the normal and abnormal functions of the gut and its complex interactions with the body's nervous systems continue to shed light on the multifactiorial origins of irritable bowel syndrome symptoms. OBJECTIVE: This article provides an overview of the current knowledge on the therapeutic approaches to irritable bowel syndrome. METHODS: A search of the online bibliographic databases MEDLINE and EMBASE was performed in order to identify all relevant articles published between 1980 and 2008. The search was enhanced with the use of a medical librarian. Bibliographies from potentially relevant articles were manually searched. RESULTS/CONCLUSIONS: The therapeutic options for irritable bowel syndrome are rapidly evolving beyond traditional symptom-based therapies, such as fiber, antispasmodics, antidiarrheals and laxatives and are moving towards agents with organ-specific receptor selectivity directed, in many cases, at specific gastrointestinal functions.


Assuntos
Sistemas de Liberação de Medicamentos , Fármacos Gastrointestinais/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Antidiarreicos/uso terapêutico , Fibras na Dieta/uso terapêutico , Fármacos Gastrointestinais/farmacologia , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/fisiopatologia , Laxantes/uso terapêutico , Parassimpatolíticos/uso terapêutico
17.
J Food Prot ; 70(9): 2036-44, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17900080

RESUMO

The objective of this study was to investigate the practicality of designing a heat treatment process in a food manufacturing operation for a product governed by a Food Safety Objective (FSO). Salmonella in cooked poultry meat was taken as the working example. Although there is no FSO for this product in current legislation, this may change in the (near) future. Four different process design calculations were explored by means of deterministic and probabilistic approaches to mathematical data handling and modeling. It was found that the probabilistic approach was a more objective, transparent, and quantifiable approach to establish the stringency of food safety management systems. It also allowed the introduction of specific prevalence rates. The key input analyzed in this study was the minimum time required for the heat treatment at a fixed temperature to produce a product that complied with the criterion for product safety, i.e., the FSO. By means of the four alternative process design calculations, the minimum time requirement at 70 degrees C was established and ranged from 0.26 to 0.43 min. This is comparable to the U.S. regulation recommendations and significantly less than that of 2 min at 70 degrees C used, for instance, in the United Kingdom regulation concerning vegetative microorganisms in ready-to-eat foods. However, the objective of this study was not to challenge existing regulations but to provide an illustration of how an FSO established by a competent authority can guide decisions on safe product and process designs in practical operation; it hopefully contributes to the collaborative work between regulators, academia, and industries that need to continue learning and gaining experience from each other in order to translate risk-based concepts such as the FSO into everyday operational practice.


Assuntos
Manipulação de Alimentos/métodos , Indústria de Processamento de Alimentos , Temperatura Alta , Produtos Avícolas/microbiologia , Produtos Avícolas/normas , Salmonella/crescimento & desenvolvimento , Animais , Contagem de Colônia Microbiana , Qualidade de Produtos para o Consumidor , Culinária/métodos , Culinária/normas , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos/normas , Microbiologia de Alimentos , Indústria de Processamento de Alimentos/métodos , Indústria de Processamento de Alimentos/normas , Humanos , Fatores de Tempo
18.
Appetite ; 48(1): 69-77, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16965835

RESUMO

Circulating angiotensin II is crucial for the activation of salt appetite after sodium depletion. We tested if angiotensin (ANG) II infused intravenously at 50 ng/kg/min overnight (chronic) can mimic the rapid salt appetite similar to furosemide and overnight sodium depletion. In experiment 1, rats received chronic ANG II or vehicle infusions all night with access to water and chow but no saline solution. In the morning, the infusions continued, but half of the vehicle-infused group was switched to ANG II (acute). Thirty minutes after the switch, all rats received 10 mg/kg furosemide SC. One hour later they were provided water and 0.3 M NaCl to drink. Rats infused with vehicle or acute ANG drank little, but the chronic ANG group drank 11+/-1 ml of saline in 90 min. In experiment 2, the furosemide was omitted, and a group receiving a chronic infusion of phenylephrine at 6.25 microg/kg/min was included. The chronic ANG group drank 10+/-1 ml saline in 90 min, but the phenylephrine group, which also incurred a significant negative sodium balance overnight, drank little. Thus, an overnight infusion of ANG II is sufficient to mimic the robust expression of salt appetite as observed after furosemide and overnight sodium depletion.


Assuntos
Angiotensina II/farmacologia , Apetite/fisiologia , Ingestão de Líquidos , Solução Salina Hipertônica/administração & dosagem , Cloreto de Sódio na Dieta/administração & dosagem , Animais , Diuréticos/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Líquidos/fisiologia , Furosemida/farmacologia , Infusões Intravenosas , Masculino , Fenilefrina , Distribuição Aleatória , Ratos , Ratos Long-Evans , Equilíbrio Hidroeletrolítico/fisiologia
19.
Am J Physiol Regul Integr Comp Physiol ; 292(4): R1690-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17194726

RESUMO

Hyperosmotic intravenous infusions of NaCl are more potent for inducing drinking and vasopressin (AVP) secretion than equally osmotic solutions of glucose or urea. The fact that all three solutes increased cerebrospinal fluid osmolality and sodium concentration led the investigators to conclude that critical sodium receptors or osmoreceptors for stimulating drinking and AVP secretion were outside the blood-brain barrier (BBB) in the circumventricular organs (CVOs). We tested an obvious prediction of this hypothesis: that all three solutes should increase c-Fos-like immunoreactivity (Fos-ir) inside the BBB, but that only NaCl should increase Fos-ir in the CVOs. We gave intravenous infusions of 3.0 Osm/l NaCl, glucose, or urea to rats for 11 or 22 min at 0.14 ml/min and perfused the rats for assay of Fos-ir at 90 min. Controls received isotonic NaCl at the same volume. Drinking latency was measured, but water was then removed. Drinking consistently occurred with short latency during hyperosmotic NaCl infusions only. Fos-ir in the forebrain CVOs, the subfornical organ, and organum vasculosum laminae terminalis was consistently elevated only by hyperosmotic NaCl. However, all three hyperosmotic solutes potently stimulated Fos-ir in the supraoptic and paraventricular nuclei of the hypothalamus inside the BBB. Hyperosmotic NaCl greatly elevated Fos-ir in the area postrema, but even glucose and urea caused moderate elevations that may be related to volume expansion rather than osmolality. The data provide strong support for the conclusion that the osmoreceptors controlling drinking are located in the CVOs.


Assuntos
Comportamento de Ingestão de Líquido/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Solução Salina Hipertônica/farmacologia , Animais , Barreira Hematoencefálica , Ventrículos Cerebrais , Hipotálamo/metabolismo , Imuno-Histoquímica , Infusões Intravenosas , Masculino , Concentração Osmolar , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Long-Evans , Solução Salina Hipertônica/administração & dosagem
20.
Physiol Behav ; 86(4): 573-7, 2005 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-16212993

RESUMO

We previously reported that an intracerebroventricular (icv) injection of the oxytocin receptor antagonist ornithine vasotocin (OVT) caused water and saline intakes, a pressor response, and Fos-like immunoreactivity (Fos-IR) in the median preoptic nucleus of the rat brain. In the present report, rats receiving an icv injection of isotonic saline vehicle followed by an icv injection of 10 microg of OVT 20 min later drank 5.5+/-1.1 ml of total water and saline intake in 60 min after the OVT; rats receiving 10 microg of losartan before the OVT drank only 0.9+/-0.3 ml of total fluid. In a separate study, rats were treated as above except that they were not allowed to drink and were perfused for analysis of Fos-IR in the median preoptic nucleus at 90 min. Fos-IR in the dorsal part of the median preoptic nucleus was significantly suppressed from 2.69+/-0.57 cells per 10,000 square mum in vehicle-treated rats to 0.89+/-0.20 in losartan-treated rats. Losartan alone had no effect on Fos-IR. Losartan did not reduce intake of saccharin in a dessert test. This suggests that the OVT-induced drinking may result from an activation or disinhibition of angiotensin type AT1 receptors in the median preoptic nucleus.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Losartan/farmacologia , Vasotocina/análogos & derivados , Vasotocina/farmacologia , Animais , Ingestão de Líquidos/efeitos dos fármacos , Interações de Medicamentos , Injeções Intraventriculares , Masculino , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Long-Evans , Sacarina/farmacologia , Cloreto de Sódio/farmacologia
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