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1.
Addict Behav ; 105: 106326, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32004832

RESUMO

Firefighting is a high-risk occupation that accounts for vulnerability to a range of mental health problems and addictive behaviours. However, no research has addressed whether this vulnerability extends to gambling problems, and the aim of this study was thus to provide new data on frequency and implications of such problems in this occupational context. The sample consisted of n = 566 career and retained firefighters who participated in a cross-sectional survey of an Australian metropolitan fire service. The Problem Gambling Severity Index (PGSI) was used to operationalise both clinically significant levels of problem gambling (PGSI ≥ 5), and 'at-risk' gambling (PGSI 1-4); alongside measures of major depression (PHQ-9), anxiety (GAD-7), Posttraumatic Stress Disorder (PCL-5) and alcohol problems (AUDIT), as well as other addictive behaviours, wellbeing and psychosocial issues. Results indicated 12.3% of firefighters that reported any gambling problems across a continuum of severity (PGSI ≥ 1), including 2.3% that were problems gamblers, and 10.0% reporting at-risk gambling. The weighted prevalence of problem gambling was comparable to other significant mental health conditions including depression and PTSD, while the rate of any gambling problems was high relative to other addictive behaviours. Gambling problems were associated with poor mental health and wellbeing, but not psychosocial indicators (e.g., financial difficulties). The findings suggest that gambling problems across a spectrum of severity may be significant yet hidden issues among emergency service workers, and thus require increased recognition and responses at the organisational level.


Assuntos
Comportamento Aditivo/epidemiologia , Bombeiros/psicologia , Jogo de Azar/epidemiologia , Saúde Mental/estatística & dados numéricos , Adolescente , Adulto , Austrália/epidemiologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente , Funcionamento Psicossocial , Índice de Gravidade de Doença , Adulto Jovem
2.
Am J Physiol Lung Cell Mol Physiol ; 315(6): L933-L944, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30234376

RESUMO

Persistent pulmonary hypertension of the newborn (PPHN) features hypoxemia, pulmonary vasoconstriction, and impaired cardiac inotropy. We previously reported low basal and stimulated cAMP in hypoxic pulmonary artery smooth muscle cells (PASMCs). We now examine pulmonary arterial adenylyl cyclase (AC) activity and regulation in hypoxic PPHN. PPHN was induced in newborn swine by normobaric hypoxia (fraction of inspired oxygen 0.10) for 72 h and compared with age-matched normoxic controls. We studied relaxation of pulmonary arterial (PA) rings to AC activator forskolin and cGMP activator sodium nitroprusside (SNP) by isometric myography, ATP content, phosphodiesterase activity, AC content, isoform expression, and catalytic activity in presence or absence of Gαs-coupled receptor agonists, forskolin, or transnitrosylating agents in human and neonatal porcine PASMCs and HEK293T stably expressing AC isoform 6, after 72 h hypoxia (10% O2) or normoxia (21% O2). Relaxation to forskolin and SNP were equally impaired in PPHN PA. AC-specific activity decreased in hypoxia. PASMC from PPHN swine had reduced AC activity despite exposure to normoxia in culture; transient hypoxia in vitro further decreased AC activity. Prostacyclin receptor ligand affinity decreased, but its association with Gαs increased in hypoxia. Total AC content was unchanged by hypoxia, but AC6 increased in hypoxic cells and PPHN pulmonary arteries. Impairment of AC6 activity in hypoxia was associated with nitrosylation. PPHN PA relaxation is impaired because of loss of AC activity. Hypoxic AC is inhibited because of S-nitrosylation; inhibition persists after removal from hypoxia. Downregulation of AC-mediated relaxation in hypoxic PA has implications for utility of Gαs-coupled receptor agonists in PPHN treatment.


Assuntos
Adenilil Ciclases/metabolismo , Animais Recém-Nascidos/metabolismo , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Síndrome da Persistência do Padrão de Circulação Fetal/metabolismo , Animais , Animais Recém-Nascidos/fisiologia , Linhagem Celular , GMP Cíclico/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Células HEK293 , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Relaxamento Muscular/fisiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/fisiologia , Nitroprussiato/farmacologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Suínos
3.
J Med Entomol ; 52(4): 683-92, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26335475

RESUMO

Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013-2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter.


Assuntos
Corvos/virologia , Febre do Nilo Ocidental/transmissão , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/genética , Migração Animal , Animais , California , Culex/virologia , Fezes/virologia , Modelos Lineares , Estações do Ano , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/veterinária
4.
Pulm Pharmacol Ther ; 30: 1-10, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25312900

RESUMO

Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity.


Assuntos
Hipóxia Celular/fisiologia , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/citologia , Receptores de Tromboxanos/metabolismo , Actinas/metabolismo , Animais , Epoprostenol/metabolismo , Humanos , Recém-Nascido , Músculo Liso Vascular/citologia , Síndrome da Persistência do Padrão de Circulação Fetal/fisiopatologia , Transdução de Sinais/fisiologia , Suínos , Tromboxanos/metabolismo
5.
Br J Pharmacol ; 171(3): 676-87, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24490858

RESUMO

BACKGROUND AND PURPOSE: Dysregulation of the thromboxane A2 (TP) receptor, resulting in agonist hypersensitivity and hyper-responsiveness, contributes to exaggerated vasoconstriction in the hypoxic pulmonary artery in neonatal persistent pulmonary hypertension. We previously reported that hypoxia inhibits TP receptor phosphorylation, causing desensitization. Hence, we examined the role of PKA-accessible serine residues in determining TP receptor affinity, using site-directed mutational analysis. EXPERIMENTAL APPROACH: Vasoconstriction to a thromboxane mimetic and phosphorylation of TP receptor serine was examined in pulmonary arteries from neonatal swine with persistent pulmonary hypertension and controls. Effects of hypoxia were determined in porcine and human TP receptors. Human TPα serines at positions 324, 329 and 331 (C-terminal tail) were mutated to alanine and transiently expressed in HEK293T cells. Saturation binding and displacement kinetics of a TP antagonist and agonist were determined in porcine TP, wild-type human TPα and all TP mutants. Agonist-elicited calcium mobilization was determined for each TP mutant, in the presence of a PKA activator or inhibitor, and in hypoxic and normoxic conditions. KEY RESULTS: The Ser324A mutant was insensitive to PKA activation and hypoxia, had a high affinity for agonist and increased agonist-induced calcium mobilization. Ser329A was no different from wild-type TP receptors. Ser331A was insensitive to hypoxia and PKA with a decreased agonist-mediated response. CONCLUSIONS AND IMPLICATIONS: In hypoxic pulmonary hypertension, loss of site-specific phosphorylation of the TP receptor causes agonist hyper-responsiveness. Ser324 is the primary residue phosphorylated by PKA, which regulates TP receptor-agonist interactions. Ser331 mutation confers loss of TP receptor-agonist interaction, regardless of PKA activity.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Síndrome da Persistência do Padrão de Circulação Fetal/metabolismo , Processamento de Proteína Pós-Traducional , Artéria Pulmonar/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/agonistas , Serina/metabolismo , Substituição de Aminoácidos , Animais , Animais Recém-Nascidos , Sinalização do Cálcio/efeitos dos fármacos , Hipóxia Celular , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/química , Ativadores de Enzimas/farmacologia , Células HEK293 , Humanos , Mutagênese Sítio-Dirigida , Proteínas Mutantes/agonistas , Proteínas Mutantes/antagonistas & inibidores , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Síndrome da Persistência do Padrão de Circulação Fetal/enzimologia , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores , Receptores de Tromboxano A2 e Prostaglandina H2/genética , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Organismos Livres de Patógenos Específicos , Sus scrofa , Tromboxano A2/análogos & derivados , Tromboxano A2/metabolismo , Tromboxano A2/farmacologia
6.
Psychol Med ; 44(3): 499-506, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23701858

RESUMO

BACKGROUND: Cannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms. METHOD: Clinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points--at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded. RESULTS: Level of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up. CONCLUSIONS: Effective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.


Assuntos
Transtorno Bipolar/epidemiologia , Abuso de Maconha/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Transtornos Psicóticos/epidemiologia , Fatores Etários , Idade de Início , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Análise de Variância , Transtorno Bipolar/psicologia , Transtorno Bipolar/terapia , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Humanos , Modelos Lineares , Londres , Estudos Longitudinais , Masculino , Abuso de Maconha/psicologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/terapia , Esquizofrenia/epidemiologia , Esquizofrenia/terapia , Distribuição por Sexo , Fumar/epidemiologia , Fumar/psicologia , Ajustamento Social , Fatores de Tempo , Adulto Jovem
8.
Pediatr Pulmonol ; 46(12): 1194-208, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21618721

RESUMO

RATIONALE: Neonatal pulmonary hypertension is characterized by hypoxia, abnormal vascular remodeling, and impaired alveolarization. Nitric oxide (NO) regulates cell replication and activation of apoptosis. Our objective was to examine cell phenotype-specific effects of hypoxia and NO exposure on cumulative apoptotic signal in neonatal pulmonary epithelial cells and arterial smooth muscle. DESIGN/METHODS: Primary cultured newborn porcine pulmonary arterial myocytes and epithelial cells were grown in normoxic (21% O2) or hypoxic conditions (10% O2). Myocyte phenotype was predetermined by serum-supplementation or -deprivation. Cells were exposed to sodium nitroprusside (10(-7) -10(-4) M) or diluent for 3 days. Cell survival was estimated by MTT assay; BAX, Bcl-2, and cleaved caspase-3 by Western blot; cell cycle entry by laser scanning cytometry. RESULTS: Hypoxic epithelial cells exhibited a small increase in anti-apoptotic Bcl2, and decrease in BAX. Cell survival and active caspase-3 were unchanged. Exposure to NO had no impact on epithelial apoptosis, but initiated necrosis. In contractile myocytes, pro-apoptotic BAX abundance and caspase-3 activation were increased by hypoxia, augmented by NO exposure promoting apoptosis. Hypoxia decreased BAX/Bcl-2 ratio and promoted survival of synthetic myocytes; NO increased apoptosis of normoxic synthetic myocytes, but decreased apoptosis of hypoxic synthetic myocytes. CONCLUSION: The effect of NO on pulmonary apoptosis is phenotype-dependent. A cumulative apoptotic effect of hypoxia and NO in vitro exerted on contractile myocytes may lead to contraction of this subpopulation, while synthetic myocyte survival and proliferation is enhanced by hypoxia and NO. Epithelial survival is unaffected. We speculate that alveolar rarefaction reported after neonatal hypoxia may arise from growth arrest in the vascular rather than the epithelial compartment.


Assuntos
Apoptose , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Mucosa Respiratória/metabolismo , Animais , Animais Recém-Nascidos , Caspase 3/análise , Sobrevivência Celular , Células Cultivadas , Células Musculares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/análise , Artéria Pulmonar/metabolismo , Suínos , Proteína X Associada a bcl-2/análise
9.
Phys Rev Lett ; 104(17): 177001, 2010 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-20482127

RESUMO

An unusual noise component is found near and below about 250 K in the normal state of underdoped YBCO and Ca-YBCO films. This noise regime, unlike the more typical noise above 250 K, has features expected for a symmetry-breaking collective electronic state. These include large individual fluctuators, a magnetic sensitivity, and aging effects. A possible interpretation in terms of fluctuating charge nematic order is presented.

10.
Artigo em Inglês | MEDLINE | ID: mdl-20483217

RESUMO

The structure, regulation and evolution of the cystic fibrosis transmembrane conductance regulator (CFTR) gene were characterized in common killifish (Fundulus heteroclitus). Killifish CFTR (kfCFTR) structure was conserved with other CFTR homologues, but was more compact than those of mammals. A motif in intron 1 was conserved across all teleost CFTR homologues except zebrafish, and was similar to a functionally important site in human CFTR. The sequence of the CFTR promoter was highly conserved across nine species within the genus Fundulus, but contained additional glucocorticoid responsive elements in seawater species. The promoters of the seawater species also contained a putative osmotic responsive element that differed by a single base in the freshwater species. The kfCFTR promoter was only active in cell lines that express the endogenous CFTR gene. Transcription from the kfCFTR promoter was unaffected by application of dexamethasone or cortisol in cell culture, but increased by 1.5-fold in response to high osmolarity. Cortisol injection in vivo increased CFTR mRNA but there was no increase in luciferase expression driven by the kfCFTR promoter in transiently transgenic fish. Administration of the cortisol blocker RU486 resulted in a significant reduction in luciferase activity driven by the kfCFTR promoter in vivo.

11.
Acta Psychiatr Scand ; 114(2): 109-17, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16836598

RESUMO

OBJECTIVE: To evaluate a cannabis-focused intervention (cannabis and psychosis therapy: CAP) for patients continuing to use cannabis following initial treatment for first-episode psychosis (FEP). METHOD: Consecutive admissions to an early psychosis program were screened and consenting individuals using cannabis in the 4 weeks prior to assessment participated. A single-blind randomized controlled trial compared CAP (n = 23) with a clinical control condition (psychoeducation, PE; n = 24). There were no significant differences between the CAP and PE groups on cannabis use at end of treatment and 6 months post-intervention. RESULTS: There were no significant group differences on psychopathology and functional ratings at follow-up. A significant reduction in cannabis use was observed for both groups over time. CONCLUSION: PE and specific cannabis-focused intervention are associated with similar reductions in cannabis use in an FEP cohort. Simple interventions may therefore be worth considering prior to intensive psychotherapeutic efforts with this population.


Assuntos
Abuso de Maconha/epidemiologia , Abuso de Maconha/terapia , Psicoterapia/métodos , Transtornos Psicóticos/epidemiologia , Adolescente , Adulto , Serviços Comunitários de Saúde Mental , Feminino , Humanos , Masculino , Método Simples-Cego
12.
Am J Physiol Lung Cell Mol Physiol ; 290(2): L375-84, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16214814

RESUMO

PPHN, caused by perinatal hypoxia or inflammation, is characterized by an increased thromboxane-prostacyclin ratio and pulmonary vasoconstriction. We examined effects of hypoxia on myocyte thromboxane responsiveness. Myocytes from 3rd-6th generation pulmonary arteries of newborn piglets were grown to confluence and synchronized in contractile phenotype by serum deprivation. On the final 3 days of culture, myocytes were exposed to 10% O2 for 3 days; control myocytes from normoxic piglets were cultured in 21% O2. PPHN was induced in newborn piglets by 3-day hypoxic exposure (Fi(O2) 0.10); pulmonary arterial myocytes from these animals were maintained in normoxia. Ca2+ mobilization to thromboxane mimetic U-46619 and ATP was quantified using fura-2 AM. Three-day hypoxic exposure in vitro results in increased basal [Ca2+]i, faster and heightened peak Ca2+ response, and decreased U-46619 EC50. These functional changes persist in myocytes exposed to hypoxia in vivo but cultured in 21% O2. Blockade of Ca2+ entry and store refilling do not alter peak U-46619 Ca2+ responses in hypoxic or normoxic myocytes. Blockade of ryanodine-sensitive or IP3-gated intracellular Ca2+ channels inhibits hypoxic augmentation of peak U-46619 response. Ca2+ response to ryanodine alone is undetectable; ATP-induced Ca2+ mobilization is unaltered by hypoxia, suggesting no independent increase in ryanodine-sensitive or IP3-linked intracellular Ca2+ pool mobilization. We conclude hypoxia has a priming effect on neonatal pulmonary arterial myocytes, resulting in increased resting Ca2+, thromboxane hypersensitivity, and hyperreactivity. We postulate that hypoxia increases agonist-induced TP-R-linked IP3 pathway activation. Myocyte thromboxane hyperresponsiveness persists in culture after removal from the initiating hypoxic stimulus, suggesting altered gene expression.


Assuntos
Hipóxia/fisiopatologia , Células Musculares/efeitos dos fármacos , Síndrome da Persistência do Padrão de Circulação Fetal/fisiopatologia , Receptores de Tromboxanos/agonistas , Vasoconstrição/efeitos dos fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Ventrículos do Coração/anatomia & histologia , Ventrículos do Coração/patologia , Humanos , Recém-Nascido , Compostos Macrocíclicos , Nifedipino/farmacologia , Tamanho do Órgão , Oxazóis/farmacologia , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Rianodina/farmacologia , Suínos
13.
J Appl Microbiol ; 96(5): 1002-12, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15078517

RESUMO

AIMS: To evaluate the effect of nitrofuran derivatives furazolidone (Fz) and nitrofurantoin (Nf) on Salmonella enterica serovar Enteritidis PT4 in vitro, with regard to cell growth, morphology and ultrastructure. METHODS AND RESULTS: The effects of Fz on the growth rates of Fz resistant (FzR) and sensitive (FzS) strains were assessed by viable counts. Over 24 h incubation, concentrations of <1 microg ml(-1) of Fz were bacteriostatic to the FzS strain. The FzR strain tolerated concentrations up to 16 microg ml(-1) before cell numbers diminished over the same time period. The effect on the growth rate of the FzS strain after 1 h exposure to supra-inhibitory concentrations of Fz, gave a maximum response at 32X minimum inhibitory concentration (MIC) of 4.5 h. Effects on the ultrastructure of bacterial cells by scanning electron and transmission microscopy, and DNA-specific staining with DAPI of the FzS strain exposed to nitrofurans were studied. Abnormalities such as extensive filamentation with sparse, sporadic nucleotide distribution and evidence of extrusions in the cell envelope in the form of blebs were evident. CONCLUSIONS: Nitrofurans exert their bactericidal effect on Salmonella by inducing extensive structural alteration after exposure at sub- or suprainhibitory concentrations, involving inhibition of cell division because of the activated drug causing an intercalating type of binding in DNA. SIGNIFICANCE AND IMPACT OF THE STUDY: These results demonstrate the in vitro activity of the nitrofuran derivatives, furazolidone and nitrofurantoin on Salmonella, defining the pharmacodynamics and physical nature of their action as therapeutic agents.


Assuntos
Anti-Infecciosos/farmacologia , Furazolidona/farmacologia , Nitrofurantoína/farmacologia , Salmonella enteritidis/efeitos dos fármacos , Animais , Anti-Infecciosos Urinários/farmacologia , Contagem de Colônia Microbiana , DNA Bacteriano/análise , Resistência Microbiana a Medicamentos , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica/métodos , Mitomicina/farmacologia , Ácido Nalidíxico/farmacologia , Aves Domésticas/microbiologia , Salmonella enteritidis/crescimento & desenvolvimento , Salmonella enteritidis/ultraestrutura
14.
Br Poult Sci ; 44(4): 567-76, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14584847

RESUMO

1. A readily identifiable strain of Escherichia coli K12 was used as a 'marker' organism to determine the sources, routes and patterns of microbial cross-contamination during mechanical defeathering of broiler chicken carcases. 2. Inoculation of scald water with the marker organism led to a relatively even pattern of carcase contamination during subsequent defeathering. Microbial cross-contamination was greater by this route of inoculation than by either surface inoculation of a 'seeder' carcase or oral inoculation of a live bird one day before slaughter. 3. Dispersal of the marker organism was strongly influenced by the mechanical action of the defeathering machines. Forward transmission of the marker occurred by aerosol or large airborne droplets and particulates such as feathers. Moving carcases through the defeathering machines when these were non-operational clearly reduced backward transmission of the marker. 4. Although microbial dispersal was unaffected by increasing the spacing between individual carcases or installing a water curtain at the entry and exit of the defeathering machines, shielding of carcases with aluminium baffles reduced counts of the marker organism from contaminated carcases by > 90%. 5. The results imply that microbial cross-contamination of broiler chicken carcases during defeathering occurs mainly via the airborne route, which could be contained by physical means.


Assuntos
Microbiologia do Ar , Infecções por Escherichia coli/veterinária , Escherichia coli/isolamento & purificação , Plumas , Doenças das Aves Domésticas/transmissão , Matadouros/normas , Criação de Animais Domésticos , Animais , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/transmissão , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/prevenção & controle , Água
15.
Vet Res Commun ; 27(4): 257-73, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12872826

RESUMO

The ability of the nitrofuran antimicrobial agents furazolidone and furaltadone to prevent, reduce or eliminate Salmonella enterica serovar enteritidis PT4 infection in artificially challenged day-old chicks was evaluated. Treating the birds with the nitrofurans failed to eliminate established infections with either furazolidone-resistant (FzR) or furazolidone-sensitive (FzS) strains. Simultaneous administration of the nitrofurans to day-old chicks challenged with FzS failed to prevent infection but reduced colonization significantly (p<0.05) compared to unmedicated controls. No reduction of colonization occurred with FzR. Challenging birds with FzS and simultaneous dosing with nitrofurans for 1 week, followed by a second week of continued treatment, resulted in an increase in the level of colonization in the second week rather than a decrease. Dosing with the nitrofurans (200 ppm) for 1 week prior to challenge with FzS and continued medication for a further week prevented colonization of the caecum, liver and spleen. However, cessation of dosing at the time of challenge with salmonella resulted in colonization. Chloramphenicol and tetracycline at concentrations of 200 ppm were both independently capable of preventing colonization by salmonella. Sulphadiazine initially reduced colonization but failed to eliminate the infection. Only when furazolidone was combined with chloramphenicol or when sulphadiazine was combined with trimethoprim, and the combined drugs were administered concurrently with the challenge, was colonization prevented.


Assuntos
Antibacterianos/uso terapêutico , Nitrofuranos/uso terapêutico , Salmonelose Animal/tratamento farmacológico , Salmonella enteritidis/fisiologia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Ceco/microbiologia , Galinhas/microbiologia , Esquema de Medicação , Farmacorresistência Bacteriana , Nitrofuranos/administração & dosagem , Nitrofuranos/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/microbiologia , Salmonelose Animal/microbiologia , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/crescimento & desenvolvimento
16.
Br Poult Sci ; 44(1): 53-9, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12737226

RESUMO

1. The extent of cross contamination between carcases and the dispersal of micro-organisms to the environs during defeathering was measured in a commercial processing plant. 2. Defeathering reduced the numbers of a marker organism, a nalidixic acid-resistant strain of Escherichia coli K12, on inoculated carcases but dispersed the organism on to preceding and following carcases. 3. The pattern of microbial dispersal during defeathering was similar for naturally occurring bacteria on the carcase, for example, total aerobic counts and counts of presumptive coliforms, suggesting that the marker organism mimics the natural situation realistically. 4. The majority of feathers, together with micro-organisms, were removed during the first 10 s of the defeathering process, which was completed in 45 s, indicating that control measures to minimise cross contamination would be most effective if applied in the early stages of the process. 5. The method of defeathering used by the machine influenced the pattern of microbial dispersal and the extent of cross contamination to other carcases on the same processing line.


Assuntos
Matadouros , Bactérias Aeróbias/isolamento & purificação , Escherichia coli/isolamento & purificação , Plumas/microbiologia , Plumas/fisiologia , Animais , Galinhas
17.
Avian Pathol ; 31(1): 49-58, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12425792

RESUMO

This study first investigates the effects of mash diet, or mash supplemented with either 2.5% mannose-oligosaccharide (MOS) or palm kernel meal (PKM), on the microflora of the hen caecal contents. Second, it investigates the effect of caecal contents of hens (HCC) fed mash or mash supplemented with MOS or PKM on the major microflora groups of chicks, and their inhibitory effect on Salmonella enterica serovar Enteritidis (PT4) colonization. Finally, this study investigates the effect over time of diets supplemented with MOS or PKM on S. Enteritidis colonization and the microflora of chicks. In hens, supplemented diets increased Bifidobacterium spp., while decreasing members of Enterobacteriaceae and Enterococcus spp., compared with the mash diet. Chicks dosed with the HCC showed, on average, increased numbers of anaerobes, while the numbers of aerobes decreased including coliforms and S. Enteritidis compared with controls without HCC. In chicks fed the MOS-supplemented or PKM-supplemented diets, S. Enteritidis colonization decreased over time, compared with mash alone. Four-week-old PKM birds showed an increase in Bifidobacterium spp. and Lactobacillus spp., with a decrease in S. Enteritidis compared with week 2. Generally, the HCC and diets supplemented with MOS or PKM affected the birds intestinal microflora by increasing the Bifidobacterium spp. and Lactobacillus spp., while decreasing the Enterobacteriaceae groups. They also reduced susceptibility in young chickens to colonization by S. Enteritidis.


Assuntos
Ceco/efeitos dos fármacos , Ceco/microbiologia , Galinhas/microbiologia , Dieta , Mananas/farmacologia , Oligossacarídeos/farmacologia , Salmonella enteritidis/efeitos dos fármacos , Ração Animal , Animais , Suplementos Nutricionais , Feminino , Conteúdo Gastrointestinal/efeitos dos fármacos , Conteúdo Gastrointestinal/microbiologia , Masculino , Mananas/administração & dosagem , Oligossacarídeos/administração & dosagem , Salmonelose Animal/microbiologia , Salmonelose Animal/prevenção & controle , Salmonella enteritidis/citologia , Fatores de Tempo
18.
Neuroscience ; 114(3): 715-29, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12220573

RESUMO

Sheep form an olfactory recognition memory for their lambs within 2 h of parturition and will subsequently reject the approaches of any strange lamb and protest vocally. In this study we report that following olfactory memory formation, ewes exposed to either their own or a strange lamb show c-fos mRNA expression in the medial frontal cortex, although levels of expression in the pyramidal output cell layer V were significantly higher in ewes that rejected strange lambs. Reversibly inactivating this region by the retrodialysis of the anaesthetic tetracaine before birth reduced aggressive motor responses towards lambs but not protest vocalisations. Similar treatment during the critical period for olfactory memory formation and lamb recognition (0-4 h post-partum) had no effect on ewes maternal behaviour towards their own lambs. It did, however, prevent the normal selective expression of aggressive rejection, and reduced protest vocalisation behaviours directed towards strange lambs. These rejection behaviours did appear 1 h after the termination of tetracaine infusions despite the ewes not being given the opportunity to interact with their own lambs during this time. Therefore, tetracaine blockade of the medial frontal cortex prevents animals from responding with motor aggression, but not vocal aggression, to odour cues from strange lambs, but has no effect on the formation of an olfactory recognition memory for their own lambs. Both pre- and post-partum aggressive rejection of strange lambs was associated with increased concentrations of dopamine, serotonin, glutamate and GABA. When these behaviours were inhibited by the tetracaine infusions, extracellular concentrations of these neurotransmitters were all increased by the anaesthetic but did not change in response to lambs. These findings suggest that a functional medial frontal cortex is not required for the formation of an olfactory recognition memory or for mediating pro-active maternal behaviours. It is however required for the mediation of motor but not vocal aspects of aggressive rejection responses directed towards aversive odour cues from strange lambs.


Assuntos
Sinais (Psicologia) , Comportamento Materno/fisiologia , Córtex Pré-Frontal/metabolismo , Reconhecimento Psicológico/fisiologia , Olfato/fisiologia , Animais , Animais Recém-Nascidos , Animais Lactentes/fisiologia , Feminino , Comportamento Materno/efeitos dos fármacos , Comportamento Materno/psicologia , Córtex Pré-Frontal/efeitos dos fármacos , Gravidez , Proteínas Proto-Oncogênicas c-fos/biossíntese , RNA Mensageiro/biossíntese , Reconhecimento Psicológico/efeitos dos fármacos , Ovinos , Olfato/efeitos dos fármacos
19.
J Food Prot ; 65(1): 41-9, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11808804

RESUMO

Two series of experiments were carried out to investigate methods of reducing contamination of lamb carcasses in low-throughput abattoirs, where cradle dressing is normally employed. In the first series, cradle design and pelt removal procedure were investigated, and a method was developed for assessing gross visible contamination. Significant improvements in microbiological and gross visible contamination (P < 0.01) were achieved by procedural changes only; modifications to the cradle design had no effect. In the second series of experiments, two improved methods of pelt removal and the effect of hand washing prior to carcass contact during the pelt removal procedure were investigated. The improved methods comprised a Frame system, in which the pelt was removed in a manner similar to that in a high-throughput inverted line, and a Hybrid system, in which the pelt was removed from the forequarters on a conventional cradle before the carcass was suspended in an "inverted" vertical position for removal of the pelt from the abdomen and hindquarters. The results of microbiological and gross visible contamination from these methods, with and without hand washing, were compared with the conventional Cradle method of pelt removal. Both the Hybrid and Frame systems had significantly less microbiological and gross visible contamination (P < 0.01). However, hand washing had no significant effect on the level of carcass contamination for all three methods of pelt removal. Greatest reductions in microbiological and gross visible contamination were achieved using techniques that minimized hand contact with the carcass during pelt removal by adoption of inverted dressing procedures. Equipment redesign did not reduce carcass contamination.


Assuntos
Matadouros/normas , Contaminação de Alimentos/prevenção & controle , Manipulação de Alimentos/métodos , Ovinos/microbiologia , Animais , Contagem de Colônia Microbiana , Desinfecção , Contaminação de Equipamentos , Desinfecção das Mãos , Humanos , Higiene
20.
Nature ; 414(6860): 165-6, 2001 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-11700543

RESUMO

The human brain has evolved specialized neural mechanisms for visual recognition of faces, which afford us a remarkable ability to discriminate between, remember and think about many hundreds of different individuals. Sheep also recognize and are attracted to individual sheep and humans by their faces, as they possess similar specialized neural systems in the temporal and frontal lobes for assisting in this important social task, including a greater involvement of the right brain hemisphere. Here we show that individual sheep can remember 50 other different sheep faces for over 2 years, and that the specialized neural circuits involved maintain selective encoding of individual sheep and human faces even after long periods of separation.


Assuntos
Face , Memória/fisiologia , Ovinos/fisiologia , Percepção Visual/fisiologia , Animais , Humanos , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Fatores de Tempo
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