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1.
BMC Biol ; 22(1): 160, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075472

RESUMO

BACKGROUND: Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown. RESULTS: We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite. CONCLUSIONS: Our results highlight the key role of keratinocytes in coho salmon's sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.


Assuntos
Copépodes , Doenças dos Peixes , Hiperplasia , Queratinócitos , Oncorhynchus kisutch , Salmo salar , Animais , Copépodes/fisiologia , Doenças dos Peixes/parasitologia , Salmo salar/parasitologia , Hiperplasia/veterinária , Queratinócitos/parasitologia , Resistência à Doença/genética , Interações Hospedeiro-Parasita
2.
Epidemiol Infect ; 149: e13, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33413718

RESUMO

Only studies in the UK on individuals dying from coronavirus disease 2019 (COVID-19) in hospital have been published, to date. Cremation law requires collection of clinical information that can improve understanding of deaths in both hospital and community settings. Age, sex, date and place of death, occupation, comorbidities and where infection acquired was recorded for all deaths from COVID-19, between 6 April and 30 May, for whom an application was made for cremation at a South Wales' crematorium. Of 752 cremations, 215 (28.6%) were COVID-19 (115 (53.5%) male and 100 (46.5%) female). Median age was 82 years (youngest patient 47 and the oldest 103 years). Over half the deaths (121/215: 56.3%) were over 80 years. Males' odds of dying in hospital, rather than the community were 1.96 times that of females (95% confidence intervals (CI) 1.03-3.74, P = 0.054) despite being of similar age and having a similar number of comorbidities. Only 21 (9.8%) of 215 patients had no comorbidities recorded. Patients dying in care homes were significantly older than those dying in hospital (median 88 years (interquartile (IQ) range 82-93 years) vs. 80 years (IQ range 71-87 years): P < 0.0001). Patients dying in hospital had significantly more comorbidities than those dying in care homes (median 2: IQ range 1-3 vs. 1: IQ range 1-2: P < 0.001). Sixty three (29.3%) of infections were hospital acquired and a further 55 (25.6%) acquired in care homes. In a series, of hospital and community deaths, persons over 80 with an average two comorbidities predominated. Men were more likely to die in hospital. Half the infections were acquired in hospitals or care homes with implications for management of the pandemic.


Assuntos
COVID-19/mortalidade , Cremação/estatística & dados numéricos , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia
3.
Fish Shellfish Immunol ; 107(Pt A): 43-53, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011432

RESUMO

Atypical Aeromonas salmonicida (aAs) and Vibrionaceae related species are bacteria routinely recovered from diseased ballan wrasse used as cleaner fish in the Atlantic salmon farming industry. Autogenous (i.e. farm specific inactivated) multivalent vaccines formulated from these microorganisms are widely used to protect farmed wrasse despite limited experimental proof that they are primary pathogens. In this study, the components of a commercial multivalent injection vaccine containing four strains of Aeromonas salmonicida and one strain of Vibrio splendidus previously isolated from ballan wrasse in Scotland, were tested for infectivity, pathogenicity and virulence via intra peritoneal injection at pre-deployment size (25-50 g) and the efficacy of the vaccine for protection against aAs assessed. Injection with 3.5 × 109, 8 × 109 1.8 × 109 and 5 × 109 cfu/fish of Vibrio splendidus, V. ichthyoenteri, Aliivibrio logeii and A. salmonicida, respectively, did not cause significant mortalities, lesions or clinical signs after a period of 14 days. IP injection with both aAs and Photobacterium indicum successfully reproduced the clinical signs and internal lesions observed during natural outbreaks of the disease. Differences in virulence (LD50 at day 8-post infection of 3.6 × 106 cfu/fish and 1.6 × 107 cfu/fish) were observed for two aAs vapA type V isolates. In addition, the LD50 for Photobacterium indicum was 2.2 × 107 cfu/fish. The autogenous vaccine was highly protective against the two aAs vapA type V isolates after 700-degree days of immunisation. The RPSFINAL values for the first isolate were 95 and 91% at 1 × 106 cfu/fish and 1 × 107 cfu/fish, respectively, and 79% at 1 × 107 cfu/fish for the second isolate tested. In addition, significantly higher anti aAs seral antibodies (IgM), were detected by ELISA in vaccinated fish in contrast with control (mock vaccinated) fish. These results suggest wrasse can be effectively immunised and protected against aAs infection by injection with oil adjuvanted vaccines prepared with inactivated homologous isolates.


Assuntos
Autovacinas/administração & dosagem , Doenças dos Peixes/imunologia , Peixes/imunologia , Vacinação/veterinária , Aeromonas salmonicida/fisiologia , Animais , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Escócia , Vibrionaceae/fisiologia
4.
Dis Aquat Organ ; 140: 47-54, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32614330

RESUMO

Healthy and/or moribund farmed and wild ballan wrasse Labrus bergylta (>0.5 to 900 g) were sampled from hatcheries (n = 2) and Atlantic salmon Salmo salar cage sites (n = 8) in Scotland between February 2016 and October 2018. Less than half of the sampled individuals (n = 43; 32.3%) had been vaccinated (autogenous polyvalent vaccine; dip and/or injection) against atypical furunculosis (type V and VI), while 20 (15.0%) fish were not vaccinated, and the rest (70 individuals, 52.7%) were of unknown vaccination status. Swab samples from skin lesions, gill, liver, spleen and kidney were inoculated onto a variety of bacteriological agar plates, and bacteriology identification and sequencing analysis was performed on significant bacterial colonies. Atypical Aeromonas salmonicida (aAs) vapA type V was the predominant bacterial species (70/215 bacterial isolates, 32.5% of bacterial samples; 43/117 positive individual fish, 36.8%) isolated in this survey followed by Vibrio species, which were the most geographically prevalent bacteria. Photobacterium indicum/profundum was also isolated from L. bergylta for the first time during this study. The collection of these bacterial isolates provides useful information for disease management. Identifying the aAs isolates involved in disease in ballan wrasse could provide vital information for improving/updating existing autogenous vaccines.


Assuntos
Aeromonas salmonicida , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas/veterinária , Perciformes , Vibrioses/veterinária , Vibrio , Animais , Photobacterium , Escócia
5.
J Appl Microbiol ; 125(3): 686-699, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29777634

RESUMO

AIMS: The aims of the current study were to characterize the outer membrane proteins (OMPs) of Francisella noatunensis subsp. orientalis (Fno) STIR-GUS-F2f7, and identify proteins recognized by sera from tilapia, Oreochromis niloticus, (L) that survived experimental challenge with Fno. METHODS AND RESULTS: The composition of the OMPs of a virulent strain of Fno (STIR-GUS-F2f7), isolated from diseased red Nile tilapia in the United Kingdom, was examined. The sarcosine-insoluble OMPs fraction was screened with tilapia hyperimmune sera by western blot analysis following separation of the proteins by 1D SDS-PAGE. Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was used to identify the various proteins present in the OMP profile. Two hundred and thirty-nine proteins were identified, of which 44 were found in the immunogenic band recognized by the tilapia hyperimmune serum. In silico analysis was performed to predict the function and location of the OMPs identified by MS. CONCLUSIONS: Using a powerful proteomic-based approach in conjugation with western immunoblotting, proteins comprising the outer membrane fraction of Fno STIR-GUS-F2f7 were identified, catalogued and screened for immune recognition by tilapia sera. SIGNIFICANCE AND IMPACT OF THE STUDY: The current study is the first report on the characterization of Fno-OMPs. The findings here provide preliminary data on bacterial surface proteins that exist in direct contact with the host's immune defences during infection and offer an insight into the pathogenesis of Fno.


Assuntos
Proteínas da Membrana Bacteriana Externa , Francisella , Proteoma , Animais , Proteínas da Membrana Bacteriana Externa/análise , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/classificação , Ciclídeos/microbiologia , Doenças dos Peixes/microbiologia , Francisella/química , Francisella/patogenicidade , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Proteoma/análise , Proteoma/química , Proteoma/classificação , Tilápia/microbiologia
6.
J Fish Dis ; 41(9): 1359-1372, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29882595

RESUMO

In vitro cell culture methods are crucial for the isolation, purification and mass propagation of intracellular pathogens of aquatic organisms. Cell culture infection models can yield insights into infection mechanisms, aid in developing methods for disease mitigation and prevention, and inform commercial-scale cultivation approaches. This study details the establishment of a larval cell line (GML-5) from the Atlantic cod (Gadus morhua) and its use in the study of microsporidia. GML-5 has survived over 100 passages in 8 years of culture. The line remains active and viable between 8 and 21°C in Leibovitz-15 (L-15) media with 10% foetal bovine serum and exhibits a myofibroblast phenotype as indicated by immuno-positive results for vimentin, α-smooth muscle actin, collagen I and S-100 proteins, while being desmin-negative. GML-5 supports the infection and development of two microsporidian parasites, an opportunistic generalist (Anncaliia algerae) and cod-specific Loma morhua. Using GML-5, spore germination and proliferation of L. morhua was found to require exposure to basic pH and cool incubation temperatures (8°C), in contrast to A. algerae, which required no cultural modifications. Loma morhua-associated xenoma-like structures were observed 2 weeks postexposure. This in vitro infection model may serve as a valuable tool for cod parasitology and aquaculture research.


Assuntos
Linhagem Celular/microbiologia , Gadus morhua/microbiologia , Larva/citologia , Larva/microbiologia , Loma/fisiologia , Técnicas de Cultura de Tecidos , Animais , Aquicultura , Técnicas de Cultura de Células/veterinária , Linhagem Celular/citologia , Meios de Cultura/química , Doenças dos Peixes/microbiologia , Gadus morhua/fisiologia , Brânquias/microbiologia , Microsporidiose/veterinária , Miofibroblastos/microbiologia
7.
J Fish Dis ; 40(8): 1041-1054, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28025825

RESUMO

Cyprinid herpesvirus 3 (CyHV-3) is an alloherpesvirus, and it is the aetiological agent of koi herpesvirus disease. Although the complex morphogenic stages of the replication cycle of CyHV-3 were shown to resemble that of other members of the Herpesvirales, detailed analysis of the sequence and timing of these events was not definitively determined. This study describes these features through a time course using cyprinid cell cultures (KF-1 and CCB) infected with CyHV-3 (KHV isolate, H361) and analysed by transmission electron microscopy. Rapid viral entry was noted, with high levels of intracellular virus within 1-4 h post-infection (hpi). Intranuclear capsid assembly, paracrystalline array formation and primary envelopment of capsids occurred within 4 hpi. Between 1 and 3 days post-infection (dpi), intracytoplasmic secondary envelopment occurred, as well as budding of infectious virions at the plasma membrane. At 5-7 dpi, the cytoplasm contained cytopathic vacuoles, enveloped virions within vesicles, and abundant non-enveloped capsids; also there was frequent nuclear deformation. Several morphological features are suggestive of inefficient viral assembly, with production of non-infectious particles, particularly in KF-1 cells. The timing of this alloherpesvirus morphogenesis is similar to other members of the Herpesvirales, but there may be possible implications of using different cell lines for CyHV-3 propagation.


Assuntos
Infecções por Vírus de DNA/patologia , Vírus de DNA/crescimento & desenvolvimento , Doenças dos Peixes/patologia , Animais , Carpas , Linhagem Celular , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/virologia , Doenças dos Peixes/virologia , Microscopia Eletrônica de Transmissão/veterinária , Morfogênese
8.
J Fish Dis ; 40(11): 1511-1527, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28470973

RESUMO

Koi herpesvirus (KHV) causes KHV disease (KHVD). The virus is highly contagious in carp or koi and can induce a high mortality. Latency and, in some cases, a lack of signs presents a challenge for virus detection. Appropriate immunological detection methods for anti-KHV antibodies have not yet been fully validated for KHV. Therefore, it was developed and validated an enzyme-linked immunosorbent assay (ELISA) to detect KHV antibodies. The assay was optimized with respect to plates, buffers, antigens and assay conditions. It demonstrated high diagnostic and analytical sensitivity and specificity and was particularly useful at the pond or farm levels. Considering the scale of the carp and koi industry worldwide, this assay represents an important practical tool for the indirect detection of KHV, also in the absence of clinical signs.


Assuntos
Anticorpos Antivirais/isolamento & purificação , Carpas , Ensaio de Imunoadsorção Enzimática/veterinária , Doenças dos Peixes/imunologia , Infecções por Herpesviridae/veterinária , Herpesviridae/isolamento & purificação , Animais , Ensaio de Imunoadsorção Enzimática/métodos , Doenças dos Peixes/virologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia
9.
J Fish Dis ; 38(5): 477-89, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24925228

RESUMO

Koi herpesvirus (KHV) causes a highly infectious disease afflicting common carp and koi, Cyprinus carpio L. Various molecular and antibody-based detection methods have been used to elucidate the rapid attachment and dissemination of the virus throughout carp tissues, facilitating ongoing development of effective diagnostic approaches. In situ hybridization (ISH) was used here to determine the target tissues of KHV during very early infection, after infecting carp with a highly virulent KHV isolate. Analysis of paraffin-embedded tissues (i.e. gills, skin, spleen, kidney, gut, liver and brain) during the first 8 h and following 10 days post-infection (hpi; dpi) revealed positive signals in skin mucus, gills and gut sections after only 1 hpi. Respiratory epithelial cells were positive as early as 2 hpi. Viral DNA was also detected within blood vessels of various tissues early in the infection. Notable increases in signal abundance were observed in the gills and kidney between 5 and 10 dpi, and viral DNA was detected in all tissues except brain. This study suggests that the gills and gut play an important role in the early pathogenesis of this Alloherpesvirus, in addition to skin, and demonstrates ISH as a useful diagnostic tool for confirmation of acutely infected carp.


Assuntos
Doenças dos Peixes/diagnóstico , Doenças dos Peixes/patologia , Infecções por Herpesviridae/veterinária , Animais , Carpas , DNA Viral/análise , Células Epiteliais/patologia , Células Epiteliais/virologia , Doenças dos Peixes/virologia , Brânquias/patologia , Brânquias/virologia , Herpesviridae , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/virologia , Hibridização In Situ , Intestinos/virologia , Muco/virologia
10.
J Fish Dis ; 38(3): 303-19, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24547985

RESUMO

Koi herpesvirus (KHV) causes an economically important, highly infectious disease in common carp and koi, Cyprinus carpio L. Since the occurrence of mass mortalities worldwide, highly specific and sensitive molecular diagnostic methods have been developed for KHV detection. The sensitivity and reliability of these assays have essentially focused at the detection of low viral DNA copy numbers during latent or persistent infections. However, the efficacy of these assays has not been investigated with regard to low-level viraemia during acute infection stages. This study was conducted to compare the sensitivity of seven different polymerase chain reaction (PCR) assays to detect KHV during the first hours and days post-infection (hpi; dpi), using lethal and non-lethal sampling methods. The results highlight the limitations of the assays for detecting virus during the first 4 dpi despite rapid mortality in experimentally infected carp. False-negative results were associated with time post-infection and the tissue sampled. Non-lethal sampling appears effective for KHV screening, with efficient detection in mucus samples obtained from external swabs during this early infection period (<5 dpi), while biopsies from gills and kidney were negative using the same PCR assays. Non-lethal sampling may improve the reliability of KHV detection in subclinical, acutely infected carp.


Assuntos
Carpas , Doenças dos Peixes/diagnóstico , Infecções por Herpesviridae/veterinária , Reação em Cadeia da Polimerase/veterinária , Animais , Brânquias/virologia , Herpesviridae/genética , Rim/virologia , Muco/virologia , Reação em Cadeia da Polimerase/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Public Health ; 123(1): e21-3, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19135694

RESUMO

Devolution in the UK has, inadvertently, provided a natural experiment for comparing the impact of different approaches to policy and practice on populations that are broadly similar by most criteria. Realizing the potential gold mine that this presents for comparing policy and practice in the field of public health, the UK Public Health Association has established a Devolution Strategic Interest Group to explore and capitalize on this. From the start, the Group has included the Republic of Ireland in its purview to add an extra dimension of diversity and innovation. Having previously looked at the organization of health care and public health, and at policy and practice on food, nutrition and obesity, the Group opted to look at transport and health this year. Here, the links between separate relevant policy streams are less obvious and clearly less developed than those for food, nutrition and obesity. Also, the perceived need to raise the issue up the public health agenda provides a new challenge to campaigning action for the Group.


Assuntos
Saúde Pública , Meios de Transporte , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Humanos , Formulação de Políticas , Reino Unido
12.
Phytopathology ; 98(1): 69-78, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18943240

RESUMO

ABSTRACT Over 4 years, the environmental conditions and the causal agents of Fusarium head blight (FHB) disease of wheat were determined in field sites in four European countries: Hungary, Ireland, Italy, and the United Kingdom. Polymerase chain reaction-based methods were used to detect each species causing FHB and quantify its DNA (as a measurement of fungal abundance) in the samples. Canonical correspondence analysis (CCA) was used to determine the relationship of the incidence and abundance of each species with weather variables. CCA indicated that little variability in the species prevalence data was explained by the weather variables. In contrast, a greater proportion of variability in abundance data was accounted for by the weather variables. Most samples contained two or more species and statistical analysis suggested that these species tended to coexist at field sites. CCA also indicated that there were differences in the relationships of the prevalence and abundance of the six FHB species with environmental variables. Fusarium poae was associated with relatively drier and warmer conditions, whereas F. graminearum was associated with warmer/humid conditions. F. avenaceum and F. culmorum were both associated with niches of cooler/wet/humid conditions. Two Microdochium species were associated with regions of relatively cool/moderate temperatures and frequent rainfalls of short duration. The results also suggested that environmental conditions differentially affect the infection and colonization processes, and the comparative abundance of the six species.


Assuntos
Ascomicetos/fisiologia , Meio Ambiente , Fusarium/fisiologia , Doenças das Plantas/microbiologia , Triticum/microbiologia , Interações Hospedeiro-Patógeno
13.
Ir J Med Sci ; 186(4): 981-987, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27796667

RESUMO

BACKGROUND: Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically ß1 (CD29) and ß2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. METHODS: T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (ß2) and CD29 (ß1) on CD3+ T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. RESULTS: CD18 was almost ubiquitously expressed on CD3+ T cells irrespective of clinical condition. However, CD29 (ß1 integrin) was lowest in SIRS patients (20.4% of CD3+ T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3+CD29+ T cells (41.7%) when compared with those with non-abdominal sources (29.5%). CONCLUSION: Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.


Assuntos
Integrinas/metabolismo , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue , Linfócitos T/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Leukemia ; 31(10): 2122-2131, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28057939

RESUMO

Janus tyrosine kinase 2 (JAK2) mediates downstream signaling of cytokine receptors in all hematological lineages, yet constitutively active JAK2 mutants are able to drive selective expansion of particular lineage(s) in myeloproliferative neoplasm (MPN). The molecular basis of lineage specificity is unclear. Here, we show that three activating JAK2 mutants with similar kinase activities in vitro elicit distinctive MPN phenotypes in mice by differentially expanding erythroid vs granulocytic precursors. Molecularly, this reflects the differential binding of JAK2 mutants to cytokine receptors EpoR and GCSFR in the erythroid vs granulocytic lineage and the creation of unique receptor/JAK2 complexes that generate qualitatively distinct downstream signals. Our results demonstrate that activating JAK2 mutants can differentially couple to selective cytokine receptors and change the signaling repertoire, revealing the molecular basis for phenotypic differences elicited by JAK2 (V617F) or mutations in exon 12. On the basis of these findings, receptor-JAK2 interactions could represent new targets of lineage-specific therapeutic approaches against MPN, which may be applicable to other cancers with aberrant JAK-STAT signaling.


Assuntos
Eritropoese/fisiologia , Janus Quinase 2/genética , Mutação de Sentido Incorreto , Mielopoese/fisiologia , Transtornos Mieloproliferativos/genética , Mutação Puntual , Receptores da Eritropoetina/metabolismo , Receptores de Fator Estimulador de Colônias de Granulócitos/metabolismo , Animais , Divisão Celular , Linhagem Celular , Linhagem da Célula , Ativação Enzimática/genética , Eritropoese/genética , Éxons/genética , Genes Reporter , Células-Tronco Hematopoéticas/patologia , Humanos , Janus Quinase 2/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Mielopoese/genética , Transtornos Mieloproliferativos/enzimologia , Fenótipo , Mapeamento de Interação de Proteínas , Quimera por Radiação , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Transdução Genética , Ensaio Tumoral de Célula-Tronco
15.
J Clin Endocrinol Metab ; 84(7): 2402-7, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10404811

RESUMO

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17beta-estradiol (50 microg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17beta-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.


Assuntos
Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Insulina/farmacologia , Noretindrona/efeitos adversos , Pós-Menopausa , Administração Cutânea , Adulto , Glicemia/análise , Método Duplo-Cego , Estradiol/administração & dosagem , Estradiol/sangue , Feminino , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Lipídeos/sangue , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/uso terapêutico , Placebos
16.
Br J Pharmacol ; 99(1): 77-86, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-1970495

RESUMO

1. The effects of an endothelium-dependent (acetylcholine) and an endothelium-independent (sodium nitroprusside) relaxant against noradrenaline-induced contractions were compared in three isolated superficial blood vessels of the rabbit, the lateral saphenous vein, plantaris vein and distal saphenous artery. Both produced concentration-related relaxations of all three vessels and were more effective against submaximal than maximal contractions to noradrenaline. Transient contractions to high concentration of acetylcholine occurred only in endothelium-intact preparations of saphenous vein and were inhibited by flurbiprofen. 2. In endothelium-denuded preparations sodium nitroprusside was 3 times more effective than in endothelium-intact preparations, while acetylcholine (less than 3 microM) was inactive. Sensitivity was similar for each relaxant: lateral saphenous vein greater than or equal to plantaris vein greater than distal saphenous artery. The similar profile of sodium nitroprusside and acetylcholine suggests that differences in susceptibility to endothelium-derived relaxing factor (EDRF) are caused by inter-vessel variations in the excitation-coupling process for noradrenaline. 3. Haemoglobin inhibited acetylcholine-induced relaxations in the endothelium-intact preparation of the lateral saphenous vein and distal saphenous artery, which suggests a similar EDRF in each preparation and the likelihood that this is a single substance, presumably nitric oxide. 4. The influence of basal, spontaneously released EDRF on alpha-adrenoceptor function was tested either by mechanical disruption of the endothelium or by adding haemoglobin to endothelium-intact segments. Endothelial disruption slightly reduced contractions to noradrenaline (NA) in distal saphenous artery but increased response size of lateral saphenous and plantaris veins, in the latter also increasing sensitivity to NA: haemoglobin mimicked endothelial disruption. Thus, basal release of EDRF like acetylcholine and nitroprusside was more effective in the veins than in the corresponding artery. 5. In lateral saphenous vein responses to phenylephrine were enhanced by endothelial disruption, but without change in sensitivity: responses to UK-14304, B-HT 920 and cirazoline, which had a relatively slow speed of onset of contraction were not affected. There was no correlation between enhancement and alpha-adrenoceptor sub-type although the agonists which were enhanced all activate alpha 1-adrenoceptors. Competitive antagonists failed to reveal an alpha-adrenoceptor subtype enhanced by endothelial disruption. However, effects of phenoxybenzamine suggest that alpha 1-adrenoceptors are necessary for the influence of basal EDRF.


Assuntos
Acetilcolina/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Animais , Artérias/efeitos dos fármacos , Artérias/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Flurbiprofeno/farmacologia , Hemoglobinas/metabolismo , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Nitroprussiato/farmacologia , Coelhos , Veia Safena/efeitos dos fármacos , Veias/efeitos dos fármacos , Veias/metabolismo
17.
Placenta ; 17(1): 75-86, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8710816

RESUMO

Trophoblast binucleate cells (BNC) in the ruminant placenta demonstrate a characteristic development, mature structure and migratory capacity whether situated in cotyledonary or intercotyledonary regions of the placenta. However, previous immunocytochemical studies demonstrated clear differences in gene expression in granule contents of BNC according to their anatomical location with some proteins being expressed in all BNC (e.g. ovine placental lactogen) whereas others were unique to a particular origin (e.g. SBU3 antigen in cotyledonary BNC only). We have used enriched preparations of binucleate cells and showed differences in steroid metabolic capacity in vitro which is more related to their species origin (sheep or goat) than to their anatomical location. The predominant product from [3H]pregnenolone is progesterone (sheep) and 5 beta-pregnane-3 alpha, 20 alpha-diol (goat) and the amount formed (corrected for the number of BNC) is similar irrespective of whether BNC were derived from the cotyledonary or intercotyledonary regions. These studies indicate specific forms of regional functional specialization of BNC and emphasize their multifunctional role in the ruminant placenta.


Assuntos
Cabras/fisiologia , Placenta/fisiologia , Ovinos/fisiologia , Trofoblastos/ultraestrutura , Animais , Núcleo Celular/ultraestrutura , Feminino , Indometacina/farmacologia , Leucócitos/metabolismo , Microscopia Eletrônica , Placenta/ultraestrutura , Gravidez , Pregnanodiol/metabolismo , Pregnenolona/metabolismo , Progesterona/metabolismo , Análise de Regressão
18.
Environ Health Perspect ; 107(6): 459-62, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10339445

RESUMO

Reports of environmental problems in the former Soviet Union, including excess use of pesticides, have led to concerns about high levels of contamination in humans, but little information is available to assess whether these concerns are warranted. Samples of breast milk from 197 women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, ss-hexachlorocyclohexane (HCH), and 18 polychlorinated biphenyl congeners, and results were compared to previous reports from Europe. The median ss-HCH concentration was 731 ng/g milk fat, which is higher than other reports from Europe but lower than reports from other parts of the world. The median DDE concentration was 2,457 ng/g milk fat, which is higher than most but not all other reports from Europe. Concentrations of other chemicals were comparable to or lower than other reports from Europe. Concentrations from the city of Kyiv were generally lower than those from Dniprodzerzhinsk, but the magnitudes of these differences were modest.


Assuntos
Hidrocarbonetos Clorados/análise , Leite Humano/química , Adulto , Envelhecimento/metabolismo , Gorduras/análise , Feminino , Humanos , Inseticidas/análise , Bifenilos Policlorados/análise , Ucrânia/epidemiologia , População Urbana
19.
Obstet Gynecol ; 95(5): 752-5, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10775742

RESUMO

OBJECTIVE: To determine whether the preterm birth rate was elevated in two urban areas of Ukraine, a former eastern bloc country that experienced serious economic, social, and health problems during its transition from a socialist republic. METHODS: We identified every pregnancy in a defined period in two urban sites where a separate study of pregnancy and childhood was being conducted. We obtained gestational age and vital status at delivery for each. Information about onset of labor and conduct of delivery was available for the subgroup enrolled in the collaborating study. RESULTS: Among 17,137 pregnancies, all but 6774 were terminated voluntarily. Among the continuing pregnancies, the preterm birth rate was 6.6% for live-born singletons of 20 or more weeks' gestation. Only 12% of preterm births involved medical intervention, the rest were idiopathic. The preterm birth rate was higher than in Europe (4.0% to 5.4%) and Canada (5.9%) but lower than for whites in the United States (8.4%). CONCLUSION: Live-born preterm birth rates are influenced by whether infants survive to be included in calculations. The high fetal mortality rate in Ukraine causes many preterm births to be excluded, thus lowering the rate. Frequent pregnancy termination and lack of ultrasound dating in Ukraine also might cause the preterm birth rate to be lower. Preterm birth rates, especially among live-born infants, are difficult to interpret and treacherous to compare across nations. Survival of the fetus and its health and development at birth are better indicators of reproductive outcome.


Assuntos
Mortalidade Infantil , Trabalho de Parto Prematuro/epidemiologia , Saúde da População Urbana/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Gravidez , Ucrânia/epidemiologia
20.
Soc Sci Med ; 30(3): 289-95, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2309126

RESUMO

This paper reports the results of 10 years of research into the prenatal identification of mothers likely to have major parenting problems. Previous published research reported the development of a set of criteria for determining risk status. These criteria were used to classify into four levels of risk a sample of mothers who were consecutive enrollments for prenatal care. The sample was monitored through various social agencies for 2 years. Results of this monitoring indicate the predictive validity of the risk code in an unselected sample. The value of prenatal identification of the 'at risk' is discussed together with the procedures adopted for implementing routine screening in the maternity hospital. The issue of causation, as distinct from prediction, is addressed.


Assuntos
Maus-Tratos Infantis/prevenção & controle , Programas de Rastreamento , Mães/psicologia , Criança , Enfermagem em Saúde Comunitária , Feminino , Humanos , Lactente , Nova Zelândia , Gravidez , Cuidado Pré-Natal/psicologia , Análise de Regressão , Fatores de Risco , Pais Solteiros/psicologia
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