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1.
Emerg Infect Dis ; 30(6): 1240-1244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782018

RESUMO

A 2022 canine gastroenteritis outbreak in the United Kingdom was associated with circulation of a new canine enteric coronavirus closely related to a 2020 variant with an additional spike gene recombination. The variants are unrelated to canine enteric coronavirus-like viruses associated with human disease but represent a model for coronavirus population adaptation.


Assuntos
Infecções por Coronavirus , Surtos de Doenças , Doenças do Cão , Gastroenterite , Filogenia , Animais , Cães , Surtos de Doenças/veterinária , Doenças do Cão/virologia , Doenças do Cão/epidemiologia , Reino Unido/epidemiologia , Gastroenterite/virologia , Gastroenterite/epidemiologia , Gastroenterite/veterinária , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavirus Canino/genética , Coronavirus Canino/classificação , Humanos , Glicoproteína da Espícula de Coronavírus/genética
2.
J Small Anim Pract ; 65(6): 361-367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38441325

RESUMO

OBJECTIVES: To use text mining approaches to identify instances of suspected adverse drug reactions recorded in first opinion veterinary free-text clinical narratives, and to evaluate whether these were also reported to either the Veterinary Medicines Directorate or the relevant Marketing Authorisation holder in order to derive an estimate of the suspected adverse drug reaction (sADR) minimum under-reporting rate. To characterise sADR reports and explore whether particular features are associated with report submission. MATERIALS AND METHODS: Two regular expressions were developed to identify mentions of "adverse drug reactions" and "side effects" in the free-text clinical narratives of electronic health records contained within the Small Animal Veterinary Surveillance Network database. Consultations containing a match for the developed regular expressions were manually reviewed for inclusion and further classified to determine the suspected product, seriousness and expectedness of the event, and an indication of whether the event had been reported. The associations between event characteristics and reporting were explored using Fisher's exact tests. RESULTS: A total of 10,565 records were manually reviewed from which 827 sADRs were identified. Approximately 90% of these sADRs were not recorded as reported. Suspected adverse drug reactions that were not considered "expected" were recorded as reported more frequently than "expected" sADRs. However, clinical severity did not appear to impact on whether there was a record of reporting. CLINICAL SIGNIFICANCE: This is the first estimate of under reporting sADRs based on real world evidence from veterinary clinical records. The under-reporting rate implied by this study highlights that further interventions are required to improve reporting rate within the veterinary profession in order to support pharmacovigilance activities and improve drug safety.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/veterinária , Mineração de Dados , Drogas Veterinárias/efeitos adversos , Registros Eletrônicos de Saúde , Medicina Veterinária , Farmacovigilância
4.
Prev Vet Med ; 197: 105499, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34583207

RESUMO

Grass seed foreign bodies (GSFBs) are a familiar presentation, especially in dogs, associated with a variety of clinical signs depending on site of penetration and extent of migration. Seasonality and risk factors for GSFB occurrence were investigated using electronic health records from a sentinel voluntary network of 245 veterinary practices in the United Kingdom between 17th March 2014 and 18th September 2020. Clinical narrative text mining of 4,580,503 canine consultations produced a final case dataset of 1,037 consultations where GSFBs had been recorded in individual dogs. Cases of GSFBs were recorded in all months, with 940 (90.6 %) recorded between June and September. In particular, the odds of GSFBs in July was almost 176 times more than that of January (Odds ratio, OR, 175.6, 95 % Confidence interval, CI, 43.5-707.7, P < 0.001). Compared to the retriever breed type, spaniel breed types were 7.7 times more likely to present with a GSFB (CI 5.4-11.0, P < 0.001). Other significant risk factors associated with recorded GSFBs for this population included being male (OR = 1.4, CI 1.2-1.6, P < 0.001), and geographical location. When compared to the South East of England, risk was lowest in Wales (OR = 0.1, CI 0.0-0.3, P=<0.001), and highest in the East of England (OR = 1.9, 1.2-2.9, P = 0.003), and overall risk in urban areas was reduced (OR = 0.8, CI 0.7-1.0, P = 0.024). These observations provide a number of areas for temporally targeted health campaigns at specific types of dogs, to reduce the impact of GSFBs on canine welfare.


Assuntos
Doenças do Cão , Corpos Estranhos , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/etiologia , Cães , Corpos Estranhos/veterinária , Melhoramento Vegetal , Poaceae , Fatores de Risco , Sementes
5.
Front Microbiol ; 12: 700698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394045

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data. OBJECTIVES: We aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories. METHODS: We summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites. RESULTS: Escherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7-70.0) and cats (90.5%, CI 89.8-91.3). Multi-drug resistance was reported in 14.1% (CI 13.5-14.8) of canine and 12.0% (CI 11.1-12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2-3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum ß-lactamase gene bla CTX-M- 15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals. CONCLUSIONS: Linking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.

6.
Emerg Infect Dis ; 27(2): 517-528, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33496240

RESUMO

The lack of population health surveillance for companion animal populations leaves them vulnerable to the effects of novel diseases without means of early detection. We present evidence on the effectiveness of a system that enabled early detection and rapid response a canine gastroenteritis outbreak in the United Kingdom. In January 2020, prolific vomiting among dogs was sporadically reported in the United Kingdom. Electronic health records from a nationwide sentinel network of veterinary practices confirmed a significant increase in dogs with signs of gastroenteric disease. Male dogs and dogs living with other vomiting dogs were more likely to be affected. Diet and vaccination status were not associated with the disease; however, a canine enteric coronavirus was significantly associated with illness. The system we describe potentially fills a gap in surveillance in neglected populations and could provide a blueprint for other countries.


Assuntos
Infecções por Coronavirus/veterinária , Coronavirus Canino , Surtos de Doenças , Doenças do Cão/epidemiologia , Vômito/veterinária , Animais , Doenças do Cão/virologia , Cães/virologia , Reino Unido/epidemiologia
8.
Front Vet Sci ; 6: 218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334254

RESUMO

Canine acute diarrhoea is frequently observed in first opinion practice, though little is known about commonly used diagnostic or therapeutic management plans, including use of antimicrobials. This retrospective observational study utilised electronic health records augmented with practitioner-completed questionnaires from 3,189 cases (3,159 dogs) collected from 179 volunteer veterinary practices between April 2014 and January 2017. We used multivariable analysis to explore factors potentially associated with pharmaceutical agent prescription, and resolution of clinical signs by 10 days post-initial presentation. Use of bacteriological and/or parasitological diagnostic tests were uncommon (3.2% of cases, 95% confidence interval, CI, 2.4-4.0), though systemic antimicrobials were the most commonly prescribed pharmaceutical agents (49.7% of cases, 95% CI 46.1-53.2). Such prescription was associated with haemorrhagic diarrhoea (odds ratio, OR, 4.1; 95% CI 3.4-5.0), body temperature in excess of 39.0°C, or moderate/severe cases (OR 1.3, 95% CI 1.1-1.7). Gastrointestinal agents (e.g., antacids) were prescribed to 37.7% of cases (95% CI 35.4-39.9), and were most frequently prescribed to vomiting dogs regardless of presence (OR 46.4, 95% CI 19.4-110.8) or absence of blood (OR 17.1, 95% CI 13.4-21.9). Endoparasiticides/endectocides were prescribed to 7.8% of cases (95% CI 6.8-9.0), such prescription being less frequent for moderate/severe cases (OR 0.5, 95% CI 0.4-0.7), though more frequent when weight loss was recorded (OR 3.4, 95% CI 1.3-9.0). Gastrointestinal nutraceuticals (e.g., probiotics) were dispensed to 60.8% of cases (95% CI 57.1-64.6), these cases less frequently presenting with moderate/severe clinical signs (OR 0.6, 95% CI 0.5-0.8). Nearly a quarter of cases were judged lost to follow-up (n=754). Insured (OR 0.7, 95% CI 0.5-0.9); neutered (OR 0.4, 95% CI 0.3-0.5), or vaccinated dogs (OR 0.3, 95% CI 0.3-0.4) were less commonly lost to follow-up. Of remaining dogs, clinical signs were deemed resolved in 95.4% of cases (95% CI 94.6-96.2). Provision of dietary modification advice and gastrointestinal nutraceuticals alone were positively associated with resolution (OR 2.8, 95% CI 1.3-6.1); no such associations were found for pharmaceutical agents, including antimicrobials. Hence, this study supports the view that antimicrobials are largely unnecessary for acute diarrhoea cases; this being of particular importance when considering the global threat posed by antimicrobial resistance.

9.
Prev Vet Med ; 159: 153-161, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30314778

RESUMO

Pharmaceutical agents (PAs) are commonly prescribed in companion animal practice in the United Kingdom. However, little is known about PA prescription on a population-level, particularly with respect to PAs authorised for human use alone prescribed via the veterinary cascade; this raises important questions regarding the efficacy and safety of PAs prescribed to companion animals. This study explored new approaches for describing PA prescription, diversity and co-prescription in dogs, cats and rabbits utilising electronic health records (EHRs) from a sentinel network of 457 companion animal-treating veterinary sites throughout the UK over a 2-year period (2014-2016). A novel text mining-based identification and classification methodology was utilised to semi-automatically map practitioner-defined product descriptions recorded in 918,333 EHRs from 413,870 dogs encompassing 1,242,270 prescriptions; 352,730 EHRs from 200,541 cats encompassing 491,554 prescriptions, and 22,526 EHRS from 13,398 rabbits encompassing 18,490 prescriptions respectively. PA prescription as a percentage of booked consultations was 65.4% (95% confidence interval, CI, 64.6-66.3) in dogs; in cats it was 69.1% (95% CI, 67.9-70.2) and in rabbits, 56.3% (95% CI, 54.7-57.8). Vaccines were the most commonly prescribed PAs in all three species, with antibiotics, antimycotics, and parasiticides also commonly prescribed. PA prescription utilising products authorised for human use only (hence, 'human-authorised') comprised 5.1% (95% CI, 4.7-5.5) of total canine prescription events; in cats it was 2.8% (95% CI, 2.6-3.0), and in rabbits, 7.8% (95% CI, 6.5-9.0). The most commonly prescribed human-authorised PA in dogs was metronidazole (antibiotic); in cats and rabbits it was ranitidine (H2 histamine receptor antagonist). Using a new approach utilising the Simpson's Diversity Index (an ecological measure of relative animal, plant etc. species abundance), we identified differences in prescription based on presenting complaint and species, with rabbits generally exposed to a less diverse range of PAs than dogs or cats, potentially reflecting the paucity of authorised PAs for use in rabbits. Finally, through a novel application of network analysis, we demonstrated the existence of three major co-prescription groups (preventive health; treatment of disease, and euthanasia); a trend commonly observed in practice. This study represents the first time PA prescription has been described across all pharmaceutical families in a large population of companion animals, encompassing PAs authorised for both veterinary and human-only use. These data form a baseline against which future studies could be compared, and provides some useful tools for understanding PA comparative efficacy and risks when prescribed in the varied setting of clinical practice.


Assuntos
Antibacterianos/administração & dosagem , Doenças do Gato/tratamento farmacológico , Mineração de Dados , Doenças do Cão/tratamento farmacológico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Coelhos , Animais , Gatos , Cães , Reino Unido
10.
Vet J ; 224: 18-24, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28697871

RESUMO

Antimicrobial resistance is an increasingly important global health threat and the use of antimicrobial agents is a key risk factor in its development. This study describes antimicrobial agent prescription (AAP) patterns over a 2year period using electronic health records (EHRs) from booked consultations in a network of 457 sentinel veterinary premises in the United Kingdom. A semi-automated classification methodology was used to map practitioner defined product codes in 918,333 EHRs from 413,870 dogs and 352,730 EHRs from 200,541 cats, including 289,789 AAPs. AAP as a proportion of total booked consultations was more frequent in dogs (18.8%, 95% confidence interval, CI, 18.2-19.4) than cats (17.5%, 95% CI 16.9-18.1). Prescription of topical antimicrobial agents was more frequent in dogs (7.4%, 95% CI 7.2-7.7) than cats (3.2%, 95% CI 3.1-3.3), whilst prescription of systemic antimicrobial agents was more frequent in cats (14.8%, 95% CI 14.2-15.4) than dogs (12.2%, 95% CI 11.7-12.7). A decreasing temporal pattern was identified for prescription of systemic antimicrobial agents in dogs and cats. Premises which prescribed antimicrobial agents frequently for dogs also prescribed frequently for cats. AAP was most frequent during pruritus consultations in dogs and trauma consultations in cats. Clavulanic acid potentiated amoxicillin was the most frequently prescribed antimicrobial agent in dogs (28.6% of prescriptions, 95% CI 27.4-29.8), whereas cefovecin, a third generation cephalosporin, was the most frequently prescribed antimicrobial agent in cats (36.2%, 95% CI 33.9-38.5). This study demonstrated patterns in AAP over time and for different conditions in a population of companion animals in the United Kingdom.


Assuntos
Anti-Infecciosos/administração & dosagem , Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Prescrições de Medicamentos/veterinária , Drogas Veterinárias/administração & dosagem , Animais , Gatos , Cães , Prescrições de Medicamentos/estatística & dados numéricos , Resistência Microbiana a Medicamentos , Registros Eletrônicos de Saúde , Padrões de Prática Médica/estatística & dados numéricos , Medicamentos sob Prescrição/administração & dosagem , Reino Unido
11.
Vet J ; 201(3): 412-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25011707

RESUMO

Using the Small Animal Veterinary Surveillance Network (SAVSNET), a national small animal disease-surveillance scheme, information on gastrointestinal disease was collected for a total of 76 days between 10 May 2010 and 8 August 2011 from 16,223 consultations (including data from 9115 individual dogs and 3462 individual cats) from 42 premises belonging to 19 UK veterinary practices. During that period, 7% of dogs and 3% of cats presented with diarrhoea. Adult dogs had a higher proportional morbidity of diarrhoea (PMD) than adult cats (P <0.001). This difference was not observed in animals <1 year old. Younger animals in both species had higher PMDs than adult animals (P < 0.001). Neutering was associated with reduced PMD in young male dogs. In adult dogs, miniature Schnauzers had the highest PMD. Most animals with diarrhoea (51%) presented having been ill for 2-4 days, but a history of vomiting or haemorrhagic diarrhoea was associated with a shorter time to presentation. The most common treatments employed were dietary modification (66% of dogs; 63% of cats) and antibacterials (63% of dogs; 49% of cats). There was variability in PMD between different practices. The SAVNET methodology facilitates rapid collection of cross-sectional data regarding diarrhoea, a recognised sentinel for infectious disease, and characterises data that could benchmark clinical practice and support the development of evidence-based medicine.


Assuntos
Doenças do Gato/epidemiologia , Diarreia/veterinária , Doenças do Cão/epidemiologia , Animais , Antibacterianos/uso terapêutico , Doenças do Gato/dietoterapia , Doenças do Gato/tratamento farmacológico , Doenças do Gato/etiologia , Gatos , Estudos Transversais , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/terapia , Doenças do Cão/dietoterapia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/etiologia , Cães , Monitoramento Epidemiológico , Feminino , Masculino , Reino Unido/epidemiologia
12.
J Small Anim Pract ; 54(3): 143-8, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23458644

RESUMO

OBJECTIVE: The aim of this study was to determine canine breed predispositions for decreased serum folate or markedly decreased cobalamin concentrations. METHODS: Retrospective analysis of samples from dogs that had serum folate and cobalamin concentrations measured, from 1990 to 2002 at the Comparative Gastroenterology Laboratory of Liverpool, were enrolled. A total of 13,069 samples were analysed. Those with trypsin-like immunoreactivity < 5·0 lg/L were excluded, and only breeds with at least 30 individuals tested were further analyzed. Breed predisposition was determined by calculating odds ratios and 95% confidence intervals for hypocobalaminaemia or decreased folate concentration. Significance was tested with a two-sided Fisher's exact test, and the level of statistical significance was set at P<0·05. RESULTS: A total of 9960 dogs fulfilled the inclusion criteria. Forty breeds contained at least 30 individuals. Predispositions for hypocobalaminaemia were identified in shar peis, Staffordshire bull terriers, German shepherd dogs and mixed breeds. Predispositions for decreased folate concentration were found in golden retrievers and boxers. CLINICAL SIGNIFICANCE: Predisposition for marked hypocobalaminaemia and decreased folate concentration differed between breeds. The shar peis had a markedly increased odds ratio for hypocobalaminaemia, as previously reported in North America, but other at-risk breeds were also identified.


Assuntos
Doenças do Cão/genética , Deficiência de Ácido Fólico/veterinária , Predisposição Genética para Doença , Deficiência de Vitamina B 12/veterinária , Animais , Cruzamento , Intervalos de Confiança , Doenças do Cão/sangue , Cães , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/genética , Masculino , Razão de Chances , Estudos Retrospectivos , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/genética
13.
Vet Rec ; 167(21): 810-4, 2010 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-21262629

RESUMO

Computerised referral histories were reviewed for dogs admitted to the University of Liverpool Small Animal Teaching Hospital between January 2000 and December 2008 with diarrhoea among the clinical signs. A total of 371 cases presenting to the referring veterinary surgeon were included in the study, and information was compiled regarding signalment, clinical signs and treatment given at the initial consultation. Various breeds, ages and sexes were represented. Antibacterials were used in 263 (71 per cent) cases, steroids in 71 (19 per cent) cases and miscellaneous antidiarrhoeal products (including probiotics, prebiotics, adsorbents and antimotility drugs) in 98 (26 per cent) cases. Other drugs used included antiemetics (48 of 371 [13 per cent] cases), gastric protectants (37 of 371 [10 per cent] cases) and sulfasalazine (26 of 371 [7 per cent] cases). Antibacterial administration was positively associated with hyperthermia (odds ratio [OR]=2.97, P=0.012) and anorexia (OR=2.17, P=0.0075), but negatively associated with both weight loss (OR=0.55, P=0.036) and tenesmus (OR=0.43, P=0.035). In contrast, use of antidiarrhoeal products was positively associated with the presence of faecal mucus (OR=1.77, P=0.043), and negatively associated with vomiting (OR=0.57, P=0.025) and weight loss (OR=0.52, P=0.033).


Assuntos
Antibacterianos/uso terapêutico , Antidiarreicos/uso terapêutico , Diarreia/veterinária , Doenças do Cão/tratamento farmacológico , Probióticos/uso terapêutico , Animais , Antibacterianos/efeitos adversos , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Diarreia/tratamento farmacológico , Cães , Feminino , Masculino , Resultado do Tratamento , Redução de Peso
15.
J Small Anim Pract ; 46(12): 585-90, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16355734

RESUMO

An unusual vascular ring anomaly consisting of a persistent right aortic arch and a left ligamentum arteriosum extending from the main pulmonary artery to an aberrant left subclavian artery and left aortic arch remnant complex was identified in a German shepherd dog and a great Dane. The left subclavian artery and left aortic arch remnant complex originated at the junction between the right distal aortic arch and the descending aorta and coursed dorsal to the oesophagus in a cranial direction. The attachment of the ligamentum arteriosum to the aberrant left subclavian artery was approximately 5 cm cranial to the point of origin of the aberrant left subclavian artery and left aortic arch remnant complex from the descending aorta in both dogs. This anomaly observed in both dogs is similar to an anomaly reported in humans, in which a persistent right aortic arch is found in conjunction with an aberrant left subclavian artery and a left aortic arch remnant (Kommerell's diverticulum). Surgical ligation and division of the left ligamentum arteriosum in both dogs, along with division of the left subclavian artery in the great Dane, resulted in resolution of clinical signs in both of the dogs in this report.


Assuntos
Aorta Torácica/anormalidades , Ligamentos/cirurgia , Artéria Subclávia/anormalidades , Procedimentos Cirúrgicos Vasculares , Animais , Aorta Torácica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/veterinária , Doenças do Cão/cirurgia , Cães , Masculino , Recidiva , Artéria Subclávia/cirurgia , Resultado do Tratamento
16.
Cancer Res ; 64(5): 1695-702, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-14996729

RESUMO

The gastric pathogen Helicobacter pylori is associated with a progression to gastric cancer. The specific targets of H. pylori that might influence this progression are still unclear. Previous studies indicated that the gastric hormone gastrin, which may be increased in H. pylori infection, stimulates gastric expression of plasminogen activator inhibitor (PAI)-2, which is an inhibitor of the urokinase plasminogen activator and has previously been shown to be increased in gastric adenocarcinoma. Here, we report that H. pylori also increases PAI-2 expression. In gastric biopsies of H. pylori-positive subjects there was increased PAI-2, including subjects with plasma gastrin concentrations in the normal range. PAI-2 was expressed mainly in chief and mucous cells. In a gastric cancer cell line (AGS), H. pylori increased PAI-2 expression, which was associated with inhibition of H. pylori-stimulated cell invasion and apoptosis. The induction of PAI-2 by H. pylori was mediated by release of interleukin-8 and activation of cyclooxygenase-2, and interestingly, gastrin stimulated PAI-2 expression by similar paracrine pathways. The activation of NFkappaB was required for interleukin-8 and cyclooxygenase-2 activation but did not occur in cells responding to these paracrine mediators. The data suggest that induction of PAI-2 is a specific target in H. pylori infection, mediated at least partly by paracrine factors; induction of PAI-2 inhibits cell invasion and apoptosis and is a candidate for influencing the progression to gastric cancer.


Assuntos
Apoptose , Mucosa Gástrica/metabolismo , Helicobacter pylori/patogenicidade , NF-kappa B/fisiologia , Inibidor 2 de Ativador de Plasminogênio/biossíntese , Neoplasias Gástricas/etiologia , Idoso , Ciclo-Oxigenase 2 , Feminino , Humanos , Interleucina-8/fisiologia , Isoenzimas/fisiologia , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Invasividade Neoplásica , Inibidor 2 de Ativador de Plasminogênio/análise , Prostaglandina-Endoperóxido Sintases/fisiologia , Transporte Proteico
17.
J Cell Sci ; 116(Pt 14): 3017-26, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12808021

RESUMO

Epithelial cell responses to bacterial infection include induction of matrix metalloproteinase 7 (MMP-7). Here, we identify increased MMP-7 expression in the gastric epithelium in response to the oncogenic bacterium Helicobacter pylori, and report on the mechanisms and consequences for gastric epithelial cell migration. In patients infected with H. pylori, there was increased MMP-7 in gastric biopsies detected by western blot. MMP-7 was localized to the advancing edge of migrating gastric epithelial cell colonies, including lamellipodia. Rates of spreading of gastric gland cells were higher in H. pylori-infected cultures compared with control, and this was inhibited by antisense oligonucleotides to MMP-7. Complementary data were obtained in a gastric cancer cell line (AGS cells). In the latter, H. pylori induced expression of an MMP-7-luciferase promoter/reporter vector through mechanisms that involved activation of Rho and Rac. RhoA acted through activation of both NF-kappaB and AP-1, whereas Rac activated NF-kappaB but not AP-1. MMP-7 is commonly upregulated in gastric cancer; since H. pylori is a recognized gastric carcinogen, the data suggest a new mechanism by which the bacterium might predispose towards gastric neoplasia.


Assuntos
Células Epiteliais/citologia , Mucosa Gástrica/metabolismo , Helicobacter pylori/metabolismo , Metaloproteinase 7 da Matriz/fisiologia , Western Blotting , Linhagem Celular Tumoral , Movimento Celular , Células Cultivadas , Células Epiteliais/enzimologia , Genes Reporter , Vetores Genéticos , Humanos , Imuno-Histoquímica , Luciferases/metabolismo , Metaloproteinase 7 da Matriz/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica , Oligonucleotídeos Antissenso/química , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Radioimunoensaio , Transdução de Sinais , Fatores de Tempo , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Transfecção , Regulação para Cima , Proteínas rac de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/fisiologia
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