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1.
J Physiol ; 602(1): 93-112, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38063489

RESUMO

The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing. KEY POINTS: The Kölliker-Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.


Assuntos
Núcleo de Kölliker-Fuse , Síndrome de Rett , Humanos , Núcleo de Kölliker-Fuse/fisiologia , Respiração , Neurônios , Simulação por Computador
2.
J Appl Microbiol ; 129(4): 1053-1061, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32259384

RESUMO

AIMS: The food supply is a potential source of antimicrobial resistance. Current surveillance programmes targeting food are limited to beef, pork and poultry and do not capture niche products. In this study, imported reptile and amphibian products were screened for antimicrobial-resistant bacteria. METHODS AND RESULTS: In all, 53 items including soft shell turtles, frog legs, geckos, snakes and a turtle carapace were purchased from specialty markets in Vancouver and Saskatoon, Canada. Samples were selectively cultured for Salmonella sp., Escherichia coli, extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and meropenem-resistant organisms. Salmonella, all pan-susceptible, were grown from six dried geckos. Escherichia coli were isolated from 19 samples, including ESBL producers from six items. One multidrug-resistant E. coli possessed both the blaCTX-M-55 and mcr-1 genes. An NDM-1-producing Acinetobacter sp. was also isolated from a dried turtle carapace. CONCLUSIONS: Our results suggest that imported reptile and amphibian meats are an underappreciated source of resistant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The international trade of food may play a role in the dissemination of resistant bacteria. The presence of these bacteria in niche market foods represents a risk of unknown magnitude to public health and a gap in current national resistance surveillance programmes.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Bactérias Gram-Negativas/isolamento & purificação , Internacionalidade , Carne/microbiologia , Anfíbios , Animais , Canadá , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Répteis
3.
Lett Appl Microbiol ; 69(5): 353-357, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31508840

RESUMO

The ability of chemotherapeutic agents to affect the growth of common bacterial pathogens and the relationship between the effects of chemotherapeutics and antimicrobials is largely unknown. The purpose of this study was to describe the susceptibility of canine bacterial isolates to chemotherapeutic agents and to compare these results to their antimicrobial susceptibility. The effects of bleomycin, doxorubicin, cytarabine, cyclophosphamide, methotrexate, 5-fluorouracil and gemcitabine on the growth of 33 Staphylococcus pseudintermedius isolates and 32 Escherichia coli isolates from dogs was determined by agar dilution. In addition to MICs, the lowest drug concentration associated with a decreased colony size was recorded. Results were compared to the MICs of a panel of antimicrobial agents. Bleomycin consistently inhibited bacterial growth of S. pseudintermedius and E. coli. Doxorubicin inhibited S. pseudintermedius but not E. coli while the opposite was seen for gemcitabine. Reduction in colony size on exposure to 5-fluorouracil for both organisms, and methotrexate for S. pseudintermedius was seen. No observable effect of cyclophosphamide or cytarabine was observed. Associations between elevated MICs to chemotherapeutic drugs and antimicrobial resistance were not found. These results indicate that chemotherapeutic agents affect the growth of bacteria, but do not support a role in the selection of antimicrobial resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that chemotherapy drugs commonly used in veterinary oncology have an effect of the growth of canine isolates of Escherichia coli and Staphylococcus pseudintermedius. No associations between susceptibility to chemotherapeutic drugs and antibiotics were found, which does not support selection of antimicrobial resistance by chemotherapy drugs.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bleomicina/farmacologia , Doenças do Cão/microbiologia , Escherichia coli/efeitos dos fármacos , Fluoruracila/farmacologia , Staphylococcus/efeitos dos fármacos , Animais , Cães , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Staphylococcus/crescimento & desenvolvimento , Staphylococcus/isolamento & purificação
4.
Can J Microbiol ; 63(6): 465-474, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28324657

RESUMO

The re-emergence of swine dysentery (Brachyspira-associated muco-haemorrhagic colitis) since the late 2000s has illuminated diagnostic challenges associated with this genus. The methods used to detect, identify, and characterize Brachyspira from clinical samples have not been standardized, and laboratories frequently rely heavily on in-house techniques. Particularly concerning is the lack of standardized methods for determining and interpreting the antimicrobial susceptibility of Brachyspira spp. The integration of laboratory data into a treatment plan is a critical component of prudent antimicrobial usage. Therefore, the lack of standardized methods is an important limitation to the evidence-based use of antimicrobials. This review will focus on describing the methodological limitations and inconsistencies between current susceptibility testing schemes employed for Brachyspira, provide an overview of what we do know about the susceptibility of these organisms, and suggest future directions to improve and standardize diagnostic strategies.


Assuntos
Anti-Infecciosos/farmacologia , Brachyspira/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Animais , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Suínos , Doenças dos Suínos/microbiologia
5.
Can J Microbiol ; 63(3): 246-251, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28177803

RESUMO

The feral horses of Sable Island are a geographically isolated population located ∼160 km off the east coast of Nova Scotia, Canada. Because these horses have no contact with domestic animals, have minimal contact with people, and have never received antimicrobials, they offer a unique opportunity to study the dissemination of antimicrobial resistance in unmanaged populations. As part of an ongoing multidisciplinary and individual-based monitoring program, we collected feces from 508 geolocalized horses (92% of the total population) between July and September 2014. We selectively cultured Escherichia coli on MacConkey and CHROMagar ESBL media. Antimicrobial susceptibilities were determined, and organisms resistant to ß-lactam antimicrobials were screened for ß-lactamase genes by PCR. Escherichia coli was recovered from 146 (28.7%) individuals, and the majority of isolates (97%) were susceptible to all drugs tested. Resistance to tetracycline was most common, including organisms isolated from 4 (2.7%) of the colonized horses. A single isolate resistant to ampicillin, ceftriaxone, and ceftiofur was identified, which possessed the CTX-M-1 gene. Our findings demonstrate that although antimicrobial resistance is not common in this remote population, clinically relevant resistance genes are present.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Cavalos/microbiologia , Animais , Animais Selvagens/microbiologia , Canadá , Farmacorresistência Bacteriana , Escherichia coli/genética , Fezes/microbiologia , Testes de Sensibilidade Microbiana , Nova Escócia , beta-Lactamases/genética
6.
Lett Appl Microbiol ; 63(1): 11-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27214496

RESUMO

UNLABELLED: The epidemiology of antimicrobial resistance is extremely complex and involves humans, domestic animals (companion and agricultural) and wildlife. In North America there have been very few investigations targeting antimicrobial-resistant organisms in wildlife. In this study, we characterized the susceptibility of Escherichia coli isolated from 75 birds including great horned owls, crows and American robins from the region of Saskatoon, Canada. The recovery rate of E. coli varied significantly between species from 44·8% of robins to 92% of crows. The majority (88·2%) of colonized birds carried only pan-susceptible organisms. Among isolates resistant to at least one antimicrobial, ampicillin resistance was most commonly identified. Three birds carried multidrug-resistant isolates (resistant to ≥3 drug classes), and extended-spectrum ß-lactamase (ESBL)-producing organisms (CTX-M-15 and SHV2a) were grown from two. We identified a significant relationship between the presence of drug-resistant E. coli and an urban (vs rural) origin of the bird. Our findings suggest that crows, due to their ubiquity and high rate of colonization with E. coli, may be efficient targets for future resistance surveillance studies targeting urban wildlife. SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial resistance is a global problem affecting people and animals. Few investigations describing the presence drug-resistant organisms in wildlife in North America have been published. In this study, resistant Escherichia coli, including extended-spectrum ß-lactamase-producing strains, were isolated from wild birds in the Saskatoon region of Canada. We found that the recovery rate of E. coli varied significantly by species and was highest among crows. There was also a significant association between drug resistance and urban vs rural birds. Our results suggest that crows may be a good target for future studies investigating antimicrobial resistance in urban wildlife.


Assuntos
Antibacterianos/farmacologia , Aves/microbiologia , Infecções por Escherichia coli/veterinária , Escherichia coli/efeitos dos fármacos , Resistência beta-Lactâmica/fisiologia , beta-Lactamases/farmacologia , Animais , Animais Selvagens , Canadá , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana
7.
Chaos ; 23(4): 046110, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24387589

RESUMO

Irregular neuronal activity is observed in a variety of brain regions and states. This work illustrates a novel mechanism by which irregular activity naturally emerges in two-cell neuronal networks featuring coupling by synaptic inhibition. We introduce a one-dimensional map that captures the irregular activity occurring in our simulations of conductance-based differential equations and mathematically analyze the instability of fixed points corresponding to synchronous and antiphase spiking for this map. We find that the irregular solutions that arise exhibit expansion, contraction, and folding in phase space, as expected in chaotic dynamics. Our analysis shows that these features are produced from the interplay of synaptic inhibition with sodium, potassium, and leak currents in a conductance-based framework and provides precise conditions on parameters that ensure that irregular activity will occur. In particular, the temporal details of spiking dynamics must be present for a model to exhibit this irregularity mechanism and must be considered analytically to capture these effects.


Assuntos
Modelos Neurológicos , Rede Nervosa/fisiologia , Transmissão Sináptica/fisiologia , Humanos , Potássio/metabolismo , Sódio/metabolismo
8.
J Chemother ; 34(2): 133-136, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34747350

RESUMO

Staphylococcus pseudintermedius is increasingly recognized as a human pathogen. We report the first case of an urinary tract infection in a male patient with this organism.


Assuntos
Doenças do Cão , Infecções Estafilocócicas , Infecções Urinárias , Animais , Antibacterianos/uso terapêutico , Cães , Humanos , Masculino , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus , Infecções Urinárias/tratamento farmacológico
9.
Comp Immunol Microbiol Infect Dis ; 89: 101870, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36088796

RESUMO

To determine the antibiotypes and frequency of toxin genes in methicillin-resistant Staphylococcus pseudintermedius (MRSP), 281 nasal swab samples were collected from dogs and dog guardians in Abakaliki, Southeastern Nigeria. Antimicrobial susceptibility testing was determined by disc diffusion technique while detection of toxin genes was carried out by PCR. Exactly 41 (28.7 %) and 6 (4.3 %) MRSP were obtained from dogs and dog guardians respectively. Isolates exhibited resistance (100-16.7 %) to amoxicillin-clavulanic acid, cephalosporins, fluoroquinolones, and carbapenems. Seccanine, lukD, siet, and exi toxin genes were harboured by 42 (89.4 %), 47 (100 %), 37 (78.7 %), and 2 (4.3 %) MRSP isolates respectively. This study has shown that dogs and dog guardians in Abakaliki, Southeastern Nigeria are colonized by multiple drug-resistant MRSP which harbour toxin genes. This represents a significant public health problem in veterinary and human medicine.


Assuntos
Anti-Infecciosos , Doenças do Cão , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Combinação Amoxicilina e Clavulanato de Potássio , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Carbapenêmicos , Cefalosporinas , Doenças do Cão/epidemiologia , Cães , Fluoroquinolonas , Humanos , Resistência a Meticilina/genética , Testes de Sensibilidade Microbiana/veterinária , Nigéria/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Staphylococcus
10.
J Chemother ; 32(3): 151-155, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124685

RESUMO

Staphylococcus pseudintermedius is a well known commensal organism of dogs but also a canine opportunistic pathogen. Reports of this organism being recovered from specimens from humans might suggest an increase prevalence in human infections and/or improved diagnostic leading to more accurate identification. Here we report a case of persistent S. pseudintermedius infection in an adult female oncology patient including colonization of the tip of an indwelling catheter. Diligence by laboratories in correctly isolating and identifying this pathogen (including susceptibility testing) is essential for optimal patient care.


Assuntos
Antineoplásicos/uso terapêutico , Zoonoses Bacterianas/diagnóstico , Neoplasias Retais/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Staphylococcus , Animais , Zoonoses Bacterianas/transmissão , Cateteres de Demora/microbiologia , Cães , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Animais de Estimação , Infecções Estafilocócicas/transmissão
11.
Vet Microbiol ; 244: 108645, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32402332

RESUMO

Brachyspira hyodysenteriae and Brachyspira pilosicoli cause economically important enteric disease in pigs. Treatment of these infections often includes antimicrobial administration, which can be most effective when therapeutic options are informed by antimicrobial susceptibility testing data. Here we describe a method for broth dilution antimicrobial susceptibility testing of these bacteria, both of which are difficult to culture in vitro. The protocol was evaluated for its fitness for use in an inter-laboratory ring trial involving eight laboratories from seven countries, and employing eleven test strains (5 Brachyspira hyodysenteriae including the type strain B78T and 6 Brachyspira pilosicoli) and six antibiotics. Overall intra- and inter-laboratory reproducibility of this method was very good (>90 % MICs at mode +/- 1 log2). Whole genome sequencing revealed good correspondence between reduced susceptibility and the presence of previously defined antimicrobial resistance determinants. Interestingly, lnu(C) was identified in B. pilosicoli isolates with elevated MICs of lincomycin, whilst tva(B) was associated with elevated MICs of pleuromutilins in this species. We designated two new control strains with MICs lying within currently tested ranges, including for the pleuromutilins, in contrast to the control strain B. hyodysenteriae B78T. These were deposited at the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH. The validation of a standard protocol and identification of new control strains facilitates comparisons between studies, establishment of robust interpretative criteria, and ultimately contributes to rational antimicrobial use when treating infected livestock.


Assuntos
Antibacterianos/farmacologia , Brachyspira hyodysenteriae/efeitos dos fármacos , Brachyspira/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Brachyspira/genética , Brachyspira hyodysenteriae/genética , Farmacorresistência Bacteriana/genética , Genômica , Internacionalidade , Laboratórios , Reprodutibilidade dos Testes
12.
Ann Surg Oncol ; 16(4): 1043-50, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19165543

RESUMO

BACKGROUND: The relationship between obesity and cancer has become of particular interest due to the rapidly growing prevalence of overweight individuals. Obesity predisposes individuals to the development of hepatic steatosis and is an independent risk factor for several neoplasms. Toll-like receptor 4 (TLR4) is the innate receptor for endotoxin, and steatotic livers are known to be sensitive to endotoxin. TLR4 signaling has been shown to have proneoplastic effects in vitro due to its effect on immune surveillance. Thus far, studies have predominantly focused on the effect of tumor-cell-derived TLR4 without regard to host TLR4 signaling. RESULTS: In the present study we show that steatotic livers have increased expression of TLR4. Obese animals developed higher metastatic tumor burden in the liver than lean controls regardless of the presence or absence of intact host TLR4. After silencing TLR4 expression using RNAi in the mouse colon cancer cell line MC38, there was a significant decrease in metastatic tumor burden within the liver of obese animals. CONCLUSIONS: These findings demonstrate that steatotic livers have increased susceptibility to metastatic tumor growth and that silencing tumor cell TLR4 reduces metastatic tumor burden in steatotic liver.


Assuntos
Neoplasias Colorretais/genética , Fígado Gorduroso/metabolismo , Inativação Gênica , Neoplasias Hepáticas/genética , Receptor 4 Toll-Like/genética , Carga Tumoral/genética , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/secundário , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Obesidade/complicações , Obesidade/genética , Obesidade/imunologia , Receptor 4 Toll-Like/biossíntese
14.
Phys Rev E ; 97(1-1): 012215, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29448375

RESUMO

Modeling and parameter estimation to capture the dynamics of physical systems are often challenging because many parameters can range over orders of magnitude and are difficult to measure experimentally. Moreover, selecting a suitable model complexity requires a sufficient understanding of the model's potential use, such as highlighting essential mechanisms underlying qualitative behavior or precisely quantifying realistic dynamics. We present an approach that can guide model development and tuning to achieve desired qualitative and quantitative solution properties. It relies on the presence of disparate time scales and employs techniques of separating the dynamics of fast and slow variables, which are well known in the analysis of qualitative solution features. We build on these methods to show how it is also possible to obtain quantitative solution features by imposing designed dynamics for the slow variables in the form of specified two-dimensional paths in a bifurcation-parameter landscape.

15.
Zoonoses Public Health ; 65(1): 134-141, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28766871

RESUMO

Surveillance is an important component of an overall strategy to address antimicrobial resistant bacteria in food animals and the food chain. The poultry market has many points of entry into the Canadian food chain, and some production practices are underrepresented in terms of surveillance. For example, pathogen carriage and antimicrobial resistance surveillance data are limited in smallholder chicken flocks raised for slaughter at provincially inspected abattoirs. In Canada, antimicrobial resistance in Escherichia coli and Salmonella isolated from commercial broiler chicken flocks, slaughtered at federally inspected abattoirs, is monitored by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). The objective of this study was to establish baseline information of antimicrobial resistance presence in E. coli and Salmonella isolated from smallholder flocks in Ontario, utilizing CIPARS collection and isolation methodologies, and to compare findings with CIPARS federally inspected abattoir data from Ontario, Canada. Five chickens per flock were sampled from 205 smallholder flocks. Of 1,025 samples, the E. coli prevalence was 99% (1,022/1,025), and 47% (483/1,022) of positive E. coli isolates were resistant to one or more of the 14 antimicrobials. Furthermore, as compared to results reported for the CIPARS commercial flocks, E. coli isolates from smallholder flocks had significantly lower resistance prevalence to six of 14 individual antimicrobials. Recovery of E. coli did not differ between federally inspected and provincially inspected flocks. Salmonella prevalence at the bird level in smallholder flocks was 0.3% (3/1,025), significantly lower (p â‰ª 0.0001, 95% CI 0.080%-0.86%) than federally inspected commercial flocks. The overall differences found between the commercial and smallholder flocks may be explained by differences in poultry husbandry practices and hatchery sources.


Assuntos
Galinhas , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Doenças das Aves Domésticas/microbiologia , Salmonella/efeitos dos fármacos , Criação de Animais Domésticos , Animais , Antibacterianos/farmacologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Ontário/epidemiologia , Doenças das Aves Domésticas/epidemiologia , Salmonella/isolamento & purificação , Salmonelose Animal/epidemiologia , Salmonelose Animal/microbiologia
16.
Diagn Microbiol Infect Dis ; 85(4): 471-6, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27241371

RESUMO

BACKGROUND: Staphylococcus pseudintermedius has been recently identified as a novel species within the genus Staphylococcus, and is commonly associated with infections in dogs. Currently, there are few reports of human infections due to this bacterium. OBJECTIVE: To use a population-based approach to describe the characteristics of human S. pseudintermedius infections in a large Canadian healthcare region. METHODS: All adult cases aged ≥18 years identified at a large regional laboratory from April 1, 2013 to April 1, 2015 who had at least one positive culture for S. pseudintermedius were retrospectively reviewed. A combination of phenotypic methods, mass spectrometry (i.e., MALDI-TOF), and cpn60 sequencing were used to identify S. pseudintermedius. Chart review was conducted, and cases were analysed descriptively. RESULTS: Twenty-seven isolates of S. pseudintermedius from 24 human cases were included for analysis. 58.3% were male with median age of 61 years (IQR 55-70.5). Most patients [22 (92.1%)] had confirmed contact with dogs at time of infection. S. pseudintermedius was isolated in 18 cases (75.0%) of skin and soft tissue infections (SSTI), and 2 invasive cases (8.3%) including a prosthetic joint and bloodstream infection. The other 4 patients were considered to be colonized (skin - 3; lung - 1). Methicillin resistance was identified in 3 cases with 6 total isolates (22.2%); multi-drug resistance was also demonstrated commonly. CONCLUSION: S. pseudintermedius is most commonly associated with SSTIs in humans. Transmission probably occurs from a pet dog. Species-level identification of S. pseudintermedius is important due to the high prevalence of antibiotic resistance, particularly to methicillin.


Assuntos
Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus/isolamento & purificação , Zoonoses/microbiologia , Zoonoses/transmissão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Técnicas Bacteriológicas , Canadá/epidemiologia , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Animais de Estimação , Estudos Retrospectivos , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Adulto Jovem
17.
J Neurosci ; 22(7): 2963-76, 2002 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11923461

RESUMO

Based on recent experimental data, we have developed a conductance-based computational network model of the subthalamic nucleus and the external segment of the globus pallidus in the indirect pathway of the basal ganglia. Computer simulations and analysis of this model illuminate the roles of the coupling architecture of the network, and associated synaptic conductances, in modulating the activity patterns displayed by this network. Depending on the relationships of these coupling parameters, the network can support three general classes of sustained firing patterns: clustering, propagating waves, and repetitive spiking that may show little regularity or correlation. Each activity pattern can occur continuously or in discrete episodes. We characterize the mechanisms underlying these rhythms, as well as the influence of parameters on details such as spiking frequency and wave speed. These results suggest that the subthalamopallidal circuit is capable both of correlated rhythmic activity and of irregular autonomous patterns of activity that block rhythmicity. Increased striatal input to, and weakened intrapallidal inhibition within, the indirect pathway can switch the behavior of the circuit from irregular to rhythmic. This may be sufficient to explain the emergence of correlated oscillatory activity in the subthalamopallidal circuit after destruction of dopaminergic neurons in Parkinson's disease and in animal models of parkinsonism.


Assuntos
Gânglios da Base/fisiologia , Simulação por Computador , Modelos Neurológicos , Rede Nervosa/fisiologia , Redes Neurais de Computação , Potenciais de Ação/fisiologia , Animais , Relógios Biológicos/fisiologia , Globo Pálido/fisiologia , Humanos , Inibição Neural/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Doença de Parkinson/etiologia , Periodicidade , Núcleo Subtalâmico/fisiologia , Transmissão Sináptica/fisiologia
18.
Biochim Biophys Acta ; 1091(1): 87-95, 1991 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-1847302

RESUMO

U937 cells can be induced to express receptor for complement 5a (C5aR) by sequential 2 day treatments of cells with dihydroxyvitamin D-3 (1,25(OH)2D3) followed by prostaglandin E2. We asked whether the action of prostaglandin E2 to cause maximal C5aR expression required only activation of the cAMP-dependent protein kinase (PKA). Prostaglandin E2 dose dependently activated PKA in control and 1,25(OH)2D3 treated cells; by 4 h the PKA did not respond to further prostaglandin E2 challenge. We hypothesized that prostaglandin E2 actions transduced via PKA should be complete by 4 h; i.e., C5aR induction should be equivalent in cells treated with prostaglandin E2 for 4 h and for 2 days. All cells were treated for the first 2 days with 1,25(OH)2D3 and the second 2 days with prostaglandin E2 or cAMP analogs. C5aR number was measured after 4 days total culture. 4 h pulse treatments with agents were given at the end of the 1,25(OH)2D3 treatment. Cells exposed to a 4 h pulse of prostaglandin E2 had only 68.2 +/- 4.4% the amount of C5aR seen in cells continuously exposed to prostaglandin E2. Continuous culture with a cAMP analog pair (50 microM each of 8-thiomethyl-cAMP + N6-benzoyl-cAMP), which caused a 41.7% +/- 10.8% increase PKA activation above basal, resulted in only 51% +/- 16% of the C5aR numbers seen in cells cultured for 2 days with prostaglandin E2, where PKA remained at basal activity. We therefore concluded that C5aR expression caused by prostaglandin E2 could not be ascribed entirely to duration or degree of activation of cAMP-dependent signalling pathways. We investigated the possibility that the calcium sensitive protein kinase C was involved. Cytoplasmic protein kinase C was increased 154% +/- 14% above control in cells treated with sequential 2 days treatments of 1,25(OH)2D3 and prostaglandin E2. A 147% +/- 2% increase in membrane associated protein kinase C was also seen 10 min after phorbol myristate acetate stimulation in the above treatment group. Finally, phorbol myristate acetate augmented the C5aR induction caused by cAMP analog. We propose that the mechanism of prostaglandin E2 synergism with 1,25(OH)2D3 in causing C5aR induction in U937 cells includes signal transduction not only by the cAMP cascade, but also via protein kinase C modulated pathways.


Assuntos
AMP Cíclico/fisiologia , Dinoprostona/fisiologia , Monócitos/citologia , Receptores de Complemento/biossíntese , Calcitriol/fisiologia , Cálcio/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular , Humanos , Isoenzimas/fisiologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Proteína Quinase C/fisiologia , Proteínas Quinases/fisiologia , Receptor da Anafilatoxina C5a , Transdução de Sinais/efeitos dos fármacos , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Regulação para Cima
19.
J Bone Miner Res ; 6(6): 631-7, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1653516

RESUMO

We have previously shown that 1,25-dihydroxyvitamin D [1,25-(OH)2D3] and glucocorticoid modulate adenylate cyclase activation by PTH in osteoblast-like cells. Here we examine whether steroid effects on PTH receptor density explain the modulation of PTH action. Receptor assays were performed on late logarithmicphase monolayers of ROS 17/2.8 cells using human PTH-like peptide (hPLP) as radioligand. Kd and receptor density were computed from competition of tracer amounts of [125I-Tyr36] hPLP-(1-36) with unlabeled hPLP-(1-36) (0.1-30 nM). Steroid treatment had little or no effect on affinity for ligand. Pretreating cells with 10 nM 1,25-(OH)2D3 for 48 h decreased PTH receptor number to 17% of control values. Treating cells with 10 nM of the glucocorticoid triamcinolone acetonide (TRM) increased receptor number 10-fold, but simultaneous treatment with 1,25-(OH)2D3 (10 nM) completely prevented this receptor increase. Steroid effects required 13-18 h of treatment. Dose-response relationships for steroid modulation, determined from binding at 0.17 nM radioligand, indicated an EC50 of 0.3 nM for glucocorticoid augmentation of PTH receptor number and 0.02 nM for 1,25-(OH)2D3 reduction of receptor number in the presence of absence of the maximum TRM effect. The initial rate of cAMP production by receptor-saturating concentrations of PTH was 11,500 molecules per receptor per minute in untreated cells, comparable to reported turnover numbers for mammalian adenylate cyclase. Control experiments were validated measuring cAMP in intact cells as an indicator of adenylate cyclase activity. Cyclic AMP production was reduced 63% by 1,25-(OH)2D3 (10 nM) treatment. Glucocorticoid (10 nM) enhanced cAMP production twofold but reduced cAMP generation per receptor by 80%.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Calcitriol/farmacologia , Osteoblastos/efeitos dos fármacos , Osteossarcoma/metabolismo , Receptores de Superfície Celular/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Osteoblastos/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo , Proteínas/farmacologia , Ensaio Radioligante , Ratos , Receptores de Hormônios Paratireóideos , Triancinolona Acetonida/antagonistas & inibidores , Triancinolona Acetonida/farmacologia , Células Tumorais Cultivadas
20.
J Bone Miner Res ; 8 Suppl 2: S573-81, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8122529

RESUMO

The discovery of piezoelectric potentials in loaded bone was instrumental in developing a plausible mechanism by which functional activity could intrinsically influence the tissue's cellular environment and thus affect skeletal mass and morphology. Using an in vivo model of osteopenia, we have demonstrated that the bone resorption that normally parallels disuse can be prevented or even reversed by the exogenous induction of electric fields. Importantly, the manner of the response (i.e., formation, turnover, resorption) is exceedingly sensitive to subtle changes in electric field parameters. Fields below 10 microV/cm, when induced at frequencies between 50 and 150 Hz for 1 h/day, were sufficient to maintain bone mass even in the absence of function. Reducing the frequency to 15 Hz made the field extremely osteogenic. Indeed, this frequency-specific sinusoidal field initiated more new bone formation than a more complex pulsed electromagnetic field (PEMF), though inducing only 0.1% of the electrical energy of the PEMF. The frequencies and field intensities most effective in the exogenous stimulation of bone formation are similar to those produced by normal functional activity. This lends strong support to the hypothesis that endogenous electric fields serve as a critical regulatory factor in both bone modeling and remodeling processes. Delineation of the field parameters most effective in retaining or promoting bone mass will accelerate the development of electricity as a unique and site-specific prophylaxis for osteopenia. Because fields of these frequencies and intensities are indigenous to bone tissue, it further suggests that such exogenous treatment can promote bone quantity and quality with minimal risk or consequence.


Assuntos
Doenças Ósseas Metabólicas/prevenção & controle , Remodelação Óssea , Campos Eletromagnéticos , Animais , Reabsorção Óssea/prevenção & controle , Estimulação Elétrica , Humanos , Técnicas In Vitro
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