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1.
Front Oncol ; 13: 1223353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731631

RESUMO

Introduction: Accurate white blood cells segmentation from cytopathological images is crucial for evaluating leukemia. However, segmentation is difficult in clinical practice. Given the very large numbers of cytopathological images to be processed, diagnosis becomes cumbersome and time consuming, and diagnostic accuracy is also closely related to experts' experience, fatigue and mood and so on. Besides, fully automatic white blood cells segmentation is challenging for several reasons. There exists cell deformation, blurred cell boundaries, and cell color differences, cells overlapping or adhesion. Methods: The proposed method improves the feature representation capability of the network while reducing parameters and computational redundancy by utilizing the feature reuse of Ghost module to reconstruct a lightweight backbone network. Additionally, a dual-stream feature fusion network (DFFN) based on the feature pyramid network is designed to enhance detailed information acquisition. Furthermore, a dual-domain attention module (DDAM) is developed to extract global features from both frequency and spatial domains simultaneously, resulting in better cell segmentation performance. Results: Experimental results on ALL-IDB and BCCD datasets demonstrate that our method outperforms existing instance segmentation networks such as Mask R-CNN, PointRend, MS R-CNN, SOLOv2, and YOLACT with an average precision (AP) of 87.41%, while significantly reducing parameters and computational cost. Discussion: Our method is significantly better than the current state-of-the-art single-stage methods in terms of both the number of parameters and FLOPs, and our method has the best performance among all compared methods. However, the performance of our method is still lower than the two-stage instance segmentation algorithms. in future work, how to design a more lightweight network model while ensuring a good accuracy will become an important problem.

2.
Front Cell Infect Microbiol ; 13: 1149541, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37021122

RESUMO

Introduction: Salmonella Typhimurium is the leading cause of foodborne illnesses in China, resulting in major epidemics and economic losses in recent years. Uridine diphosphate-glucose pyrophosphorylase galU plays an important role in thebiosynthesis of the bacterial envelope. Herein, we evaluated the role of galU in S. Typhimurium infection in chicken. Methods: A galU gene mutant was successfully constructed by red homologous recombination technology, and biological characteristics were studied. Results: The galU mutant strain had a rough phenotype;was defective in biofilm formation, autoagglutination, and motility; exhibited greater sensitivity to most antibiotics, serum, and egg albumen; and had lowercapacity for adhesion to chicken embryo fibroblasts cell line (DF-1). The galU mutant showed dramatically attenuated pathogenicity in chicken embryos (100,000-fold), BALB/c mice (420-fold), and chicks (100-fold). Discussion: The results imply that galU is an important virulence factor in the pathogenicity of S. Typhimurium, and it may serve a target for the development of veterinary drugs, providing a theoretical basis for the prevention and control of S. Typhimurium.


Assuntos
Antibacterianos , Salmonella typhimurium , Camundongos , Embrião de Galinha , Animais , Virulência/genética , Salmonella typhimurium/genética , Galinhas , Biofilmes , Proteínas de Bactérias/genética
3.
Front Microbiol ; 14: 1133241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37082181

RESUMO

Introduction: Salmonella is a ubiquitous foodborne pathogen and mainly transmitted to human farm-to-fork chain through contaminated foods of animal origin. Methods: In this study, we investigated the serotypes, antimicrobial resistance and virulence of Salmonella from China. Results: A total of 617 Salmonella isolates were collected from 4 major food animal species across 23 provi nces in China from 2015-2021. Highest Salmonella prevalence were observed in Guangdong (44.4%) and Sandong (23.7%). Chickens (43.0%) was shown to be the major source of Salmonella contamination, followed by pigs (34.5%) and ducks (18.5%). The number of Salmonella increased significantly from 5.51% to 27.23% during 2015-2020. S. Derby (17.3%), S. Enteritidis (13.1%) and S. Typhimurium (11.4%) were the most common serotypes among 41 serotypes identifiedin this study. Antibiotic susceptibility testing showing that the majority of the Salmonella isolates were resistant to neomycin (99.7%), tetracycline (98.1%), ampicillin (97.4%), sulfadiazine/trimethoprim (97.1%), nalidixic acid (89.1%), doxycycline (83.1%), ceftria xone (70.3%), spectinomycin (67.7%), florfenicol (60.0%), cefotaxime (52.0%) and lomefloxacin (59.8%). The rates of resistance to multiple antibiotics in S. Derby and S.Typhimurium were higher than that in S. Enteritidis. However, the rate of resistance to fosfomycin were observed from higher to lower by S. Derby, S. Enteritidis, and S. Typhimurium. Biofilm formation ability analysis found that 88.49%of the Salmonella were able to produce biofilms, of which 236 Salmonella isolates were strong biofilm producer. Among the 26 types of antibiotics resistance genes (ARGs) were identified in this study, 4 ARGs (tetB,sul2,aadA2, and aph(3')-IIa) were highly prevalent. In addition, 5 ß-lactam resistance genes (bla TEM, bla SHV, bla CMY-2, bla CTX-M, and bla OXA) and 7 quinolone resistance genes (oqxA, oqxB, qnrB, qnrC, qnrD, qnrS, and qeqA) were detected among these isolates. 12 out of 17 virulence genes selected in this study were commonly presented in the chromosomes of tested isolate, with a detection rate of over 80%, including misL, spiA, stn, pagC, iroN, fim, msgA, sopB, prgH, sitC, ttrC, spaN. Discussion: This study provided a systematical updating on surveillance on prevalence of Salmonella from food animals in China, shedding the light on continued vigilance for Salmonella in food animals.

4.
Bioorg Chem ; 133: 106332, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36773454

RESUMO

Pyrrole-imidazole alkaloids (PIAs) constitute a highly diverse and densely functionalized subclass of marine natural products. Among them, the uncommon dimeric PIAs with ornate molecular architectures, attractive biological properties and interesting biosynthetic origin have spurred a considerable interest of chemists and biologists. The present review comprehensively summarized 84 dimeric PIAs discovered during the period from 1981 to September 2022, covering their source organisms, chemical structures, biological activities as well as biosynthesis. For a better understanding, these structurally intricate PIA dimers are firstly classified and presented according to their carbon skeleton features as well as biosynthesis pathways. Furthermore, relevant summaries focusing on the source organisms and the associated bioactivities of these compounds belonging to different chemical classes are also provided, which will help elucidate the fascinating chemistry and biology of these unusual PIA dimers.


Assuntos
Alcaloides , Produtos Biológicos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Imidazóis/química , Pirróis/química
5.
Microb Pathog ; 162: 105323, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34843921

RESUMO

Pseudomonas aeruginosa strains are potential pathogens that cause respiratory diseases in minks, and caused serious economic loss to mink breeding industry. In this study, we identified antimicrobial resistance and virulence genes in 125 P. aeruginosa isolates from mink in China from 2011 to 2020. The results showed at least one mutation in the gyrA (Thr83Val or Asp87Gly) and parC (Ser87 Leu) genes as well as single mutations in 56 isolates. At least 4-fold reductions in the fluoroquinolone minimum inhibitory concentration values were found when tested in the presence of PAßN in 23 isolates, while 44 isolates were positive for the extended spectrum ß-lactamases and 15 antibiotic resistance genes were identified in this population with a prevalence between 1-32%, including qnrA, CTX-M-1G, ermB and C, cmlA, flor, catl, intl1, tetA, B, C, and D as well as sul1, 2, and 3 genes. Interestingly, one isolate carried ten resistance genes. Five virulence genes were detected, where exoS and algD were the most frequently detected (76.8%), which were followed by plcH (76%), lasB (73.6%), and pilB (31.2%). The isolates carrying the antibiotic resistance or virulence genes were genetically variable, suggesting a horizontal spread through the population. Hence, this study provides novel and important data on the resistance and pathogenicity of P. aeruginosa in farmed mink infections. These data provide important insights into the mechanism of fluoroquinolone resistance in P. aeruginosa, highlighting its usefulness in the treatment and control of P. aeruginosa infections in minks.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Vison , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/veterinária , Pseudomonas aeruginosa/genética , Virulência , Fatores de Virulência/genética
6.
Front Vet Sci ; 8: 715887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869712

RESUMO

Tulathromycin is a semi-synthetic macrolide antimicrobial that has an important role in veterinary medicine for respiratory disease. The objective of the study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to examine the efficacy and determine an optimal dosage of tulathromycin intramuscular (IM) treatment against Haemophilus parasuis infection induced after intraperitoneal inoculation in neutropenic guinea pigs. The PKs of tulathromycin in serum and lung tissue after intramuscular administration at doses of 1, 10, and 20 mg/kg in H. parasuis-infected neutropenic guinea pigs were evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The tulathromycin minimum inhibitory concentration (MIC) against H. parasuis was ~16 times lower in guinea pig serum (0.03 µg/mL) than in cation-adjusted Mueller-Hinton broth (CAMHB) (0.5 µg/mL). The ratio of the 168-h area under the concentration-time curve (AUC) to MIC (AUC168h/MIC) positively correlated with the in vivo antibacterial effectiveness of tulathromycin (R 2 = 0.9878 in serum and R 2 = 0.9911 in lung tissue). The computed doses to achieve a reduction of 2-log10 CFU/lung from the ratios of AUC72h/MIC were 5.7 mg/kg for serum and 2.5 mg/kg for lung tissue, which lower than the values of 13.2 mg/kg for serum and 8.9 mg/kg for lung tissue with AUC168h/MIC. In addition, using as objective a 2-log10 reduction and an AUC0-72h as the value of the PK/PD index could be more realistic. The results of this study could provide a solid foundation for the application of PK/PD models in research on macrolide antibiotics used to treat respiratory diseases.

7.
Antibiotics (Basel) ; 10(11)2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34827355

RESUMO

This study aimed to determine the global prevalence and molecular characterization of CTX-M-producing Salmonella Typhimurium isolates. A total of 330 (15.2%, 330/21779) blaCTX-M-positive S. Typhimurium were obtained from the public databases in July 2021. Thirteen variants were found in the 330 members of the blaCTX-M group, and blaCTX-M-9 (26.4%, 88/330) was the most prevalent. The majority of blaCTX-M-positive S. Typhimurium were obtained from humans (59.7%, 197/330) and animals (31.5%, 104/330). The number of blaCTX-M-positive S. Typhimurium increased annually (p < 0.0001). These isolates were primarily found from China, the United Kingdom, Australia, the USA, and Germany. In addition, these isolates possessed 14 distinct sequence types (ST), and three predominated: ST34 (42.7%, 141/330), ST19 (37.0%, 122/330), and ST313 (10.3%, 34/330). The majority of ST34 S. Typhimurium isolates were distributed in China and mainly from swine. However, the majority of ST19 were distributed in the United Kingdom and Australia. Analysis of contigs showed that the major type of blaCTX-M-carrying plasmid was identified as IncI plasmid (52.9%, 27/51) and IncHI2 plasmid (17.6%, 9/51) in 51 blaCTX-M-positive S. Typhimurium isolates. In addition, WGS analysis further revealed that blaCTX-M co-existed with nine antibiotic-resistant genes with a detection rate over 50%, conferring resistance to five classes of antimicrobials. The 154 virulence genes were detected among these isolates, of which 107 virulence genes were highly common. This study revealed that China has been severely contaminated by blaCTX-M-positive S. Typhimurium isolates, these isolates possessed numerous ARGs and virulence genes, and highlighted that continued vigilance for blaCTX-M-positive S. Typhimurium in animals and humans is urgently needed.

8.
Front Cell Dev Biol ; 9: 803181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34993205

RESUMO

Chlorpyrifos (CPF), a widely used organophosphate pesticide, is reported to severely impair mammalian reproductive system. Pterostilbene (PTS), an effective free radical scavenger, is considered as beneficial for mammalian reproduction. However, the toxicity of CPF on oocyte maturation and whether PTS can eliminate the detrimental effect of CPF on oocytes remain unclear. Here, porcine oocytes were applied to investigate the potential effect and possible mechanism of CPF and PTS during oocyte maturation. This work demonstrated that CPF significantly delayed the meiotic progression and decreased the polar body extrusion by disturbing spindle assembly and chromosome alignment and causing DNA damage in oocytes (p < 0.05). And, CPF significantly impaired oocyte cytoplasmic maturation by inducing the high level of reactive oxygen species and decreasing glutathione content (p < 0.05). Moreover, CPF significantly triggered embryo apoptosis and reduced the blastocyst rate and cell number following parthenogenetic activation (p < 0.05). Whereas CPF-exposed oocytes were treated with PTS, these defects caused by CPF were obviously rescued, and oocyte maturation and subsequent embryonic development were also significantly ameliorated (p < 0.05). In conclusion, these results revealed that CPF exerted the toxic effect on porcine oocytes, while PTS effectively alleviated CPF-induced damage on oocytes. This work provides a potential strategy to protect oocyte maturation in mammalian species.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30476621

RESUMO

INTRODUCTION: Haemophilus parasuis, one of the major swine pathogens, has at least fifteen different types, all of which have significant economic effects on the global swine industry. The aim of this study was to establish an experimental intraperitoneal infection model for H. parasuis in neutropenic guinea pigs. METHODS: Intraperitoneal administration of cyclophosphamide and Haemophilus parasuis was conducted in guinea pigs. Clinical signs, gross pathology, and histopathology were observed in neutropenic guinea pigs infected with H. parasuis. RESULTS: Intraperitoneal administration of 100 mg/kg cyclophosphamide led to immunosuppression with white blood cells, lymphocytes, and neutrophils all <1000 mm3, while no histological tissue damage was observed. Intraperitoneal administration of 109 colony-forming units (CFU) of H. parasuis led to typical respiratory symptoms, 90% morbidity, and 20% mortality in a 72 h-period. Bacteriological screening revealed that multiple organs, including the heart, liver, spleen, lungs, kidneys, and blood, were infected with H. parasuis. The threshold loads of bacteria in blood and the lungs were (7.04 ±â€¯0.53)log10 CFU/mL and (6.24 ±â€¯0.62)log10 CFU/g, respectively, at 3 d after infection. Gross pathology examination showed celiac effusion, intestinal mucosal hemorrhage, and liver, spleen, or lung swelling, necrosis, and hemorrhage. Congestion, mild interstitial pneumonia, inflammatory exudation, and endothelial cell proliferation were observed in the histological examination. DISCUSSION: All the results suggest that we have established an experimental intraperitoneal infection model for H. parasuis in neutropenic guinea pigs. It is especially useful as a tool for pharmacokinetics, pharmacodynamics, or a pharmacokinetics/pharmacodynamics (PK/PD) model of antimicrobial agents against respiratory disease.


Assuntos
Modelos Animais de Doenças , Infecções por Haemophilus/imunologia , Haemophilus parasuis/imunologia , Imunossupressores/administração & dosagem , Modelos Animais , Neutropenia/induzido quimicamente , Animais , Ciclofosfamida/administração & dosagem , Feminino , Cobaias , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/patogenicidade , Injeções Intraperitoneais , Pulmão , Masculino , Camundongos , Neutropenia/imunologia , Suínos
10.
Can J Vet Res ; 82(4): 256-263, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30363376

RESUMO

Pseudomonas aeruginosa is an important animal pathogen and contributes to hemorrhagic pneumonia in mink. Between April 2011 and December 2016, samples of lung, liver, and spleen were collected from mink with this disease on 11 mink farms in 5 Chinese provinces. From these samples, we obtained 98 isolates of P. aeruginosa that belonged to 5 serotypes: G (n = 58), I (n = 15), C (n = 8), M (n = 5), and B (n = 2); 10 isolates were not typeable (10/98). More than 90% of the isolates formed biofilms, and 85% produced slime. All 98 isolates were resistant to 10 antibiotics (oxacillin, ampicillin, penicillin G, amoxicillin, ceftriaxone, cefazolin, cefaclor, tilmicosin, tildipirosin, and sulfonamide). However, almost all were susceptible to gentamicin, polymyxin B, and amikacin. We identified 56 unique genotypes by pulsed-field gel electrophoresis. These findings have revealed genetic diversity and high antimicrobial resistance in P. aeruginosa isolated from mink with hemorrhagic pneumonia and will facilitate the prevention and control of this disease.


Pseudomonas aeruginosa est un agent pathogène animal important et contribue à la pneumonie hémorragique du vison. Entre avril 2011 et décembre 2016, des échantillons de poumon, foie, et rate ont été prélevés de visons avec cette condition dans 11 élevages retrouvés dans cinq provinces chinoises. À partir de ces échantillons nous avons obtenu 98 isolats de P. aeruginosa qui appartenaient à cinq sérotypes : G (n = 58), I (n = 15), C (n = 8), M (n = 5), et B (n = 2); 10 isolats étaient non-typables (10/98). Plus de 90 % des isolats produisaient du biofilm, et 85 % produisaient de la substance visqueuse. Les 98 isolats étaient résistants à 10 antibiotiques (oxacilline, ampicilline, pénicilline G, amoxicilline, ceftriaxone, céfazolin, céfaclor, tilmicosine, tildipirosine, et sulfonamide). Toutefois, presque tous étaient sensibles à la gentamycine, la polymyxine B, et l'amikacine. Nous avons identifié 56 génotypes uniques par électrophorèse en champs pulsés. Ces résultats ont révélé une diversité génétique et une résistance élevée aux antibiotiques chez les isolats de P. aeruginosa provenant de visons avec la pneumonie hémorragique et faciliteront la prévention et la maitrise de cette maladie.(Traduit par Docteur Serge Messier).


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Vison/microbiologia , Epidemiologia Molecular , Infecções por Pseudomonas/veterinária , Pseudomonas aeruginosa/genética , Animais , China/epidemiologia , Eletroforese em Gel de Campo Pulsado , Variação Genética , Genótipo , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/veterinária , Pseudomonas aeruginosa/efeitos dos fármacos
11.
PeerJ ; 6: e5040, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29915708

RESUMO

BACKGROUND: Haemophilus parasuis is a commensal organism of the upper respiratory tract of healthy pigs and causes high morbidity and mortality in piglets. The aim of this study was to investigate the epidemiology of H. parasuis in China from 2014 to 2017. METHODS: We characterized 143 H. parasuis isolates by serotyping, antimicrobial susceptibility, biofilm formation and with enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) assays. RESULTS: Serotyping revealed serovar 5 as the most prevalent (26.6%) followed by serovars 4 (22.4%), 7 (9.1 %), 13 (6.3%), 12 (5.6 %), and non-typeable (8.4%). In a panel of 23 antimicrobials, the minimum inhibitory concentration 50% (MIC50) were in the range of 0.25-16 µg/mL and MIC90 were 2->512 µg/mL. A total of 99 isolates of H. parasuis (69.2%) were able to form biofilms and 59.6% (59/99) performed weak biofilm-forming ability. ERIC-PCR revealed a very heterogeneous pattern with 87 clusters. DISCUSSION: These H. parasuis isolates showed a high serovar and genotypic lineage diversity, different abilities to form biofilms and a high degree of genetic diversity. Biofilm formation was related to antimicrobial susceptibility but there were no statistically significant associations between the antimicrobial susceptibility and either the serovars or the ERIC-PCR clusters. This study showed a high prevalence of high-MIC H. parasuis strains and suggests the need for a continuous surveillance of clinical isolates of H. parasuis.

12.
PeerJ ; 6: e4613, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666765

RESUMO

BACKGROUND: Haemophilus parasuis is a common porcine respiratory pathogen that causes high rates of morbidity and mortality in farmed swine. We performed a molecular characterization of antimicrobial resistance genes harbored by H. parasuis from pig farms in China. METHODS: We screened 143 H. parasuis isolates for antimicrobial susceptibility against six fluoroquinolone antibiotics testing by the broth microdilution method, and the presence of 64 antimicrobial resistance genes by PCR amplification and DNA sequence analysis. We determined quinolone resistance determining region mutations of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE). The genetic relatedness among the strains was analyzed by pulsed-field gel electrophoresis. RESULTS: Susceptibility test showed that all isolates were low resistance to lomefloxacin (28.67%), levofloxacin (20.28%), norfloxacin (22.38%), ciprofloxacin (23.78%), however, high resistance levels were found to nalidixic acid (82.52%) and enrofloxacin (55.94%). In addition, we found 14 antimicrobial resistance genes were present in these isolates, including blaTEM-1, blaROB-1, ermB, ermA, flor, catl, tetB, tetC, rmtB, rmtD, aadA1, aac(3')-llc, sul1, and sul2 genes. Interestingly, one isolate carried five antibiotic resistance genes (tetB, tetC, flor, rmtB, sul1). The genes tetB, rmtB, and flor were the most prevalent resistance genes in H. parasuis in China. Alterations in the gyrA gene (S83F/Y, D87Y/N/H/G) were detected in 81% of the strains and parC mutations were often accompanied by a gyrA mutation. Pulsed-field gel electrophoresis typing revealed 51 unique patterns in the isolates carrying high-level antibiotic resistance genes, indicating considerable genetic diversity and suggesting that the genes were spread horizontally. DISCUSSION: The current study demonstrated that the high antibiotic resistance of H. parasuis in piglets is a combination of transferable antibiotic resistance genes and multiple target gene mutations. These data provide novel insights for the better understanding of the prevalence and epidemiology of antimicrobial resistance in H. parasuis.

13.
PLoS One ; 13(12): e0209177, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30596709

RESUMO

The objective of the study was to develop an ex-vivo PK/PD model of intramuscular (IM) administration of tulathromycin and to test its efficacy against Haemophilus parasuis (H. parasuis) infection in intraperitoneal-inoculated neutropenic guinea pigs. The pharmacokinetics (PKs) of tulathromycin at doses of 1 and 10 mg/kg in H. parasuis-infected neutropenic guinea pig were studied by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). In vitro minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutant prevention concentration (MPC), post-antibiotic effect (PAE) and dynamic time-kill curve experiments were carried out using H. parasuis strain 13R. Tulathromycin exhibited concentration-dependent activity and PAE persisted long after administration of the antibiotic. The ratio of the 24-h area under the concentration-time curve (AUC) to MIC in serum (AUC24h/MICserum) was recognized as an important PK/PD parameter that positively correlated with the in vitro antibacterial effectiveness of tulathromycin (R2 = 0.9961 or R2 = 1). For the 1 and 10 mg/kg treatments with tulathromycin, the values of AUC24h/MIC for H. parasuis bacteriostatic action, bactericidal action and virtual bacterial eradication were respectively 22.73, 34.5 and 88.03 h for the 1 mg/kg treatment and respectively 24.94, 30.94 and 49.92 h for the 10 mg/kg treatment. In addition, we demonstrated that doses of 7.2-8.0 mg/kg of tulathromycin resulted in high eradication rates (99.99%). Using a previously published conversion factor of 0.296, we were able to estimate an approximate dose, 2.1-2.4 mg/kg, that should also obtain high eradication rates in the target animal, pigs. This study can help optimize tulathromycin efficacy against H. parasuis infections in swine farming.


Assuntos
Dissacarídeos/farmacologia , Haemophilus parasuis/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Animais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Dissacarídeos/sangue , Dissacarídeos/farmacocinética , Dissacarídeos/uso terapêutico , Cobaias , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/microbiologia , Meia-Vida , Compostos Heterocíclicos/sangue , Compostos Heterocíclicos/farmacocinética , Compostos Heterocíclicos/uso terapêutico , Testes de Sensibilidade Microbiana , Modelos Biológicos , Curva ROC , Espectrometria de Massas em Tandem
14.
J Mater Sci Mater Med ; 24(4): 903-10, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23354736

RESUMO

Drug delivery systems based on polymer microspheres have received considerable attention. Ceftiofur sodium and ceftiofur hydrochloride is widely used for the treatment of bacterial diseases in animals but the delivery in vivo has not been reported. In this paper, we report the synthesis of microspheres from gelatin and PLGA, two kinds of typical natural and artificial materials, for loading ceftiofur and the in vivo investigation of the pharmacokinetics in beagle dogs. By controlling the synthesis parameters, gelatin and PLGA microspheres with diameter between 5 and 35 microns were obtained. Assay procedures based on high performance liquid chromatography were evaluated and confirmed. The dogs were randomly divided into three groups, i.e., control group, gelatin group, and PLGA group and administrated via intravenous injection. Plasma concentrations of ceftiofur over time were measured and analyzed. Results indicate that the main kinetic parameters do not show significant difference for the gelatin group and control group, but the area under the curve, plasma half-life, apparent volume of distribution, and clearance ratio of PLGA group show significant difference from the gelatin group and the control group. The PLGA microspheres show a low area under the curve but long time release.


Assuntos
Cefalosporinas/administração & dosagem , Gelatina/administração & dosagem , Ácido Láctico/administração & dosagem , Microesferas , Ácido Poliglicólico/administração & dosagem , Animais , Cromatografia Líquida de Alta Pressão , Cães , Masculino , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
15.
J Antimicrob Chemother ; 66(3): 539-42, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21217127

RESUMO

OBJECTIVES: To perform molecular characterization of fluoroquinolone-resistant Haemophilus parasuis isolated from South China. METHODS: H. parasuis isolates were investigated for quinolone and fluoroquinolone susceptibility and screened for plasmid-mediated quinolone resistance (PMQR) determinants by PCR amplification and DNA sequence analysis. Additionally, quinolone resistance-determining region (QRDR) mutations of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) were determined. The genetic relatedness among the strains was analysed by PFGE. RESULTS: These H. parasuis isolates showed higher MIC values of nalidixic acid, enrofloxacin, ciprofloxacin, levofloxacin, norfloxacin and lomefloxacin. Moreover, qnrA1, qnrB6 and aac(6')-Ib-cr were present in 2.61%, 0.87% and 2.61% of the 115 isolates, respectively. One strain possessed both aac(6')-Ib-cr and qnrA1. Mutation analysis of QRDRs showed that the resistant strains carried at least one mutation in gyrA (at codon 83 or 87), but no mutation was detected in gyrB. PFGE analysis showed great genetic diversity among these resistant H. parasuis strains. CONCLUSIONS: The data presented here highlight the presence of qnr and aac(6')-Ib-cr genes in H. parasuis strains from South China. Moreover, the gyrA (at codon 83 or 87) mutation is linked to fluoroquinolone resistance in H. parasuis. Transferable PMQR determinants and multiple target gene mutations play important roles in the fluoroquinolone resistance of H. parasuis. These data provide important insights into the mechanism of fluoroquinolone resistance in H. parasuis, thereby highlighting the usefulness of fluoroquinolones for the treatment and control of this infection.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/efeitos dos fármacos , Haemophilus parasuis/genética , Doenças dos Suínos/microbiologia , Animais , Técnicas de Tipagem Bacteriana , China , Análise por Conglomerados , DNA Girase/genética , DNA Topoisomerase IV/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Eletroforese em Gel de Campo Pulsado , Genótipo , Infecções por Haemophilus/microbiologia , Haemophilus parasuis/isolamento & purificação , Dados de Sequência Molecular , Tipagem Molecular , Plasmídeos , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Suínos
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