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1.
Int J Biomater ; 2019: 1063643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001340

RESUMO

Surgical meshes have become the standard procedure for a variety of surgical applications with 20 million meshes being implanted each year. The popularity of mesh usage among surgeons is backed by the multiple studies that support its functionality as a tool for improving surgical outcomes. However, their use has also been associated with infectious surgical complications and many surgeons have turned to biologic meshes. While there have been several studies investigating synthetic meshes, there is limited data comparing synthetic and biologic meshes in vitro in an infection model. This study evaluates the in vitro susceptibility of both synthetic and biologic meshes to single-species methicillin-resistant Staphylococcus aureus (MRSA) biofilms. This research compares biofilm biomass, average thickness, and coverage between the three meshes through florescent in situ hybridization (FISH), confocal scanning microscopy (CSLM), and image analysis. We also report the varying levels of planktonic and attached bacteria through sonication and cfu counts. While the data illustrates increased biofilm formation on biologic mesh in vitro, the study must further be investigated in vivo to confirm the study observations.

2.
PLoS One ; 11(3): e0149891, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26977929

RESUMO

Haemophilus influenzae is an opportunistic pathogen. The emergence of virulent, non-typeable strains (NTHi) emphasizes the importance of developing new interventional targets. We screened the NTHi supragenome for genes encoding surface-exposed proteins suggestive of immune evasion, identifying a large family containing Sel1-like repeats (SLRs). Clustering identified ten SLR-containing gene subfamilies, each with various numbers of SLRs per gene. Individual strains also had varying numbers of SLR-containing genes from one or more of the subfamilies. Statistical genetic analyses of gene possession among 210 NTHi strains typed as either disease or carriage found a significant association between possession of the SlrVA subfamily (which we have termed, macrophage survival factor, msf) and the disease isolates. The PittII strain contains four chromosomally contiguous msf genes. Deleting all four of these genes (msfA1-4) (KO) resulted in a highly significant decrease in phagocytosis and survival in macrophages; which was fully complemented by a single copy of the msfA1 gene. Using the chinchilla model of otitis media and invasive disease, the KO strain displayed a significant decrease in fitness compared to the WT in co-infections; and in single infections, the KO lost its ability to invade the brain. The singly complemented strain showed only a partial ability to compete with the WT suggesting gene dosage is important in vivo. The transcriptional profiles of the KO and WT in planktonic growth were compared using the NTHi supragenome array, which revealed highly significant changes in the expression of operons involved in virulence and anaerobiosis. These findings demonstrate that the msfA1-4 genes are virulence factors for phagocytosis, persistence, and trafficking to non-mucosal sites.


Assuntos
Genes Bacterianos , Haemophilus influenzae/patogenicidade , Virulência/genética , Sequência de Aminoácidos , Animais , Chinchila , Cromossomos Bacterianos , Haemophilus influenzae/genética , Macrófagos/microbiologia , Modelos Animais , Dados de Sequência Molecular , Filogenia
3.
BMC Cancer ; 16: 52, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26841926

RESUMO

BACKGROUND: Toll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR-mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis. METHODS: We surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization. RESULTS: Gene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett's esophagus (60%) and esophageal adenocarcinoma (100%), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett's esophagus (50-70%) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20-30%). E. coli was detected in the Barrett's esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups. CONCLUSIONS: We demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Receptores Toll-Like/genética , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Animais , Esôfago de Barrett/microbiologia , Esôfago de Barrett/patologia , Carcinogênese/genética , Modelos Animais de Doenças , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Neoplasias Esofágicas/microbiologia , Neoplasias Esofágicas/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Microbiota/genética , Ratos , Transdução de Sinais/genética , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/patogenicidade , Receptores Toll-Like/biossíntese
4.
Expert Opin Drug Saf ; 10(6): 883-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21545242

RESUMO

INTRODUCTION: Depression during pregnancy can affect up to 20% of all women and may be treated effectively with antidepressants. Currently, information on > 20,000 women exposed to antidepressants with pregnancy outcomes is available in the literature. However, there is a continuing fear of physicians prescribing and women taking these drugs during pregnancy, probably due to many of the studies reporting conflicting outcomes and subsequently, the dissemination of these results. AREAS COVERED: The authors searched the literature using Medline, Embase and Reprotox followed by a manual search of retrieved articles and reviews of the topic. The authors then selected key publications in this field which they considered relevant to the subsequent discussion of this topic. EXPERT OPINION: In this review, the authors evaluate the safety of different classes of antidepressants and find no convincing evidence of an increased risk for any adverse outcomes in an appreciable fashion. The authors note that even in studies documenting a potential for harm, the risk is marginal with rarely an odds ratio above 2. Therefore, it is important that each woman discusses the risks/benefits of treatment with her healthcare provider to allow an informed decision to be made based on scientific evidence.


Assuntos
Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/psicologia , Resultado da Gravidez , Animais , Ensaios Clínicos como Assunto , Feminino , Humanos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
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