36 research outputs found
Management of histoplasmosis by infectious disease physicians
BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines for the management of histoplasmosis were last revised 15 years ago. Since those guidelines were compiled, new antifungal treatment options have been developed. Furthermore, the ongoing development of immunomodulatory therapies has increased the population at increased risk to develop histoplasmosis.
METHODS: An electronic survey about the management practices of histoplasmosis was distributed to the adult infectious disease (ID) physician members of the IDSA\u27s Emerging Infections Network.
RESULTS: The survey response rate was 37% (551/1477). Only 46% (253/551) of respondents reported seeing patients with histoplasmosis. Regions considered endemic had 82% (158/193) of physicians report seeing patients with histoplasmosis compared to 27% (95/358) of physicians in regions not classically considered endemic (
CONCLUSIONS: Though there are increased reports of histoplasmosis diagnoses outside regions classically considered endemic, a majority of ID physicians reported not seeing patients with histoplasmosis. Most respondents reported adherence to IDSA guidelines recommending itraconazole in each clinical situation. New histoplasmosis guidelines need to reflect the growing need for updated general guidance, particularly for immunocompromised populations
Mechanistic definition of the cardiovascular mPGES-1/COX-2/ADMA axis
Aims: Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of eNOS, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA. Methods and Results: Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalisation of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors. Conclusions: These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA
Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy
Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible for the latter. To elucidate the role of POX in oxLDL-mediated cytotoxicity, we knocked down POX via small interfering RNA and found that this (i) further reduced viability of cancer cells treated with oxLDL; (ii) decreased oxLDL-associated reactive oxygen species generation; (iii) decreased autophagy measured via beclin-1 protein level and light-chain 3 protein (LC3)-I into LC3-II conversion. Using POX-expressing cell model, we established that single POX overexpression was sufficient to activate autophagy. Thus, it led to autophagosomes accumulation and increased conversion of LC3-I into LC3-II. Moreover, beclin-1 gene expression was directly dependent on POX catalytic activity, namely the generation of POX-dependent superoxide. We conclude that POX is critical in the cellular response to the noxious effects of oxLDL by activating protective autophagy
Antimicrobial resistance of Campylobacter isolates from small scale and backyard chicken in Kenya
Background Thermophilic Campylobacter species are a major cause of bacterial
foodborne diarrhoea in humans worldwide. Poultry and their products are the
predominant source for human campylobacteriosis. Resistance of Campylobacter
to antibiotics is increasing worldwide, but little is known about the
antibiotic resistance in Campylobacter isolated from chicken in Kenya. In this
study, 35 suspected Campylobacter strains isolated from faeces and cloacal
swabs of chicken were tested for their susceptibility to seven antibiotics
using a broth microdilution assay and molecular biological investigations.
Results Overall, DNA of thermophilic Campylobacter was identified in 53
samples by PCR (34 C. jejuni, 18 C. coli and one mix of both species) but only
35 Campylobacter isolates (31 C. jejuni and 4 C. coli) could be re-cultivated
after transportation to Germany. Isolates were tested for their susceptibility
to antibiotics using a broth microdilution assay. Additionally, molecular
biological detection of antibiotic resistance genes was carried out. C. jejuni
isolates showed a high rate of resistance to nalidixic acid, tetracycline and
ciprofloxacin of 77.4, 71.0 and 71.0 %, respectively. Low resistance (25.8 %)
was detected for gentamicin and chloramphenicol. Multidrug resistance in C.
jejuni could be detected in 19 (61.3 %) isolates. Resistance pattern of C.
coli isolates was comparable. Resistance to ciprofloxacin was confirmed by
MAMA–PCR and PCR–RFLP in all phenotypically resistant isolates. The tet(O)
gene was detected only in 54.5 % of tetracycline resistant C. jejuni isolates.
The tet(A) gene, which is also responsible for tetracycline resistance, was
found in 90.3 % of C. jejuni and in all C. coli isolates. Thirteen
phenotypically erythromycin-resistant isolates could not be characterised by
using PCR–RFLP and MAMA–PCR. Conclusions To the best of our knowledge, this
study is the first report about resistance to antibiotics in thermophilic
Campylobacter originating from chicken in Kenya. Campylobacter spp. show a
high level of resistance to ciprofloxacin, nalidixic acid and tetracycline but
also a remarkable one to chloramphenicol and gentamicin and they are multidrug
resistant. Resistance to antibiotics is a global public health concern. In
Kenya, resistance surveillance needs further attention in the future. Efforts
to establish at least a National Laboratory with facilities for performing
phenotypic and genotypic characterization of thermophilic Campylobacter is
highly recommended
Genotyping and antibiotic resistance of thermophilic Campylobacter isolated from chicken and pig meat in Vietnam
Background Campylobacter species are recognized as the most common cause of
foodborne bacterial gastroenteritis in humans. In this study nine
Campylobacter strains isolated from chicken meat and pork in Hanoi, Vietnam,
were characterized using molecular methods and tested for antibiotic
resistance. Results The nine isolates (eight C. jejuni and one C. coli) were
identified by multiplex PCR, and tested for the presence or absence of 29 gene
loci associated with virulence, lipooligosaccharide (LOS) biosynthesis and
further functions. flaA typing, multilocus sequence typing and microarray
assay investigation showed a high degree of genetic diversity among these
isolates. In all isolates motility genes (flaA, flaB, flhA, fliM),
colonization associated genes (cadF, docB), toxin production genes (cdtA,
cdtB, secD, secF), and the LOS biosynthesis gene pglB were detected. Eight
gene loci (fliY, virB11, Cje1278, Cj1434c, Cj1138, Cj1438c, Cj1440c, Cj1136)
could not be detected by PCR. A differing presence of the gene loci ciaB (22.2
%), Cje1280 (77.8 %), docC (66.7 %), and cgtB (55.6 %) was found. iamA, cdtC,
and the type 6 secretion system were present in all C. jejuni isolates but not
in C. coli. flaA typing resulted in five different genotypes within C. jejuni,
MLST classified the isolates into seven sequence types (ST-5155, ST-6736,
ST-2837, ST-4395, ST-5799, ST-4099 and ST-860). The microarray assay analysis
showed a high genetic diversity within Vietnamese Campylobacter isolates which
resulted in eight different types for C. jejuni. Antibiotic susceptibility
profiles showed that all isolates were sensitive to gentamicin and most
isolates (88.8 %) were sensitive to chloramphenicol, erythromycin and
streptomycin. Resistance rates to nalidixic acid, tetracycline and
ciprofloxacin were 88.9, 77.8 and 66.7 %, respectively. Conclusions To the
best of our knowledge, this study is the first report that shows high genetic
diversity and remarkable antibiotic resistance of Campylobacter strains
isolated from meat in Vietnam which can be considered of high public health
significance. These preliminary data show that large scale screenings are
justified to assess the relevance of Campylobacter infections on human health
in Vietnam
Trends in antibiotic sensitivity pattern and molecular detection of tet(O)-mediated tetracycline resistance in Campylobacter jejuni isolates from human and poultry sources
This study was conducted to determine the trends in Campylobacter antibiotic resistance occurring in our setting and to assess the differences in the isolates using patterns of plasmid profiles. One hundred Campylobacter jejuni strains of human and poultry origin isolated in 2002-2003 (phase A) and 2005-2006 (phase B) in the Kingdom of Bahrain were evaluated. Susceptibility to erythromycin, ciprofloxacin and tetracycline was determined, and plasmid extraction and polymerase chain reaction detection of the tet(O) gene was carried out. A single erythromycin-resistant isolate was identified, in sharp contrast to the high ciprofloxacin resistance which also showed an increment in phase B. Tetracycline resistance was higher in chicken (80.9%) compared to human (41.3%) isolates (P < 0.01). Most isolates harbored two plasmids (23 kb and 35 kb) with significant correlation between tetracycline resistance and plasmid carriage in chicken isolates. The findings show continued effectiveness of erythromycin for campylobacteriosis but an increasing trend of high ciprofloxacin and tetracycline resistance. Tetracycline resistance is most likely due to the transfer of plasmids carrying the tet(O) gene between isolates