Kinkeliba, <Emphasis Type="Italic">Combretum micranthum</Emphasis> G. Don ou <Emphasis Type="Italic">Combretum raimbauldii</Emphasis> (<Emphasis Type="Italic">Combrétacées</Emphasis>)

Sans résumé     

Ginseng <Emphasis Type="Italic">versus</Emphasis> ginseng

Sans résumé     

Microbial substitution of <Emphasis Type="Italic">Mycobacterium avium-intracellulare</Emphasis> to <Emphasis Type="Italic">Mycobacterium abscessus</Emphasis> during clinical course

Mycobacterium avium-intracellulare (MAI) is, among acid-fast bacilli, the most common cause of nontuberculous pulmonary diseases, and MAI infections are often treated according to the guidelines of the American Thoracic Society. However, despite the use of multiple drugs, patients sometimes do not recover with the initial round of treatment. Other kinds of nontuberculous mycobacteria are sometimes found in patients' respiratory samples, even during such treatment for MAI pulmonary disease. We experienced three patients with pulmonary disease due to Mycobacterium abscessus (MA) in whom the disease was difficult to treat because of resistance to all the antituberculous agents used. MA infection had occurred in these patients after long-term treatment with multiple drugs for previous MAI pulmonary disease. We considered that the MA infection in these patients appeared to be the result of insufficient efficacy of the drugs used for MAI and insufficiently aggressive use of antituberculous agents. It thus appeared that MA infection was the result of microbial substitution, and that, if this is the case, the guidelines for the treatment of MAI may need to be modified to eliminate microbial substitution.     

Dissemination of extended-spectrum β-lactamase-producing <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> and <Emphasis Type="Italic">Escherichia coli</Emphasis> in Thai hospitals

Fifty clinical isolates of Klebsiella pneumoniae and Escherichia coli with reduced susceptibility to third-generation cephalosporins, collected from 11 hospitals in Thailand, were studied. All isolates were found to produce extended-spectrum β-lactamase (ESBL), as judged by double-disk synergy and combination disk methods. Most ESBL-producing K. pneumoniae isolates were resistant to ceftazidime (94%) and aztreonam (90%). In contrast, most ESBL-producing E. coli isolates were resistant to ceftriaxone (95%) and cefotaxime (74%). Plasmid DNA was isolated and β-lactamase genes were identified by PCR and sequencing. We found that SHV-12 and CTX-M-14 were the main ESBLs responsible for resistance in K. pneumoniae and E. coli, respectively. SHV-27, SHV-28, and CTX-M-14 were detected in three, two, and four K. pneumoniae isolates, respectively. A high genetic diversity among ESBL-producing K. pneumoniae and E. coli isolates was observed. In addition, the finding of a few isolates that produced identical restriction patterns on pulsed field gel electrophoresis (PFGE) suggests the clonal spread of resistant bacteria within the hospital.     

Characterization of oxacillin-susceptible <Emphasis Type="Italic">mecA</Emphasis>-positive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>: a new type of MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) has been defined as S. aureus having the mecA gene or showing a minimum inhibitory concentration (MIC) of oxacillin higher than 4 mg/l. However, some clinical isolates are mecA-positive and oxacillin-susceptible. Therefore, we surveyed the occurrence of S. aureus having the mecA gene and an MIC of oxacillin of less than 2 mg/l (oxacillin-susceptible MRSA; OS-MRSA) in a total of 480 strains of S. aureus collected from 11 hospitals in different location in Japan isolated from 2003 through 2005. We found 6 strains matching the criteria for OS-MRSA. All 6 strains were staphylococcal cassette chromosome (SCC) mec-positive, without exception, and 4 strains showed the SCCmec type III-variant, which is unique in Japan. These OS-MRSAs were least resistant to oxacillin among the MRSAs tested and they were within the susceptible range to seven other beta-lactam antibiotics tested. Thus, OS-MRSA may become a high-resistant MRSA upon the treatment of patients with beta-lactam antibiotics. To characterize whether these OS-MRSAs were hospital-acquired or community-acquired MRSAs, we tested for the presence of the genes encoding toxins. Genes encoding hemolysin, exfoliative toxin, enterotoxin, toxic shock syndrome toxin-1, and Panton-Valentine leukocidin were found in 6, 4, 0, 0, and 0 strains, respectively. These results revealed that OS-MRSAs could be classified as a new type of MRSA that exhibits properties distinguishable from either hospital- or community-acquired MRSA. Coagulase typing of the OS-MRSAs supported the above conclusion. In this study, the occurrence of OS-MRSA at a certain frequency was noted; precautions are called for in the classification of oxacillin-resistant S. aureus and in the treatment of OS-MRSA infection.     

First isolation of <Emphasis Type="Italic">bla</Emphasis><Subscript>IMP-7</Subscript> in a <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> in Japan

We report here the first isolation in Japan of a carbapenem-resistant Pseudomonas aeruginosa strain that carries the metallo-β-lactamase gene bla _IMP-7. This isolate revealed high-level resistance to all of the tested antibiotics except for piperacillin, showing a multidrug-resistant phenotype.     

Animal Models of Neurodegenerative Disease: Insights from <Emphasis Type="Italic">In vivo</Emphasis> Imaging Studies

Animal models have been used extensively to understand the etiology and pathophysiology of human neurodegenerative diseases, and are an essential component in the development of therapeutic interventions for these disorders. In recent years, technical advances in imaging modalities such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have allowed the use of these techniques for the evaluation of functional, neurochemical, and anatomical changes in the brains of animals. Combining animal models of neurodegenerative disorders with neuroimaging provides a powerful tool to follow the disease process, to examine compensatory mechanisms, and to investigate the effects of potential treatments preclinically to derive knowledge that will ultimately inform our clinical decisions. This article reviews the literature on the use of PET and MRI in animal models of Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease, and evaluates the strengths and limitations of brain imaging in animal models of neurodegenerative diseases.     

Molecular epidemiology of uropathogenic <Emphasis Type="Italic">Escherichia coli</Emphasis>

Escherichia coli is the most common cause of complicated as well as uncomplicated urinary tract infections (UTIs). Most of these uropathogenic E. coli (UPEC) strains exhibit certain virulence factors (VFs), including adhesins, iron uptake systems, synthesis of cytotoxins, and specific O:K:H serotypes. Molecular epidemiological studies of UPEC have contributed to the discovery of uropathogenic VFs, to an understanding of the pathogenesis of UTIs as ascending infections, and to the clarification of genetic linkages between different virulence genes such as pathogenicity islands (PAIs), which are one of the mechanisms for horizontal VF gene transfers between the same or related species. Uropathogenic VFs not only play an important role individually but also work cooperatively in a fine-tuned manner with coordinated regulation and expression.     

Impact of restriction of third generation cephalosporins on the burden of third generation cephalosporin resistant <Emphasis Type="Italic">K. pneumoniae</Emphasis> and <Emphasis Type="Italic">E. coli</Emphasis> in an ICU

Objective  To test whether a reduction of third generation cephalosporin (3GC) use has a sustainable positive impact on the high endemic prevalence of 3GC resistant K. pneumoniae and E. coli. Design  Segmented regression analysis of interrupted time series was used to analyse antibiotic consumption and resistance data 30 months before and 30 after the intervention. Setting  Surgical intensive care unit (ICU) with 16-bed unit in a teaching hospital. Intervention  In July 2004, 3GCs were switched to piperacillin in combination with a β-lactamase-inhibitor as standard therapy for peritonitis and other intraabdominal infections. Results  Segmented regression analysis showed that the intervention achieved a significant and sustainable decrease in the use of 3GCs of −110.2 daily defined doses (DDD)/1,000 pd. 3GC use decreased from a level of 178.9 DDD/1,000 pd before to 68.7 DDD/1,000 pd after the intervention. The intervention resulted in a mean estimated reduction in total antibiotic use of 27%. Piperacillin/tazobactam showed a significant increase in level of 64.4 DDD/1,000 pd, and continued to increase by 2.3 DDD/1,000 pd per month after the intervention. The intervention was not associated with a significant change in the resistance densities of 3GC resistant K. pneumoniae and E. coli. Conclusion  Reducing 3GCs does not necessarily impact positively on the resistance situation in the ICU setting. Likewise, replacing piperacillin with β-lactamase inhibitor might provide a selection pressure on 3GC resistant E. coli and K. pneumoniae. To improve resistance, it might not be sufficient to restrict interventions to a risk area.     

Chronic <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection is associated with peripheral arterial disease

It is reported that Helicobacter pylori infection is associated with coronary atherosclerosis both epidemiologically and pathogenetically, but no conclusions have yet been reached. Therefore, we investigated the relationship between H. pylori infection and peripheral arterial disease (PAD). Sixty-nine patients with PAD attending Harasanshin General Hospital (Fukuoka, Japan) were compared with 143 controls (age-matched asymptomatic outpatients with hyperlipidemia). H. pylori infection was diagnosed by the detection of IgG antibodies, the (13)C-urea breath test, and histological examination. Multiple logistic regression analysis was used to assess the data. The 69 PAD patients and 143 controls were aged from 50 to 92 years. According to the Fontaine classification, 43/69 PAD patients (62.3%) were grade I, 25 (36.2%) were grade II, and 1 (0.14%) was grade III. The prevalence of H. pylori infection was higher in the PAD patients than in the controls (79.7% versus 44.8%; P < 0.01). Stepwise logistic regression analysis revealed that H. pylori infection and hypertension had a significant influence on the occurrence of PAD. Our results suggest that chronic H. pylori infection may be one of the risk factors for PAD.     

Fusion of <Emphasis Type="Italic">Gaussia</Emphasis> Luciferase to an Engineered Anti-carcinoembryonic Antigen (CEA) Antibody for <Emphasis Type="Italic">In Vivo</Emphasis> Optical Imaging

The bioluminescent protein Gaussia luciferase (GLuc) was fused to an anti-carcinoembryonic antigen (CEA) antibody fragment, the diabody, for in vivo optical tumor imaging. A 15-amino acid N-terminal truncation (GLΔ15) resulted in a brighter protein. Fusions of the anti-CEA diabody to full-length GLuc and GLΔ15 retained high affinity for the antigen, emitted light, and exhibited excellent enzymatic stability. In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of diabody-GLΔ15 to CEA-positive xenografts, with a tumor/background ratio of 3.8 ± 0.4 at four hours after tail-vein injection, compared to antigen-negative tumors at 1.3 ± 0.1 (p = 0.001). MicroPET imaging using ¹²⁴I-diabody-GLΔ15 demonstrated specific uptake in the CEA-positive tumor (2.6% ID [injected dose]/g) compared to the CEA-negative tumor (0.4% ID/g) at 21 hours. Although further optimization of this fusion protein may be needed to improve in vivo performance, the diabody-GLΔ15 is a promising optical imaging probe for tumor detection in vivo.