A sequential bioorthogonal dual strategy: ManNAl and SiaNAl as distinct tools to unravel sialic acid metabolic pathways.

Recent methodological developments in metabolic oligosaccharide engineering (MOE) pave the way for tremendous advances in glycobiology. Herein, we propose a Sequential Bioorthogonal Dual Strategy (SBDS) combining the use of two unprotected alkyne-tagged monosaccharide reporters (ManNAl and SiaNAl) with the bioligation of fluorescent probes by copper-catalysed azide-alkyne cycloaddition (CuAAC). With SBDS, we are able to shed light on trafficking and cellular uptake mechanisms of sialic acid. Using their corresponding analogues, we visualized that SiaNAl enters via endocytosis, whereas its biosynthetic intermediate ManNAl uptake is mediated by a yet unknown but specific plasma membrane transporter. Sialin, a lysosomal protein, is shown to be crucial for the export of exogenous sialic acid from lysosomes to the cytosol. Metabolic labeling with alkyne-tagged derivatives of N-acetylneuraminic acid (Neu5Ac) or N-acetylmannosamine (ManNAc) could thus be used to follow endocytosis in physiological vs. pathological conditions.

Genomic deletion marking an emerging subclone of Francisella tularensis subsp. holarctica in France and the Iberian Peninsula.

Francisella tularensis subsp. holarctica is widely disseminated in North America and the boreal and temperate regions of the Eurasian continent. Comparative genomic analyses identified a 1.59-kb genomic deletion specific to F. tularensis subsp. holarctica isolates from Spain and France. Phylogenetic analysis of strains carrying this deletion by multiple-locus variable-number tandem repeat analysis showed that the strains comprise a highly related set of genotypes, implying that these strains were recently introduced or recently emerged by clonal expansion in France and the Iberian Peninsula.

Photocatalytic oxidation of VX-simulation substance.

Experimental studies of photocatalytic oxidation (PCO) of VX-gas simulation substance cysteamine-S-phosphate sodium salt (NaHPO3S-CH2-CH2-NH2, CPSS) at various initial concentrations and pH were undertaken. PCO ultimately resulted in complete mineralisation of CPSS. The PCO byproducts of CPSS include acetate, oxalate and trace amounts of formate ions. The formation rates of acetate and phosphate were equal to the rate of degradation of CPSS, which indicates easy breakage of P-S, C-S and C-N bonds. Sulphate was formed more slowly due to stepwise oxidation of reduced sulphur. Amino group, generally transformed to ammonia, was partially oxidised to nitrite and nitrate in alkaline media. The fastest mineralisation in terms of both TOC degradation and phosphate formation was observed in neutral media. Under neutral media conditions, the PCO rate increased linearly with the CPSS concentration increase. The maximum efficiency by TOC degradation was observed as large as 77 mg per Wh of incident UV flux with quantum efficiency 3.8%.

Antimicrobial susceptibilities of Pasteurella strains isolated from humans.

The in vitro susceptibilities of 192 consecutive clinical strains of Pasteurella spp. isolated between 1996 and 2003 from soft tissue pus (n = 146), respiratory tract specimens (n = 38) and blood (n = 8) were studied by an agar dilution method. All isolates were susceptible to minocycline, cefotaxime, ofloxacin, ciprofloxacin and levofloxacin. Most strains were susceptible to moxifloxacin, amoxicillin, azithromycin and clarithromycin, whereas lower susceptibility rates to telithromycin (89.4%) were observed among respiratory tract isolates.

[Study of 12 epidemical cases of legionnaire's disease occurred in Meurthe-et-Moselle (France) between July and August 2004]. / Etude de douze cas épidémiques de légionellose survenus en Meurthe-et-Moselle en juillet-août 2004.

PATIENTS AND METHOD: To describe epidemiological, clinical, biological, radiological data and therapeutic features of legionnaire's disease during an outbreak occurring in Meurthe-et-Moselle between July-August 2004. RESULTS: 12 cases were recorded including 11 men, 6 smokers, 4 alcoholo-nicotinic, 3 diabetics, 3 with hemopathy, 1 with corticotherapy; in one case no risks factors were found; mean age was 68.5 years [minimum=48; maximum=96]. Nine cases had sudden symptoms. Nine cases had a fever up to 40 degrees C, 9 with dyspnoea, 7 with cough, 7 with a relative bradycardia, 3 with diarrhoea, 3 felt faint, 3 with confusion. Radiology: unilateral unilobe localisation in 10 cases. Biological data: cytolysis in 8 cases, CRP >300 mg/l in 8. The diagnosis confirmed with urinary antigen of Legionella pneumophila serogroup 1 (UrAgLp1) in 12 cases. In 2 cases, UrAgLp1 appeared negative between 3rd and 10th day after the beginning of a treatment although UrAgLp1 was positive before the treatment. In all cases, the first serology realised during first days following occurrence the first symptoms remained negative. Two serology of control in four were positive. One search of L. pneumophila serogroup 1 in sputum was positive in 7. Bitherapy was used in 7 cases with preferential association: fluoroquinolone+rifampicin. Two patients died. Origin of the contamination remains unknown. CONCLUSION: Culture of Legionella is essential, in epidemic context, to compare clinical and environmental Legionella and to locate the origin of contamination.

[Eleven cases of leptospirosis: clinical and microbiological features]. / La leptospirose: étude clinique et microbiologique à propos de 11 cas.

OBJECTIVE: The authors had for aim, to describe clinical and biological features of 11 cases of leptospirosis observed in Lorraine between 1996 and 2002, and to assess the interest of diagnostic methods. PATIENTS AND METHODS: A retrospective study was performed. The inclusion criteria was positive serological test for Leptospira. RESULTS: The contamination was mainly linked to water sports, during the summer holidays. The main symptom was fever, associated with moderate increase of aminotransferase serum level. Leptospira icterohaemorragiae was the most frequently identified serogroup. One 17-year-old male patient died after infection during water sports practice. CONCLUSION: Preventive measures should be considered for people exposed to Leptospira when practicing water sports.

Francisella tularensis bacteremia.

Bacteremia caused by Francisella tularensis is rare and has been reported mainly in the United States and infrequently in Europe. We report herein the first case of bacteremic F. tularensis pneumonia in an immunocompetent individual in southern Europe.

In vitro synergy between cefepime and vancomycin against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis.

The in vitro activity of cefepime combined with vancomycin was assessed by the chequerboard method against 35 clinical isolates of methicillin-susceptible (MSSA, n = 8) or -resistant (MRSA, n = 10) Staphylococcus aureus and methicillin-susceptible (MSSE, n = 9) or -resistant (MRSE, n = 8) Staphylococcus epidermidis and S. aureus ATCC 25923 (MSSA). The combination was synergic against 16 isolates and additive/indifferent against 20. For 10 of the clinical isolates (two MSSA, three MRSA, two MSSE, three MRSE) and the reference strain, the interaction of cefepime and vancomycin was also determined by the time-kill method. Except for one MRSA isolate, synergic killing was demonstrated with clinically achievable concentrations of vancomycin (0.5-1 mg/L) and cefepime (methicillin-susceptible isolates: 0.5-1 mg/L; methicillin-resistant isolates: 2-64 mg/L).

Radioprotective Activity and Synthesis of Siladithioacetals and Germadithioacetals Derived from N-substituted Naphthylethylimidazoline.

A number of organosilicon and organogermanium derivatives and some related compounds including the N-substituted. 2-[1-naphthylmethyl]-2-imidazoline and 2-[1-(1-naphthyl)ethyl]-2-imidazoline have been prepared and the toxicity of some compounds have been determined in mice. In this paper we report the synthesis and the evaluation of the pharmacological activity of new organosilicon and organogermanium, compounds such as sila- and germadithioacetals derived from N-substituted naphthylimidazolne.

Comparison of the in vitro activity of pristinamycin and quinupristin/dalfopristin against Streptococcus pneumoniae.

The in vitro activity of quinupristin/dalfopristin, a new injectable streptogramin, and pristinamycin was evaluated against 200 recently isolated clinical Streptococcus pneumoniae strains expressing various degrees of susceptibility to penicillin G and erythromycin. MICs were determined by the agar dilution method. All strains were susceptible to pristinamycin irrespective of their susceptibility to penicillin G or erythromycin (MIC90: 0.25 mg/L for each phenotype). The activity of quinupristin/dalfopristin was slightly lower than that of pristinamycin against 42 penicillin G-susceptible/erythromycin-susceptible strains (MIC90: 0.5 mg/L), 13 penicillin G-susceptible/erythromycin-resistant strains (MIC90: 1 mg/L), 25 penicillin G-intermediate or -resistant/erythromycin-susceptible strains (MIC90: 0.5 mg/L) and 120 penicillin G-intermediate or -resistant/erythromycin-resistant strains (MIC90: 0.5 mg/L). The activity of both streptogramins was not significantly altered in case of erythromycin resistance. Thus, both streptogramins might be useful for the treatment of penumococcal infections, especially in cases of multiresistant strains.

Value of enterobacterial repetitive intergenic consensus PCR for study of Pasteurella multocida strains isolated from mouths of dogs.

Fifty-six Pasteurella multocida strains (40 P. multocida subsp. septica and 16 P. multocida subsp. multocida strains) isolated from the mouths of 56 dogs among the 134 living in a French canine military training center (132e Groupe Cynophile de l'Armée de Terre, Suippes, France) were studied by use of enterobacterial repetitive intergenic consensus-PCR (ERIC-PCR) and restriction fragment length polymorphism (RFLP) techniques. Both techniques showed genomic heterogeneity of the strains studied. However, RFLP was more discriminatory than ERIC-PCR for differentiating P. multocida strains. All but three pairs of strains were discriminated by RFLP, suggesting a limited circulation of strains between these dogs living in proximity. Although ERIC-PCR is easier and faster to perform, it cannot be recommended for epidemiological studies of P. multocida strains.

Antibacterial activity of Aristolochia paucinervis Pomel.

Several fractions of the methanolic extract of the rhizome or the leaves of Aristolochia paucinervis Pomel were screened for antibacterial activity using the agar dilution method against fourteen reference bacterial strains. Only three fractions (defatted chloroformic rhizome fraction: APRC, rhizome ethyl acetate fraction: APRE and leaf chloroform fraction: APLC) showed an activity against at least one of the microorganisms tested. The minimum inhibitory concentration (MIC) determination showed that APRC was the most active against Clostridium perfringens, Clostridium difficile, Enterococcus faecalis, Micrococcus luteus and Bacillus subtilis. The high bacteriostatic activity of APRC was confirmed by its MIC determination against clinical strains of C. perfringens (n = 32), C. difficile (n = 31), and E. faecalis (n = 22). Results of this study suggest the potential interest of this highly active fraction and support the use of A. paucinervis Pomel in Moroccan traditional medicine to treat skin and soft-tissue infections, especially gas gangrene and intestinal diseases.

A Review on the Radioprotective Activity of organogermanium and Organosilicon Compounds.

The present review describes the work carried out during the last 20 years in the field of the radioprotective activity and toxicity of several classes of organosilicon and organogermanium compounds (i.e. metallathiazolidines, metalladithioacetals, metallatranes and germathianes).

Effectiveness of low dose urokinase on dialysis catheter thrombolysis.

Thrombosis, a major cause of hemodialysis catheter dysfunction, can be treated with urokinase. We compared protocols using full strength urokinase to the volume of the catheter with low dose therapy. Clotting episodes and successful declottings (blood flow > 200 ml/min) were tracked for 6 months. One hundred four clotting episodes were treated with 5,000 U/ml urokinase to the volume of the catheter lumen for a 1 hr dwell. If unsuccessful, a second dose of 5,000 U/ml was administered and, if needed, a third dose of 125,000 U/lumen. Post treatment, catheters were locked with 5,000 U/ml heparin to the volume of the lumen. Using new protocols, clotting episodes were treated with 2,500 U/lumen urokinase, followed by saline to the volume of the lumen for a 1 hr dwell. A mid dwell injection of 0.2 ml/lumen saline was added to advance the front of active urokinase. If unsuccessful, a second 2,500 U/lumen dose was administered. Heparin lock was 10,000 U/ml heparin to the volume of the lumen. Revised protocols decreased clotting episodes 60% and urokinase charges 81%, while maintaining successful declottings at 74%. Low dose urokinase was as effective as full strength when the active front was advanced mid dwell.

Synthesis and radioprotective activity of new organosilicon and germanium compounds.

Silathiazolidine and metalladithioacetals (M = Si, Ge) have been prepared by the interaction of dialkyldichloro- or bis(diethylamino)dialkylsilanes and -germanes with 3-[N-(2- thioethyl)]amino-propanamide (WR-2529) and [1-thioethyl-2-(1-naphtylmethyl)]-2- imidazoline. The study of these compounds in the field of chemical radioprotection has shown a notable decrease in the toxicity and a rather large increase in the radioprotective activity of these new derivatives in comparison with the starting organic compounds.

Capnocytophaga canimorsus infections in human: review of the literature and cases report.

Capnocytophaga canimorsus, formerly designated Dysgonic fermenter 2 (DF-2) was first described in 1976; it is a commensal bacterium of dogs and cats saliva, which can be transmitted to man by bite (54% of cases), scratch (8.5%), or mere exposure to animals (27%). We present a review of the clinical and microbiological characteristics of the Capnocytophaga canimorsus infections and 12 cases of infection in France. Over 100 cases of human infections have been reported, mainly septicemia in patients with diminished defences, due to splenectomy (33%), alcohol abuse (24%), immunosuppression (5%). However 40% of septicemia occur in patients with no predisposing conditions. Other infections are less frequent: meningitis, endocarditis, arthritis, pleural and localized eye infections. These infections range from mild to fulminating disease, with shock, respiratory distress, disseminated intravascular coagulation. Dermatological lesions (macular or maculopapular rash, purpura) or gangrene are common. This fastidious Gram-negative bacterium grows slowly on chocolate agar or on heart infusion agar with 5% rabbit blood incubated in 5% CO2. In spite of a great susceptibility of bacteria to antibiotics, the mortality is of 30%. Because of the severity of these infections, taking into account this organism in the management of bites is necessary, especially in patients with predisposing factors.