Serum lipidomics reveals early differential effects of gastric bypass compared with banding on phospholipids and sphingolipids independent of differences in weight loss.

BACKGROUND/OBJECTIVES: Circulating phospholipids and sphingolipids are implicated in obesity-related comorbidities such as insulin resistance and cardiovascular disease. How bariatric surgery affects these important lipid markers is poorly understood. We sought to determine whether Roux-en-Y gastric bypass (RYGB), which is associated with greater metabolic improvement, differentially affects the phosphosphingolipidome compared with adjustable gastric banding (AGB). SUBJECTS/METHODS: Fasting sera were available from 59 obese women (body mass index range 37-51 kg m-2; n=37 RYGB and 22 AGB) before surgery, then at 1 (21 RYGB, 12 AGB) and 3 months follow-up (19 RYGB, 12 AGB). HPLC-MS/MS was used to quantify 131 lipids from nine structural classes. DXA measurements and laboratory parameters were also obtained. The associations between lipids and clinical measurements were studied with P-values adjusted for the false discovery rate (FDR). RESULTS: Both surgical procedures rapidly induced weight loss and improved clinical profiles, with RYGB producing better improvements in fat mass, and serum total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and orosomucoid (FDR <10%). Ninety-three (of 131) lipids were altered by surgery-the majority decreasing-with 29 lipids differentially affected by RYGB during the study period. The differential effect of the surgeries remained statistically significant for 20 of these lipids after adjusting for differences in weight loss between surgery types. The RYGB signature consisted of phosphatidylcholine species not exceeding 36 carbons, and ceramides and sphingomyelins containing C22 to C25 fatty acids. RYGB also led to a sustained increase in unsaturated ceramide and sphingomyelin species. The RYGB-specific lipid changes were associated with decreases in body weight, total and LDL-C, orosomucoid and increased HOMA-S (FDR <10%). CONCLUSIONS: Concomitant with greater metabolic improvement, RYGB induced early and sustained changes in phosphatidylcholines, sphingomyelins and ceramides that were independent of greater weight loss. These data suggest that RYGB may specifically alter sphingolipid metabolism, which, in part, could explain the better metabolic outcomes of this surgical procedure.

The Fusarium oxysporum effector Six6 contributes to virulence and suppresses I-2-mediated cell death.

Plant pathogens secrete effectors to manipulate their host and facilitate colonization. Fusarium oxysporum f. sp. lycopersici is the causal agent of Fusarium wilt disease in tomato. Upon infection, F. oxysporum f. sp. lycopersici secretes numerous small proteins into the xylem sap (Six proteins). Most Six proteins are unique to F. oxysporum, but Six6 is an exception; a homolog is also present in two Colletotrichum spp. SIX6 expression was found to require living host cells and a knockout of SIX6 in F. oxysporum f. sp. lycopersici compromised virulence, classifying it as a genuine effector. Heterologous expression of SIX6 did not affect growth of Agrobacterium tumefaciens in Nicotiana benthamiana leaves or susceptibility of Arabidopsis thaliana toward Verticillium dahliae, Pseudomonas syringae, or F. oxysporum, suggesting a specific function for F. oxysporum f. sp. lycopersici Six6 in the F. oxysporum f. sp. lycopersici- tomato pathosystem. Remarkably, Six6 was found to specifically suppress I-2-mediated cell death (I2CD) upon transient expression in N. benthamiana, whereas it did not compromise the activity of other cell-death-inducing genes. Still, this I2CD suppressing activity of Six6 does not allow the fungus to overcome I-2 resistance in tomato, suggesting that I-2-mediated resistance is independent from cell death.

Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults. A prospective general practice study.

A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

Five versus ten days treatment of streptococcal pharyngotonsillitis: a randomized controlled trial comparing cefpodoxime proxetil and phenoxymethyl penicillin.

A total of 220 adults and children > 10 years old (mean 29.5 +/- 11.7 years) with pharyngitis/tonsillitis were randomized to receive either cefpodoxime proxetil 100 mg bid for 5 days (n = 113) or phenoxymethyl penicillin, 600 mg tid for 10 days (n = 107). At the end of treatment of the 166 evaluable patients, a satisfactory clinical response was obtained in 85/88 (96.6%) patients treated with cefpodoxime proxetil and in 75/78 (96.1%) treated with phenoxymethyl penicillin. Group A beta-hemolytic streptococci (GABHS) eradication was similar in both groups: 79/82 (96.3%) patients in the cefpodoxime proxetil group and 64/68 (94.1%) patients in the phenoxymethyl penicillin group. At follow-up (20-30 days after the end of treatment) the GABHS eradication persisted in 67/72 (93.1%) patients treated with cefpodoxime proxetil and in 56/61 (91.8%) patients treated with phenoxymethyl penicillin. Significantly better compliance (p < 0.01) was noticed with the cefpodoxime proxetil regimen compared with the phenoxymethyl penicillin regimen, with only 2/110 (2%) poorly compliant patients in the cefpodoxime proxetil group vs 17/104 (16%) in the phenoxymethyl penicillin group. Thus, the shorter duration of therapy, in conjunction with demonstrated clinical and bacteriological efficacy that is equivalent to standard therapy, makes cefpodoxime proxetil an acceptable alternative for the treatment of GABHS pharyngitis/tonsillitis.

Concentrations of cefpodoxime in plasma and tonsillar tissue after a single oral dose of cefpodoxime proxetil.

Seventeen patients undergoing tonsillectomy received cefpodoxime proxetil orally in a dose equivalent to 100 mg cefpodoxime 4, 7 or 12 h before operation. Plasma and tonsillar tissue concentrations of cefpodoxime were assayed by a microbiological method. Tonsillar tissue concentrations after 4 and 7 h were 0.24 and 0.09 mg/kg respectively--being 23% of the plasma concentration. The tonsillar tissue concentration after 12 h was less than 0.06 mg/kg. As the MIC for Streptococcus pyogenes is less than 0.06 mg/l, cefpodoxime proxetil may be of value in acute tonsillitis.

Efficacy and tolerance of cefpodoxime proxetil compared with ceftriaxone in vulnerable patients with bronchopneumonia.

This multicentre, randomized study compared the efficacy and tolerance of cefpodoxime proxetil and ceftriaxone in vulnerable patients with bronchopneumonia. Patients received cefpodoxime proxetil 200 mg bd orally or ceftriaxone 1 g daily im for a ten-day period. They were evaluated at days 10 and 30. Ninety-six patients were evaluated for tolerance, 85 for clinical efficacy and 65 for bacteriological efficacy. At entry all patients had radiographic evidence of pneumonia and 74% of bacteriological samples were positive. The percentage of overall success (cured or improved) was 97.7% (43/44) in the cefpodoxime proxetil group and 95.1% (39/41) in the ceftriaxone group. The bacteriological efficacy was 94.3% in the cefpodoxime proxetil group and 97.4% in the ceftriaxone group. Clinical tolerance was satisfactory in both groups. In this study, the clinical and bacteriological results obtained with cefpodoxime proxetil were comparable with those obtained with ceftriaxone in the treatment of community-acquired bronchopneumonia in patients with additional risk factors.

[In vivo study of the sensitivity of Treponema pallidum to ofloxacin]. / Etude in vivo de la sensibilité de Treponema pallidum à l'ofloxacine.

Treponema pallidum has not been yet cultivated. Hence any in vitro investigation is excluded, and it is owing to the experimental animal model, the rabbit, that we have studied the susceptibility of that germ to ofloxacin. This quinolone, owing to its pharmacokinetic and therapeutic properties, can specially be indicated in the treatment of Sexually Transmitted Diseases. Thus, its appeared to be of the utmost importance to know if the suggested schedule of treatment for STD, might not be susceptible to modify the course of a co-existing incubating syphilis by either delaying or inhibiting the apparition of the clinical features of primary syphilis. This study was undertaken at the incubation period, in syphilitic rabbits, using kinetic data obtained in man, after a given dosage of ofloxacin. Results were appraised upon converging data: lesions, bacteriology, and serology of the tested lot compared with two control batches of infected rabbits, the first one being untreated, the other having received the reference antibiotic treatment. From the data obtained and in the experimental settled conditions where this study was done, it results that ofloxacin has no effect on the course of the experimental syphilitic infection.

Bactericidal effect of ofloxacin alone and combined with fosfomycin or vancomycin against Staphylococcus aureus in vitro and in sera from volunteers.

The bactericidal activity of ofloxacin alone and in combination was evaluated against strains of Staphylococcus aureus by measuring MBCs, FBC indexes and by the killing curve technique. Bactericidal titres were determined in sera from volunteers given ofloxacin alone or in combination with fosfomycin or vancomycin. FBC indices less than 0.75 were observed with fosfomycin, showing moderate synergy. FBC indices of 1 were seen with vancomycin. Killing kinetic experiments indicated that ofloxacin (1 and 4 mg/l) exerted a rapid bactericidal effect (99.9% killing in 4 h); the combination of ofloxacin and fosfomycin was synergistic for one of three strains, while killing kinetics of ofloxacin were unaltered by fosfomycin for two of three strains or by vancomycin for the three strains. Sera collected two hours after ofloxacin or fosfomycin had been administered had bactericidal titres less than 1/2. Bactericidal titres were significantly greater in sera from volunteers given the combination of these two drugs. Similar bactericidal titres were obtained in sera after the administration of vancomycin alone or in combination with ofloxacin. A loading dose of 400 mg ofloxacin with subsequent doses of 200 mg had no significantly prolonged effect on bactericidal titres.