Rapid selection of quinolone resistance in Campylobacter jejuni but not in Escherichia coli in individually housed broilers

OBJECTIVE: To determine the within-host population dynamics of Campylobacter jejuni and Escherichia coli in chickens during and after treatment with fluoroquinolones. MATERIALS AND METHODS: Total and resistant faecal counts were determined from cloacal swabs during and after treatment with enrofloxacin. Chickens were housed individually to avoid confounding as a result of interaction between animals, and to be able to focus solely on the within-host dynamics. To determine the molecular basis of resistance, a number of isolates were checked for mutations in gyrA. RESULTS: Treatment with enrofloxacin at doses routinely prescribed (50 ppm) rapidly reduced the faecal counts of E. coli below the detection limit and did not induce resistance. In C. jejuni, on the other hand, treatment with enrofloxacin quickly selected for high frequencies of fluoroquinolone-resistant strains. In all phenotypically resistant isolates, resistance was traced to mutations in the gyrA gene. CONCLUSIONS: (1) A licensed dosage (50 ppm) of enrofloxacin in drinking water of chickens is effective (i.e. markedly reduced faecal counts) and is safe on a short time scale in E. coli (i.e. did not rapidly select for resistance), but is neither safe nor effective in C. jejuni. (2) The rapid emergence of resistance to quinolones in C. jejuni does not necessarily result from horizontal transmission of resistant strains among chickens, but could solely be the result of de novo selection of resistance in individual chickens.     

Ultrasound-induced microbubble coalescence

We studied the interaction of ultrasound contrast agent bubbles coated with a layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the submicrosecond timescale reveals that some bubbles bounce off each other, while others show very fast coalescence during bubble expansion. This fast coalescence cannot be explained by dissipation-limited film drainage rates. We conclude that the lipid shell ruptures upon expansion, exposing clean free bubble interfaces that support plug flow profiles in the film and inertia-limited drainage whose time scales match those of the observed coalescence.     

Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long-term deconditioning (spinal cord-injured individuals, SCI) as well as after moderate, short-term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre- and post-ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of N ^G-monomethyl- l -arginine ( l -NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37 ± 4 versus 31 ± 2 arbitrary units (AU), P = 0.06). Deconditioning altered neither the vasoconstrictor response to l -NMMA (increase in resistance in SCI versus controls: 102 ± 33% versus 69 ± 9%; pre- versus post-ULLS: 95 ± 18% versus 119 ± 15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.     

Functional defects in the fanconi anemia pathway in pancreatic cancer cells

Biallelic BRCA2-mutations can cause Fanconi anemia and are found in approximately 7% of pancreatic cancers. Recently, several sequence changes in FANCC and FANCG were reported in pancreatic cancer. Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C. The functional implications of mutations in the Fanconi pathway in cancer have not been fully studied yet; these studies are needed to pave the way for clinical trials of treatment with crosslinking agents of Fanconi-defective cancers. The competence of the proximal Fanconi pathway was screened in 21 pancreatic cancer cell lines by an assay of Fancd2 monoubiquitination using a Fancd2 immunoblot. The pancreatic cancer cell lines Hs766T and PL11 were defective in Fancd2 monoubiquitination. In PL11, this defect led to the identification of a large homozygous deletion in FANCC, the first cancer cell line found to be FANCC-null. The Fanconi-defective cell lines Hs766T, PL11, and CAPAN1 were hypersensitive to the crosslinking agent mitomycin C and some to cis-platin, as measured by cell survival assays and G(2)/M cell-cycle arrest. These results support the practical exploration of crosslinking agents for non-Fanconi anemia patients that have tumors defective in the Fanconi pathway.     

The effect of bed rest and an exercise countermeasure on leg venous function

This study was performed to assess the effect of resistive vibration exercise during bed rest deconditioning on venous vascular dimension and function, as measured with ultrasound in the popliteal vein. Sixteen men were assigned to bed rest (BR-Ctrl) or bed rest with resistive vibration exercise (BR-RVE). Before and at 25 and 52 days of bed rest, popliteal vein diameter was measured at increasing cuff pressures. Venous capacitance and compliance were calculated from the pressure–volume curve. After 52 days of bed rest, BR-Ctrl showed no change in baseline popliteal vein diameter or compliance, while venous capacitance decreased. Resistive vibration exercise had no effect on the response in venous diameter, capacitance or compliance to 52 days of bed rest. The decline in venous capacitance due to long-term bed rest is not effectively counteracted by resistive vibration exercise, indicating that an alternative factor during bed rest deconditioning is responsible for venous changes.