An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole

The susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole (TZ) was examined. The minimal bactericidal concentration (MBC) of TZ against the mobile spirochetes was >128 μg/ml at 37°C in micro-oxic atmosphere when incubated for 14 days. TZ significantly reduced the conversion of mobile spirochetes to cystic forms during incubation. The MBC for older (10- months-old) cysts at 37°C in a micro-oxic atmosphere was >0.5 μg/ml, but >0.125 μg/ml for young (1-day-old) cysts. Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that, when the concentration of TZ was ≥ MBC, the contents of the cysts were partly degraded, core structures did not develop inside the young cysts, and the amount of RNA in these cysts decreased significantly. When cysts were exposed to TZ, both the spirochetal structures and core structures inside the cysts dissolved, and the production of blebs was significantly reduced. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of TZ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi. [Int Microbiol 2004; 7(2):139–142

Susceptibility of motile and cystic forms of Borrelia burgdorferi to ranitidine bismuth citrate

Gastrointestinal symptoms accompanying Lyme disease have not been considered in the treatment of Lyme patients yet. Here we examine the effect of ranitidine bismuthcitr ate (RBC) on motile and cystic forms of Borrelia burgdorferi in vitro, to determine whether it could cure this bacterial infection in the gastrointestinal tract. When motile forms of B. burgdorferi were exposed to RBC for 1 week at 37°C, the minimal bactericidal concentration (MBC) was >64 mg/ml. At 30°C, the MBC was >256 mg/ml. When the incubation lasted for 2 weeks at 37°C, the MBC dropped to >2 mg/ml. Bismuth aggregates were present on the surface of B. burgdorferi when RBC ≥ MBC, as shown by transmission electron microscopy (TEM). Cystic forms of B. burgdorferi, exposed to RBC for 2 weeks at 37°C, were examined by cultivation in BSK-H medium (Sigma B3528). They were stained with acridine orange (pH 6.4, pH 7.4) and studied by TEM. The MBC for RBC for young cystic forms (1 day old) and old cysts (8 months old) was estimated to be >0.125 mg/ml and >2 mg/ml, respectively. Bismuth aggregates were attached to the cysts and, in some, the pin-shaped aggregates penetrated the cyst wall. The bismuth aggregates also bound strongly to blebs and granules of B. burgdorferi when RBC ≥ MBC. When B. burgdorferi is responsible for gastrointestinal symptoms, bismuth compounds may be candidates for eradication of the bacterium from the gastrointestinal tract

An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine

In this work the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine (HCQ) was studied. The minimalba ctericidal concentration (MBC) of HCQ against the mobile spirochetes was >32 μg/mlat 37°C, and >128 μg/ml at 30°C. Incubation with HCQ significantly reduced the conversion of mobile spirochetes to cystic forms. When incubated at 37°C, the MBC for young biologically active cysts (1-day old) was >8 μg/ml, but it was >32 μg/ml for old cysts (1-week old). Acridine orange staining, dark-field microscopy and transmission electron microscopy revealed that the contents of the cysts were partly degraded when the concentration of HCQ was ≥MBC. At high concentrations of HCQ (256 lg/ml) about 95% of the cysts were ruptured. When the concentration of HCQ was ≥MBC, core structures did not develop inside the cysts, and the amount of RNA in these cysts decreased significantly. Spirochetal structures inside the cysts dissolved in the presence of high concentrations of HCQ. When the concentration of HCQ was ≥MBC, the core structures inside the cysts were eliminated. These observations may be valuable in the treatment of resistant infections caused by B. burgdorferi, and suggest that a combination of HCQ and a macrolide antibiotic could eradicate both cystic and mobile forms of B. burgdorferi

Spontaneous decay rates in active waveguides

We present a new method to measure the guided, radiated and total decay rates in one-dimensional waveguides. It is also theoretically shown that large modifications of the total decay rate can be achieved in realistic EDFAs and EDWAs with effective mode area radii smaller than ~ 1 micrometer.Comment: 3 pages, latex, 2 figures, 1 table, title change, published versio

Evaluation of electrospray differential mobility analysis for virus particle analysis: Potential applications for biomanufacturing.

The technique of electrospray differential mobility analysis (ES-DMA) was examined as a potential potency assay for routine virus particle analysis in biomanufacturing environments (e.g., evaluation of vaccines and gene delivery products for lot release) in the context of the International Committee of Harmonisation (ICH) Q2 guidelines. ES-DMA is a rapid particle sizing method capable of characterizing certain aspects of the structure (such as capsid proteins) and obtaining complete size distributions of viruses and virus-like particles. It was shown that ES-DMA can distinguish intact virus particles from degraded particles and measure the concentration of virus particles when calibrated with nanoparticles of known concentration. The technique has a measurement uncertainty of ≈20%, is linear over nearly 3 orders of magnitude, and has a lower limit of detection of ≈10(9)particles/mL. This quantitative assay was demonstrated for non-enveloped viruses. It is expected that ES-DMA will be a useful method for applications involving production and quality control of vaccines and gene therapy vectors for human use