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

Association between multiple sclerosis and cystic structures in cerebrospinal fluid

Abstract Background: The aim of the study was to search for infectious agents in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS). Patients and Methods: CSF from ten patients with the diagnosis relapsing remitting MS and from five controls without MS were examined by transmission electron microscopy (TEM), dark field microscopy (DF), interference contrast microscopy (ICM) and UV-microscopic examination of acridine orange staining (AO). All CSF samples from patients and controls were cultured. Results: Cystic structures were observed in CSF of all ten patients by AO and TEM. DF revealed eight cyst-positive patients out of nine. One of five control persons had such structures in the CSF; this person had suffered from erythema migrans. Spirochete or rod-like structures emerged after culturing two of the MS patient CSF samples and these structures could be propagated. Conclusion: A significant association of CSF cysts and MS was identified in this small study among residents in a coastal area of southern Norway. The cysts could be of spirochetal origin. Our study may encourage other researchers to study larger patient groups

Anomalous Behavior Of The Complex Conductivity Of Y_{1-x}Pr_xBa_2Cu_3O_7 Observed With THz Spectroscopy

We have measured the electrodynamic properties of Y_{1-x}Pr_xBa_2Cu_3O_7 single crystal thin films as a function of temperature using coherent THz-time-domain spectroscopy. We obtain directly the complex conductivity $\sigma=\sigma_1+i\sigma_2$, the London penetration depth $\lambda_L$, the plasma frequency $\omega_p$, and the quasiparticle scattering rate $1/\tau$. We find that $1/\tau$ drops exponentially rapidly with $T$ below the critical temperature in {\em all} the superconducting samples, implying that this behavior is a {\em signature} of high-$T_c$ superconductivity. The plasma frequency decreases with increasing Pr content, providing evidence that Pr depletes carriers, leaving the CuO planes {\em underdoped}. Both the conductivity in the THz region and the dc resistivity yield evidence for the opening of a spin gap {\em above} $T_c$.Comment: 9 pages, REVTEX 3.

The Danish Shoulder Arthroplasty Registry: clinical outcome and short-term survival of 2,137 primary shoulder replacements

The Danish Shoulder Arthroplasty Registry (DSR) was established in 2004. Data are reported electronically by the surgeons. Patient-reported outcome is collected 10–14 months postoperatively using the Western Ontario osteoarthritis of the shoulder index (WOOS). 2,137 primary shoulder arthroplasties (70% women) were reported to the registry between January 2006 and December 2008. Mean age at surgery was 69 years (SD 12). The most common indications were a displaced proximal humeral fracture (54%) or osteoarthritis (30%). 61% were stemmed hemiarthroplasties, 28% resurfacing hemiarthroplasties, 8% reverse shoulder arthroplasties, and 3% total arthroplasties. Median WOOS was 59% (IQR: 37–82). 5% had been revised by the end of June 2010. The most frequent indications for revision were dislocation or glenoid attrition

Gene Expression and Distribution of Key Bone Turnover Markers in the Callus of Estrogen-Deficient, Vitamin D-Depleted Rats

An experimental rat model was used to test the hypothesis that in osteoporosis (OP) the molecular composition of the extracellular matrix in the fracture callus is disturbed. OP was induced at 10 weeks of age by ovariectomy and a vitamin D3-deficient diet, and sham-operated animals fed normal diet served as controls. Three months later a closed tibial fracture was made and stabilized with an intramedullary nail. After 3 and 6 weeks of healing, the animals were killed and the fracture calluses examined with global gene expression, in situ mRNA expression, and ultrastructural protein distribution of four bone turnover markers: osteopontin, bone sialoprotein, tartrate-resistant acid phosphatase, and cathepsin K. Global gene expression showed a relatively small number of differently regulated genes, mostly upregulated and at 3 weeks. The four chosen markers were not differently regulated, and only minor differences in the in situ mRNA expression and ultrastructural protein distribution were detected. Gene expression and composition of fracture calluses are not generally disturbed in experimental OP

Universal relationship between the penetration depth and the normal-state conductivity in YBaCuO

The absolute values of the conductivity in the normal state sigma_n and of the low temperature penetration depths lambda(0) were measured for a number of different samples of the YBaCuO family. We found a striking correlation between sigma_n and 1/lambda^2, regardless of doping, oxygen reduction or defects, thus providing a simple method to predict the superconducting penetration depth and to have an estimate of the sample quality by measuring the normal-state conductivity.Comment: 7 pages, 1 figure, Europhys. Lett., accepte

Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity

Recent application of ultrafast pump/probe optical techniques to superconductors has renewed interest in nonequilibrium superconductivity and the predictions that would be available for novel superconductors, such as the high-Tc cuprates. We have reexamined two of the classical models which have been used in the past to interpret nonequilibrium experiments with some success: the mu* model of Owen and Scalapino and the T* model of Parker. Predictions depend on pairing symmetry. For instance, the gap suppression due to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave as opposed to n for s-wave. Finally, we consider these models in the context of S-I-N tunneling and optical excitation experiments. While we confirm that recent pump/probe experiments in YBCO, as presently interpreted, are in conflict with d-wave pairing, we refute the further claim that they agree with s-wave.Comment: 14 pages, 11 figure

Expression of NR2B in Cerebellar Granule Cells Specifically Facilitates Effect of Motor Training on Motor Learning

It is believed that gene/environment interaction (GEI) plays a pivotal role in the development of motor skills, which are acquired via practicing or motor training. However, the underlying molecular/neuronal mechanisms are still unclear. Here, we reported that the expression of NR2B, a subunit of NMDA receptors, in cerebellar granule cells specifically enhanced the effect of voluntary motor training on motor learning in the mouse. Moreover, this effect was characterized as motor learning-specific and developmental stage-dependent, because neither emotional/spatial memory was affected nor was the enhanced motor learning observed when the motor training was conducted starting at the age of 3 months old in these transgenic mice. These results indicate that changes in the expression of gene(s) that are involved in regulating synaptic plasticity in cerebellar granule cells may constitute a molecular basis for the cerebellum to be involved in the GEI by facilitating motor skill learning