Canine Orientia tsutsugamushi infection: report of a case and its epidemicity.

A lethargic household dog was referred to a private hospital in Japan. Diagnosis was carried out by the polymerase chain reaction (PCR) method developed for human Orientia tsutsugamushi infection using the dog's anticoagulated peripheral blood. Karp, Kato and Kuroki-type genomes were detected and the dog was diagnosed with O. tsutsugamushi infection. These findings demonstrate that dogs can act as a host for O. tsutsugamushi and the PCR method developed for human beings can be used for the diagnosis of canine O. tsutsugamushi infection. A concurrent epidemiological study examined 10 asymptomatic dogs that were fed in the same area as the sick dog. Kuroki-type genome in all dogs, Gilliam-type genome in 6 dogs and Kawasaki-type genome in 3 dogs were detected. These results provide further evidence that dogs can be naturally infected with O. tsutsugamushi outdoors and that dogs play a role as a host in the lifecycle of O. tsutsugamushi.

K-685, a TRPV1 antagonist, blocks PKC-sensitized TRPV1 activation and improves the inflammatory pain in a rat complete Freund's adjuvant model.

Transient receptor potential vanilloid 1 (TRPV1) is a Ca(2+)-permeable non-selective cation channel that transmits pain signals. TRPV1 is activated by multiple stimuli such as capsaicin, acid, and heat. During inflammation, TRPV1 is reported to be sensitized by protein kinase C (PKC) in dorsal root ganglia (DRG) neurons, which leads to reduction in the threshold of the temperature for TRPV1 activation to body temperature. This sensitization is considered to contribute to chronic inflammatory pain. In a previous study, we discovered orally active 5,5-diarylpentadienamide TRPV1 antagonists. To examine the effects of our TRPV1 antagonists on PKC-sensitized TRPV1, we developed an in vitro assay system to monitor the TRPV1 sensitization by PKC. In this assay system, our TRPV1 antagonists, such as (2E,4Z)-N-[(3R)-3-hydroxy-2-oxo-1,2,3,4-tetrahydro-5-quinolyl]-5-(4-isopropoxyphenyl)-5-(4-trifluoromethylphenyl)-2,4-pentadienamide (K-685), inhibited the activation of TRPV1 sensitized by PKC. The potentiation of heat-induced inward currents by PKC was seen in rat DRG neurons, and K-685 attenuated these currents. Furthermore, K-685 reversed the thermal hyperalgesia and mechanical allodynia in a rat complete Freund's adjuvant-induced inflammatory pain model. These results therefore suggest that K-685 has a strong potential as a new analgesic drug for the treatment of inflammatory pain.

Reduction of vanadium(V) to vanadium(IV) by NADPH, and vanadium(IV) to vanadium(III) by cysteine methyl ester in the presence of biologically relevant ligands.

To better understand the mechanism of vanadium reduction in ascidians, we examined the reduction of vanadium(V) to vanadium(IV) by NADPH and the reduction of vanadium(IV) to vanadium(III) by L-cysteine methyl ester (CysME). UV-vis and electron paramagnetic resonance spectroscopic studies indicated that in the presence of several biologically relevant ligands vanadium(V) and vanadium(IV) were reduced by NADPH and CysME, respectively. Specifically, NADPH directly reduced vanadium(V) to vanadium(IV) with the assistance of ligands that have a formation constant with vanadium(IV) of greater than 7. Also, glycylhistidine and glycylaspartic acid were found to assist the reduction of vanadium(IV) to vanadium(III) by CysME.