The role of cottontail rabbits (Sylvilagus spp.) in the ecology of Rickettsia rickettsii in the United States.

Rocky Mountain (Sylvilagus nuttallii) and eastern (S. floridanus) cottontails were examined for their susceptibility to virulent and avirulent strains of the spotted fever agent, Rickettsia rickettsii. Both species of rabbits responded to inoculation of yolk sac suspensions containing 500 egg LD50 of either virulent or avirulent rickettsiae, with rickettsemias detectable as early as 3 days after inoculation and lasting up to 7 days. When fed upon by infected ticks, only one of three Rocky Mountain and one of four eastern cottontails developed rickettsemias detectable in embryonated hens' eggs. Rickettsial concentrations in the peripheral blood fo Rocky Mountain cottontails, infected either by syringe or by bites of one or more Dermacentor andersoni ticks harboring virulent R. rickettsii, were sufficient to infect simultaneously feeding normal larvae of this tick species. However, infection rates wre low and did not exceed 11.7%. In a single experiment, the bites of D. variabilis, infected with an avirulent strain of R. rickettsii, did not produce rickettsemias sufficient to infect normal D. variabilis larvae. These laboratory findings suggest that cottontail rabbits, although susceptible to R. rickettsii, do not serve as efficient reservoirs for infecting ticks.

Ultrasonography of the canine prostate with histologic correlation.

The present study assessed the canine prostate gland using B-mode real-time ultrasonography and correlated these findings with corresponding histologic sections. The prostate glands of 10 dogs were suspended in a saline bath and were scanned with an ultrasound probe. The glands were fixed and histologic sections were made. The sonograms were visually compared with the histologic sections. Areas having high collagenous tissue content appeared hyperechoic on the ultrasound scans. This hyperechogenicity was seen in the diffusely hyperechoic immature gland, the hyperechoic periurethral stroma, and the hyperechoic butterfly-shaped area seen on transverse scans. The butterfly-shaped area was isoechoic, with an elongated oval area seen on transverse scans. Areas of glandular epithelial content appeared hypoechoic on ultrasound scans. No zones comparable to the human prostate were observed.

Evaluation of drug-induced prostatic involution in dogs by transabdominal B-mode ultrasonography.

The relative antiandrogen-induced prostate involution activity of the newly synthesized hydroxyflutamide pro-drug was compared with that of flutamide in 25 Beagles. Secondary antiandrogen activity of both drugs on the testes and mammary tissue was investigated. Daily oral administration of both compounds at 2 dosages (ie, 2.5 and 5.0 mg/kg of body weight) during a 7-week period was monitored by transabdominal ultrasonography of the prostate twice a week. Cross-sectional area estimates of the prostate gland calculated from oblique dorsoventral, and transverse sonographic measurements were diminished significantly in some of the treated dogs as early as day 14 of drug administration. All treated dogs had significant differences in reduction by day 47. Involution was related directly to dose (P less than 0.05), but no difference was observed between test compounds. Differences in secondary antiandrogen activity were not remarkable. Flutamide was not found to have any activity advantage in vivo over hydroxyflutamide. It was concluded that ultrasonography can be a highly effective means of monitoring prostate size, and of monitoring drug-induced involution over time.

Antibacterial properties of a tri-sodium citrate modified glass polyalkenoate cement.

Primary deep infection following joint replacement surgery accounts for 7% of all revisions. Glass polyalkenoate cements (GPCs) have previously been shown to exhibit antibacterial properties. The present study had two objectives. The first was to determine if addition of tri-sodium citrate (TSC) to the powder phase of an Al-free GPC (0.04 SrO-0.12 CaO-0.36 ZnO-0.48 SiO2, by mole fraction) enhanced the resultant cement's antibacterial properties against three strains of bacteria that are commonly found in periprosthetic sites following total joint replacements (TJRs); namely, E. coli, B. fragilis, and S. epidermidis. Four cement sets were prepared, which contained 0 wt% TSC (control), 5 wt% TSC, 10 wt% TSC, and 15 wt% TSC. All the TSC-modified cements were found to exhibit large inhibition zones against all the bacterial strains, especially the cement containing 15 wt% TSC against E. coli. The antibacterial properties of the TSC containing GPCs are attributed to the release of Zn and Na ions from the cements and the presence of the TSC. The second objective was to investigate if, when a modified GPC is embedded in a bovine bone model, ionic transfer occurs. It was found that Zn ions migrated from the cement to the surrounding bone, particularly at the cement-bone interface. This is a desirable outcome as Zn ions are known to play a vital role in both bone metabolism and the regeneration of healthy bone. The present results point to the potential clinical benefits of using TSC-modified GPCs in TJRs.

Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.

Pathogenic bacteria secrete protein toxins that weaken or disable their host, and thereby act as virulence factors. We have determined the crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, including necrotizing fasciitis. The structure, determined for the 40-kDa precursor form of SpeB at 1.6-A resolution, reveals that the protein is a distant homologue of the papain superfamily that includes the mammalian cathepsins B, K, L, and S. Despite negligible sequence identity, the protease portion has the canonical papain fold, albeit with major loop insertions and deletions. The catalytic site differs from most other cysteine proteases in that it lacks the Asn residue of the Cys-His-Asn triad. The prosegment has a unique fold and inactivation mechanism that involves displacement of the catalytically essential His residue by a loop inserted into the active site. The structure also reveals the surface location of an integrin-binding Arg-Gly-Asp (RGD) motif that is a feature unique to SpeB among cysteine proteases and is linked to the pathogenesis of the most invasive strains of S. pyogenes.