Effects of cyclic pressure on bone marrow cell cultures

The present in-vitro study used bone marrow cell cultures and investigated the effects of cyclic pressure on osteoclastic bone resorption. Compared to control (cells maintained under static conditions), the number of tartrate resistant acid phosphatase (TRAP)-positive, osteoclastic cells was significantly (p<0.05) lower when, immediately upon harvesting, bone marrow cells were exposed to cyclic pressure (10-40 kPa at 1.0 Hz). In contrast, once precursors in bone marrow cells differentiated into osteoclastic cells under static culture conditions for 7 days, subsequent exposure to the cyclic pressure of interest to the present study did not affect the number of osteoclastic cells. Most important, exposure of bone marrow cells to cyclic pressure for 1 h daily for 7 consecutive days resulted in significantly (p<0.05) lower osteoclastic bone resorption and in lowered mRNA expression for interleukin-1 (IL-1) and tumor necrosisfactor-a (TNF-a), cytokines that are known activators of osteoclast function. In addition to unique contributions to osteoclast physiology, the present study provided new evidence of a correlation between mechanical loading and bone homeostasis as well as insight into the molecular mechanisms of bone adaptation to mechanical loading, namely cytokine-mediated control of osteoclast functions.     

Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates

Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.     

Chlamydial Induction of Hydrosalpinx in 11 Strains of Mice Reveals Multiple Host Mechanisms for Preventing Upper Genital Tract Pathology

The female lower genital tract is constantly exposed to microbial infection, some of which can ascend to and cause pathology such as hydrosalpinx in the upper genital tract, which can affect fertility. To understand host mechanisms for preventing upper genital tract pathology, we screened 11 inbred strains of mice for hydrosalpinx induction by C. muridarum. When examined on days 60 to 80 after intravaginal infection, the 11 strains fell into 3 groups based on their hydrosalpinx severity: CBA/J and SJL/J mice were highly susceptible with a hydrosalpinx score of 5 or greater; Balb/c, C57BL/6J, C57BL/10J, C3H/HeJ and C3H/HeN were susceptible with a score between 1 and <5; NOD/ShiLtJ, DBA/1J, DBA/2J and A/J were resistant with a score of <1. The diverse range of mouse susceptibility to hydrosalpinx induction may reflect the varied clinical outcomes of C. trachomatis-infected women. When the 11 strains were infected via an intrauterine inoculation to bypass the requirement for ascension, higher incidence and more severe hydrosalpinges were induced in most mice, indicating that the interaction between chlamydial ascension and host control of ascension is critical for determining susceptibility to hydrosalpinx development in many mice. However, a few mouse strains resisted significant exacerbation of hydrosalpinx by intrauterine infection, indicating that these mice have evolved ascension-independent mechanisms for preventing upper genital tract pathology. Together, the above observations have demonstrated that different strains of mice can prevent upper genital tract pathology by using different mechanisms.