Supraspinatus Tendons Have Different Mechanical Properties Across Sex.

Sex differences in the mechanical properties of different musculoskeletal tissues and their impact on tendon function and disease are becoming increasingly recognized. Tendon mechanical properties are influenced by the presence or absence of sex hormones and these effects appear to be tendon- or ligament-specific. The objective of this study was to determine how sex and hormone differences in rats affect supraspinatus tendon and muscle properties. We hypothesized that male supraspinatus tendons would have increased cross-sectional area but no differences in tendon material properties or muscle composition when compared to supraspinatus tendons from female or ovariectomized (OVX) female rats. Uninjured supraspinatus tendons and muscles from male, female, and OVX female rats were collected and mechanical and histological properties were determined. Our analysis demonstrated decreased dynamic modulus and increased hysteresis and cross-sectional area in male tendons. We found that male tendons exhibited decreased dynamic modulus (during low strain frequency sweep and high strain fatigue loading), increased hysteresis, and increased cross-sectional area compared to female and OVX female tendons. Despite robust mechanical differences, tendon cell density and shape, and muscle composition remained unchanged between groups. Interestingly, these differences were unique compared to previously reported sex differences in rat Achilles tendons, which further supports the concept that the effect of sex on tendon varies anatomically. These differences may partially provide a mechanistic explanation for the increased rate of acute supraspinatus tendon ruptures seen in young males.

Toward developing a universal treatment for fungal disease using radioimmunotherapy targeting common fungal antigens.

BACKGROUND: Previously, we demonstrated the ability of radiolabeled antibodies recognizing the cryptococcal polysaccharide capsule to kill Cryptococcus neoformans both in vitro and in infected mice. This approach, known as radioimmunotherapy (RIT), uses the exquisite ability of antibodies to bind antigens to deliver microbicidal radiation. To create RIT reagents which would be efficacious against all major medically important fungi, we have selected monoclonal antibodies (mAbs) to common surface fungal antigens such as heat shock protein 60 (HSP60), which is found on the surface of diverse fungi; beta (1,3)-glucan, which is a major constituent of fungal cell walls; ceramide which is found at the cell surface, and melanin, a polymer present in the fungal cell wall. METHODS: MAbs 4E12, an IgG2a to fungal HSP60; 2G8, an IgG2b to beta-(1,3)-glucan; and 6D2, an IgM to melanin, were labeled with the alpha particle emitting radionuclide 213-Bismuth ((213)Bi) using the chelator CHXA". B11, an IgM antibody to glucosylceramide, was labeled with the beta emitter 188-Rhenium ((188)Re). Model organisms Cryptococcus neoformans and Candida albicans were used to assess the cytotoxicity of these compounds after exposure to either radiolabeled mAbs or controls. RESULTS: (213)Bi-mAbs to HSP60 and to the beta-(1,3)-glucan each reduced the viability of both fungi by 80-100%. The (213)Bi-6D2 mAb to melanin killed 22% of C. neoformans, but did not kill C. albicans. B11 mAb against fungal ceramide was effective against wild-type C. neoformans, but was unable to kill a mutant lacking the ceramide target. Unlabeled mAbs and radiolabeled irrelevant control mAbs caused no killing. CONCLUSION: Our results suggest that it is feasible to develop RIT against fungal pathogens by targeting common antigens and such an approach could be developed against fungal diseases for which existing therapy is unsatisfactory.