Use of Cis-[18F]Fluoro-Proline for Assessment of Exercise-Related Collagen Synthesis in Musculoskeletal Connective Tissue

Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[18F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis

Response of a floodplain fish community to river-floodplain connectivity: natural versus managed reconnection

To restore lateral connectivity in highly regulated river-floodplain systems, it has become necessary to implement localized, "managed" connection flows, made possible using floodplain irrigation infrastructure. These managed flows contrast with "natural", large-scale, overbank flood pulses. We compared the effects of a managed and a natural connection event on (i) the composition of the large-bodied fish community and (ii) the structure of an endangered catfish population of a large floodplain lake. The change in community composition following the managed connection was not greater than that exhibited between seasons or years during disconnection. By contrast, the change in fish community structure following the natural connection was much larger than that attributed to background, within-and between-year variability during disconnection. Catfish population structure only changed significantly following the natural flood. While the natural flood increased various population rates of native fishes, it also increased those of non-native carp, a pest species. To have a positive influence on native biodiversity, environmental flows may need to be delivered to floodplains in a way that simulates the properties of natural flood pulses. A challenge, however, will be managing river-floodplain connectivity to benefit native more than non-native species

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis

BACKGROUND: Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated as an etiological agent of Crohn’s disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients. RHB-104, a drug formula with active ingredients composed of (63.3 %) CLA, (6.7 %) CLO, and (30 %) RIF, has been recently subjected to investigation in an FDA approved Phase III clinical trial to treat patients with moderate to severe CD. In this study, we determined the efficacy of RHB-104 active ingredients against MAP strains isolated from the blood, tissue, and milk of CD patients. Based on fluorescence quenching technology using the Bactec MGIT Para-TB medium, we determined the minimum inhibitory concentration (MIC) of CLA, CLO, RIF individually and in dual and triple combinations against 16 MAP clinical strains and 19 other mycobacteria. RESULTS: The MIC of all drugs against 35 different mycobacteria ranged between 0.25–20 μg/mL. However, the MIC of RHB-104 active ingredients regimen was the lowest at 0.25–10 μg/mL compared to the MIC of the other drugs at 0.5–20 μg/mL. The components of RHB-104 active ingredients at their individual concentrations or in dual combinations were not effective against all microorganisms compared to the triple combinations at MIC level. The MIC of CLA–CLO, CLA–RIF, and CLO–RIF regimens ranged between 0.5–1.25 μg/mL compared to 0.25 μg/mL of bactericidal effect of the triple combination. CONCLUSION: The data clearly demonstrated that lower concentrations of the triple combination of RHB-104 active ingredients provided synergistic anti-MAP growth activity compared to individual or dual combinations of the drugs. Consequently, this is favorable and should lead to tolerable dosage that is desirable for long-term treatment of CD and Mycobacterium avium complex disease