Parathyroid hormone (PTH) is essential for calcium homeostasis and its action is mediated by the PTH type 1 receptor (PTHR1), a class B G-protein-coupled receptor. Hypoparathyroidism and osteoporosis can be treated with PTH injections; however, no orally effective PTH analogue is available. Here we show that PCO371 is a novel, orally active small molecule that acts as a full agonist of PTHR1. PCO371 does not affect the PTH type 2 receptor (PTHR2), and analysis using PTHR1–PTHR2 chimeric receptors indicated that Proline 415 of PTHR1 is critical for PCO371-mediated PTHR1 activation. Oral administration of PCO371 to osteopenic rats provokes a significant increase in bone turnover with limited increase in bone mass. In hypocalcemic rats, PCO371 restores serum calcium levels without increasing urinary calcium, and with stronger and longer-lasting effects than PTH injections. These results strongly suggest that PCO371 can provide a new treatment option for PTH-related disorders, including hypoparathyroidism.
Single-wall carbon nanotube/polystyrene (SWCNT/PS) nanocomposites were prepared by solution coagulation. Characterization was performed using Raman and infrared spectroscopy to elucidate the interactions between the SWCNTs and PS inside the nanocomposites. It was found that the G − , G + , and G′ SWCNT bands shifted to higher wavenumbers when incorporated into the nanocomposites. We determined that this upshift was induced exclusively by a mechanical compression transfer from PS to the SWCNTs. From the magnitude of the upshift, the mechanical compression transfer was estimated to be ∼518 MPa. Interestingly, we found that the upshift of the radial breathing mode was dominated by two factors: a van der Waals effect due to separation of the SWCNTs and mechanical compression from the PS system. A comparison of the laser heating effects on pristine SWCNTs and on the nanocomposites showed that thermal expansion of the SWCNTs in the nanocomposites was suppressed by the mechanical compression from the PS system. The combination of Raman and infrared spectroscopy enabled detailed characterization of the interactions occurring the nanocomposites, which cannot be achieved using other conventional methods.
The ePCWP was the reliable echocardiographic parameter to predict PCWP in primary and secondary MR and might also be useful in MR with atrial fibrillation. The ePCWP may have an incremental value in a clinical setting.
We evaluated the prevalence of CoxieUla burnetii antibodies in 626 human serum samples (275 from veterinarians, 107 from meat-processing workers, 184 from respiratory-disorder patients, and 60 from healthy humans) by the indirect immunofluorescence test. Of the serum samples examined, 54 (8.6%) and 103 (16.5%) reacted positively to phase I and II antigens, respectively, of C. burnetii. The rates differed for healthy humans and respiratory-disorder patients. Antibody prevalence was high for healthy humans living in close contact with animals (e.g., veterinarians and meat-processing workers).
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