Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder.

BACKGROUND: Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. METHODS: Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. RESULTS: Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium/hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. CONCLUSION: EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia. J. Med. Invest. 70 : 260-270, February, 2023.

Sign and speech: amodal commonality in left hemisphere dominance for comprehension of sentences.

The neural basis of functional lateralization in language processing is a fundamental issue in systems neuroscience. We used functional MRI (fMRI) to examine hemispheric dominance during the processing of signed and spoken sentences. By using tasks involving comprehension of sentences (Sc) and sentential non-word detection (Sn), we compared different groups and stimulus conditions. Under the sign condition with sentence stimuli in Japanese Sign Language (JSL), we tested two groups of subjects: Deaf signers (Deaf) of JSL, and hearing bilinguals (children of Deaf adults, CODA) of JSL and Japanese (JPN). Under the speech condition, we tested hearing monolinguals (Mono) of JPN with auditory JPN stimuli alone (AUD), or with an audiovisual presentation of JPN and JSL stimuli (A&V). We found that the overall bilateral activation patterns under the four experimental conditions of Deaf, CODA, AUD and A&V were almost identical, despite differences in stimuli (JSL and JPN) and groups (Deaf, CODA and Mono). Moreover, consistently left-dominant activations involving frontal and temporo-parietal regions were observed across all four conditions. Furthermore, irrespective of the modalities of sign and speech, the main effects of task (Sc-Sn) were found primarily in the left regions: the ventral part of the inferior frontal gyrus (F3t/F3O), the precentral sulcus, the superior frontal gyrus, the middle temporal gyrus, the angular gyrus and the inferior parietal gyrus. Among these regions, only the left F3t/F3O showed no main effects of modality condition. These results demonstrate amodal commonality in the functional dominance of the left cortical regions for comprehension of sentences, as well as the essential and universal role of the left F3t/F3O in processing linguistic information from both signed and spoken sentences.