Publications by authors named "Y Shirasaka"
Magenstrasse (stomach road) is reported to potentially influence the absorption of orally administered drugs by facilitating a gastric emptying of ingested water under postprandial condition. We hypothesized the Magenstrasse is a consequence of the formation of protein aggregates due to the decrease in gastric pH associated with stimulated gastric acid secretion. The formation mechanism of the Magenstrasse was examined in vitro using a gastric chamber system which reproduces postprandial conditions in the stomach.
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- - Excessive or insufficient levels of soluble uric acid (sUA) are linked to various health issues, while sUA at normal levels appears to be important for overall health, though its specific functions are not well understood.
- - This study shows that sUA can inhibit the enzyme CD38, which is involved in the breakdown of NAD, through a reversible non-competitive mechanism, particularly affecting purine metabolism.
- - At physiological levels, sUA may help to reduce systemic inflammation and peritonitis in mice, suggesting a significant role in regulating NAD availability and supporting the immune system by interacting with CD38.
This study aimed to analyze the contributions of multiple transport mechanisms to the intestinal uptake of serotonin (5-HT) by employing a variety of in vitro experimental techniques, focusing on organic cation transporters expressed in the gastrointestinal (GI) tract, such as SERT, PMAT, THTR2, OCT3, and OCTN2. Analysis of the concentration dependence of 5-HT uptake by Caco-2 cells revealed multi-affinity kinetics with high-affinity and low-affinity components, suggesting that multiple transporters are involved in the intestinal 5-HT uptake. Comparative analysis of transporters using K values obtained in Xenopus oocyte expression systems suggested that SERT is responsible for the high-affinity transport, while PMAT, THTR2, and OCT3 contribute to the low-affinity transport.
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- Dotinurad is a uricosuric agent that targets the URAT1 transporter in kidneys, inhibiting the reabsorption of urate.
- The study identifies specific binding sites of dotinurad in URAT1, with H142 and R487 being crucial for its selectivity, highlighting their unique presence in URAT1 compared to other UA transporters.
- Findings suggest that mutations in these amino acids significantly affect dotinurad's inhibitory effects, thereby establishing their role in the drug's selectivity and efficacy.
The outcomes of unresectable gastric cancer (GC) are unfavorable even with chemotherapy; therefore, a new treatment modality is required. The combination of an oncolytic virus and photodynamic therapy can be one of the promising modalities to overcome this. Mammalian orthoreovirus (MRV) is an oncolytic virus that has been used in clinical trials for several cancers.
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