Publications by authors named "Tamai I"

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.
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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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  • Drug-induced kidney injury (DIKI) is a key factor in acute kidney injury (AKI), primarily affecting renal proximal tubular epithelial cells (RPTECs) which play a crucial role in drug processing in the kidneys.* -
  • The study utilized three-dimensional cultured human RPTECs (3D-RPTECs) and found that certain drugs, like tenofovir and cisplatin, reduced ATP levels in these cells, indicating potential toxicity.* -
  • 3D-RPTECs demonstrated high sensitivity (82.4% to 88.2%) and specificity (100% to 93.3%) in predicting DIKI when compared to traditional two-dimensional cell cultures, suggesting they are a valuable tool
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Background: Despite the prevalence of echogenic foci floating in the urinary bladder seen in ultrasonography in dogs, surprisingly little has been written on its significance, including its potential association with urinalysis. The objective of the study was to determine the diagnostic value of the echogenic foci floating in urinary bladders in dogs.

Results: - Cystosonography was performed on 45 dogs.

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Background: Periodontal diseases are the most frequently diagnosed problem in cats. It has been well-established that periodontal diseases could not only cause various oral health issues but could also contribute to systemic diseases. Oxidative stress is a possible link between systemic diseases and periodontitis.

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  • - Hyperuricemia (HUA), characterized by high uric acid levels, is linked to conditions like gout, hypertension, and chronic kidney disease, and is influenced by gut microbiota (GM).
  • - A study involving 478 participants used advanced sequencing and machine learning to analyze gut microbiomes, revealing that those with HUA had lower microbial diversity, especially notable in the genera Collinsella and Faecalibacterium.
  • - The findings suggest that a higher abundance of the gut bacteria Collinsella correlates with increased blood uric acid levels, indicating a potential predictive relationship between specific gut microbes and HUA.
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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.
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  • * A study using genetically modified Slc17a3 mice found that the plasma levels of 11 biological substances, including 3-indoxyl sulfate, were significantly higher compared to wild-type mice, and that urinary excretion of 3-indoxyl sulfate was reduced in Slc17a3 mice.
  • * The research confirmed that 3-indoxyl sulfate is a new substrate for NPT4, indicating that this transporter plays a role in controlling the levels of this compound in the body by managing its
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Controlling RAS mutant cancer progression remains a significant challenge in developing anticancer drugs. Whereas Ras G12C-covalent binders have received clinical approval, the emergence of further mutations, along with the activation of Ras-related proteins and signals, has led to resistance to Ras binders. To discover novel compounds to overcome this bottleneck, we focused on the concurrent and sustained blocking of two major signaling pathways downstream of Ras.

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Owing to renal reabsorption and the loss of uricase activity, uric acid (UA) is strictly maintained at a higher physiological level in humans than in other mammals, which provides a survival advantage during evolution but increases susceptibility to certain diseases such as gout. Although monosodium urate (MSU) crystal precipitation has been detected in different tissues of patients as a trigger for disease, the pathological role of soluble UA remains controversial due to the lack of causality in the clinical setting. Abnormal elevation or reduction of UA levels has been linked to some of pathological status, also known as U-shaped association, implying that the physiological levels of UA regulated by multiple enzymes and transporters are crucial for the maintenance of health.

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Otitis media (OM) in calves, is caused by different bacteria. OM treatment requires identification of etiological agents and antibiotic sensitivity testing. The gold standard method of bacteriological study of OM is tympanocentesis, but using this technique in farm condition would be difficult.

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We recently reported that the gastrointestinal (GI) fluid volume is influenced by the solution osmolality, and proposed that this effect may play a role in beverage-drug interactions. Here, we investigated whether osmolality-dependent fluid secretion can explain the difference in the magnitudes of fruit juice-drug interactions depending on the type of fruit juice (grapefruit juice (GFJ), orange juice (OJ), and apple juice (AJ)). The osmolality of GFJ, OJ, and AJ used in this study was found to be 552, 686, and 749 mOsm/kg, respectively.

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The aim of this study was firstly to investigate the effect of membrane permeability on the intestinal availability (F ) of 10 cytochrome P450 3A4 substrates with differing permeability (P ) and metabolic activity (CL ) using Madin-Darby canine kidney II (MDCKII) cells expressing human CYP3A4 (MDCKII/CYP3A4 cells), and secondly to confirm the essential factors by simulations. A membrane permeation assay using MDCKII/CYP3A4 cells showed a significant correlation between human intestinal extraction ratio (ER) (E (=1 - F )) and in vitro cellular ER (r = 0.834).

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Access to clean water for irrigation and drinking has long been a global concern. The need for fast, precise, and cost-effective methods to detect harmful bacteria like Enterohemorrhagic Escherichia coli (EHEC) serotype O157:H7 is high due to the potential for severe infectious diseases. Fortunately, recent research has led to developing and utilizing rapid bacterial detection methods.

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  • * Analysts discovered a new type of SeM (SeM-97) among the streptococcal isolates, which was correlated with factors like age, sex, race, clinical symptoms, and geographic area; the SeM-97 allele is newly identified and has not been previously documented.
  • * The research identified a specific genotype (Streptococcus equi subsp. equi) with clinical signs like nasal discharge and fever, and the
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Objectives: Stroke patients frequently exhibit loss of independence of urination, and their lower urinary tract symptoms change with the phase of stroke. However, it is unclear whether switching prescribed drugs for lower urinary tract symptoms during hospitalization from acute care wards to convalescence rehabilitation wards affects patients' independence of urination at discharge. It is also unclear whether the impact of switching varies by stroke type.

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  • The study investigates how fluid dynamics in the gastrointestinal (GI) tract affect drug absorption in rats by analyzing fluid absorption and secretion along the GI tract using a closed-loop technique with specific tracers.
  • Results show that the volume of luminal fluid decreases in the jejunum and ileum but remains steady in the colon, while a tracer for water disappeared quickly across all regions.
  • The findings indicate that fluid secretion is more significant than absorption in determining differences in fluid dynamics among GI regions, especially under varying osmotic conditions.
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  • Urate transporter 1 (URAT1) is important for uric acid reabsorption in the kidneys and is a target for drugs like probenecid and the newly approved dotinurad in Japan.
  • Dotinurad shows a unique mechanism of URAT1 inhibition that might not be solely due to direct competition with uric acid, suggesting it also functions by inactivating the transporter when it accumulates inside cells.
  • Unlike other uricosuric agents, dotinurad not only competes with uric acid for uptake but also inhibits the transporter’s ability to efflux other important molecules, enhancing its overall effectiveness in reducing uric acid reabsorption.
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Biliary excretion is a major drug elimination pathway that affects their efficacy and safety. The currently available in vitro sandwich-cultured hepatocyte method is cumbersome because drugs accumulate in the closed bile canalicular lumen formed between hepatocytes and their amounts cannot be mealsured directly. This study proposes a hepatocyte culture model for the rapid evaluation of drug biliary excretion using permeation assays.

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Purpose: Plant-derived extracellular vesicles (EVs) have been reported to exert biological activity on intestinal tissues by delivering their contents into intestinal cells. We previously reported that ASBT/SLC10A2 mRNA was downregulated by apple-derived extracellular vesicles (APEVs). ASBT downregulation is effective in the treatment of cholestasis and chronic constipation, similar to the beneficial effects of apples.

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Resistance to synthetic antifungals has become one of the leading public health challenges around the world. Accordingly, novel antifungal products like naturally occurring molecules can be one of the potential ways to reach efficient curative approaches to control candidiasis. This work evaluated the effect of menthol on cell surface hydrophobicity (CSH), biofilm formation, growth, and ergosterol content of Candida glabrata, a yeast with a high resistance against antifungal agents.

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The proximal tubule plays an important role in the kidney and is a major site of drug interaction and toxicity. Analysis of kidney toxicity via in vitro assays is challenging, because only a few assays that reflect functions of drug transporters in renal proximal tubular epithelial cells (RPTECs) are available. In this study, we aimed to develop a simple and reproducible method for culturing RPTECs by monitoring organic anion transporter 1 (OAT1) as a selection marker.

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Apples are known to exhibit various beneficial effects on human health. In the present study, we investigated the effect of continuous intake of apple juice (AJ) on constipation status. A single dose of loperamide in rats as the constipation model markedly decreased the weight and number of fecal pellets compared to saline-administered rats as a control.

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Since the processes of dissolution and membrane permeation are affected by the water content in the gastrointestinal (GI) tract, the water dynamics in the GI tract is expected to have a significant impact on the absorption of orally administered drugs. Here, we aimed to develop a physiologically based fluid kinetic (PBFK) model using GI water kinetic parameters obtained from in situ closed-loop studies in rats in order to quantitatively predict GI water dynamics. By incorporating the experimentally measured site-specific parameters of GI water absorption and secretion into a GI compartment model, we developed a bottom-up PBFK model that successfully simulates the reported GI fluid dynamics in rats and humans observed using positron emission tomography and magnetic resonance imaging, respectively.

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