• Journal of Pharmaceutical Investigation
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• v.21 no.4
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• pp.215-222
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• 1991

The absorption characteristics of itraconazole, which is an antifungal agent, from intestinal segments in the anesthetized rat i1l situ were investigated in order to design an effective oral drug delivery system. The pH-solubility profile of itraconazole, the rate and extent of absorption of itraconazole, the optimal absorption site(s) of itraconazole and the absorption enhancing effect of sodium cholate on itraconazole were examined in the present study. In situ single-pass perfusion method and recirculating perfusion technique using duodenum(D), jejunum(J) and ileum(I) were employed for the calculation of apparent permeability(Pe) and apparent first-order rate constant(Kobs). respectively. The results of this study were as follows; (1) Itraconazole showed appreciable aqueous solubility only at pH values of below 2.0. (2) pe(cm/sec) decreased in the following order: $D(10.24{\pm}1.78{\times}10^{-4})>J(8.86{\pm}0.79{\times}10^{-4})>I(3.78{\pm}0.13 X 10^{-4})$. (3) $Kobs(min^{-1})$ decreased in the following order: $J(17.12{\pm}3.19{\times}10^{-3})>D(13.37{\pm}0.6{\times}10^{-3})>I(11.05{\pm}0.91{\times}10^{-3})$. (4) The solubility of itraconazole markedly increased with the increase of the concentration of sodium cholate. (5) The addition of 10 mM sodium cholate significantly increased the apparent first-order rate constant of itraconazole in the ileum by a factor of 6.8.

• Journal of Animal Science and Technology
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• v.63 no.2
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• pp.211-247
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• 2021

Livestock species experience several stresses, particularly weaning, transportation, overproduction, crowding, temperature, and diseases in their life. Heat stress (HS) is one of the most stressors, which is encountered in livestock production systems throughout the world, especially in the tropical regions and is likely to be intensified due to global rise in environmental temperature. The gut has emerged as one of the major target organs affected by HS. The alpha- and beta-diversity of gut microbiota composition are altered due to heat exposure to animals with greater colonization of pathogenic microbiota groups. HS also induces several changes in the gut including damages of microstructures of the mucosal epithelia, increased oxidative insults, reduced immunity, and increased permeability of the gut to toxins and pathogens. Vulnerability of the intestinal barrier integrity leads to invasion of pathogenic microbes and translocation of antigens to the blood circulations, which ultimately may cause systematic inflammations and immune responses. Moreover, digestion of nutrients in the guts may be impaired due to reduced enzymatic activity in the digesta, reduced surface areas for absorption and injury to the mucosal structure and altered expressions of the nutrient transport proteins and genes. The systematic hormonal changes due to HS along with alterations in immune and inflammatory responses often cause reduced feed intake and production performance in livestock and poultry. The altered microbiome likely orchestrates to the hosts for various relevant biological phenomena occurring in the body, but the exact mechanisms how functional communications occur between the microbiota and HS responses are yet to be elucidated. This review aims to discuss the effects of HS on microbiota composition, mucosal structure, oxidant-antioxidant balance mechanism, immunity, and barrier integrity in the gut, and production performance of farm animals along with the dietary ameliorations of HS. Also, this review attempts to explain the mechanisms how these biological responses are affected by HS.

• Food Science of Animal Resources
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• v.43 no.4
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• pp.594-611
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• 2023

Whey protein (WP) has nutritional value, but the presence of β-lactoglobulin (β-LG) and α-lactalbumin (α-LA) cause allergic reactions. In this study, hypoallergenic whey protein hydrolyate (HWPH) was prepared by decomposing β-LG and α-LA of WP using exo- and endo-type proteases. The enzyme mixing ratio and reaction conditions were optimized using response surface methodology (RSM). Degradation of α-LA and β-LG was confirmed through gel electrophoresis, and digestion, and absorption rate, and immunostimulatory response were measured using in vitro and in vivo systems. Through RSM analysis, the optimal hydrolysis conditions for degradation of α-LA and β-LG included a 1:1 mixture of Alcalase and Prozyme reacted for 10 h at a 1.0% enzyme concentration relative to substrate. The molecular weight of HWPH was <5 kDa, and leucine was the prominent free amino acid. Both in vitro and in vivo tests showed that digestibility and intestinal permeability were higher in HWPH than in WP. In BALB/c mice, as compared to WP, HWPH reduced allergic reactions by inducing elevated Type 1/Type 2 helper T cell ratio in the blood, splenocytes, and small intestine. Thus, HWPH may be utilized in a variety of low allergenicity products intended for infants, adults, and the elderly.

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.161-169
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• 2013

The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol$^{(R)}$, sodium cholate, sodium caprate, hydroxypropyl ${\beta}$-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and $P_{app}$ of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the $AUC_{0-24\;h}$ of ZMR in the lungs following oral administration of PO-SC was $125.22{\pm}27.25$ ng hr $ml^{-1}$ with a $C_{max}$ of $156.00{\pm}24.00$ ng/ml reached at $0.50{\pm}0.00$ h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the $IC_{50}$ concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.127-134
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• 2008

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.656-668
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• 2018

Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

• Journal of Korean Society of Environmental Engineers
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• v.29 no.7
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• pp.820-825
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• 2007

Earthworm casting was the natural fertilizer that contained high concentrations of nutrients such as nitrogen, phosphate and potassium and of over $10^8$ CFU/ml of microorganisms. Greater than 80% of feed was excreted through the fermentation by the intestinal enzyme, after worm had eaten feeds such as fallen leaves and rotten roots under the ground. Also, the soil structure of casting was known to be very efficient in the aspects of the porosity, the water permeability, and deodorizing activities. In this research, the biofilter packed with a biomedia made of casting and waste polyurethane foam, a binder, which helped to improve the durability and perpetuity of casting, was investigated to degrade malodorous hydrogen sulfide gas. The biomedia had no need of extra supply of nutrients and of microbial inoculations. On the beginning of the operations, it showed 100% removal of hydrogen sulfide gas without lag phase. At SV of 50 $h^{-1}$, hydrogen sulfide gas from the outlet of the biofilter was not detected, when inlet concentration increased to 450 ppmv. After that, removal efficiency decreased as increasing inlet hydrogen sulfide concentration. Hydrogen sulfide removal was maintained at almost 93% until inlet concentration was increased up to 950 ppmv, at which the elimination capacity of $H_2S$ was 61.2 g $S{\cdot}m^{-3}{\cdot}h^{-1}$. Maximum elimination capacity guaranteing 90% removal was 61.2, 65.9, 84.7, 89.4 g $S{\cdot}m^{-3}{\cdot}h^{-1}$ at SV ranging from 50 $h^{-1}$ to 300 $h^{-1}$, but was 59.3 g $S{\cdot}m^{-3}{\cdot}h^{-1}$ at SV of 400 $h^{-1}$. The results calculated from Michaelis-Menten equation revealed that $V_m$ increased from 66.04, 88.96, 117.35, 224.15, to 227.54 g $S{\cdot}m^{-3}{\cdot}h^{-1}$ with increasing space velocity in the range of 50 $h^{-1}$ to 400 $h^{-1}$. However, saturation constant$(K_s)$ decreased from 79.97 ppmv to 64.95 and 65.37 ppmv, and then increased to 127.72 and 157.43 ppmv.