• Title/Summary/Keyword: Gastrointestinal Tract Development

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YH18968, a Novel 1,2,4-Triazolone G-Protein Coupled Receptor 119 Agonist for the Treatment of Type 2 Diabetes Mellitus

  • Han, Taedong;Lee, Byoung Moon;Park, Yoo Hoi;Lee, Dong Hoon;Choi, Hyun Ho;Lee, Taehoon;Kim, Hakwon
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.201-209
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    • 2018
  • G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

In vitro and In vivo Activities Studies of Chois Mastic Using Self-microemulsifying Drug Delivery System (SMEDDS) against Helicobactor pylori (자가미세유화시스템을 이용한 매스틱의 헬리코박터파일로리 대한 In vitro 및 In vivo 활성 연구)

  • Kim, Su-Ji;Jeong, Sang-Young;Gil, Young-Sig;Shin, Byung-Cheol;Hwang, Sung-Joo;Cho, Sun-Hang
    • YAKHAK HOEJI
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    • v.55 no.1
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    • pp.1-10
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    • 2011
  • Mastic is a bleed resin formed in pistacia lentiscus tree extract form the anacatdiaceae family. Mastic is used as a food ingredient in the Mediteraanean resin, and has been used by local inhabitants as a traditional medicine for relief of upper abdominal discomfort, dyspepsiaand peptic ulcer. Clinically, mastic has been effective in the treatment of benign gastric and duodenal, ulcers, giving symptomatic relief and endoscopically proven healing. In this study, to enhance activiteies of poorly water soluble Mastic with oils, surfactants and cosurfactants and then the mixure was microemulsified in aqueous media under condition of gentle agitation and digestive motility that would be encountered in the gastrointestinal tract. Formulation development and screening were based on phase diagrams and characteristics of resultant microemulsion. For optimum mastic formulation, microemulsions with various ratio (w/w%) of mastics, oils, surfactants and cosurfactants were prepared and their solubility was evaluated by monitoring particles size in their buffer through visual asessment and electrophoretic light scattering spectrophotomerter (ELS). In vitro activity of self microemulsified mastic (SME mastic) was determined by minimum ingibition concentration (MIC) test against a panel of Helicobacter pylori (H. pylori) clinical strains. Additionally, in vivo activity of SME masitc was investigated us mouse infected by CH275 of H. pylori. The mean diameter of SME mastic was less then 100 nm in water and SME mastic was showed similar antiboisis effect compared to tometronidazole, clarithromycin and omeproazole. Consequently, SME mastic would be effective system to exterminate H. pylori. If mastic were dose with combined treatment, mastic might augur well for effect of H. pylori eradication as good remedy.

Diffuse Large B Cell Lymphoma in Submandibular Gland (악하선에 발생한 미만성 대형 B세포 림프종 1례)

  • Lee Chang-Haeng;Choi Jee-Hoon;Baek Seung-Kuk;Woo Jeong-Su;Jung Kwang-Yoon
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.1
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    • pp.67-70
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    • 2003
  • Out of entire salivary tumor, 1.7% are malignant lymphoma developed in salivary gland and it is usually mucosa associated lymphoid tissue (MALT) lymphoma developed in salivary gland. In the case of Non-Hodgkin lymphoma, the most frequently involved extanodal sites of diffuse large B cell lymphoma are bone, skin, thyroid, gastrointestinal tract, and lung. Development in salivary gland is very rare. A 69 years old male patient who have found Lt. submandibular gland (SMG) mass a month ago is suspected of malignancy from his FNA result, so histologic exam by SMG resection was operated. According to histopathologic exam, large B cell lymphocyte infiltratration were generally shown as diffuse and lymphoepitheliallesion were not found. In immunostaining, CD79a showed positive and CD3, CAM5.2 showed negative which diagnosed as diffuse large B cell lymphoma. As Ann Arbor stage I, CEOP-B chemotherapy was used 3 times as treatment without any recurrence. In the case of malignant lymphoma in salivary gland, it develops as painless mass in ipsilateral side. If found in parotid gland, it is rare to have facial nerve falsy and pathologically diagnosed as lymphocytes of abnormal type of monoclonal immunostaining must be provided as evidence. Combined therapy is known as most effective treatment for intermediate grade.

Development and evaluation of probiotic delivery systems using the rennet-induced gelation of milk proteins

  • Ha, Ho-Kyung;Hong, Ji-Young;Ayu, Istifiani Lola;Lee, Mee-Ryung;Lee, Won-Jae
    • Journal of Animal Science and Technology
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    • v.63 no.5
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    • pp.1182-1193
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    • 2021
  • The aims of this study were to develop a milk protein-based probiotic delivery system using a modified rennet-induced gelation method and to determine how the skim milk powder concentration level and pH, which can affect the rennet-induced intra- and inter-molecular association of milk proteins, affect the physicochemical properties of the probiotic delivery systems, such as the particle size, size distribution, encapsulation efficiency, and viability of probiotics in simulated gastrointestinal tract. To prepare a milk protein-based delivery system, skim milk powder was used as a source of milk proteins with various concentration levels from 3 to 10% (w/w) and rennet was added to skim milk solutions followed by adjustment of pH from 5.4 or 6.2. Lactobacillus rhamnosus GG was used as a probiotic culture. In confocal laser scanning microscopic images, globular particles with a size ranging from 10 ㎛ to 20 ㎛ were observed, indicating that milk protein-based probiotic delivery systems were successfully created. When the skim milk powder concentration was increased from 3 to 10% (w/w), the size of the delivery system was significantly (p < 0.05) increased from 27.5 to 44.4 ㎛, while a significant (p < 0.05) increase in size from 26.3 to 34.5 ㎛ was observed as the pH was increased from 5.4 to 6.4. An increase in skim milk powder concentration level and a decrease in pH led to a significant (p < 0.05) increase in the encapsulation efficiency of probiotics. The viability of probiotics in a simulated stomach condition was increased when probiotics were encapsulated in milk protein-based delivery systems. An increase in the skim milk powder concentration and a decrease in pH resulted in an increase in the viability of probiotics in simulated stomach conditions. It was concluded that the protein content by modulating skim milk powder concentration level and pH were the key manufacturing variables affecting the physicochemical properties of milk protein-based probiotic delivery systems.

Development and industrial application of low-calorie food ingredients derived from starches (전분 유래 저열량 식품소재의 개발과 산업적 이용)

  • Chung, Hyun-Jung
    • Food Science and Industry
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    • v.52 no.4
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    • pp.358-374
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    • 2019
  • Indigestible carbohydrates as dietary fiber have attracted interest of consumers due to their several physiological benefits. Recent definitions of dietary fiber have included other indigestible carbohydrates such as resistant starch and resistant maltodextrins, which are natural, colorless, odorless and tasteless low-calorie food ingredients. Unlike some carbohydrates and digestible starches, indigestible starch and maltodextrin resist enzymatic hydrolysis in the upper gastrointestinal tract, resulting in little or no direct glucose absorption. In addition, there is increased microbial fermentation production of short-chain fatty acids in the large intestine. As an emerging functional low-calorie food ingredient, resistant starch and maltodextrin have been shown to have equivalent or superior impacts on human health compared to conventional fiber-enriched food ingredients. In this paper, the definition, strategies to enhance dietary fiber content in foods, some potential health benefits, and applications in food industry for indigestible starch and maltodextrin are summarized and discussed.

Integrated Power Optimization with Battery Friendly Algorithm in Wireless Capsule Endoscopy

  • Mehmood, Tariq;Naeem, Nadeem;Parveen, Sajida
    • International Journal of Computer Science & Network Security
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    • v.21 no.11
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    • pp.338-344
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    • 2021
  • The recently continuous enhancement and development in the biomedical side for the betterment of human life. The Wireless Body Area Networks is a significant tool for the current researcher to design and transfer data with greater data rates among the sensors and sensor nodes for biomedical applications. The core area for research in WBANs is power efficiency, battery-driven devices for health and medical, the Charging limitation is a major and serious problem for the WBANs.this research work is proposed to find out the optimal solution for battery-friendly technology. In this research we have addressed the solution to increasing the battery lifetime with variable data transmission rates from medical equipment as Wireless Endoscopy Capsules, this device will analyze a patient's inner body gastrointestinal tract by capturing images and visualization at the workstation. The second major issue is that the Wireless Endoscopy Capsule based systems are currently not used for clinical applications due to their low data rate as well as low resolution and limited battery lifetime, in case of these devices are more enhanced in these cases it will be the best solution for the medical applications. The main objective of this research is to power optimization by reducing the power consumption of the battery in the Wireless Endoscopy Capsule to make it battery-friendly. To overcome the problem we have proposed the algorithm for "Battery Friendly Algorithm" and we have compared the different frame rates of buffer sizes for Transmissions. The proposed Battery Friendly Algorithm is to send the images on average frame rate instead of transmitting the images on maximum or minimum frame rates. The proposed algorithm extends the battery lifetime in comparison with the previous baseline proposed algorithm as well as increased the battery lifetime of the capsule.

IL-17 and IL-17C Signaling Protects the Intestinal Epithelium against Diisopropyl Fluorophosphate Exposure in an Acute Model of Gulf War Veterans' Illnesses

  • Kristen M. Patterson;Tyler G. Vajdic;Gustavo J. Martinez;Axel G. Feller;Joseph M. Reynolds
    • IMMUNE NETWORK
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    • v.21 no.5
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    • pp.35.1-35.16
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    • 2021
  • Gulf War Veterans' Illnesses (GWI) encompasses a broad range of unexplained symptomology specific to Veterans of the Persian Gulf War. Gastrointestinal (GI) distress is prominent in veterans with GWI and often presents as irritable bowel syndrome (IBS). Neurotoxins, including organophosphorus pesticides and sarin gas, are believed to have contributed to the development of GWI, at least in a subset of Veterans. However, the effects of such agents have not been extensively studied for their potential impact to GI disorders and immunological stability. Here we utilized an established murine model of GWI to investigate deleterious effects of diisopropyl fluorophosphate (DFP) exposure on the mucosal epithelium in vivo and in vitro. In vivo, acute DFP exposure negatively impacts the mucosal epithelium by reducing tight junction proteins and antimicrobial peptides as well as altering intestinal microbiome composition. Furthermore, DFP treatment reduced the expression of IL-17 in the colonic epithelium. Conversely, both IL-17 and IL-17C treatment could combat the negative effects of DFP and other cholinesterase inhibitors in murine intestinal organoid cells. Our findings demonstrate that acute exposure to DFP can result in rapid deterioration of mechanisms protecting the GI tract from disease. These results are relevant to suspected GWI exposures and could help explain the propensity for GI disorders in GWI Veterans.

Characterization of L-(+)-Lactic Acid Producing Weizmannia coagulans Strains from Tree Barks and Probiogenomic Evaluation of BKMTCR2-2

  • Jenjuiree Mahittikon;Sitanan Thitiprasert;Sitanan Thitiprasert;Naoto Tanaka;Yuh Shiwa;Nitcha Chamroensaksri;Somboon Tanasupawat
    • Microbiology and Biotechnology Letters
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    • v.51 no.4
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    • pp.403-415
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    • 2023
  • This study aimed to isolate and identify L-(+)-lactic acid-producing bacteria from tree barks collected in Thailand and evaluate the potential strain as probiotics. Twelve strains were isolated and characterized phenotypically and genotypically. The strains exhibited a rod-shaped morphology, high-temperature tolerance, and the ability to ferment different sugars into lactic acid. Based on 16S rRNA gene analysis, all strains were identified as belonging to Weizmannia coagulans. Among the isolated strains, BKMTCR2-2 demonstrated exceptional lactic acid production, with 96.41% optical purity, 2.33 g/l of lactic acid production, 1.44 g/g of lactic acid yield (per gram of glucose consumption), and 0.0049 g/l/h of lactic acid productivity. This strain also displayed a wide range of pH tolerance, suggesting suitability for the human gastrointestinal tract and potential probiotic applications. The whole-genome sequence of BKMTCR2-2 was assembled using a hybridization approach that combined long and short reads. The genomic analysis confirmed its identification as W. coagulans and safety assessments revealed its non-pathogenic attribute compared to type strains and commercial probiotic strains. Furthermore, this strain exhibited resilience to acidic and bile conditions, along with the presence of potential probiotic-related genes and metabolic capabilities. These findings suggest that BKMTCR2-2 holds promise as a safe and effective probiotic strain with significant lactic acid production capabilities.

Bioequivalence of Levopid Tablet to Levopride Tablet (Levosulpiride 25 mg) (레보프라이드 정(레보설피리드 25 mg)에 대한 레보피드 정의 생물학적 동등성)

  • Cho, Hea-Young;Kang, Hyun-Ah;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.2
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    • pp.127-133
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    • 2002
  • Levosulpiride is the 1evo-enantiomer form of racemic sulpiride, a benzamide derivative selectively inhibiting dopaminergic $D_2$ receptors at the trigger zone both in the central nervous system and in the gastrointestinal tract. The purpose of the present study was to evaluate the bioequiva1ence of two levosulpiride tablets, Levopride (SK Pharmaceutical Co., Ltd.) and Levopid (Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The levosulpiride release from the two levosulpiride tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight normal male volunteers, $23.82{\pm}3.26$ years in age and $69.13{\pm}8.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of levosulpiride was orally administered, blood was taken at predetermined time intervals and the concentrations of levosulpiride in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two levosulpiride tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Levopride were -1.17%, 1.20% and -1.09%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.93){\sim}log(1.07)\;and\;log(0.90){\sim}log(1.14)\;for\;AUC_t\;and\;C_{max}$, respectively). The 90% confidence interval using untransformed data was within ${\pm}20%$ $(e.g.,\;-19.47{\sim}16.20\;for\;T_{max})$. All parameters met the criteria of KFDA guideline for bioequivalence, indicating that Levopid tablet is bioequivalent to Levopride tablet.

Standardization Studies for the Oriental Mineral Medicine (광물성 약재(광물약)의 표준화에 관한 연구)

  • Kim, Seon-Ok;Park, Maeng-Eon
    • Economic and Environmental Geology
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    • v.48 no.3
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    • pp.187-197
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    • 2015
  • Oriental mineral medicines are single or mixture of more than one mineral species or rock/fossil which are used to treat disease. Mineral medicines remove harmful or useless substances to decrease toxicity and secondary effects, and cause the manufacture of medical compounds with increased efficacy. The extraction test is an accepted in vitro system to predict the bioaccessibility of major and minor elements from mineral medicine. It incorporates gastrointerstinal tract parameters representative of a human body that including stomach and small intestinal pH which are the same as digestion condition. The bioaccessibility of a mineral medicine is the fraction that is soluble in the gastrointestinal environment and is available for absorption. Reaction path modeling in the human body can predict digestion with gastric fluid as well as absorption in the small intestine, existence in body fluids and reaction progress of the exhaust process according to pH conditions in body. Also reaction path modeling can predict bioavailability, which is equal to existence rate in the body and the form and amount of a medicine in the body after intake. The study results from predicating the existence form mineral medicines in the body, and proving the effective ingredient using bioaccessibitily and human risk assessment, suggest these that should be necessary data for new medicine development.