• Title/Summary/Keyword: Gastrointestinal drugs

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Alteration in Response to Chemicals Induced by Physical Exercise (육체운동에 의해 유발되는 화학물질에 대한 반응성의 변화)

  • 김영철
    • Toxicological Research
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    • v.18 no.3
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    • pp.215-226
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    • 2002
  • Acute or repeated physical exercise affects a large number of physiological parameters including hemodynamics, respiration, pH, temperature, gastrointestinal function and biotransformation, which determine the pharmacokinetics of drugs and chemicals. The rate and the amount of a chemical reaching the active site are altered by physical exercise, which results in significant changes in pharmacolosical/toxicological activity of the chemical. This aspect of physical exercise has vast implication in therapeutics and in safety evaluation, particularly for chemicals that have a low margin of safety. However there appears to be a wide inter- and intraindividual variation in the effects of physical exercise depend-ing on the duration, intensity and type of exercise, and also on the properties of each chemical. It is suggested that more studies need to be done to determine which factor(s) plays a major role in the disposition of chemicals in human/animals performing physical exercise. Certain chemicals induce severe toxicity due to metabolic conversion to reactive intermediate metabolites. it is suggested that repeated exercise may enhance the free radical scavenging system by increasing the activity of antioxidant enzymes. This area of research remain to be explored to elucidate the interaction of exercise and chemical on the antioxidant system.

Failure of Fecal Microbiota Transplantation in a Three-Year-Old Child with Severe Refractory Ulcerative Colitis

  • Kumagai, Hideki;Yokoyama, Koji;Imagawa, Tomoyuki;Inoue, Shun;Tulyeu, Janyerkye;Tanaka, Mamoru;Yamagata, Takanori
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.19 no.3
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    • pp.214-220
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    • 2016
  • Fecal microbiota transplantation (FMT) is a treatment designed to correct gut dysbiosis by administration of feces from a healthy volunteer. It is still unclear whether FMT for children with ulcerative colitis (UC) is effective or hazardous. Here we describe a young patient to have received FMT for UC. A three-year-old girl was admitted to our hospital with severe active UC, and treated with aminosalicylates and various immunosuppressive drugs. As remission was not achieved, we decided to try FMT before colectomy. We administered donor fecal material a total of six times by retention enema (${\times}2$) and via a nasoduodenal tube (${\times}4$) within 10 days. The patient developed abdominal pain and pyrexia after each FMT session. Analyses revealed the transferred donor fecal microbiota had not been retained by the patient, who ultimately underwent colectomy. The severity of the UC and/or timing of FMT may have partly accounted for the poor outcome.

Physical properties of cyclosporin A-loaded nanostructured lipid carriers (Cyclosporin A가 봉입된 nanostructured lipid carriers의 물리적 특성연구)

  • Song, Chung-Kil;Chung, Suk-Jae;Shim, Chang-Koo;Kim, Dae-Duk
    • Journal of Pharmaceutical Investigation
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    • v.38 no.1
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    • pp.39-43
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    • 2008
  • Cyclosporin A (CyA), a potent immunosuppressive drug used in allogeneic transplants and autoimmune disease, is a typical water-insoluble drug. Recently, nanoparticle carriers were investigated to improve the intestinal absorption of drugs. In this study, CyA-loaded nanostructured lipid carriers (NLCs) were prepared from a hot o/w emulsion using the high pressure homogenization method. The NLCs were consisted of cationic lipids, solid lipids, liquid lipids (oils), surfactant and stabilizer. Encapsulation efficiency of CyA in NLCs was approximately 71%. The average particle size and zeta potential of NLCs were below 250 nm and above +40 mV, respectively. The morphology of NLCs was confirmed by transmission electron microscopy (TEM) analysis. Compared to the CyA powder, higher in vitro release of CyA from NLCs was observed after burst release within 30 min. Thus, CyA-loaded NLCs could be applied not only for parenteral route but also for gastrointestinal administration, which needs further investigation.

Suppressive Actions of Astragali Radix (AR) Ethanol Extract and Isolated Astragaloside I on HCl/ethanol-Induced Gastric Lesions

  • Jeong, Jeong-Suk;Lee, Je-Hyuk;Lee, Sang-Hyup;Kang, Sam-Sik;Jeong, Choon-Sik
    • Biomolecules & Therapeutics
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    • v.17 no.1
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    • pp.62-69
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    • 2009
  • Roots of Astragalus membranaceus (A. membranaceus) (Astragali Radix, AR) has been used as a herbal medicine for gastrointestinal disorders in China, Korea, Japan, and other Asia countries. In this study we investigated the effects of the AR 70% ethanol extract and compounds isolated from AR on gastritis in rats and growth of human gastric cancer cells. AR 70% ethanol extract showed the potent acid-neutralizing capacities and partly cytotoxicity of Helicobacter pylori and human AGS gastric cancers cell. Astragaloside I and daucosterol, which were isolated from AR, significantly inhibited HCl/ethanol-induced gastric lesions. In addition, daucosterol increased the mucus content to almost the same as the positive control. The results of this study suggest that astragaloside I and daucosterol may be good candidates for the development of new drugs or neutraceuticals which can be used for the treatment or prevention of gastritis.

Studies on the Efficacy of Combined Preparation of Crude Drugs (XXIX) -Effects of Insamyangwee-tang on Gastrointestinal Tract- (생약(生藥) 복합(複合) 제제(製劑)의 약효(藥效) 연구(硏究)(제29보)(第29報) -인삼양위탕(人蔘養胃湯)이 위장관(胃腸管)에 미치는 영향(影響)-)

  • Hong, Nam-Doo;Jeong, Gyu-Man;Lee, Dong-Hyun;Joo, Soo-Man
    • Korean Journal of Pharmacognosy
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    • v.17 no.3
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    • pp.215-222
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    • 1986
  • Although the 'Insamyangwee-tang' has been widely used in clinical purposes in the oriental medicine, its clinical efficacy is only documentated for the cases of gastritis, gastric ulcer and enteritis, but the experimental study on these has not been undertaken. So, to investigate the clinical efficacy of 'Insamyangwee-tang' comparing with animal experiments, This study was carried out. The results showed that relaxing action was shown on the isolated ileum in mice and that strong antagonistic actions were seen on $BaCl_2$, acetylcholine and histamine induced contraction of the ileum in mice, rats, rabbits and guinea-pigs that the relaxing effect of the intestinal smooth muscle was recognized. Inhibitory effects on transport rate in the small intestine of mice. Strong antagonistic actions were seen on acetylcholine induced contraction of duodenum in rats and remarkably inhibiting actions were seen of duodenum in rats. Inhibitory action on the secretion of gastric juice and pepsin, anti-ulceration effect was recognized.

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Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells

  • An, JaeJin;Ha, Eun-Mi
    • Journal of Microbiology and Biotechnology
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    • v.26 no.8
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    • pp.1490-1503
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    • 2016
  • Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT-116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.

Comparison of Gastrointestinal Permeability of Caffeine, Propranolol, Atenolol, Ofloxacin, and Quinidine Measured Using Ussing Chamber System and Caco-2 Cell Monolayer

  • Song, Im-Sook;Choi, Young A;Choi, Min-Koo
    • Mass Spectrometry Letters
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    • v.8 no.2
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    • pp.34-38
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    • 2017
  • The purpose of this study was to develop a cocktail approach for the measurement of the permeability of marker compounds, caffeine and propranolol (high permeability), ofloxacin (intermediate), atenolol (low), and quinidine (P-glycoprotein substrate), simultaneously. Then we compared the permeability in Caco-2 cells with that in rat intestinal segments. The difference between individual measurement and cocktail approach was less than 20 %, and the permeabilities of these compounds were similar to those previously reported, suggesting that the cocktail transport study and simultaneous drug analysis were successfully developed and validated in this study. Additionally, in the application of this cocktail method, the permeability of five drugs in rat jejunum was similar to that in ileum but different from that in colon, which was measured using the Ussing chamber system. Moreover, permeability in jejunum and ileum was similar to that in Caco-2 cells. In conclusion, the permeability in Caco-2 cells was equivalent to the permeability in rat jejunum and ileum determined with the Ussing system. Therefore, this newly developed cocktail assay and its application to the Ussing system can be a useful tool for robust and rapid screening for site-specific permeability in rat intestine, thus accelerating the prediction of absorption of new chemical entities.

Long-limb Roux-en-Y Reconstruction after Subtotal Gastrectomy to Treat Severe Diabetic Gastroparesis

  • Park, Joong-Min;Kim, Jong Won;Chi, Kyong-Choun
    • Journal of Gastric Cancer
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    • v.19 no.3
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    • pp.365-371
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    • 2019
  • The role of surgical intervention in patients with diabetic gastroparesis is unclear. We report a case of a 37-year-old man with a history of recurrent episodes of vomiting and long-standing type 2 diabetes mellitus. Esophagogastroduodenoscopy did not reveal any findings of reflux esophagitis or obstructive lesions. A gastric emptying time scan showed prolonged gastric emptying half-time (344 minutes) indicating delayed gastric emptying. Laboratory tests revealed elevated fasting serum glucose and glycosylated hemoglobin (HbA1c, 12.9%) and normal fasting C-peptide and insulin levels. We performed Roux-en-Y reconstruction after subtotal gastrectomy to treat gastroparesis and improve glycemic control, and the patient showed complete resolution of gastrointestinal symptoms postoperatively. Barium swallow test and gastric emptying time scan performed at follow-up revealed regular progression of barium and normal gastric emptying. Three months postoperatively, his fasting serum glucose level was within normal limits without the administration of insulin or oral antidiabetic drugs with a reduced HbA1c level (6.9%). Long-limb Roux-en-Y reconstruction after subtotal gastrectomy may be useful to treat severe diabetic gastroparesis by improving gastric emptying and glycemic control.

Multimodal Treatment Strategies in Esophagogastric Junction Cancer: a Western Perspective

  • Goetze, Thorsten Oliver;Al-Batran, Salah-Eddin;Berlth, Felix;Hoelscher, Arnulf Heinrich
    • Journal of Gastric Cancer
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    • v.19 no.2
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    • pp.148-156
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    • 2019
  • Esophagogastric junction (EGJ) cancer is a solid tumor entity with rapidly increasing incidence in the Western countries. Given the high proportion of advanced cancers in the West, treatment strategies routinely employed include surgery and chemotherapy perioperatively, and chemoradiation in neoadjuvant settings. Neoadjuvant chemoradiation and perioperative chemotherapy are mostly performed in esophageal cancer that extends to the EGJ and gastric as well as EGJ cancers, respectively. Recent trials have tried to combine both strategies in a perioperative context, which might have beneficial outcomes, especially in patients with EGJ cancer. However, it is difficult to recruit patients for trials, exclusively for EGJ cancers; therefore, the results have to be carefully reviewed before establishing a standard protocol. Trastuzumab was the first drug for targeted therapy that was positively evaluated for this tumor entity, and there are several ongoing trials investigating more targeted drugs in order to customize effective therapies based on tissue characteristics. The current study reviews the multimodal treatment concept for EGJ cancers in the West and summarizes the latest reports.

The Ameliorative Effect of Rubi Fructus on DSS-induced Colitis in Mice

  • Myung, Noh-Yil
    • Korean Journal of Plant Resources
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    • v.34 no.3
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    • pp.216-222
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    • 2021
  • Ulcerative colitis (UC) is an inflammatory bowel disease and a chronic gastrointestinal disorder. Rubi Fructus (RF), the fruit of Rubus coreanus Miquel, is known to exert several pharmacological effects including anti-oxidative, anti-obesity and anti-inflammatory properties. However, the improving effect and mechanism of RF on intestinal inflammation is not been fully understood. The purpose of this study was to investigate the regulatory effect of RF on dextran sulfate sodium (DSS)-induced colitis in mice. We evaluated the effects of RF on DSS-induced clinical signs by analyzing weight loss and colon length. The inhibitory effects of RF on inflammatory mediators such as prostaglandin E2 (PGE2), cyclooxygenase (COX)-2, as well as the activation of nuclear factor-κB (NF-κB), were determined in colitis tissue. Our data indicated that mice treated with DSS showed clinical symptoms of colitis, including weight loss, colon length decrease and diarrhea. However, we observed that RF treatment significantly improved these clinical symptoms of weight loss, colon length decrease and diarrhea induced by DSS. RF inhibited the enhanced levels of COX-2 and PGE2 caused by DSS. We also showed that the anti-inflammatory mechanism of RF by suppressing the activation of NF-kB in DSS-treated colon tissues. Collectively, the findings of this study indicate the prospect of developing new drugs from RF for UC treatment.