• Title/Summary/Keyword: Gastrointestinal drugs

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Response to Capecitabine Treatment Following Palliative Chemotherapy for Metastatic Colorectal Cancer: A Case Report (고식적 항암화학요법 후에 Capecitabine 단독치료에 반응을 보인 전이성 대장암 환자 1례)

  • Dae Hwa Park;Ju Seok Kim;Sun Hyung Kang;Hee Seok Moon;Jae Kyu Sung;Hyun Yong Jeong
    • Journal of Digestive Cancer Research
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    • v.5 no.1
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    • pp.66-69
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    • 2017
  • Approximately 40% of patients with colorectal cancer have metastatic lesions at the time of diagnosis, and chemotherapy is generally prescribed for these patients. Though several drugs are used, 5-FU has long been the backbone of chemotherapy for colorectal cancer. Capecitabine is an oral 5-FU prodrug approved by the FDA in 2005 and is used alone or in combination for treatment of colorectal cancer. Recently, capecitabine has been used for a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer. Here, we report a rare case of a 59-year-old woman, diagnosed with metastatic colorectal cancer who first presented with abdominal discomfort and dyspepsia. She showed a partial response to palliative first line FOLFOX chemotherapy, which had to be stopped due to peripheral neuropathy, as a side effect. She was next put on a second line chemotherapy regimen with capecitabine alone, since then she showed good treatment response without any disease progression.

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Current Status of the Diagnosis and Management of Pancreatic Neuroendocrine Tumors in Japan

  • Tetsuhide Ito;Masami Miki;Keijiro Ueda;Lingaku Lee;Ken Kawabe;Hisato Igarashi;Nao Fujimori;Kazuhiko Nakamura;Kohei Yasunaga;Robert T. Jensen;Takao Ohtsuka;Yoshihiro Ogawa
    • Journal of Digestive Cancer Research
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    • v.4 no.2
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    • pp.51-57
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    • 2016
  • The epidemiology of pancreatic neuroendocrine neoplasms (PNENs) in Asia has been clarified through epidemiological studies, including one conducted in Japan, and subsequently another in South Korea. As endoscopic ultrasonography (EUS) has become more widely accessible, endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been performed in pancreatic tumors for which the clinical course was only monitored previously. This has enabled accurate diagnosis of pancreatic tumors based on the 2010 WHO classification; as a result, the number of patients with an accurate diagnosis has increased. Although surgery has been the standard therapy for PNENs, new treatment options have become available in Japan for the treatment of advanced or inoperable PNENs; of particular note is the recent introduction of molecular target drugs (such as everolimus and sunitinib) and streptozocin. Treatment for progressive PNENs needs to be selected for each patient with consideration of the performance status, degree of tumor differentiation, tumor mass, and proliferation rate. Somatostatin receptor (SSTR)-2 is expressed in many patients with neuroendocrine tumor. Somatostatin receptor scintigraphy (SRS), which can visualize SSTR-2 expression, has been approved in Japan. The SRS will be a useful diagnostic tool for locating neuroendocrine neoplasms, detecting distant metastasis, and evaluating therapy outcomes. In this manuscript, we review the latest diagnostic methods and treatments for PNENs.

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Prospective Targets for Colon Cancer Prevention: from Basic Research, Epidemiology and Clinical Trial

  • Shingo Miyamoto;Masaru Terasaki;Rikako Ishigamori;Gen Fujii;Michihiro Mutoh
    • Journal of Digestive Cancer Research
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    • v.4 no.2
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    • pp.64-76
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    • 2016
  • The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

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A Comparative Study of Effect of Secondary Anti-tuberculosis Drugs in the Retreatment of Pulmonary Tuberculosis (폐결핵 재치료에서 이차항결핵제 복합처방의 효과에 관한 비교 연구)

  • Ha, Hyun-Cheol;Kwon, Eun-Soo;Choi, In-Hwan;Hwang, Su-Hee;Park, Seung-Kyu;Song, Sun-Dae
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1154-1166
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    • 1998
  • Background : In the management of patients whose primary chemotherapy has failed, careful assessment is essential. It is important to find out as accurate a chemotherapy history as possible. Preferably it should contain the drugs which has never used before. The purpose of present study is establishment of retreatment regimen for pulmonary tuberculosis. The present report concerns the results of retreatment of pulmonary tuberculosis patients treated at National Masan Tuberculosis Hospital. Methods : Retrospective cohort study was made of 104 drug-resistant pulmonary tuberculosis patients who were treated by five regimens between Jan. 1994 and Nov. 1996. All the patients taken medicine for second anti-tuberculosis regimens for the first time. We separated the patients by three groups(Group I ; OFX+PTA+CS+PAS+Aminoglycoside, Group II : PZA+PTA+CS+PAS+Aminoglycoside, Group III : PZA+OFX+PTA+PAS+Aminoglycoside). Results : The age distribution was most frequent in fourth decade(36patients, 34.6%) and the mean age was 42.6 year. The sex distribution was more frequent in the males(81 patients, 85.7%). There was 31 patients(29.8%) with combined diseaes, 18 patients with complication and 24 patients(27.9%) with family history. Primary chemotherapy regimens were HERZ(S or K) in 48 patients (46.2%), HER(S or K) in 41 patients(39.4%) and others in 15 patients(14.4%). Result of drug sensitivity test showed that the resistance to INH and RFP is in 68 patients(65.4%), RFP is 12 patients(11.5%), INH is in 3 patients(2.9%) and all sensitive to INH and RFP is 3 patients(2.9%). The clinical symptoms on admission were coughing(89.4%), sputum(69.2%), dyspnea on exertion(37.5%), weight loss(33.7%) blood tinged sputum(15.4%) and others. The extent of disease on the radiograph was far-advanced in 73 patients(70.2%), moderate in 28 patients(26.9%) and minimal in 3 patients(2.9%). The side effects for drugs were gastrointestinal troubles in 31 patients(29.8%), arthralgia in 22 patients(21.2%), skin rash in 12 patients(11.5%) and others. The negative conversion rate on sputum AFB smear was 85.6%(87.5% in Group I, 80.0% in Group II and 90.5% in Group III). The average negative conversion time on sputum was 4 month(4.0 month in Group I, 4.6 month in Group II and 3.0 month in Group III). Conclusion : In the retreatment of pulmonary tuberculosis, ofloxacin is useful drug for the patients who are not available to use PZA and combination of PZA and OFX can be use effectively substituting for CS.

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Clinical Manifestation of Extrapulmonary Tuberculosis in Children : A Single Center Experience (단일기관에서 경험한 소아 폐외결핵의 임상적 고찰)

  • Seung, So Jin;Kwak, Ga Young;Lee, Soo Young;Kang, Jin Han
    • Pediatric Infection and Vaccine
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    • v.15 no.2
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    • pp.167-173
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    • 2008
  • Purpose : We evaluated the prevalence and clinical, microbiological features of extrapulmonary tuberculosis (EPT) in pediatric patients. Methods : We retrospectively reviewed medical records of pediatric patients diagnosed with EPT at The Catholic University of Korea, Incheon St. Mary's Hospital between 2000 and 2007. Results : Of 109 patients diagnosed with tuberculosis (TB), 12 patients (11%) were admitted with EPT. At 2006-2007, the proportion of patients with EPT among patients with TB was the highest (20%) comparing with last 6 years. The ratio of male to female patients was 1.4:1 and the mean age was 9.2 years (range, 3 months-15 years). The involved sites were pleura in 5 (41.6%), central nervous system in 3 (25%), miliary TB in 2 (16.7%), gastrointestinal tract in 1 (8.3%) and bone and joint in 1 (8.3%). The most common symptom at admission was fever (91.6%) and mean duration of fever was 15.8 days (range, 0-47 days) in spite of the proper treatment. Confirmed rate for acid fast bacillus stain, culture, and polymerase chain reaction were 33.3%, 41.6% and 41.6%. Of 5 culture proven cases, 4 (80%) were resistant to more than one antituberculosis drugs. Eleven patients recovered without complication and 1 patient died. Conclusion : Total incidence of TB decreased steadily according to the nationwide survey. However, our results suggest that the proportion of diagnosis with EPT among diagnosis with TB in children has increased. Microbiological diagnosis of EPT in children was more difficult than that of pulmonary TB. And drug resistance rate has increased.

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Niacin Upper Level Recommendation and Exposure Assessment of Foods and Multivitamin drugs (Niacin의 상한섭취량 제안 및 식품과 복합비타민제 섭취를 통한 인체 노출평가)

  • Park Shin Hee;Lee Hyo Min;Yoon Eun Kyung;Min Chung Sik;Kim Hyeon Jeong;Jun Eun Ah;Ze Keum Ryon
    • Journal of Food Hygiene and Safety
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    • v.20 no.2
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    • pp.77-82
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    • 2005
  • Niacin (vitamin $B_{3}$) is the generic term for nicotinic acid (pyridine 3-carboxylic acid) and nicotinamide (nicotinic acid amide), and coenzyme forms of the vitamin. Large doses of nicotinic acid are associated with a number of adverse effects in human. The effects include flushing, skin itching, nausea, vomiting and gastrointestinal disturbance. This study was conducted to estimate daily intake of niacin by ingestion of food and multivitamin, and to identify risk value related with side effects, which can be caused by large dose intake in population having a typical lifestyle. Induced risk values by comparing only dietary intake level and intake level from both food and multivitamin with upper level as 35 mg/day were 0.53 and $0.81\~6.24$ respectively. Hazard Index over 1 means that occurrence of side effects would be expected in some population. When people intake multivitamin and functional food including niacin, risk value may increase more than risk value identified in this study.

Effect of Pilocarpine Mouthwash on Xerostomia (구강건조증에 대한 필로카핀 구강양치액의 효과)

  • Kim, Ji-Hyun;Park, Ju-Hyun;Kwon, Jeong-Seung;Ahn, Hyung-Joon
    • Journal of Oral Medicine and Pain
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    • v.36 no.1
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    • pp.21-24
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    • 2011
  • Xerostomia is subjective feeling of dry mouth, a symptom that may or may not be accompanied by hyposalivation, an objective decrease in salivary flow. There are many causes induced xerostomia like drugs, salivary gland diseases, radiation therapy to the head and neck region, Sjogren syndrome, emotional stress etc. Insufficient salivary flow creates complications with oral candidiasis, dental caries, periodontitis, halitosis, dysgeusia. So finally, these complications lead to an overall decline in quality of life. Managements of xerostomia are eliminating or alterating the etiologic factors, relieving symptoms, preventing or correcting the consequences of salivary dysfunction, treating underlying disease and stimulating salivation. One of the salivation stimulation agents studied to treat xerostomia was the pilocarpine muscarinic agonist. Pilocarpine is one of salivation stimulants, a parasympathomimetic drug and non-selective muscarinic receptor agonist. Systemic pilocarpine has been used to stimulate salivary secretion. But systemic administration of pilocarpine has limitations such as increased risk of side effects and contraindications. Side effects of systemic pilocarpine administration are sweating, urinary and gastrointestinal disturbance, risk of cardiovascular and pulmonary disorders. This drug must be used carefully by patients with controlled asthma, chronic bronchitis, pulmonary or cardiac disease. Patient with acute asthma, narrow angle glaucoma, iritis should not use pilocarpine. Like this, systemic pilocarpine has many limitations. So, many investigators also have looked at the effectiveness of topical pilocarpine. Here we present patients with xerostomia which was relieved by pilocarpine mouthwash.

Design of swelling gastroretentive drug delivery system for sustained release of metformin (메트포르민의 서방출을 위한 팽윤성 위체류 약물전달시스템 설계)

  • Weon, Kwon Yeon;Kim, Se Gie
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.3
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    • pp.215-222
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    • 2020
  • Metformin is a recommended first-line therapy drug for type 2 diabetes patients. However, compared to other oral antidiabetic drugs (OAD), metformin has a large unit dosage, with bioavailability of 40-60%. This limiting bioavailability is because metformin is absorbed only in the upper gastrointestinal tract as a BCS class 3 drug. Hence, we propose that applying the Gastroretentive Drug Delivery System (GRDDS) and extending drug release time in the stomach will result in improved bioavailability. We selected the swelling type delivery system, as it is considered the most stable gastroretention technology compared to other GRDDSs. We modified the swelling excipient by using a natural swelling excipient to form a swelling tablet made of carrageenan and hydroxypropyl methylcellulose (HPMC). Our results indicate that the swelling complex tablet made of carrageenan and HPMC has a good swelling ability and shows required sustained release in a dissolution pattern. In addition, the carrageenan complex has a better swelling ability than the marketed metformin tablet, as determined by the ratio, (swelling ability)/(excipient weight). Taken together, our results indicate that the carrageenan complex can be developed as a good swelling excipient. Further optimizations are required for the commercialization of the carrageenan complex.

Disorders of Potassium Metabolism (칼륨 대사 장애)

  • Lee, Joo-Hoon
    • Childhood Kidney Diseases
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    • v.14 no.2
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    • pp.132-142
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    • 2010
  • Hypokalemia usually reflects total body potassium deficiency, but less commonly results from transcellular potassium redistribution with normal body potassium stores. The differential diagnosis of hypokalemia includes pseudohypokalemia, cellular potassium redistribution, inadequate potassium intake, excessive cutaneous or gastrointestinal potassium loss, and renal potassium wasting. To discriminate excessive renal from extrarenal potassium losses as a cause for hypokalemia, urine potassium concentration or TTKG should be measured. Decreased values are indicative of extrarenal losses or inadequate intake. In contrast, excessive renal potassium losses are expected with increased values. Renal potassium wasting with normal or low blood pressure suggests hypokalemia associated with acidosis, vomiting, tubular disorders or increased renal potassium secretion. In hypokalemia associated with hypertension, plasam renin and aldosterone should be measured to differentiated among hyperreninemic hyperaldosteronism, primary hyperaldosteronism, and mineralocorticoid excess other than aldosterone or target organ activation. Hypokalemia may manifest as weakness, seizure, myalgia, rhabdomyolysis, constipation, ileus, arrhythmia, paresthesias, etc. Therapy for hypokalemia consists of treatment of underlying disease and potassium supplementation. The evaluation of hyperkalemia is also a multistep process. The differential diagnosis of hyperkalemia includes pseudohypokalemia, redistribution, and true hyperkalemia. True hyperkalemia associated with decreased glomerular filtration rate is associated with renal failure or increased body potassium contents. When glomerular filtration rate is above 15 mL/min/$1.73m^2$, plasma renin and aldosterone must be measured to differentiate hyporeninemic hypoaldosteronism, primary aldosteronism, disturbance of aldosterone action or target organ dysfunction. Hyperkalemia can cause arrhythmia, paresthesias, fatigue, etc. Therapy for hyperkalemia consists of administration of calcium gluconate, insulin, beta2 agonist, bicarbonate, furosemide, resin and dialysis. Potassium intake must be restricted and associated drugs should be withdrawn.

Effect of Solubilizing and Microemulsifying Excipients in Polyethylene Glycol 6000 Solid Dispersion on Enhanced Dissolution and Bioavailability of Ketoconazole

  • Heo, Min-Young;Piao, Zong-Zhu;Kim, Tae-Wan;Cao, Qing-Ri;Kim, Ae-Ra;Lee, Beom-Jin
    • Archives of Pharmacal Research
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    • v.28 no.5
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    • pp.604-611
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    • 2005
  • Polyethylene glycol (PEG) 6000-based solid dispersions (SDs), by incorporating various pharmaceutical excipients or microemulsion systems, were prepared using a fusion method, t o compare the dissolution rates and bioavailabilities in rats. The amorphous structure of the drug in SDs was also characterized by powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). The ketoconazole (KT), as an antifungal agent, was selected as a model drug. The dissolution rate of KT increased when solubilizing excipients were incorporated into the PEG-based SDs. When hydrophilic and lipophilic excipients were combined and incorporated into PEG-based SDs, a remarkable enhancement of the dissolution rate was observed. The PEG-based SDs, incorporating a self microemulsifying drug delivery system (SMEDDS) or microemulsion (ME), were also useful at improving the dissolution rate by forming a microemulsion or dispersible particles within the aqueous medium. However, due to the limited solubilization capacity, these PEG-based SDs showed dissolution rates, below 50% in this study, under sink conditions. The PEG-based SD, with no pharmaceutical excipients incorporated, increased the maximum plasma concentration (C$_{max}$) and area under the plasma concentration curve (AUC$_{0-6h}$) two-fold compared to the drug only. The bioavailability was more pronounced in the cases of solubilizing and microemulsifying PEG-based SDs. The thermograms of the PEG-based SDs showed the characteristic peak of the carrier matrix around 60$^{\circ}C$, without a drug peak, indicating that the drug had changed into an amorphous structure. The diffraction pattern of the pure drug showed the drug to be highly crystalline in nature, as indicated by numerous distinctive peaks. The lack of the numerous distinctive peaks of the drug in the PEG-based SDs demonstrated that a high concentration of the drug molecules was dissolved in the solid-state carrier matrix of the amorphous structure. The utilization of oils, fatty acid and surfactant, or their mixtures, in PEG-based SD could be a useful tool to enhance the dissolution and bioavailability of poorly water-soluble drugs by forming solubilizing and microemulsifying systems when exposed to gastrointestinal fluid.