• Journal of Ginseng Research
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• 제35권4호
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• pp.471-478
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• 2011

Ginseng, the root of Panax ginseng, is one of the oldest herbal medicines. It has a variety of physiological and pharmacological effects. Recently, we isolated a subset of glycolipoproteins that we designated gintonin, and demonstrated that it induced transient change in intracellular calcium concentration $([Ca^{2+}]_i)$ in cells via G-protein-coupled receptor signaling pathway(s). The previous method for gintonin isolation included multiple steps using methanol, butanol, and other organic solvents. In the present study, we developed a much simple method for the preparation of gintonin from ginseng root using 80% ethanol extraction. The extracted fraction was designated edible gintonin. This method produced a high yield of gintonin (0.20%). The chemical characteristics of gintonin such as molecular weight and the composition of the extract product were almost identical as the gintonin prepared using the previous extraction regimen involving various organic solvents. We also examined the physiological effects of edible gintonin on endogenous $Ca^{2+}$-activated $Cl^-$ channel activity of Xenopus oocytes. The 50% effective dose was $1.03{\pm}0.3\;{\mu}g$/mL. Finally, since gintonin preparation through ethanol extraction is easily reproducible, gintonin could be commercially applied for ginseng-derived functional health food and/or drug following the confirmations of in vitro and in vivo physiological and pharmacological effects of gintonin.

• Journal of Chest Surgery
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• 제38권11호
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• pp.746-760
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• 2005

배경: 인공심장판막 시술 후에 환자들은 혈전색전증의 위험성을 감소시키기 위해서 평생 warfarin투여를 받게 된다 한국인 환자에서 목표 INR 2.0-3.0을 유지하는 것은 여러 가지 이유로 어려움이 따른다. 이 연구의 목적은 약사에 의해서 운영되는 anticoagulation service (ACS)을 받는 한국 인공심장판막 외래환자에서 치료 범위를 벗어난 INR의 원인을 분석하고 warfarin치료에의 복약불이행과 관련된 요인들을 확인하고자 하였다. 대상 및 방법: 1997년 3월에서 2000년 9월까지 서울대학교병원에서 ACS를 방문한 모든 환자의 의무기록을 후향적으로 검토하였다. 수술 후 6개월이 경과된 화자로 INR 2.0 미만과 INR 3.0초과가 한 번 이상 있는 환자 866명(5,304회 방문)을 대상으로 치료 범위를 벗어난 INR의 가능한 모든 원인들을 환자 방문 때마다 분석하였다 성별, 연령, ACS 상담을 받은 기간 및 warfarin 치료 기간과 복약불이행과의 상관성은 단변수 분석으로 확인하였다. 걸과· 비치료범위의 INR의 원인은 다음과 같았다: 부적절한 용량 조절$(21\%)$, 복약불이행$(13\%)$, 약물-약물/한약 상호작용$(12\%)$, 식이의 변화$(7\%)$, 확인불가$(42\%)$. 낮은 연령, 짧은 ACS 상담 기간, 장기간의 warfarin 치료가 복약불이행과 관련이 있었다 결론: 이 연구에서 복약불이행, 약물과 식이의 상호작용이 비치료범위의 INR의 중요한 요인임이 확인되었다. 낮은 연령과 장기간의 warfarin치료 기간이 복약불이행과 상관이 있었던 반면 ACS 등록된 기간이 길수록 warf arin에 대한 치료 순응도가 높아졌다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6089-6092
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• 2015

Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Clinical and Experimental Pediatrics
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• 제53권4호
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• pp.571-578
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• 2010

목 적: 간질 환자의 20-30%는 난치성 간질로 알려졌는데, 기존의 항경련제나 새로운 항경련제에 반응하지 않는 난치성 간질환자에게 LEV를 부가요법으로 투여 후 효과와 부작용을 알아보고자 본 연구를 시행하였다. 방 법: 1989년 3월부터 2009년 3월까지 충남대학교병원 소아청소년과를 방문하여 난치성 간질로 진단받은 환자 중 6개월 이상 추적 관찰한 86명을 대상으로, LEV 투여 전 6개월간의 평균 경련 횟수를 기준으로 LEV외에 다른 항경련제를 추가하기 전까지의 평균 경련 감소 정도를 백분율로 분석하였다. 결 과: 86명의 환자 중 남자는 47명, 여자는 39명이었고, 발작 소실은 86명 중 44명(51.1%), 50% 이상 발작 감소는 86명 중 62명(72.1%)이었고, 19.8%는 변화가 없었으며, 5.8%는 발작이 증가했다. 나이, 동반질환, 발작형 및 치료 전 6개월간 발작 횟수는 발작 소실이나 50% 이상 발작 감소율과 관계가 없었다. 통계적으로 의미 있는 발작 소실과 50% 이상 발작 감소를 보인 경우는, 질병기간, LEV 투여 전 치료기간, LEV의 용량과 치료 전 사용한 항경련제의 숫자였으며, LEV 치료 기간과 뇌파는 발작 소실에만 의의가 있었고, 원인은 50% 이상 감소율에만 의의가 있었다. 부작용은 86명 중 40명(46%)에서 나타났고, 부작용은 기면, 과잉 행동, 과민성, 공격성, 피로 등이었으며, 대부분 일시적이거나 경미하여 치료 도중 소실되었다. 결 론: 난치성 소아 간질의 치료에 LEV의 부가 요법은 부분 발작뿐만 아니라 전신발작에도 효과와 반응이 좋고, 심각한 부작용도 없었다.

• 대한소아치과학회지
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• 제33권1호
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• pp.53-61
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• 2006

미다졸람은 소아 환자의 진정시 흔히 사용되는 약물로서 안전성이 뛰어나고 사용이 편리하며 투여 방법이 다양하다. 여러 투여 방법 중, 주로 사용되는 근육내 투여 방법은 동통을 유발하기 때문에 어린이의 치과에 대한 공포를 가중시킬 수 있다. 따라서 근육내 투여의 이런 단점을 완화할 수 있도록 용량에 따른 미다졸람 경구 투여의 진정 효과를 근육내 투여시의 진정 효과와 비교 평가하고자 하였다. 총 12명의 환자를 실험대상으로 하였으며 이중 맹검법에 의해 두 번의 내원중 임의로 한 번은 Midazolam 0.75 mg/kg을 경구 투여하고, 한 번은 미다졸람 0.3mg/kg을 근육내 투여하여 치료하였으며, 치료과정 동안 환자의 생징후(말초 동맥혈 산소 포화도, 심박수)와 행동양상을 Ohio State University Behavior rating scale과 Automated Counting System을 사용하여 평가하였다. 생징후의 경우 양 군 모두 정상범위 내에서 안정된 양상을 보였으며, 임상적으로 바람직한 행동양상(Q:Quiet)의 비율이양 군에서 대부분 높게 나타났으며 양군간에 유의 한 차이를 보이지 않았다(p>0.05). 본 연구에서 미다졸람을 근육내 투여한 군과 경구 투여한 군 모두 진정 효과가 양호한 결과를 보였으며 양군간에 유의한 차이를 보이지 않았다(pgt;0.05).

• Tuberculosis and Respiratory Diseases
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• 제63권5호
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• pp.417-422
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• 2007

연구배경: 일차 항결핵제 치료 5개월 이후 배양 음전되었으나 도말 양성을 보이는 폐결핵 환자들의 임상적 특성과 치료 후 경과에 대하여 알아보고자 하였다. 방 법: 2002년 1월 1일부터 2003년 12월 31일까지 일개 결핵 전문 병원에 입원한 환자 중 일차 항결핵제로 치료를 종결하였고 약제감수성 검사상 일차 항결핵제에 모두 감성이거나 리팜핀을 제외한 단일 약제 내성이면서 추적관찰이 되었던 환자를 대상으로 임상적 특성과 재발여부와 이에 관련한 위험인자를 후향적으로 분석하였다. 결 과: 대상 환자는 60명이었고 모두 치료에 성공하였다. 객담 도말 검사상 음전은 평균 $8.3{\pm}2.3$개월이었고, 객담 배양 검사상 음전은 평균 $2.0{\pm}0.8$개월이었다. 당뇨는 14명(23%), 초치료는 46명(77%), 약제감수성 검사상 일차 항결핵제에 모두 감성인 경우가 37명(62%), 흉부방사선사진상 중증인 경우가 49명(81%)이었다. 재발률은 치료 1년 후 3.8%, 2년 후 10%, 5년 후 25.8%이었고 나이, 성별, 당뇨, 치료 2개월째의 배양검사 결과, 과거 치료력, 흉부방사선 사진 소견, 치료기간에 따라 재발률의 차이는 통계적으로 유의하지 않았다. 결 론: 일차 항결핵제로 치료시작 후 5개월에 객담 배양검사는 음전되었으나 도말검사는 양성인 환자들에서 치료약제의 변경 없이 모든 환자에서 치료가 성공되었다. 그러나 높은 재발률에 대한 추가적인 연구가 필요할 것으로 사료된다.

• 한국임상약학회지
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• 제19권1호
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• pp.18-22
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• 2009

Oxaliplatin is a tolerable and effective drug of choice in the treatment of advanced or metastatic gastric cancer. However, it has many dose-limiting neurotoxicities. This study was performed to assess the incidence and types of oxaliplatin-related neurotoxicities. Sixty-four patients receiving oxaliplatin-involved regimen as salvage therapy on metastatic gastric cancer or as the first-line therapy on advanced gastric cancer were evaluated during the period between September 1, 2006 and February 29, 2008. The patients were treated with oxaliplatin 100 $mg/m^2$ and leucovorin 100 $mg/m^2$ simultaneously as 2-hour-lasting infusion on Day-1 followed by 5-FU 1200 $mg/m^2$ as a 22-hour-lasting continuous infusion both on Day-1 and Day-2 by every other week. We developed questionnaires to evaluate patient-recognized neurotoxic symptoms rather than the observer-described events. Surveys were completed at bedside or via telephone interview. Acute and chronic neurotoxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC, version 3) as well as the Oxaliplatin-specific Neurotoxicity Scale. The Grade-3 neuropathy was reported in 19% of the patients (n=12) and grade-1/2 neuropathy occurred in 70% (n=45). The most common symptom was cold-related dysesthesia (83%) regarded as nociperception by the patients. Some patients (19%) experienced functional impairment affecting activities of daily living such as writing, buttoning, and walking. Even though 74% of the patients (42/57) were prescribed with gabapentin to reduce these peripheral symptoms, it did not appear to derive any benefit from this medication. It is suggested that notify the patients about their oxaliplatin-associated, debilitating symptoms, and educate them any self-care strategy at the initiating phase of the chemotherapy. Moreover, it needs to design the intervention studies regarding the prevention and management of the peripheral neuropathy.

• Translational and Clinical Pharmacology
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• 제26권4호
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.

• Journal of Digestive Cancer Research
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• 제5권2호
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• pp.113-119
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• 2017

Background: Second line chemotherapy is often considered in advanced gastric cancers. We assessed irinotecan in combination with fluorouracil in patients experienced diseases progression after first line chemotherapy. Methods: Prospective trial was done at 7 centers in republic of Korea. Patients aged 18 years or older with advanced gastric adenocarcinoma and disease progression on or within 4 months after first-line chemotherapy were assigned to receive irinotecan 180 mg/m² and 5-fluorouraicl 400 mg/m² intravenously bolus injection on days 1 and leucovorin 200 mg/m² for 2 hours and 5-fluorouracil 600 mg/m² for 22 hours intravenously infusion on day 2 of a 14-day cycle (FOLFIRI group). The primary endpoint was objective tumor response (OR). Efficacy analysis was by per-protocol, and safety analysis included all patients who received at least one treatment with study drug. Results: Between January 1, 2014 and December 31, 2016, 28 patients were assigned to FOLFIRI treatment. Of those 20 patients were completed the study protocol. Per-protocol analysis, two patients among 20 subjects (10.0%) showed partial response. Overall survivals of FOLFIRI group; median 10.1 months [95% CI 4.9-15.3] Grade 3 and higher adverse event that occurred about 5%, but grade 3 or higher febrile neutropenia or life threatening complication was not reported. Conclusion: Combination chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients previously treated with platinum-based chemotherapy