Spectral analysis of aegelin isolated from maja leaves (Aegle marmelos Corr.)

Aegelin is an alkaloid which isolated from Maja (Aegle marmelos Corr.) leaves. The molecular structure of the compound contains a chiral carbon atom. In our earlier publications the existence and influence of a chiral carbon atom have not been discussed yet. The existing of the chiral carbon atom gave rise two pair of doublets at d 3.67 J=3.4 Hz and d 3.43 J=8.5 Hz in the proton nmr spectrum. The doublets are signal of two proton which attached on adjacent atom of the chiral carbon atom which is confirmed bythe two dimension nmr spectrum (HMQC). The two protons are magnetic unequivalent which cause their chemical shifts are different. The protons appear as two doublet with different J value because its couple to a proton attached at the chiral carbon atom and the spin-spin splitting is observed. The existence of the two pairs of the doublets at d 3.67 d,J=3.4 Hz and d 3.42 d,J=8.5 Hz because the isolated aegelin from E.marmelos leaves contains of its enantimeer.Key words: E. marmelos, aegelin, enantiomeer, spectroscop

キナ植物体内に生息するエンドファイト糸状菌もキナアルカロイドを産生する(発表論文抄録(2011))

We report that the endophytic filamentous fungus Diaporthe sp., isolated from Cinchona ledgeriana and cultivated in a synthetic liquid medium, produces Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine). This shows that Cinchona alkaloids are produced not only in Cinchona plant cells, but also in endophytic microbe cells.We report that the endophytic filamentous fungus Diaporthe sp., isolated from Cinchona ledgeriana and cultivated in a synthetic liquid medium, produces Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine). This shows that Cinchona alkaloids are produced not only in Cinchona plant cells, but also in endophytic microbe cells

PGV-1 decreases angiogenic factor (VEGF and COX-2) expression on T47D cell induced by estrogen

Breast cancer is the most common cancer occurring in women after cervix cancer in Indonesia. Tumor metastasis is the major cause of mortality in breast cancer. For a tumor cell to metastasize effectively, it must induce angiogenesis. 17 β-estradiol has been shown to stimulate the proliferation and angiogenesis of breast cancer cells which express estrogen receptor (ER), T47D (human breast cancer cell line). In the present study Pentagamavunon-1 or PGV-1 [2,5-bis-(4’-hydroxy-3’,5’-dimethylbenzylidene)-cyclopentanone], an analogue of curcumin [1,7-bis-(4’-hydroxy-3’-methoxyphenyl)-1,6-heptadiena-3,5-dion], were tested on their cytotoxicity and suppression effect on angiogenic factors (i.e. VEGF and COX-2) on the breast cancer cell lines (T47D) induced by 17 β-estradiol 10-8 M. The results showed that PGV-1 performed cytotoxicity effect againts T47D cells with IC50 values 3,16 μM. This was more potent than curcumin (IC50 = 19,05 μM). PGV-1 5 μM and curcumin 20 μM decrease VEGF and COX-2 expression. These results suggest both compounds possessed antiangio-genic potensial.Key words : PGV-1, curcumin, 17 β-estradiol, angiogenesi

Rasio Senyawa Enansiomer sesamin di dalam kulit batang Pentaspadon motleyi (Anacardiaceae)

The barks of Pentaspadon motleyi Hook. f. (Anacardiaceae) were collected from the Poso district in Central Sulawesi, Indonesia, in 1992 which it has been used traditionally as a remedy for malaria and tuberculosis in the local area. It was found that a mixture of (+)-sesamin (1) and (-)-sesamin (2) in a ratio of 100:86 were present together with lupeol in the bark of Pentaspadon motleyi. This was the first evidence of sesamin being isolated in almost equivalent amounts of (+)- and (-)-forms from a single plant species, and indicates that the biosynthetic pathway of sesamin in the plant is not enantioselective or fuzzy.Kulit batang Pentaspadon motleyi Hook. F (Anacardiaceae ) yang dikoleksi dari daerah Poso (Sulawesi Tengah), Indonesia tahun 1992 dan secara tradisional digunakan untuk pengobatan malaria dan tuberkolosis. Senyawa kimia dalam bentuk campuran (+)-sesamin (1) dan (-)-sesamin (2) dengan perbandingan 100:86 bersama dengan senyawa lupeol telah ditemukan dari kulit batang Pentaspadon motleyi. Ini adalah laporan yang pertama kali bahwa sesamin yang diisolasi yang mempunyai jumlah hampir sama antara (+)-sesamin dan (-)-sesamin dari satu spesies tanaman ini, dan ini menunjukkan bahwa jalan biosíntesis sesamin dalam tanaman tersebut tidak enansioselektif atau tidak begitu jelas

A Proposal for Practical Diagnosis of Renal Hypouricemia : Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests

Pediatric differentiated thyroid carcinoma in stage I: risk factor analysis for disease free survival

<p>Abstract</p> <p>Background</p> <p>To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial.</p> <p>Methods</p> <p>We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients.</p> <p>Results</p> <p>Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients.</p> <p>Conclusion</p> <p>Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.</p

経皮的旧バルーン動脈形成術後の再狭窄に関する5HT_2A受容体拮抗薬(塩酸サルポグレラート)の有用性

〔背景〕セロトニン受容体,特に5HT_2受容体は血管収縮および血小板凝集に大いに関与し,また,経皮的冠動脈形成術(PTCA)後の血管内皮機能障害の進行にも影響を及ぼしている. 〔目的〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)が経皮的旧バルーン動脈形成術(POBA)後の再狭窄率の減少に有用であるか否かアスピリンと対比し検討する.〔方法〕1996年3月より1997年6月までに急性冠症候群の診断で入院となりPOBAを施行した56例(男性45例,女性11例;平均年齢63歳)について検討した. 56例中無作為に抽出した26例に対し5HT_2A受容体拮抗薬150mg(分3)を投与し,残りの30例に対してはアスピリン81mg(分1)を投与した.また,QCA法により計測し6ヵ月後(follow up時)の冠動脈造影上で標的血管に50%以上の狭窄を認めた場合を再狭窄と定義した.〔結果〕56例すべてにおいてfollow upを行った. POBA前後での両群間における対照血管最小血管経(MLD)に有意差は認めなかった(5HT_2A群vsアスピリン群:2.67±0.53mm vs 2.79±0.56mm; p=0.42). POBA後6ヵ月後(follow up時)のMLDは5HT_2A群の方がアスピリン群より有意に大きい結果であった(5HT_2A群vsアスピリン群: 1.64±0.69mm vs 1.06±0.91mm; p=0.03).再狭窄率は5HT_2A群7/26(27%),アスピリン群13/30(43%)であった.また, 5HT_2A群において,診断造影上右冠動脈に有意狭窄を認めた症例でPOBA後の再狭窄が少ない傾向を認めた.全経過中に明らかな合併症は認めなかった.〔結語〕5HT_2A受容体拮抗薬(塩酸サルポグレラート)はPOBA後の再狭窄率の減少に有用かつ明らかな合併症を認めない安全な薬剤であり,診断造影上右冠動脈に有意狭窄を認めた症例においては特に有用な薬剤であると思われる.Background: Serotonin receptors, especially 5HT_2 receptors, are important in vasoconstriction and platelet aggregation and are involved in the chronic progression of endothelial dysfunction after percutaneous transluminal coronary angioplasty (PTCA). Objective: To determine whether the 5HT_2A receptor antagonist, sarpogrelate hydrochloride, was more effective than aspirin in reducing the rate of restenosis after percutaneous old balloon angioplasty (POBA). Methods: Between March 1996 and June 1997, 45 men and 11 women (average age of 63 years) underwent POBA for acute coronary syndromes. Of these, 26 received the 5HT_2A receptor antagonist 50 mg three times a day and 30 received aspirin 81 mg daily in a randomized, open trial. Restenosis was defined as a narrowing of the target vessel of at least 50% at follow-up, as measured by quantitative coronary angiography (QCA). Results: The angiographic follow-up rate was 100%. The reference minimal lumen diameter (MLD) before and after POBA did not differ significantly between the two groups (post MLD: 2.67 (0.53) in the 5HT_2A group and 2.79 (0.56) in the aspirin group; p=0.42). The mean (SD) MLD at 6 months was significantly larger in the 5HT_2A group than in the aspirin group (1.64 (0.69) mm vs 1.06 (0.91) mm; p =0.03). Angiographically identified restenosis occurred in 7/26 (27%) of the patients in the 5HT_2A group and in 13/30 (43%) of those in the aspirin group. In the 5HT_2A group, restenosis rate was likely to be less frequent in patients with right coronary artery (RCA) stenosis on the initial diagnostic angiogram (p=0.040). No complications were observed during the follow-up period. Conclusions: The 5HT_2A receptor antagonist, sarpogrelate hydrochloride, reduced the rate of restenosis after POBA, especially in patients with RCA stenosis on the initial diagnostic angiogram. No adverse events were reported in this series