Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. RESULTS: The MTD for patients in group A was Oxal 100 mg/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m(2), LV 400 mg/m(2), and FU 1,400 mg/m(2) by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. CONCLUSION: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.     

薄层扫描法测定垂阴茶糖浆中岩白菜素的含量

目的:建立垂阴茶糖浆岩白菜素的测定方法,方法:λs=275 nm,λR=320nm,用薄层色谱法测定岩白菜素的含量.结果:岩白菜素在0.505～3.030μg范围内线性关系良好(r=0.999 9),平均回收率为96.52%.RSD=0.44%.结论:该法灵敏度高,重现性好,可用于该制剂中岩白菜素的含量测定及质量控制.     

Chlorination diversifies Cimicifuga racemosa triterpene glycosides

Extracts from the roots and rhizomes of black cohosh (Cimicifuga racemosa) are widely used as dietary supplements to alleviate menopausal symptoms. State-of-the-art quality control measures involve phytochemical fingerprinting of the triterpene glycosides for species identification and chemical standardization by HPLC. In the course of developing materials and methods for standardization procedures, the major C. racemosa triterpene glycoside (1) was isolated and initially thought to be cimicifugoside (2). Detailed HR-LC-MS and 1D and 2D NMR analysis of 1 and 2 unambiguously revealed that 1 is the chlorine-containing derivative of 2, namely, 25-chlorodeoxycimigenol-3-O-beta-d-xyloside. Accordingly, HPLC profiles of black cohosh preparations require revision of the assignments of the chlorinated (1) and nonchlorinated (2) pair. Besides explaining the substantial shift in polarity (DeltatR[RP-18] ca. 20 min), 25-deoxychlorination opens a new pathway of structural diversification in triterpene glycoside chemistry. As chemical conversion of 2 into 1 could be demonstrated, deoxychlorination may be interpreted as artifact formation. Simultaneously, however, it is a potentially significant pathway for the gastric in vivo conversion ("nature's prodrug") of the relatively polar triterpene glycosides into significantly less polar chlorinated derivatives with altered pharmacological properties.     

青蒿挥发油成分的GC-MS分析与化学计量学解析法

目的:分析青蒿挥发油的化学成分.方法:用水蒸气蒸馏法从青蒿中提取挥发油成分,采用气相色谱-质谱(GC-MS)联用技术,结合化学计量学解析法(CRM)对重叠色谱峰进行分辨解析,并利用程序升温保留指数辅助定性.结果:共分辨出73个色谱峰,鉴定了其中66个组分,占青蒿挥发油总含量的95.25%,其主要化学成分为:丁子香烯、丁子香烯环氧化物、稚槛蓝(树)油烯、α-甜没药萜醇等.结论:使用CRM解析色谱峰,比单独使用GC-MS法能更真实、全面地反映其挥发油化学成分.     

诸子蜂起 百家争鸣(二)——英国中医药的现状与展望

中医药面临着"诸子蜂起,百家争鸣"的国际医药保健时代,处于有机会又有曲折的局面.故从1)中医药在国外的发展.2)中医药在英国的现状.3)英国推动中医教育的经验.4)英国偶尔发生的中医事故影响中医界整体形象.5)英国中医的立法过程与国际影响.6)建立中医药企业文化和品牌标准--英国的经验.7)中医药发展展望.8)中医药的宣传和外交等方面论述.指出在"诸子蜂起,百家争鸣"的新"全球医学"时代,中医界人士需团结一致,既往开来,为把中医真正纳入世界主流医学,并能恩泽于全人类而全心全力、努力不懈!     

Mechanisms of the dilator action of the Erigerontis Herba on rat aorta

Ethnopharmacological relevance

Erigerontis Herba is widely used as a traditional Chinese medicine and is commonly used for neuroprotection and vascular protection.

Aim of study

In this study, the vasodilator effects of Erigerontis Herba (DZXX) were investigated using rat isolated aorta rings.

Material and method

The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. The involvement of K⁺ channels was studied by pretreatment of the aorta rings with various K⁺ channel inhibitors. The involvement of Ca²⁺ channel was studied by incubating aorta rings with Ca²⁺-free solution, primed with U46619 prior to elicit contraction by addition of Ca²⁺ solution.

Results

DZXX (0.2–2 mg/ml) induced a concentration-dependent relaxation on U44619-precontracted aorta rings with EC₅₀ of 0.354±0.036 mg/ml. Removal of endothelium or pretreatment with a BK_Ca inhibitor iberiotoxin, K_IR inhibitor barium chloride or K_v inhibitor 4-aminopyridine produced no effect on the DZXX-induced vasorelaxation. However, pretreatment with a K_ATP inhibitor glibenclamide or a non-selective K⁺ channel inhibitor tetraethylammonium produced significant inhibition on the DZXX-induced vasorelaxation by 29.9% and 21.3%, respectively. Pretreatment with DZXX (0.4, 1.2 and 2 mg/ml) produced a concentration-dependent inhibition on Ca²⁺-induced vasoconstriction.

Conclusions

These results suggest that the vasodilator effect of DZXX was endothelium-independent, mediated by decreasing the influx of Ca²⁺ by calcium channel inhibition and increasing the influx of K⁺ by opening of a K_ATP channel.     

Interstitial retinol-binding protein and cellular retinal-binding protein in the mammalian pineal

Antibodies against bovine interstitial retinol-binding protein (IRBP) and cellular retinal-binding protein (CRA1BP) were used in immunochemical and immunocytochemical studies of the pineal glands of cattle, hamsters and rats (RCS and RCS-rdy+). On immunoblots, IRBP (Mr 144,000) was identified in cattle, hamster and rat pineal extracts. The abundance of IRBP in bovine pineals was 33 +/- 6 ng.mg-1 (mean +/- SD, n = 12) soluble protein. RCS (Royal College of Surgeons) rat pineals gave a strong IRBP reaction on immunoblots, even when virtually no IRBP could be found in the eye due to photoreceptor degeneration. In the hamster retina IRBP immunostaining was distributed throughout the entire interphotoreceptor matrix and the outer segment layer. The pineal also showed strong IRBP-like immunostaining scattered uniformly throughout the gland. Other hamster brain regions showed no specific immunostaining; however, an immunoreactive protein with the same Mr as IRBP was detected on Western blots of bovine cerebral cortex, spinal cord and brainstem soluble proteins. Immunoreactive proteins at lower Mr were also detected in these tissues. CRA1BP immunoreactivity (Mr about 32,000) was observed in immunoblots of bovine, hamster and rat pineal proteins. These findings suggest that some mammalian pinealocytes are related to the retinal cells that contain CRA1BP (i.e. pigment epithelium, Muller cells) while others are related to the photoreceptors, which synthesize IRBP.     

Chemical constituents from Amentotaxus yunnanensis and Torreyayunnanensis

In a chemical study of taxonomically related Taxaceae plants of Yunnan Province, China, seven compounds, including a new amentoflavone biflavonoid, 2,3-dihydro-7,7' '-dimethoxyamentoflavone (1), were isolated from Amentotaxus yunnanensis, and 12 isolates were obtained from Torreya yunnanensis. From the latter plant, a new abietane diterpene, torreyayunnin (7), is reported for the first time. The known isolates from A. yunnanensis have been identified as sequoiaflavone (3), sotetsuflavone (4), 7,7' '-dimethoxyamentoflavone (5), lutein, beta-sitosterol, and sequoyitol. Amentoflavone (2), sotetsuflavone (4), sciadopitysin (6), 12-hydroxydehydroabietinol, meridinol, balanophonin, (+)-pinoresinol monomethyl ether, (+)-pinoresinol monomethyl ether glucoside, erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-[2-formyl-(E)-vinyl]-2- methoxyphenoxy]propane-1,3-diol, threo-1-(4-hydroxy-3-methoxyphenyl)-2- [4-[2-formyl-(E)-vinyl]-2-methoxyphenoxy] propane-1,3-diol, and (E)-2-butenedioic acid were identified as known isolates from T. yunnanensis. The presence of the amentoflavone biflavonoids (1, 3-5) in A. yunnanensis supports its placement in the Taxaceae. The occurrence of the biflavonoid sotetsuflavone (4) in both A. yunnanensis and T. yunnanensis suggests that these two genera are closely related. The identification and structural elucidation of these isolates were based on spectral data analysis including 1D and 2D NMR.