LC-EI-MS determination of veratridine and cevadine in two fatal cases of Veratrum album poisoning.
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We report two fatal poisonings due to the ingestion of plant material. The two deceased were discovered in the water of a mountain lake about one month after the postmortem immersion of the corpses. Macroscopic examination of the stomachs revealed the presence of a very large number of small blackish granules, which were later identified as seeds of a Veratrum species. Veratridine and cevadine were identified and quantitated by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Measured blood concentrations were 0.17 and 0.40 ng/mL for veratridine and 0.32 and 0.48 ng/mL for cevadine. The absence of other toxic substance led to the assumption that this massive ingestion was the cause of death, although the circumstances surrounding intake remained unknown. (+info)
Interactions of veratrum alkaloids, procaine, and calcium with monolayers of stearic acid and their implications for pharmacological action.
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The interactions of veratridine, cevadine, veracevine, and veratramine with monolayers of stearic acid show marked differences. Veratridine and cevadine, at concentrations that are known from potential, ionic flux, and other measurements to affect living membranes, react strongly with the film and appear to cause an "interfacial dissolution" whereby both the alkaloid and the stearate leave the surface. Veracevine at the same concentration does not interact with the film. The veratramine reaction is weak, much like that of the local anesthetic procaine. The veratridine and cevadine effects are antagonized by 10(-3)M Ca(++), low pH, and 3.7 and 7.4 x 10(-3)M procaine. These differences among the veratrum alkaloids and the antagonisms parallel effects observed in living systems. Such parallelism suggests that similar physical interactions are involved in the stearate film and in natural membranes. (+info)
OBSERVATIONS ON THE APPLICATION OF THE ROBBINS-MONRO PROCESS TO SEQUENTIAL TOXICITY ASSAYS.
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The Robbins-Monro process is a sequential procedure which can be used in toxicity assays. The principal advantages are maximal economy of drug and animals and immediate availability of an estimate of the LD50 at any stage in the assay. The disadvantages are the need to wait for the outcome in each group of animals before testing the next group and the lack of an accurate method for determining confidence limits. Some practical details of the application of the method are given. (+info)
Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies.
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Resveratrol, trans-3,5,4'-trihydroxystilbene, was first isolated in 1940 as a constituent of the roots of white hellebore (Veratrum grandiflorum O. Loes), but has since been found in various plants, including grapes, berries and peanuts. Besides cardioprotective effects, resveratrol exhibits anticancer properties, as suggested by its ability to suppress proliferation of a wide variety of tumor cells, including lymphoid and myeloid cancers; multiple myeloma; cancers of the breast, prostate, stomach, colon, pancreas, and thyroid; melanoma; head and neck squamous cell carcinoma; ovarian carcinoma; and cervical carcinoma. The growth-inhibitory effects of resveratrol are mediated through cell-cycle arrest; upregulation of p21Cip1/WAF1, p53 and Bax; down-regulation of survivin, cyclin D1, cyclin E, Bcl-2, Bcl-xL and clAPs; and activation of caspases. Resveratrol has been shown to suppress the activation of several transcription factors, including NF-kappaB, AP-1 and Egr-1; to inhibit protein kinases including IkappaBalpha kinase, JNK, MAPK, Akt, PKC, PKD and casein kinase II; and to down-regulate products of genes such as COX-2, 5-LOX, VEGF, IL-1, IL-6, IL-8, AR and PSA. These activities account for the suppression of angiogenesis by this stilbene. Resveratrol also has been shown to potentiate the apoptotic effects of cytokines (e.g., TRAIL), chemotherapeutic agents and gamma-radiation. Phamacokinetic studies revealed that the target organs of resveratrol are liver and kidney, where it is concentrated after absorption and is mainly converted to a sulfated form and a glucuronide conjugate. In vivo, resveratrol blocks the multistep process of carcinogenesis at various stages: it blocks carcinogen activation by inhibiting aryl hydrocarbon-induced CYP1A1 expression and activity, and suppresses tumor initiation, promotion and progression. Besides chemopreventive effects, resveratrol appears to exhibit therapeutic effects against cancer. Limited data in humans have revealed that resveratrol is pharmacologically quite safe. Currently, structural analogues of resveratrol with improved bioavailability are being pursued as potential therapeutic agents for cancer. (+info)
Gitksan medicinal plants--cultural choice and efficacy.
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BACKGROUND: The use of plants for healing by any cultural group is integrally related to local concepts of the nature of disease, the nature of plants, and the world view of the culture. The physical and chemical properties of the plants themselves also bear on their selection by people for medicines, as does the array of plants available for people to choose from. I examine use of medicinal plants from a "biobehavioral" perspective to illuminate cultural selection of plants used for medicine by the Gitksan of northwestern British Columbia, Canada. METHODS: Consultant consensus, "intercultural consensus", independent use of the same plants by other cultural groups, and phytochemistry and bioassay results from the literature, were employed in analysis of probable empirical efficacy of plant uses. RESULTS: 70% of 37 Gitksan medicinal plants were used similarly by other cultures where direct diffusion is not known to have occurred; eleven plants, including the eight most frequently mentioned medicinal plants, also show active phytochemicals or bioassays indicating probable physiologically based therapeutic effects. CONCLUSION: Analysis of intercultural consensus revealed that the majority of cultures in the British Columbia region within the plant ranges use the same plants, or closely related species, in similar ways. The rigor of this analysis is effected by the lack of consistent data on all taxa of interest for all cultures within the region. (+info)
Accidental intoxication with Veratrum album.
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A 49-year-old man consumed two glasses (approximately 2 x 20 mL) of a beverage containing yellow gentian (Gentiana lutea). Shortly after ingestion, he developed nausea, vomiting, and oral paraesthesia. On admission to the hospital he suffered from severe bradycardia (35 beats/min) and hypotension (50/30 mm Hg), and he was treated with activated charcoal, antiemetics (metoclopramide, ondansetron), atropine, and intravenous electrolytic solution. The initial suspicion of Veratrum poisoning could be confirmed by identifying protoveratrines A (ProA) and protoveratrine B (ProB) in a sample from the beverage as well as in the patients serum by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS). The yellow-colored beverage contained 25% ethanol (by headspace gas chromatography), 20.4 mg/L ProA, and 13.7 mg/L ProB. The serum concentration of ProA was 1162 ng/L and ProB was 402 ng/L. Veratridine, cevadine, and jervine were not detected, neither in the beverage nor in the serum sample. The lower limits of quantitation for all compounds is 10 microg/L (S/N > 10, beverage) and 100 ng/L (S/N > 10, serum). After treatment, the patient completely recovered from the symptoms within 24 h and was discharged from the hospital. The analytical method described was developed for the simultaneous identification and quantitation of five Veratrum alkaloids. The method is based on a liquid-liquid extraction followed by LC-MS-MS analysis. The time needed for analysis was 6 min. (+info)
Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer.
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