Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study

Although the prevalence of drug-drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions. A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged a parts per thousand yen60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age a parts per thousand yen80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson comorbidity index a parts per thousand yen4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44). The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.

Avaliação quantitativa de cardenolídeos no cultivar experimental de Digitalis lanata do maciço do itatiaia e perspectivas de seu emprego industrial

The content of digoxin and lanatoside C (jointly quantified), lanatoside A, lanatoside B, glucoevatromonoside, odorobioside G, glucogitoroside, glucoverodoxine, glucodigifucoside and digitalinum verum was determined by HPLC in Digitalis lanata harvested in Brazil, as well as in clones industrially employed for the production of cardenolides. The Brazilian plants presented greater variation in the contents of cardenolides than the analyzed clones. Lanatoside C and digoxin concentrations were higher in the clones (6120±640 nmol/g dry leaf) than in the Brazilian plants (1820±900 nmol/g dry leaf). The concentrations of these glycosides were found to be within the range described for native species and also were similar to an European cultivar, what makes possible its industrial use for the cardenolides production.

Nucleophilic Addition of Potassium Alkynyltrifluoroborates to D-Glucal Mediated by BF(3)center dot OEt(2): Highly Stereoselective Synthesis of alpha-C-glycosides

A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF(3)center dot OEt(2) and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.

DOSY NMR applied to analysis of flavonoid glycosides from Bidens sulphurea

2D DOSY (1)H NMR has proved to be a useful technique in the identification of the molecular skeleton of the four major compounds of ethyl acetate extract of aerial parts of Bidens sulphurea (Asteraceae). The combination of this technique with HPLC, mass spectrometry and other NMR techniques enabled the identification of four flavonoid glycosides: quercetin-3-O-beta-D-galactopyranoside, quercetin-3-O-beta-D-glycopyranoside, quercetin-3-O-alpha-L-arabinofuranoside and quercetin-3-O-beta-D-rhamnopyranoside. Copyright (C) 2009 John Wiley & Sons, Ltd.

Detrimental effects of latex and cardiac glycosides on survival and growth of first-instar monarch butterfly larvae Danaus plexippus feeding on the sandhill milkweed Asclepias humistrata

1. A novel experimental method was developed to study negative physical and chemical effects of latex and cardiac glycosides on first-instar monarch butterfly larvae in their natural environment in north central Florida. Forceps were used to nibble through the petioles of leaves of the sandhill milkweed Asclepias humistrata, mimicking the behaviour of mature monarch larvae. This notching cut off the supply-of latex to the leaves without significantly reducing either their cardiac glycoside concentration or water content. 2. The mean cardiac glycoside concentration in larvae that fed on intact leaves was nearly two: and a half times greater than in larvae that fed on notched leaves. This was probably because more latex is present in the gut of the larvae that fed on the intact leaves. Supporting this is the fact that the mean concentration of cardiac glycosides in the latex was 34-47 times that in the leaves. 3. Wet weights, dry weights, and growth rates of first-instar larvae that fed on intact leaves over a 72-h period were less than half those of larvae that fed on notched leaves. 4. Mortality due to miring in the latex was 27% on the intact leaves compared with 2% on the notched leaves. 5. Latex, cardiac glycosides, and other as yet undetermined plant factors all have a negative effect on:first-instar larval survival. 6. Video-analyses indicated that ingestion of latex caused the larvae to become cataleptic and increased their chances of being mired on the leaf by the setting latex glue. Dysfunction resulting from latex ingestion may lead to the larvae falling off the plant and being killed by invertebrate predators. 7. The difficulty of neonate monarch larvae surviving on A. humistrata - one of the principal milkweed species fed on each spring as monarchs remigrate from Mexico into the southern U.S.A. - is evidence that a co-evolutionary arms race is operating in this plant-herbivore system.

Bioactive glycosides from Chinese medicines

Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent years. (1) Pheolic glycosides from Chinese medicines: Gastrodia elata, acontium austroynanense and Helicia erratica, three bioactive phenolic glycosides were discovered and two of them have been developed into new drugs. (2) Terpenoidal glycosides: a) Monoterpenoid: the sweroside from Swertia mollensis has been developed intro an anti-hepatitis drug; b) Diterpenoid: Phlomis betonicoides contains sweet glycoides; c) Triterpenoid: many biologically active triterpenoid glycosides were isolated from Panax plants and Siraitia grosvenorii. (3) Steroidal glycosides: a) C21-steroid: Cynanchum otophyllum and C. atratrum contain anti-epilepsy and-tumor glycosides; b) C27-steroid Hemostatic saponins were found in Paris polyphylla.

Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke

The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.

Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions.

CONTENTS: Summary 28 I. Historic background and introduction 29 II. Diversity of cardenolide forms 29 III. Biosynthesis 30 IV. Cardenolide variation among plant parts 31 V. Phylogenetic distribution of cardenolides 32 VI. Geographic distribution of cardenolides 34 VII. Ecological genetics of cardenolide production 34 VIII. Environmental regulation of cardenolide production 34 IX. Biotic induction of cardenolides 36 X. Mode of action and toxicity of cardenolides 38 XI. Direct and indirect effects of cardenolides on specialist and generalist insect herbivores 39 XII. Cardenolides and insect oviposition 39 XIII. Target site insensitivity 40 XIV. Alternative mechanisms of cardenolide resistance 40 XV. Cardenolide sequestration 41 Acknowledgements 42 References 42 SUMMARY: Cardenolides are remarkable steroidal toxins that have become model systems, critical in the development of theories for chemical ecology and coevolution. Because cardenolides inhibit the ubiquitous and essential animal enzyme Na(+) /K(+) -ATPase, most insects that feed on cardenolide-containing plants are highly specialized. With a huge diversity of chemical forms, these secondary metabolites are sporadically distributed across 12 botanical families, but dominate the Apocynaceae where they are found in > 30 genera. Studies over the past decade have demonstrated patterns in the distribution of cardenolides among plant organs, including all tissue types, and across broad geographic gradients within and across species. Cardenolide production has a genetic basis and is subject to natural selection by herbivores. In addition, there is strong evidence for phenotypic plasticity, with the biotic and abiotic environment predictably impacting cardenolide production. Mounting evidence indicates a high degree of specificity in herbivore-induced cardenolides in Asclepias. While herbivores of cardenolide-containing plants often sequester the toxins, are aposematic, and possess several physiological adaptations (including target site insensitivity), there is strong evidence that these specialists are nonetheless negatively impacted by cardenolides. While reviewing both the mechanisms and evolutionary ecology of cardenolide-mediated interactions, we advance novel hypotheses and suggest directions for future work.

Monitoring of aglycons of yew glycosides (3,5-dimethoxyphenol, myrtenol and 1-octen-3-ol) as first indicator of yew presence.

The toxicity of yew (Taxus spp) is well known from ancient times and is mainly due to taxins acting as inhibitors of calcium and sodium transport across the cell membrane of cardiac myocytes. The confirmation of yew taxins in body fluids can be carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, before selecting this precise but expensive technique, an orientation test should be done to ascertain yew presence as toxic agent in the organism. As the 3,5-dimethoxyphenol (3,5-DMP), myrtenol and 1-octen-3-ol appear as glycosidically bound volatile compounds and are very yew specific, the detection of 3,5-DMP and the measurement of 1-octen-3-ol / myrtenol concentration ratio constitute reliable indicators of yew presence in forensic cases. The detection of these compounds is easily performed by gas chromatography-mass spectrometry (GC-MS) (SIM) after an enzymatic hydrolysis (β-glucosidase) allowing the release of volatile compounds from yew glycosides. Copyright © 2012 John Wiley & Sons, Ltd.

Translocation of cyanogenic glycosides in rubber tree crown clones resistant to South American leaf blight

The objective of this work was to assess the possible transport of cyanogenic glycosides from leaves of rubber tree crown clones (Hevea spp.) resistant to South American leaf blight to the trunk of the panel clones in which they are grafted. The cyanogenic potential (HCNp) of the crown clones was determined in the trunk bark, at different distances from the cambium, and its gradient was evaluated along the trunk. The correlation between the HCNp of the crown leaves and that of the trunk bark was also evaluated. HCNp determined in leaves showed a wide range variation in the species studied as crown clones, with the lowest values registered in H. nitida clones, and the highest ones in H. rigidifolia. In the trunk bark, the tissue layer nearer the cambium showed higher HCNp values. A positive basipetal gradient was observed along the trunk, i.e., there was an increase in HCNp from the apex toward the base. Although the grafted crowns influence the cyanogenic potential of the trunk bark of panel clones, the absence of correlation between the HCNp of the leaves and trunk bark indicates that the crown is not the main source of the cyanogenic glycosides found in the trunk.

LC/ESI-MS method applied to characterization of flavonoids glycosides in B. forficata subsp. pruinosa

Bauhinia forficata is used in folk medicine for its hypoglycemiant effect. In the south of Brazil, the subspecies pruinosa is found in a region with the characteristic flora, pampa biome. This species has been consumed by the local population as a tea for diabetes treatment. We studied the chemical composition of hydroethanolic extracts using LC/ESI-MS. The leaf extracts were prepared by percolation with 50% (v/v) ethanol. The chromatographic analyses were performed using a reverse-phase system, gradient elution with acetonitrile:phosphoric acid 0.05%, and ESI-MS in the positive ion mode. The chemical profile of the flavonoids was suggested to involve four quercetin and kaempferol glycosides.

Antioxidant flavonol glycosides from Nectandra grandiflora (Lauraceae)

The bioassay-guided fractionation of the ethanol extract from Nectandra grandiflora leaves led to the isolation of two flavonol glycosides which inhibited the bleaching of beta -carotene on the TLC assay. Both compounds had their molecular structures elucidated by means of extensive use of uni- and bidimensional NMR techniques and were identified as 3-O-beta -rhamnosylkaempferol and 3-O-beta -rhamnosylquercetine.

Isolation of lignans glycosides from Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography

Enantiomeric aglycone lignans contained in a mixture were separated from a fraction of the extract of the stems of Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography. An efficient and fast separation can be achieved with methanol-water (30:70, v/v). Their structures were identified as (+)-lyoniresinol 3alpha-O-beta-glucopyranoside and (-)-lyoniresinol 3alpha-O-beta-glucopyranoside, being reported for the first time in Rubiaceae.