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Biomedical subjects

O R Gottlieb

Publications and source records attributed to O R Gottlieb.

18 recordsLinked to original sources

Burchellin: effects on Triatoma infestans and on Trypanosoma cruzi within this vector.

Supplementation of blood with the neolignan burchellin (50 microg/ml), a compound from the arboreous Lauraceae Aniba burchelli, affected the ingestion of blood and the course of excretion of fourth- and fifth-instar larvae of Triatoma infestans, the latter especially within the first 4 h after feeding. The total resultant weight loss of treated fourth instars within 24 and 48 h after feeding was only 24% and 28% vs 41% and 48%, respectively, in untreated bugs. In fifth instars, the total weight losses of untreated bugs within 24 and 48 h after feeding were 38% and 41% whereas the weight of treated bugs decreased by 28% and 34%, respectively. In a treatment of Trypanosoma cruzi-infected fourth instars, burchellin significantly reduced the population density of the established infection in the rectum at 5 and 10 days after feeding. This was especially due to a significant increase in the number of the main dividing stage, the epimastigote.

Animals↗

Rhodnius prolixus: effects of the neolignan burchellin on in vivo and in vitro diuresis.

Supplementation of blood with the neolignan burchellin (100 microg/ml), a compound from the arboreous Lauraceae Aniba burchelli, affected the course of excretion of fourth-instar larvae of Rhodnius prolixus, especially directly after feeding, and reduced the volume of feces/urine excreted within 6 h of feeding to about 18% and, on the simultaneous addition of the diuretic hormone analogue 5-hydroxytryptamine (5-HT), about 71% of that observed in untreated bugs. In the latter, 5-HT induced a significant 60% increase in excretion. Regardless of whether Malpighian tubules originating from unfed, untreated or fed, burchellin-treated bugs were incubated in vitro in the hemolymph of these bugs or in physiological saline supplemented with 5-HT with or without burchellin or in homogenates of thoracic ganglionic masses of untreated and treated bugs, burchellin was consistently found to affect the secretion rates. Therefore, burchellin not only depresses the release of the diuretic hormone or induces the release of antidiuretic factors but also directly affects the Malpighian tubules.

Animals↗

Effects of lignoids on a hematophagous bug, Rhodnius prolixus: feeding, ecdysis and diuresis.

The effects of lignoids on feeding, ecdysis and diuresis in fourth-instar larvae of Rhodnius prolixus (Hemiptera) were investigated. Up to 100 microg/ml burchellin, podophyllotoxin, pinoresinol, sesamin, licarin A, or nordihydroguaiaretic acid (NDGA) in the diet did not induce antifeedant effects. Pinoresinol and NDGA significantly inhibited ecdysis. In experiments in vivo, burchellin and podophyllotoxin reduced the production of urine after feeding. 5-Hydroxytryptamine (5-HT), a diuretic hormone, partially counteracted this effect of burchellin. In experiments in vitro, using isolated Malpighian tubules, (i) burchellin reduced diuretic hormone levels in the hemolymph but not the amount of diuretic hormone stored in the thoracic ganglionic masses (including axons), (ii) burchellin decreased the volume of urine secreted by isolated Malpighian tubules, and (iii) 5-HT could not overcome the effect of burchellin upon the Malpighian tubules. We conclude that burchellin interfered with the release, but not with the production of diuretic hormone by the thoracic ganglionic mass or induced an antidiuretic hormone and directly affected the Malpighian tubules.

Animals↗

Biodiversity: modelling angiosperms as networks.

In the neotropics, one of the last biological frontiers, the major ecological concern should not involve local strategies, but global effects often responsible for irreparable damage. For a holistic approach, angiosperms are ideal model systems dominating most land areas of the present world in an astonishing variety of form and function. Recognition of biogeographical patterns requires new methodologies and entails several questions, such as their nature, dynamics and mechanism. Demographical patterns of families, modelled via species dominance, reveal the existence of South American angiosperm networks converging at the central Brazilian plateau. Biodiversity of habitats, measured via taxonomic uniqueness, reveal higher creative power at this point of convergence than in more peripheral regions. Compositional affinities of habitats, measured via bioconnectivity, reveal the decisive role of ecotones in the exchange or redistribution of information, energy and organisms among the ecosystems. Forming dynamic boundaries, ecotones generate and relay evolutionary novelty, and integrate all neotropical ecosystems into a single vegetation net. Connectivity in such plant webs may depend on mycorrhizal links. If sufficiently general such means of metabolic transfer will require revision of the chemical composition of many plants.

Conservation of Natural Resources↗

Effects of some lignans and neolignans on the development and excretion of Rhodnius prolixus.

The effects of six lignans and neolignans as inhibitors of ecdysis and on the water balance in fourth-instar larvae of Rhodnius prolixus were studied by oral, topical and continuous contact treatments. The main results may be summarised as follows: (i) burchellin, pinoresinol, sesamin, licarin A and nordihydroguaiaretic acid (NDGA) did not cause feeding inhibition at doses of 100 micrograms/ml blood; podophyllotoxin had no antifeedant effect but caused a high moulting inhibition and significant toxicity when applied either orally or topically; (ii) the highest ecdysis inhibitory effects were observed with pinoresinol and NDGA when applied orally at a dose of 100 micrograms/ml (58% and 50% of moulting inhibition, respectively); burchellin inhibited 30% of the moulting at this concentration; (iii) by topical treatment none of the compounds presented any influence on the moulting cycle; and (iv) podophyllotoxin and burchellin significantly reduced the excretion of the insect in 24 h; the other compounds had no effect on excretion. The implications of these findings in relation to the pertinent biological events in R. prolixus are discussed.

Animals↗

Neolignans inhibit Trypanosoma cruzi infection of its triatomine insect vector, Rhodnius prolixus.

Two neolignans, burchellin and nordihydroguaiaretic acid (NDGA), were toxic only to Trypanosoma cruzi clone Dm28c maintained in brain heart infusion (BHI) medium at a concentration of 100 microg/ml, not 10 microg/ml. When Rhodnius prolixus was fed with epimastigotes of T. cruzi and treated simultaneously with a single dose of burchellin or NDGA at 10 pg/ml of blood meal the number of parasites in the gut decreased. Whereas burchellin was only partially active, NDGA drastically reduced the number of epimastigotes and metacyclic trypomastigotes of T. cruzi in the excreta (urine plus feces). When the insect larvae were pretreated with burchellin or NDGA at 20 days before the infection with T. cruzi a significant reduction in the number of parasites in the gut occurred. However, when both compounds were applied at 20 days after the establishment of T. cruzi infection, although burchellin significantly reduced the gut infection, neither compound could abolish the infection entirely within the subsequent 15 days.

Animals↗

Evolution of angiosperms via modulation of antagonisms.

The controversies concerning the evolutionary mechanisms of flowering plants continue unabated in spite of the current trends toward the analysis of macromolecular data and of the growing body of distributional micromolecular data. The usual narrative approach to this latter effort is here replaced by a novel technique, quantitative phytochemistry. An evolutionary outline emerges and reveals modulation of antagonisms as the fundamental mechanism of angiosperm evolutionary ecology. Origin or operation of many systems can be rationalized analogously. It is concluded that the impact of opposing features possesses universal relevance.

Biological Evolution↗

Hepatoprotective activity of xanthones and xanthonolignoids against tert-butylhydroperoxide-induced toxicity in isolated rat hepatocytes--comparison with silybin.

PURPOSE: Synthesize and evaluate the protective activity against tertbutylhydroperoxide-induced toxicity in freshly isolated rat hepatocytes of trans-kielcorin, trans-isokielcorin B, as well as their respective building blocks 3,4-dihydroxy-2-methoxyxanthone and 2,3-dihydroxy-4-methoxyxanthone. METHODS: Wistar rats, weighing 200-250g were used. Hepatocyte isolation was performed by collagenase perfusion. Incubations were performed at 37 degrees C, using 1 million cells per milliliter in modified Krebs--Henseleit buffer. The protective activity was evaluated by measuring reduced and oxidized glutathione, lipid peroxidation and cell viability after inducing toxicity with tert-butylhydroperoxide (1.0 mM, 30 min), with or without the studied compounds in the concentrations of 0.025, 0.050, 0.100 and 0.200 mM. Silybin was tested in the same experimental conditions to serve as a positive control. RESULTS: Using these concentrations, the tested compounds prevented tert-butylhydroperoxide-induced lipid peroxidation and cell death in freshly isolated rat hepatocytes. All compounds were also effective in preventing perturbation of cell glutathione homeostasis in some extent. 3,4-Dihydroxy-2-methoxyxanthone and 2,3-dihydroxy-4-methoxyxanthone were more effective than trans-kielcorin and trans-isokielcorin B respectively. Silybin was less effective in protecting cells against lipid peroxidation and loss of cell viability than the four xanthonic derivatives. CONCLUSIONS: The tested compounds protected the freshly isolated rat hepatocytes against tert-butylhydroperoxide-induced toxicity.

Animals↗

The rational search for natural neolignans.

A rational method of search for natural neolignans of desired structures is outlined. This involves consultation of a collection of chemical profiles of plant families. The profiles are assembled considering the biosynthetic class (in the present case lignoids), subclass (neolignans), structural types (neolignan skeletal) and relative frequency of substitutional derivatives belonging to each type (known compounds). The method is of course applicable to any class of natural products. Its use in the case of neolignans is here selected as an example in view of the recently discovered antagonism towards PAF of kadsurenone, a representative of this subclass of phytochemicals. Application of the chemical profiles to phylogenetic studies is illustrated.

Benzofurans↗

Comparative ethnopharmacology: a rational method for the search of bioactive compounds in plants.

In the present preliminary communication on comparative ethnopharmacology a limited universe of data extracted from the Journal of Ethnopharmacology (vols. 1-25) was used for the construction of ethnopharmacological profiles of ten families of dicotyledons. Intraprofile analysis suggested the main uses of plant species (indicated by the maximal citation frequencies), as opposed to the spurious ones (represented by base line fluctuations), to possess a solid chemotaxonomic basis. Interprofile analysis via correlation of ethnopharmacological distances and morphological (evolutionary) distances among the same plant families suggested comparative ethnopharmacology to possess also a phylogenetic (chemosystematic) basis. This result establishes comparative ethnopharmacology as a novel and potentially useful scientific discipline.

Plants, Medicinal↗

Ethnopharmacology versus chemosystematics in the search for biologically active principles in plants.

The chemicals to which Brazilian angiosperms owe their use in the preparation of arrow poisons, hallucinogens, fish poisons, drugs, stimulants, spices, perfumes and pigments are correlated with the systematic position of the species in which they occur. Most compounds are produced either by the primitive Magnoliidae (sensu Cronquist) or by the advanced Asteridae. The Rosidae-Dilleniidae, precisely the group of subclasses of widest distribution over the country, have heretofore yielded relatively few useful compounds. This fact can be rationalized by the presence in their species of massive quantities of gallo- and ellagitannins, general defences which make the presence of specific alleochemics superfluous. The natural occurrence of specific biologically active compounds is thus ecologically and systematically conditioned and it should be possible to build a system capable of predicting the existence and the nature of useful chemicals in plant taxa.

Animals↗

Ocotea quixos, American cinnamon.

Among the three South American Lauraceae with cinnamon odours, Ocotea quixos Lam. is distinguished with the richest historical legacy. Cinnamaldehyde, its odoriferous principle, occurs besides o-methoxycinnamaldehyde, cinnamic acid and methyl cinnamate in the fruit calyx. In contradistinction, 1-nitro-2-phenylethane is responsible for the cinnamon odour of bark and leaves of Aniba canelilla (H..B.K.) Mez and Ocotea pretiosa (Nees) Mez.

Cinnamomum zeylanicum↗

Chemical studies on medicinal Myristicaceae from Amazonia.

Drugs from Myristicaceae species are used in the Amazon region as hallucinogens and arrow poisons, as well as for the healing of infected wounds. The former effects were attributed by Schultes and Holmstedt to tryptamines and carbolines. The latter activity is now tentatively ascribed to pterocarpans and neolignans. This, and a proposal that the red colour of the bark resins may be due to oxidative dimers of flavans, are based on a review of the chemistry of Amazonian Myristicaceae.

Alkalies↗

Medicinal products: regulation of biosynthesis in space and time.

We live in a "Demon-Haunted World". Human health care requires the ever increasing resistance of pathogens to be confronted by a correspondingly fast rate of discovery of novel antibiotics. One of the possible strategies towards this objective involves the rational localization of bioactive phytochemicals. The conceptual basis of the method consists in the surprisingly little known gearings of natural products with morphology, ecology and evolution of their plant source, i. e. an introspection into the general mechanisms of nature.

Biological Factors↗