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Biomedical subjects

E Elisabetsky

Publications and source records attributed to E Elisabetsky.

At least 37 records · Page 2Linked to original sources

A neuropharmacological analysis of PTZ-induced kindling in mice.

1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic changes associated with epileptic features. 2. The aim of this study was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, significantly increased (169.8%) the specific binding of [3H]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ-induced kindling and that, as in rats, the kindling increases the specific [3H]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena.

Aging↗

Anticonvulsant properties of gamma-decanolactone in mice.

Lactones have been proven to be bioactive. We have shown that compounds present in the essential oil from Aeollanthus suaveolens, used as an anticonvulsant in the Brazilian Amazon, has sedative properties. This paper reports on the evaluation of the systemic administration of gamma-decanolactone, structurally related to lactones present in the essential oil of A. suaveolens, on mice experimental models useful for detecting psychopharmacological activity. The results show that gamma-decanolactone has dose-dependent marked effects on the central nervous system, including hypnotic, anticonvulsant and hypothermic activity. The effects of gamma-decanolactone revealed by this evaluation point to the validity of exploring lactones as sources of new anticonvulsant agents.

Animals↗

Effect of gamma-decanolactone on glutamate binding in the rat cerebral cortex.

Epilepsy is one of the most common neurological disorders. Even though antiepileptic drugs can afford a reasonably satisfactory treatment for 80% of diagnosed patients, chronic intractable epilepsy still affects a significant number of people and more effective and less harmful antiepileptic drugs are needed. Previous studies have shown that gamma-decanolactone has dose-dependent sedative effects, including hypnotic, anticonvulsant and hypothermic properties in mice. The present study reports an inhibitory effect of gamma-decanolactone on glutamate binding (96.8% with 5 mM) in rat cortex membranes. The non competitive nature of glutamate binding inhibition as a neurochemical correlate of the anticonvulsant activity of gamma-decanolactone may be a relevant mode of action for further drug development.

Animals↗

Effects of Psychotria colorata alkaloids in brain opioid system.

An ethnopharmacological survey showed that home remedies prepared with flowers and fruits of Psychotria colorata are used by Amazonian peasants as pain killers. Psychopharmacological in vivo evaluation of alkaloids obtained from leaves and flowers of this species showed a marked dose-dependent naloxone-reversible analgesic activity, therefore suggesting an opioid-like pharmacological profile. This paper reports an inhibitory effect of P. colorata flower alkaloids on [3H]naloxone binding in rat striata as well as a decrease in adenylate cyclase basal activity. The alkaloids did not affect [3H] GMP-PNP binding. These findings provide a neurochemical basis for the opioid-like activity previously detected in vivo and point to Psychotria alkaloids as a potential source of new bioactive opiate derivatives.

Adenylyl Cyclases↗

Medicinal plant genetic resources and international cooperation: the Brazilian perspective.

Brazil is a gene rich country, host to 24% of known primate species, between 10 and 15 million species of insects, and 22% of the world's higher plant species. The debate over how and by whom these resources should be protected has intensified over the last few years due to a growing awareness of the links between sustainable utilization of natural resources, conservation of biodiversity, and economic development. Within this context the pharmaceutical exploitation of natural products for drug development has a prominent place. For a significant portion of Brazilian society, fair cooperation is welcome and can facilitate drug discovery. Nevertheless, the complexity of the consequences of patenting and utilization of natural resources calls for a thorough cost/benefit analysis in order to promote policies that can ensure significant and long term benefits for the country.

Brazil↗

Absence of alkaloids in Psychotria carthagenensis Jacq. (Rubiaceae).

Psychotria viridis and P. carthagenensis are often discussed in relation to the hallucinogenic beverage Ayahuasca, used for religious, medicinal and social purposes. The significance of including Psychotria species in this beverage has been understood on the basis of substantial amounts of tryptamine alkaloids detected on leaves of both P. viridis and P. carthagenensis. Nevertheless, there is a long lasting debate over the identification of which Psychotria species are actually traditionally employed. We here report that a P. carthagenensis leaf ethanol extract was found to be devoid of alkaloids. The extract significantly decreased mice body temperature (350 and 500 mg/kg). Toxicity assessment revealed that the extract induced sedation and slight ptoses (75% of animals treated with 1000 mg/kg). Lethality was not observed within 48 h. The data indicate that P. carthagenensis does have bioactive compound(s), possibly active at the central nervous system, but unlikely to be tryptamine alkaloids as in the case of P. viridis. Therefore, if P. carthagenensis is indeed used by ayahuasqueros, its chemical and pharmacological significance have yet to be elucidated.

Analysis of Variance↗

Effects of Linalool on glutamatergic system in the rat cerebral cortex.

Linalool is a monoterpene compound reported to be a major component of essential oils in various aromatic species. Several Linalool-producing species are used in traditional medical systems, including Aeolanthus suaveolens G. Dom (Labiatae) used as anticonvulsant in the Brazilian Amazon. Psychopharmacological in vivo evaluation of Linalool showed that this compound have dose-dependent marked sedative effects at the Central Nervous System, including hypnotic, anticonvulsant and hypothermic properties. The present study reports an inhibitory effect of Linalool on Glutamate binding in rat cortex. It is suggested that this neurochemical effect might be underlining Linalool psychopharmacological effects. These findings provide a rational basis for many of the traditional medical use of Linalool producing plant species.

Acyclic Monoterpenes↗

Analgesic activity of Psychotria colorata (Willd. ex R. & S.) Muell. Arg. alkaloids.

An ethnopharmacological survey showed that home remedies prepared with flowers, fruits and roots of Psychotria colorata (Wild. ex R. & S.) Muell. Arg. (RUBIACEAE) are used by Amazonian caboclos as pain killers. These data led to the evaluation of analgesic activity of extracts of P. colorata, using the formalin, writhing and tail-flick methods. This paper reports the Naloxone reversible opioid-like analgesic activity of alkaloids present in leafs and flowers of P. colorata.

Alkaloids↗

Ethnopharmacological search for antiviral compounds: treatment of gastrointestinal disorders by Kayapó medical specialists.

The Mebengokrê (Kayapó) of Brazil have a highly developed medical and pharmacological tradition based on diverse specialization in knowledge and practice. Shamans (wayangas) are prepared to treat all kinds of diseases including those related to spirits; curers (mãkuté pidjà mari) can deal only with diseases not related to spirits. Both utilize plant- and animal-based remedies, among other practices. Elaborate disease categories (kanê) include those known as hak-kanê (bird disease) and tep-kanê (fish disease). The complexity of the two categories defies easy description but both use gastrointestinal disorders as basic indicative symptoms. Given that an important percentage of gastrointestinal disorders are caused by viruses and that new antiviral drugs are sorely needed, plants used by the Kayapó for hak and tep diseases are presented and discussed as potential leads in the search for antiviral compounds.

Antiviral Agents↗

Ethnopharmacology in the Brazilian Amazon.

The potential pharmaceutical wealth of the Brazilian Amazon has attracted international attention from the general and scientific community. The role that ethnopharmacology can have in the discovery and development of new drugs from a region hosting such enormous cultural and biological diversity is discussed. A review is given of ethnopharmacological and ethnobotanical studies that have been conducted in the Brazilian Amazon over the past twenty years.

Brazil↗

The status of ethnopharmacology in Brazil.

Brazil is a country of interest to ethnopharmacology because of its great wealth of cultural and biological diversity. This paper describes relevant research activities in the areas of botany, chemistry, basic and clinical pharmacology, and discusses the key factors that shaped ethnopharmacology development in the country. Specific attention is given to analyzing ongoing attempts to include medicinal plant based formulations in the official health care system.

Animals↗

Sociopolitical, economical and ethical issues in medicinal plant research.

Medicinal plant research may be pursued with several goals: the understanding of a native medical system, the elucidation of the rational basis for the medicinal use of a certain plant species, the development of low cost phytotherapeutics, the discovery of prototypic drugs, and so on. More often than not, the research project starts with the collection of indigenous medical knowledge in various parts of the world and generates a dissertation, a scientific paper or a drug. Usually, indigenous knowledge was crucial to the development of such products; nevertheless, indigenous groups tend not to benefit from the achievements of research. Ethnopharmacology involves a series of sociopolitical, economic and ethical dilemmas, at various levels. Most research projects involve more than one country (e.g., field work in a remote part of an underdeveloped country). Frequently host country scientists, visiting scientists, and informants disagree about these dilemmas. As a result, such research efforts are perceived as scientific imperialism; scientists are accused of stealing plant materials and appropriating traditional plant knowledge for financial profit and/or professional advancement. Many governments, as well as indigenous societies are increasingly reluctant to permit such research. Increasingly, funding for field work utilizing indigenous informants is coming from industry. Historically neither native populations nor host countries have shared to a significant extent the financial benefits from any drug that reaches the market. Unless these issues are amply discussed and fairy resolved, medicinal plant research runs the risk of serving ethically questionable purposes.

Economics↗

Use of contraceptive and related plants by the Kayapo Indians (Brazil).

Interest in plant sources of prototypic contraceptive compounds is evidenced by numerous investigations and research projects. We suggest that the success rates of programs devised to evaluate pharmacological effects of traditionally employed contraceptives would be increased if native concepts of conception/contraception were taken into account. If ethnomedical and ethnopharmacological data are not carefully analysed, selection of plants to be evaluated will include those with little cross-cultural application. Kayapo concepts of menstruation, fertility, and contraception are presented, uses of related plants in culturally different groups are also analysed in order to indicate promising fertility-regulating plants used by the Kayapo.

Abortifacient Agents↗

Effect of brain serotonin level on induced hippocampal paroxysmal activity in rats.

Experiments were performed to study the involvement of brain 5-HT in an experimental model of epilepsy induced by repeated electrical stimulation of the dorsal hippocampus of rats. The experiments included: (1) systemic injections of 5-hydroxytryptophan (5-HTP) and p-chlorophenylalanine (pCPA) and (2) electrolytic lesions of the midbrain raphe nuclei. The pCPA group showed a significant increase while animals which received systemic injections of 5-HTP showed a great reduction in the electrographic seizure activity. Although several reports have shown that midbrain raphe lesions do not modify the epileptic susceptibility, we observed a clear enhancement in the epileptiform activity in lesioned animals. The results presented here support the view that serotonergic systems may exert a tonic inhibitory effect on hippocampal epileptic activity.

5-Hydroxytryptophan↗

Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation.

The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 microgram/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED50 being 1.0 microgram/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46-60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning.

Amnesia↗

Effect of various forms of training and stimulation on the incorporation of 32P into the nuclear phosphoproteins of the rat brain.

Incorporation of 32P into acid-extractable nuclear proteins was measured in the hippocampus, caudate nucleus, rest of the brain, and liver of rats submitted to various different behavioral treatments in a shuttle-box. After 5 min of classical conditioning, of avoidance without CS-US pairing, and of avoidance with CS-US pairing (standard shuttle avoidance), there was an increased 32P uptake by acid-extractable nuclear proteins in the hippocampus and caudate nucleus. The effect disappeared between 5 and 25 min of training. After 25 min of buzzers alone, or of footshocks alone, a similar 32P uptake change was noted in the same brain structure, which raises doubts as to the specificity of the phenomenon in terms of learning mechanisms.

Animals↗

The role of opioid peptides in memory and learning.

Evidence is discussed which points to the existence of a physiologic amnesic mechanism mediated by beta-endorphin and perhaps by other opioid peptides as well. This mechanism is triggered by various forms of training and by either painful or painless stimulation. It may operate through the inhibition of central dopaminergic and beta-adrenergic systems that modulate the memory consolidation process. This amnesic mechanism in unrelated to the regulation of pain perception, and operates at opioid peptide levels several orders of magnitude below those that are needed to cause analgesia or other effects. In addition, shuttle avoidance and habituation learning seem to be dependent on a state induced by the release of beta-endorphin. It is possible that this may be related to the amnesic properties of this substance. Therefore, it appears that the endogenous opioid peptides may exert their primary function in the modulation of memory processes.

Amnesia↗