Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model.

BACKGROUND: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium's ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR - with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. METHODS: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother's brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. RESULTS: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. CONCLUSION: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat's maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

Comparison of the antidepressant like activity of homeopathic remedies (Argentum nitricum, Staphysagria and Ignatia amara) and their effect on the behavior of rodents.

The majority of the world population suffers from mental and behavioral disorder. It is the need of the time to find an alternate of presently available medicines in order to decrease the medical expense. Homeopathic remedies are available and prescribed by homeopaths for treatment of anxiety and depression. Unfortunately, no data are available that proves its potential to relieve mental illness. The current study is designed to assess neuro behavioral and antidepressant like effects of homeopathic remedies Staphysagria, Argentum nitricum and Ignatia amara in comparison with standard drug (escitalopram). Different neuro behavioral activities were analyzed. The animals were administered the doses of all homeopathic remedied (60 µl to the rats) and escitalopram (0.042 mg to rats) through the oral route. The activities were observed on day 30th and day 60th. Our result suggests that the swimming time in Staphysagria treated group were significantly improved (p<0.001) after day 60th and significance rise was observed (p<0.01) in Ignatia amara treated animals, whereas significant decline (p<0.05) in struggling time was observed in Argentum nitricum administered animals after the 60th day as compared to 30th day. The central square crossings were improved highly significantly (p<0.001) after the 30th day dosing, by all three remedies and peripheral squares crossing were found highly significantly increased (p<0.001) after chronic dosing in Staphysagria and Ignatia amara treated groups. It is concluded from the results that all three homeopathic remedies produce comparable effects like standard drug while among all three remedies Staphysagria possess a potent antidepressant activity. To the best of our knowledge the current study reports first time the anti-depressant potential of homeopathic remedies in rodents.

Serial dilutions: a new area of research for animal behavior.

This paper attempts to stimulate the psychological investigation of homeopathy and serially agitated dilutions. The history of homeopathy and serial dilutions is provided in a literature review of selected research areas. Two original illustrative experiments are also presented and discussed. The first examined the effect of serially agitated dilutions of Sevin on the mortality rate of honey bees (Apis mellifera). In a second experiment, the effect of serially agitated dilutions of sucrose on proboscis extension in honey bees was assessed. No differences were found between serially agitated dilutions of pesticides and sucrose compared with dilutions alone. Implications, limitations, and proposed further work are discussed.

[Analysis of liposoluble constituents in Holotrichia diomphalia by GC-MS and investigation their anti-inflammatory and analgesic activities].

OBJECTIVE: To analysis liposoluble constituents of Holotrichia diomphalia by GC-MS and measure their anti-inflammatory and analgesic activities. METHODS: The composition of liposoluble constituents were determined by GC-MS. The dimethylbenzene-induced mice inflammatory models were established. The pain models were obtained by hot plate and acetic acid in mice. RESULTS: Twenty-two components were identified from the petroleum ether extract of Holotrichia diomphalia. The major components were oleic acid, palmitic acid and palmitoleic acid. The petroleum ether extract was able to significantly inhibit the mice ear edema induced by dimethyl-benzene. The pain in mice caused by acetic acid and hot plate were evidently suppressed by the petroleum ether extract. CONCLUSION: The petroleum ether extract of Holotrichia diomphalia has obvious anti-inflammation and analgesic effects.

Cognition and memory impairment attenuation via reduction of oxidative stress in acute and chronic mice models of epilepsy using antiepileptogenic Nux vomica.

Ethnopharmacological relevance Processed Nux vomica seed extracts and homeopathic medicinal preparations (HMPs) are widely used in traditional Indian and Chinese medicine for respiratory, digestive, neurological and behavioral disorders. Antioxidant property of Nux vomica is well known and recent investigation has highlighted the anticonvulsant potential of its homeopathic formulation. AIM OF THE STUDY: To explore the anticonvulsant and antiepileptogenic potential of Nux vomica HMPs (6CH, 12CH and 30CH potency) in pentylenetetrazole (PTZ) induced acute and chronic experimental seizure models in mice and investigate their effects on cognition, memory, motor activity and oxidative stress markers in kindled animals. MATERIALS AND METHODS: Acute seizures were induced in the animals through 70 mg/kg (i.p.) administration of PTZ followed by the evaluation of latency and duration of Generalized tonic-clonic seizures (GTCS). Subconvulsive PTZ doses (35 mg/kg, i.p.) induced kindling in 29 days, which was followed by assessment of cognition, memory and motor impairment through validated behavioral techniques. The status of oxidative stress was estimated through measurement of MDA, GSH and SOD. RESULTS: HMPs delayed the latency and reduced the duration of GTCS in acute model signifying possible regulation of GABAergic neurotransmission. Kindling was significantly hindered by the HMPs that justified the ameliorated cognition, memory and motor activity impairment. The HMPs attenuated lipid peroxidation by reducing MDA level and strengthened the antioxidant mechanism by enhancing the GSH and SOD levels in the kindled animals. CONCLUSIONS: Nux vomica HMPs showed anticonvulsant and antiepileptogenic potency in acute and chronic models of epilepsy. The test drugs attenuated behavioral impairment and reduced the oxidative stress against PTZ induced kindling owing to which they can be further explored for their cellular and molecular mechanism(s).

Cellular and molecular mechanisms of drug dependence.

The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs.

The rat in basic therapeutic research in homeopathy.

The Similia Principle, the basis of homeopathy, implies that substances initiating symptoms when applied to healthy biological systems can be utilized as remedies to treat a diseased system with similar symptoms. Depending whether the remedy substance was of the same type as the etiologic agent, treatment is classified as either homologous or heterologous. The intact rat is the biological system most utilized in basic science homeopathic research. The Homeopathy Basic Research experiments (HomBRex) database (about 1300 experiments on model biological systems in homeopathic research) was analyzed for homologous and heterologous treatments of disease states of intact rats. The relationship between the Similia Principle and hormesis is discussed.

Assays of homeopathic remedies in rodent behavioural and psychopathological models.

The first part of this paper reviews the effects of homeopathic remedies on several models of anxiety-like behaviours developed and described in rodents. The existing literature in this field comprises some fifteen exploratory studies, often published in non-indexed and non-peer-reviewed journals. Only a few results have been confirmed by multiple laboratories, and concern Ignatia, Gelsemium, Chamomilla (in homeopathic dilutions/potencies). Nevertheless, there are some interesting results pointing to the possible efficacy of other remedies, and confirming a statistically significant effect of high dilutions of neurotrophic molecules and antibodies. In the second part of this paper we report some recent results obtained in our laboratory, testing Aconitum, Nux vomica, Belladonna, Argentum nitricum, Tabacum (all 5CH potency) and Gelsemium (5, 7, 9 and 30CH potencies) on mice using ethological models of behaviour. The test was performed using coded drugs and controls in double blind (operations and calculations). After an initial screening that showed all the tested remedies (except for Belladonna) to have some effects on the behavioural parameters (light-dark test and open-field test), but with high experimental variability, we focused our study on Gelsemium, and carried out two complete series of experiments. The results showed that Gelsemium had several effects on the exploratory behaviour of mice, which in some models were highly statistically significant (p < 0.001), in all the dilutions/dynamizations used, but with complex differences according to the experimental conditions and test performed. Finally, some methodological issues of animal research in this field of homeopathy are discussed. The "Gelsemium model" - encompassing experimental studies in vitro and in vivo from different laboratories and with different methods, including significant effects of its major active principle gelsemine - may play a pivotal rule for investigations on other homeopathic remedies.

A double-blind placebo-controlled study into the efficacy of a homeopathic remedy for fear of firework noises in the dog (Canis familiaris).

Seventy-five dogs that showed a fear response to fireworks participated in a double-blinded, placebo-controlled clinical trial to assess the efficacy of a homeopathic remedy for the alleviation of their behavioural signs. Dogs were randomly assigned to one of two treatments; the homeopathic treatment or the placebo treatment. At the baseline assessments the owners identified the behavioural signs of fear that their dogs normally displayed in response to fireworks, rated their frequency and intensity, and assessed the global severity of their dog's responses. These measures were repeated at the final assessment and owners also completed weekly diaries for the length of the trial. There were significant improvements in the owners' rating of 14/15 behavioural signs of fear in the placebo treatment group and all 15 behavioural signs in the homeopathic treatment group. Both treatment groups also showed significant improvement in the owners' rating of the global severity of their dog's responses. However, there was no significant difference in the response seen between the two treatment groups.

An animal model for the study of Chamomilla in stress and depression: pilot study.

The behavioral and hematological effects of treatment with Chamomilla 6cH in mice subjected to experimental stress are described. Swiss mice were randomly divided into pairs, one animal was inoculated with Ehrlich's tumor, the other was treated daily with Chamomilla 6cH or control or received no treatment. After 7 days, the animals were observed in an open-field arena and blood samples taken. Mice who cohabitated with a sick cage-mate showed a decrease in their general activity, but those treated with Chamomilla 6cH were less severely affected (p=0.0426). No hematological changes were observed. In a second experiment, the forced swimming test was applied to mice pre-treated with Chamomilla 6cH, controls were: water, 10% ethanol or amitriptyline. Only the amitriptyline and ethanol treated groups showed significant excitatory behavior (p=0.0020), Chamomilla 6cH treated animals' scores intermediate between water control and ethanol or amitriptyline. A decrease in the leukocyte count was observed in the amitriptyline and Chamomilla 6cH treated groups (p=0.039). These data suggest that treatment with Chamomilla 6cH is related to the recovery of basal behavioral conditions in mice subjected to stressful conditions.

Role of cAMP response element-binding protein in the rat locus ceruleus: regulation of neuronal activity and opiate withdrawal behaviors.

The transcription factor cAMP response element-binding protein (CREB) is implicated in mediating the actions of chronic morphine in the locus ceruleus (LC), but direct evidence to support such a role is limited. Here, we investigated the influence of CREB on LC neuronal activity and opiate withdrawal behaviors by selectively manipulating CREB activity in the LC using viral vectors encoding genes for CREBGFP (wild-type CREB tagged with green fluorescent protein), caCREBGFP (a constitutively active CREB mutant), dnCREBGFP (a dominant-negative CREB mutant), or GFP alone as a control. Our results show that in vivo overexpression of CREBGFP in the LC significantly aggravated particular morphine withdrawal behaviors, whereas dnCREBGFP expression attenuated these behaviors. At the cellular level, CREBGFP expression in the LC in vivo and in vitro had no significant effect on neuronal firing at baseline but enhanced the excitatory effect of forskolin (an activator of adenylyl cyclase) on these neurons, which suggests that the cAMP signaling pathway in these neurons was sensitized after CREB expression. Moreover, in vitro studies showed that caCREBGFP-expressing LC neurons fired significantly faster and had a more depolarized resting membrane potential compared with GFP-expressing control cells. Conversely, LC neuronal activity was decreased by dnCREBGFP, and the neurons were hyperpolarized by this treatment. Together, these data provide direct evidence that CREB plays an important role in controlling the electrical excitability of LC neurons and that morphine-induced increases in CREB activity contribute to the behavioral and neural adaptations associated with opiate dependence and withdrawal.

Pharmacological analysis of paregoric elixir and its constituents: in vitro and in vivo studies.

Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross-tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents.

[Effects of Tongxinluo capsule on atherosclerosis obliterans in iliofemoral artery of rabbits].

OBJECTIVE: To explore the effects of Tongxinluo capsule (TXL) on the atherosclerosis obliterans (ASO) in iliofemoral artery of rabbits. METHOD: Rabbits were randomly divided into 7 groups: sham, model, TXL (0.8, 0.4, 0.2 g x kg(-1)), Tongsaimai tablet (0.8 g x kg(-1)) and Laishike (0.002 g x kg(-1)). The animal model of ASO was established with a combined method of mechanical trauma, immunologic injury and high fat fodder feeding. Rabbits were administrated the drugs 8 weeks after surgery. The levels of TC, TG, HDL-C and LDL-C in serum were determined at the time points below: pre-experiment (0 week), pre-drug administration (8 weeks post-surgery), 4 weeks after drug administration (12 weeks post-surgery), 8 weeks after drug administration (16 weeks post-surgery), 12 weeks after drug administration (20 weeks post-surgery). Meanwhile, the behavioral study was performed, the distal skin temperature of the injured hind limb detected. The histopathological changes in iliofemoral artery were examined after opacification. RESULT: The levels of TC, TG, LDL-C, VLDL-C and TC/HDL-C were decreased significantly in serum of ASO rabbits. The severity of lameness in the injured hind limb was improved. The distal skin temperature was increased. The thickness and the ratio of intima area of the iliofemoral artery of the injured hind limb were decreased, while the stenosis extent was improved. CONCLUSION: TXL might be beneficial to modulate blood lipid, as well as the prevention and treatment for ASO.

Is the addition of spray homeopathic in feed able to change dog behavior? / A adição de spray homeopático na ração é capaz de alterar o comportamento de cães?

This study aimed to determine if the homeopathic formulation based on Natrum muriaticum, Matricaria, Chamomilla, and Ignatia amara was effective for stress control in dogs in order to prevent and/or reduce the frequency of unwanted behaviors. Ten male beagle dogs were divided into two groups, with five animals per group. The control group was animals receiving 0.5 mL/day of placebo via spray in the feed for 30 consecutive days as a preventive. The treated group received 0.5 mL/day of tested drug spray in the feed for 30 consecutive days as a preventive. Behavioral tests were performed at two time points, before and after receiving the tested drug. We performed the following behavioral tests: a) persons known and unknown in the internal and external environment; b) interaction with toys; c) interaction with an unknown dog, d) test with a leash; and e) firecracker test. There was more engagement in digging and scaling the fence in the control group than in the treatment group (P < 0.05). The animals that received homeopathic medicine sat 2.54 times longer than the control (P = 0.0269). Dogs that received homeopathic showed 4.49 times more interest in general at D30 than at D1 (P = 0.0214). Animals in the treated group showed an 83% less chance of urinating than the control group in the tests involving displacements. We conclude that the preventive addition of homeopathic medicine containing Natrum muriaticum, Chamomilla, and Ignatia amara reduced undesirable behaviors related to anxiety and increased the incidence of interest behavior.(AU)

Este estudo visou determinar se a formulação homeopática baseada em Natrum muriaticum, Matricaria, Chamomilla, e Ignatia amara foi eficaz para o controle de stress em cães, a fim de prevenir e/ou reduzir a frequência de comportamentos indesejados. Dez cães beagle machos foram divididos em dois grupos, com cinco animais por grupo. O grupo controle recebeu 0,5 mL/dia de placebo via spray na ração durante 30 dias consecutivos, como preventivo. O grupo tratado recebeu 0,5 mL/dia de homeopático via spray na ração durante 30 dias consecutivos, como preventivo. Os testes comportamentais foram realiza-dos em dois momentos, antes e depois de receber o fármaco testado. Foram realizados os seguintes testes comportamentais: a) pessoas conhecidas e desconhecidas no ambiente interno e externo; b) interação com brinquedos; c) interação com um cão desconhecido, d) teste com a guia; e teste com fogos de artifício. Houve um aumento nos comportamentos cavar e escalar a grade no controle (P < 0,05). Os animais que receberam o homeopático sentaram-se 2,54 vezes mais do que o grupo con-trole (P = 0,0269). Os cães que receberam homeopático mostraram 4,49 vezes mais interesse em geral no D30 do que no D1 (P = 0,0214). Os animais do grupo tratado mostraram uma probabilidade 83% menor de urinar do que o grupo controle nos testes envolvendo deslocamento. Concluímos que a adição preventiva de medicamentos homeopáticos contendo Natrum muriaticum, Chamomilla, e Ignatia amara reduziu os comportamentos indesejáveis relacionados com a ansiedade e aumentou a incidência de comportamentos de interesse.(AU)

[The effect of four kinds of traditional Chinese herbal compound on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis].

OBJECTIVE: To study the effects of four kinds of traditional Chinese herbal compound, Sini powder, Banxiahoupu soup, Ganmaidazao soup and Guizhigancaolonggumuli soup, on the experimental acute stress behaviors and the hypothalamus-pituitary-adrenal gland axis. METHOD: Rats were divide into 7 groups: normal group, model 1 and 2 groups, Sini powder group, Banxiahoupu soup group, Ganmaidazao soup group, and Guizhigancaolonggumuli soup group. The behaviors of the rats and their CRH of the hypothalamus, ACTH of plasma and CORT of serum (by the means of radio-immunity) were detected. RESULT: Sini powder could reduce the crossing times of open-field test( P < 0.01) and the contents of CRH and CORT (P < 0.01, P < 0.05); Banxiahoupu soup could extent the still time of tail-hanging test ( P < 0.05) and the content of CRH (P < 0.05); Ganmaidazao soup could prolong the still time (P < 0.05) and reduce the struggle times (P < 0.01) of tail-hanging test and reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05); Guizhigancaolonggumuli soup could reduce the crossing times of open-field test (P < 0.01) , extent the still time (P < 0.05) and reduce the struggle times ( P < 0.01) of tail-hanging test of tail-hanging test, also reduce the contents of CRH, ACTH and CORT (P < 0.01, P < 0.05). CONCLUSION: The four kinds of traditional Chinese herbal compound can increase the ability of anti stress by affect the different taches of the hypothalamus-pituitary-adrenal gland axle and change the stress behaviors, which are based on their respective functions of regulating Qi, dispersing phlegm, tonifying Qi and warming Yang.

Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model.

ETHNOPHARMACOLOGICAL RELEVANCE: Gelsemium sempervirens (L.) J.St.-Hil is a herb used for the treatment of various neuroses in both homeopathic and Ayurvedic systems. The present study examines whether Gelsemium reconstituted tincture can protect against scopolamine induced cognitive discrepancies in amnesic mouse model. In order to investigate the protective mechanism of Gelsemium against dementia, in vitro acetyl cholinesterase and ß-secretase enzyme inhibition and estimation of glutathione level in mouse brain were carried out. MATERIALS AND METHODS: The inhibition study on acetyl cholinesterase and ß-secretase enzyme was conducted on brain homogenate supernatant spectrophotometrically using specific substrate. Cognitive enhancement activity was assessed by elevated plus maze and passive avoidance study in scopolamine induced dementia mouse model. Glutathione, an anti-oxidant, was measured spectrophotometrically from scopolamine induced amnesic mice brain supernatant using 5,5'-dithiobis 2-nitrobenzoic acid in the presence and absence of Gelsemium tincture. RESULTS: Significant inhibition was found with Gelsemium on AChE and ß-secretase enzyme with an IC50 of 9.25 and 16.25 µg/ml, respectively, followed by increasing glutathione levels in comparison to the untreated dementia group. The effect of Gelsemium of scopolamine-induced cognitive deficits was determined by measuring the behavioral parameters and the antioxidant status of the brain after scopolamine (1mg/kg i.p.) injected amnesic mice. Gelsemium significantly demonstrated in vivo anti-dementia activity (60% protection) and increased exploratory behavior. CONCLUSION: Our investigations indicated that alkaloid, iridoids and coumarin enriched reconstituted Gelsemium tincture extract displays promising cognitive enhancement in adult mice after short-term oral treatment. Hence, Gelsemium can be a promising anti-dementia agent, mediating the protection against amnesia, attention disorders and learning dysfunctions through dual inhibition of both acetyl cholinesterases (no false positive effect was shown), ß-secretase and antioxidant activity.

Comparative anxiolytic activity profile of various preparations of Passiflora incarnata linneaus: a comment on medicinal plants' standardization.

OBJECTIVES: Mother tincture preparation of Passiflora incarnata from five reputable manufacturers of homeopathic medicines were compared to the bioactive fraction of methanol extract of P. incarnata (standard) for their anxiolytic activity in mice using the elevated plus-maze model of anxiety. MATERIALS AND METHODS: The extracts of P. incarnata were further subdivided in four doses, i.e., 100, 200, 300, and 400 mg/kg, suspended in a vehicle, and administered orally to groups of mice. Methanol extract of P. incarnata (125 mg/kg, orally) was taken as a standard. Anxiolytic activity was measured using the elevated plus-maze model. All treatments were given orally. Forty-five (45) minutes after the treatments, mice were placed on the center of the elevated plus-maze and the number of entries in open arms were measured for 5 minutes. SUBJECTS: Studies were performed with Swiss albino mice. RESULTS: The dried mother tincture preparations exhibited maximum anxiolytic activity at 300 mg/kg (SBL); 400 mg/kg (DWSI and DWSG); 200 mg/kg (DRCG), and nil (BHL) respectively, with reference to anxiolytic activity exhibited by the methanol extract of aerial parts of P. incarnata (125 mg/kg). CONCLUSIONS: To ensure uniformity and consistency of the biologic effects exhibited by plant-derived phytopharmaceuticals, uniform standards are required globally. The monographs on P. incarnata mention standardization of the plant using any known flavonoid as the chemical marker and the marker compound was not the one responsible for the plants multifarious biologic effects. The recent report of a trisubstituted benzoflavone compound (BZF) as the main bioactive phytoconstituent of P. incarnata made it feasible to resort to biologic standardization of this plant using BZF as the biomarker compound. The biologic standardization would ensure bioequivalence of the medicinal preparations of P. incarnata. These studies also recommend the incorporation of leaf constants, ash values, extractive values, thin layer chromatography profile (vital "fingerprints" specific for a plant), and the quantitative assay by determining the bioactive BZF moiety in pharmacopoeias in order to ensure uniform biologic results and standards of P. incarnata because the plant currently has tremendous usefulness. The herbal pharmacopoeias, which are still in their "infancy," can be strengthened by incorporating the appropriate bioactive constituents that need to be identified by using modern technological procedures. Once the appropriate bioactive constituent(s) are established and authenticated, their qualitative and quantitative assay procedures can be developed. Reporting the vital fingerprint parameters of the plant and incorporation of assay procedures of the bioactive phytomoiety in the official monographs of medicinal plants, will certainly strengthen the herbal pharmacopoeias. This is perhaps the most important scientific approach that would ensure uniform standards and bioequivalence of plant-medicines - a need to revive faith in the healing potentials of plant-derived medicines.

[Spectrum of psychotropic effects and mechanism of action of ultra low doses of the antibodies to S-100 protein (proproten)]. / Spektr psikhotropnykh effectov i mekhanizm deistviia sverkhmalykh doz antitel k belku S-100 (proproten).

Proproten contains ultra-low doses of affinity purified antibodies to S-100 protein dynamized according to the rules of homeopathy. S-100 is regulator of brain integrative activity and takes part in synaptic processes. In experiment on outbred rats proproten demonstrates significant anxiolytic, antidepressant and antiamnestic effects after single and repeated administration. Proproten is similar to the well-known reference preparations diazepam, amitriptyline and piracetam in activity. Proporten's advantage over these drugs is no sedative, myorelaxation and amnestic effects. Psychotropic effects of proproten are likely to result from modulation of synaptic transmission in limbic structures of brain.

Therapeutic and pathogenetic animal models for Dolichos pruriens.

The therapeutic and pathogenetic effects of Dolichos pruriens were evaluated using experimental models in rats. In the therapeutic experiment Wistar rats were housed in a heated environment (25+/-3 degrees C) to induce itch, and treated with ascending potencies D. pruriens (6 cH, 9 cH, 12 cH and 30 cH), each for 10 days. The positive control group received vehicle (ethanol 30% in water). The negative control group received no treatment and were kept at a standard temperature. In the pathogenetic experiment, all animals were kept at a temperature of 20+/-3 degrees C and treated for 30 consecutive days with D. pruriens 6 or 30 cH, or ethanol vehicle, or no treatment. The experiments were performed blind. The statistical analysis used Bartlett's test, followed by ANOVA/Tuckey-Krammer or Kruskal-Wallis/Dunn. The results point to the existence of therapeutic effects, with inhibition of the itching, skin lesions and fur thinning produced by heat, more evident in later observations, with the 9 12, and 30 cH potencies (Kruskal-Wallis/Dunn; P=0.001). No changes were observed in the other parameters, such as open field activity and laterality of the itching. In the pathogenetic experiment, no changes were observed in any parameters examined. We conclude that the proposed experimental model demonstrates the therapeutic effect of D. pruriens, but not its pathogenetic effects.