Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice

The present study was undertaken to compare medicinal plants against mixed anxiety-depressive disorder (MAD) to evaluate their potency in combating MAD disorders. Previous studies from our lab have shown that Bacopa monniera (BM), and Panax quniquefolium (PQ) have significant adaptogenic properties. Hence, we have further confirmed their activity in stress related disorders like anxiety and depression in animal model, rodents and assessed their efficacy. In our experimental protocol, gross behaviour was observed through Digiscan animal activity monitor. Anxiety was studied through light dark test, elevated plus maze test and holeboard test. Depression experiments were conducted following tail suspension test and forced swim test. Further, rotarod test was also used to study any defects in motor in-coordination in mice. It was observed that BM at the dose of 80 mg/kg (po) and PQ at 100 mg/kg (po) were effective as an anti-anxiety as well anti-depressant activity and had no motor in-coordination in mice. Hence, these extracts can be used as a potent therapeutic agent in treating mixed anxiety-depressive disorder (MAD).     

Neuropeptides in spinal cord injury: Comparative experimental models

The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that β-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its “anti-endorphin” actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-μ receptors. Dynorphin, an endogenous opioid with a high affinity for the κ receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at κ receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury.     

Estimation of possible use of interferon inductors for prevention of postvaccional reactions to TEOVac in animal models

The experiments on guinea pigs showed that arbidol administered orally in a single dose 24 hours prior vaccination with TEOVAC and ridostin administered in a single dose intranasally on the 4th day after the vaccination lowered the vaccine virus accumulation in the animal organs and tissue without any effect on the vaccine immunogeneity. The results are someway indicative of the possible use of the interferon inductors for prevention of postvaccinal reactions to TEOVAC.     

Comparative systemic analysis of experimental models of chemical hepatic carcinogenesis in the rat

The aim of this work is to compare several experimental protocols inducing hepatocarcinogenesis in the rat. The results show that the experimental protocols using an initiator and a promotor are not equivalent (in term of latency period and premalignant lesions) to experimental protocols using a chronic administration of one carcinogenic compound.     

Optimization of purine-nitrile TbcatB inhibitors for use in vivo and evaluation of efficacy in murine models

There are currently only four clinical drugs available for treating human African trypanosomiasis (HAT), three of which were developed over 60 years ago. Despite years of effort, there has been relatively little progress towards identifying orally available chemotypes active against the parasite in vivo. Here, we report the lead optimization of a purine-nitrile scaffold that inhibits the essential TbcatB protease and its evaluation in murine models. A lead inhibitor that had potent activity against the trypanosomal protease TbcatB in vitro and cultured parasites ex vivo was optimized by rationally driven medicinal chemistry to an inhibitor that is orally available, penetrates the CNS, has a promising pharmacokinetic profile, and is non-toxic at 200mg/kg in a repeat dosage study. Efficacy models using oral administration of this lead inhibitor showed a significantly increased survival time in Trypanosoma brucei brucei infected mice but little effect on Trypanosoma brucei rhodesiense infected mice.     

Study of possible influence of mixed lymphocyte reaction on experimental models used in biological dosimetry]

The study aimed to investigate whether "mixed lymphocyte reactions" could interfere with the results of experiments in which irradiated blood from one person is mixed with non-irradiated blood from another. This experimental model had been designed to simulate, in vitro, non-homogeneous in vivo exposure such as could occur after accidents with ionizing radiation. The results show that the experimental models gives valid results for donors with related blood characteristics.     

Molecular alterations of canalicular transport systems in experimental models of cholestasis: possible functional correlations.

The discovery of unidirectional, ATP-dependent canalicular transport systems (also termed "export pumps") for bile salts, amphiphilic anionic conjugates, lipophilic cations, and phospholipids has opened new opportunities for understanding biliary physiology and the pathophysiology of cholestasis. In addition, ATP-independent canalicular transport systems for glutathione and bicarbonate contribute to (bile acid-independent) bile formation. Canalicular excretion of bile salts and several non-bile acid organic anions is impaired in various experimental models of cholestasis. Recent cloning of several canalicular transport systems now facilitates studies on their molecular regulation in cholestasis. Although the picture is far from complete, experimental evidence now exists that decreased or even absent expression of canalicular transport proteins may explain impaired transport function resulting in hyperbilirubinemia and cholestasis. With the increasing availability of molecular probes for these transport systems in humans, new information on the molecular regulation of canalicular transport proteins in human cholestatic liver diseases is beginning to emerge and should bring new insights into their pathophysiology and treatment. This article gives an overview on molecular alterations of canalicular transport systems in experimental models of cholestasis and discusses the potential implications of these changes for the pathophysiology of cholestasis.     

Development and validation of experimental protocols for use of cardinal models for prediction of microorganism growth in food products

An experimental protocol to validate secondary-model application to foods was suggested. Escherichia coli, Listeria monocytogenes, Bacillus cereus, Clostridium perfringens, and Salmonella were observed in various food categories, such as meat, dairy, egg, or seafood products. The secondary model validated in this study was based on the gamma concept, in which the environmental factors temperature, pH, and water activity (aw) were introduced as individual terms with microbe-dependent parameters, and the effect of foodstuffs on the growth rates of these species was described with a food- and microbe-dependent parameter. This food-oriented approach was carried out by challenge testing, generally at 15 and 10 degrees C for L. monocytogenes, E. coli, B. cereus, and Salmonella and at 25 and 20 degrees C for C. perfringens. About 222 kinetics in foods were generated. The results were compared to simulations generated by existing software, such as PMP. The bias factor was also calculated. The methodology to obtain a food-dependent parameter (fitting step) and therefore to compare results given by models with new independent data (validation step) is discussed in regard to its food safety application. The proposed methods were used within the French national program of predictive microbiology, Sym'Previus, to include challenge test results in the database and to obtain predictive models designed for microbial growth in food products.     

The possible role of enantiodiscrimination in bilirubin toxicity

The possibility that enantiodiscrimination of bilirubin might be involved in neuronal membrane destabilization, and therefore in bilirubin toxicity, was investigated, by circular dichroism, on model membranes composed of phospholipids. The equilibrium between bilirubin enantiomers is displaced at some extent by the interaction with certain phospholipids. The extent of equilibrium displacement depends on the molecular structure of phospholipids and on the state of charge of bilirubin. The results obtained validate the hypothesis of a possible involvement of chirality in bilirubin toxicity and support a previously suggested model for the molecular mechanism of the interaction of bilirubin with the synaptic membrane.     

Histopathological investigation of experimental ocular toxocariasis in gerbils

Male gerbils were inoculated intragastrically with embryonated Toxocara canis eggs. They were euthanised, and their eyes were excised at different days p.i. to identify the number of larvae as well as lesions resulting in these organs. In most animals, larvae were detected from day 5 to day 60 p.i. (end of the study). From days 10 to 20 p.i., larvae and haemorrhage were observed in the choroid and in the ciliary process. At days 30 and 40 p.i., some eyes had larvae surrounded by an infiltrate of neutrophils, oedema, haemorrhages and tissue damage in the retina or the ciliary process. On day 60 p.i., there were granulomatous lesions in the retina. This study provides a model for the study of ocular toxocariasis.     

Comparative evaluation of the toxicity of aqueous extracts of the ashes of brown coals

The toxicity of industrial waste--the ashes of brown coals in connection with the possibility of their utilization in agriculture has been studied. It has been proved that ash water extracts which give low pH values are practically nontoxic for test objects. Ash extracts rich in calcium and magnesium oxides provide high pH values and has a negative effect on hydrobionts. The neutralization removes the acute toxic effect.     

Investigation of bacterial growth on mixed substrates: experimental evaluation of cybernetic models

Cybernetic models, developed earlier by the authors, have been evaluated experimentally for the growth of Klebsiella oxytoca in batch cultures using mixed substrates from glucose, xylose, arabinose, lactose, and fructose. Based entirely on information procured from batch growth on single substrates, the models accurately predict without further parameter fitting, diauxic growth on mixed substrates, automatically predicting the order in which the substrates are consumed. Even triauxic growth on a mixture of glucose, xylose, and lactose is predicted by the model based on single substrate data. Growth on glucose-fructose mixtures appears to need a slightly modified strategy for cybernetic variables.     

Sensitivity of Pseudomonas mallei to fluoroquinolones and their efficacy in experimental glanders]

Thirteen strains of P. mallei were found to be highly sensitive to ciprofloxacin and ofloxacin and resistant to norfloxacin. Ciprofloxacin and ofloxacin showed a high efficacy on models of malleus in guinea pigs and hamsters. The animals were infected with various strains of P. mallei. In the in vitro experiments, ciprofloxacin proved to be the most active and efficient. Norfloxacin appeared to be inefficient.     

Liver and kidney toxicity in chronic use of opioids: An experimental long term treatment model

In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180–220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups (P<0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage Presented at the 10th XX Annual ESRA Congress, 6–9 April 2002, Warsaw, Poland.