scholarly journals Comparison of the therapeutic effects of tri-iodothyronine and methylprednisolone during early sepsis in laboratory animals

2012 ◽  
Vol 113 (06) ◽  
pp. 339-346
Author(s):  
F. Coskun ◽  
B. Saylam ◽  
B. Kulah ◽  
I. Dolapci ◽  
A. Sungur ◽  
...  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Seçkin ÖZKANLAR ◽  
Fatih AKÇAY ◽  
Zekai HALICI ◽  
Muhammet Hamidullah UYANIK

Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.


2019 ◽  
Vol 9 (1) ◽  
pp. 244-247 ◽  
Author(s):  
Sucheta Gautam ◽  
Neetu Sachan ◽  
Alankar Shrivastav ◽  
Dilipkumar Pal

Abstract Objective: Abies webbiana and Berberis aristata is an herbal plant that has several therapeutic effects. It also heals depression, grief, nervous stress and tension. In the present study we evaluated anti-depressant effect of ethanolic extract from Abies webbiana and Berberis aristata by using Forced Swimming Test (FST) and Tail Suspension Test (TST). Methods: Two doses of ethanolic extract of Abies webbiana and berberis aristata (200 mg/kg and 400 mg/kg) was given orally. Immobility time were measured after 30 min after the dosing and compared with control group and Flouxetine (25mg/kg) as a standard group. Results: The ethanolic extract of BA and AW (400 mg/kg) was found to be effective and it exhibited activity similar to that of the conventional drug Flouxetine (25mg/kg) (p<0.001) whereas 200 mg/kg dose showed higher activity with significantly increased swimming time and suspension time and decreased immobility time than 400 mg/kg of ethanolic extracts and Flouxetine (25mg/kg). Conclusion: These results proposed 400 mg/kg of ethanolic extract was showed higher anti-depressant activity as compared to control which is similar to the standard.


2020 ◽  
Vol 18 (9) ◽  
pp. 705-712 ◽  
Author(s):  
Eric Murillo-Rodríguez ◽  
Diana Millán-Aldaco ◽  
Marcela Palomero-Rivero ◽  
Daniela Morales-Lara ◽  
Raphael Mechoulam ◽  
...  

Background: Excessive daytime sleepiness and cataplexy are among the symptoms of narcolepsy, a sleep disorder caused by the loss of hypocretin/orexin (HCRT/OX) neurons placed into the Hypothalamus (LH). Several treatments for managing narcolepsy include diverse drugs to induce alertness, such as antidepressants, amphetamine, or modafinil, etc. Recent evidence has shown that cannabidiol (CBD), a non-psychotropic derived from Cannabis sativa, shows positive therapeutic effects in neurodegenerative disorders, including Parkinson´s disease. Furthermore, CBD provokes alertness and enhances wake-related neurochemicals in laboratory animals. Thus, it is plausible to hypothesize that excessive somnolence observed in narcolepsy might be blocked by CBD. Objective: Here, we determined whether the systemic injection of CBD (5mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model. Methods: To test this idea, the neurotoxin hypocretin-2-saporin (HCRT2/SAP) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior. Since excessive somnolence in HCRT2/SAP lesioned rats has been observed during the lights-off period, CBD was administered at the beginning of the dark phase. Results: Hourly analysis of sleep data showed that CBD blocked the sleepiness during the lights-off period across 7h post-injection in lesioned rats. Conclusion: Taking together, these preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.


1995 ◽  
Vol 10 (S1) ◽  
pp. 39s-46s ◽  
Author(s):  
AY Deutch

SummaryThe mechanisms of action which account for the effectiveness of clozapine as a pharmacotherapy for the treatment of neuroleptic non-responders and neuroleptic intolerant schizophrenic subjects remain elusive. We review recent data concerning the actions of clozapine in laboratory animals, and discuss the likely sites of action of clozapine and the receptors through which clozapine acts. We suggest that actions at dopamine D2 receptors in the caudate nucleus and putamen underlie the extrapyramidal side effects of conventional neuroleptics. In contrast, we propose that clozapine acts in the prefrontal cortex, specifically targeting an as yet unidentified DA receptor of the D2 family, to exert therapeutic actions in neuroleptic non-responders. We suggest that the ability of clozapine to augment extracellular dopamine levels in the prefrontal cortex may represent a key mechanism contributing to the therapeutic effects of this drug, and suggest some alternative approaches which might be expected to result in effects similar to those of clozapine.


2020 ◽  
Vol 8 (1) ◽  
pp. 14-24
Author(s):  
M. I. Kogan ◽  
S. S. Todorov ◽  
I. V. Popov ◽  
I. V. Popov ◽  
M. A. Kulishova ◽  
...  

Introduction. Erectile dysfunction is a multifactorial condition that is the inability to achieve or maintain an erection sufficient for sexual intercourse. The classic method for studying the fundamental aspects of erectile reactions in normal and pathological conditions, as well as creating new methods of treatment, is experimental animal models used in preclinical studies. However, for more than 30 years of studying this problem in experimental researches, the specific moment of occurrence of morphological alterations in the cavernous bodies of the penis has not been established. In addition, the choice of the time frame of the developed therapeutic effects on the penis is not substantiated and differs for various authors, which indicates the lack of validity of their results.Purpose of the study. To determine the features of morphological alterations and the severity of fibrogenic pathological process in the cavernous bodies of the penis in the time dynamics of experimental modeling of hypotestosteronemia.Materials and methods. Laboratory animals is 20 white male rabbits, «New Zealand» breed, Oryctolagus cuniculus genus. Penile cavernous fibrosis in rabbits was induced by hypotestosteinemia due to bilateral orchiectomy. The level of total testosterone in the systemic blood flow in laboratory animals was determined on 1, 2, 3, 14, 21, and 28 days. Biopsies of penile tissues were evaluated by pathomorphological examination (Hematoxylin-eosin, Masson’s trichrome, Weigert’s staining, and light microscopy). Statistical processing of the obtained data was performed using Microsoft Excel and «Statistica 10.0» programs using the Student`s T-criteria.Results. Castration of rabbits leads to a 10-fold decrease in blood testosterone levels after 1 day after castration. Testosterone deficiency occurs by day 28. Morphological signs of the restructuring of smooth muscle cells, sinuses and connective tissue structures in the cavernous bodies of the penis are clearly defined by the day 7 after castration. Severe fibrotic changes in the cavernous tissues of the penis were noted at day 28.Conclusion. Thus, the obtained data demonstrate the dynamics of morphological alterations in penile tissues as early as 7 days after inducing hypotestosteronemia, which indicates the need to revise the time frame of therapeutic effects in studies using the castration animal model of erectile dysfunction.


2021 ◽  
Vol 12 (5) ◽  
pp. 93-100
Author(s):  
K. V. Zhdanov ◽  
A. V. Saulevich ◽  
K. V. Kozlov ◽  
S. M. Zakharenko ◽  
V. S. Sukachev ◽  
...  

Aim. To evaluate the antifibrotic effect of bicyclol with promising clinical effects on diffuse parenchymal liver diseases.Materials and methods: We have included 40 adult male Wistar rats (weight, 180 to 200g) with experimentally inducted toxic F3 stage liver fibrosis. Control group consisted of 16 rats that received standart chow, experimental group of 24 rats also received 30-day bicyclol supply. To evaluate the results we used histological, biochemical, molecular genetic and statistical methods.Results. In experimental group interlobular fibrosis was maintained in 4,16% (p<0,001) of cases after the end of the therapy, stromal fibrosis of portal tracts was observed in 62,5% (p<0,001) of cases. Periportal fibrosis detection rate in experimental group was 66,7% (p<0,001). Rats from experimental group showed regression of liver fibrosis to F1- F2 stage in 16,6% (METAVIR) whereas control group had F3 stage liver fibrosis in 62,5% (p <0,05). Statistically significant increase in ALT activity and decreased total protein levels in control group were observed. No changes in gut microbiome profile in experimental animals were found.Conclusion. Use of bicyclol led to pronounced suppression of liver fibrotic changes in laboratory animals and temporary decreased serum ALT level. Our study showed no link between therapeutic effects of the drug and gut microbiome status.


2021 ◽  
Vol 28 (4) ◽  
pp. 78-87
Author(s):  
Aleksey M. Chaulin ◽  
Yulia V. Grigorieva ◽  
Galina N. Suvorova ◽  
Dmitry V. Duplyakov

Atherosclerosis is the main cause of cardiovascular diseases, which, despite a number of new advances in their diagnosis and treatment, still occupy a leading position. Experimental modeling of atherosclerosis in laboratory animals plays an important role in the study of the fundamental pathophysiological processes and pathology of atherosclerosis. Rabbits are among the most suitable animals for simulating atherosclerosis, as they are widely available, inexpensive to maintain, and easy to manipulate. The key advantage of rabbits over other animals is that their lipid metabolism is practically similar to that of humans. The aim of the study was to analyze literature data on experimental models of atherosclerosis in rabbits. The review shows that the history of the study of atherosclerosis by means of experimental models is very rich and originates from the works of the well-known Russian pathologists A.I. Ignatovsky, N.N. Anichkov, S.S. Khalatov (1908-1915), who developed a cholesterol model of the formation of atherosclerosis in rabbits. The principle of this model is to feed laboratory animals with food containing elevated levels of lipids and cholesterol. The composition of the cholesterol (atherogenic) diet may vary, determining the existence of modifications of this model. Most often, a diet with a cholesterol content of 0.3-0.5% is used, in cases where it is necessary to accelerate the development of atherosclerosis, a short-term use of a diet with a 1% cholesterol content is allowed. In addition to cholesterol, it is recommended to use vegetable oils (soybean, coconut or corn) in the atherogenic diet as they improve the absorption of cholesterol in the intestine. In 1980, Japanese researcher Y. Watanabe deduced a new model of atherosclerosis formation - on hereditarily determined hyperlipidemic rabbits Watanabe (WHHL-rabbits). WHHL rabbits contain a genetic mutation in the gene encoding low-density lipoprotein receptors, which results in these animals having high plasma cholesterol levels with a normal diet. Thanks to modern genetic technologies, various genetic models of atherosclerosis in rabbits have also been created: transgenic and “knocked out” rabbits. The main method for obtaining transgenic rabbits is pronuclear microinjection, which allows the introduction of a transgene (additional DNA fragment) into their genome. To date, using this technology, it has been possible to introduce more than a dozen genes responsible for lipid metabolism. The principle of creating knocked out rabbits consists in specific inactivation using genome editing technologies (ZFN, TALEN, CRISPR / Cas9) of a certain working gene. Experimental models of atherosclerosis in rabbits have not lost their significance and continue to be used to study the fundamental morphological (pathological) and pathological mechanisms underlying atherosclerosis, to search for new diagnostic biomarkers and potential targets for therapeutic effects, as well as to conduct preclinical trials of newly developed drugs.


2004 ◽  
Vol 74 (1) ◽  
pp. 74-85 ◽  
Author(s):  
Liu ◽  
Russell ◽  
Smith ◽  
Bronson ◽  
Milbury ◽  
...  

Because reactive oxygen species have been implicated as mediators of inflammatory bowel disease (IBD), we evaluated the potential preventive and therapeutic effects of two dietary antioxidants, glutathione (GSH) and coenzyme Q10 (CoQ10) on dextran sulfate sodium (DSS)-induced colitis in mice. Fifty female 8-wk old Swiss-Webster mice were randomly assigned to 4 groups for a pre-treatment 'prevention' study: (1) GSH (1% of diet); (2) CoQ10 (200 mg/kg/d); (3) DSS only (3% of drinking water); (4) control (no treatment). The mice in groups 1 and 2 were fed with GSH or CoQ10 for 21 wks, and the mice in groups 1, 2 and 3 were provided DSS from wk 7 for 4 cycles (1 cycle = 1 wk DSS followed by 2-wk water). Another 50 mice were randomly assigned to 4 groups for a 21-wk 'treatment' study where the mice in groups 1, 2, and 3 were administered DSS for 6 cycles (18 wks) to induce colitis. GSH and CoQ10 were added from wk 7 until the completion of the protocol. Loose stools and hemocult positivity were modestly but significantly reduced with GSH or CoQ10 at several periods during the intervention in both the prevention and treatment studies. In contrast, histological evaluation revealed increases in colonic dysplasia and ulceration with GSH or CoQ10. Thus, in this mouse model, GSH and CoQ10 appear to have a beneficial effect on acute signs of IBD, but may have an adverse impact on the chronic pathophysiology of the disease. Further studies using additional animal models are required to determine whether GSH or CoQ10 provide a favorable or unfavorable benefit:risk ratio in the prevention or treatment of IBD.


Sign in / Sign up

Export Citation Format

Share Document