Evaluation of the cumulative properties of the drug Delcid 7,5®

2021 ◽  
Vol 1 (5) ◽  
pp. 39-43
Author(s):  
M. I. Burmistrova ◽  
◽  
S. V. Engashev ◽  
A. A. Deltsov ◽  
E. S. Engasheva ◽  
...  
Keyword(s):  
Repeated Administration ◽  
Single Administration ◽  
Quantitative Indicator ◽  
Multiple Administration ◽  
Pharmacological Substance

Cumulative properties (accumulation of a substance or its effect upon repeated administration in equal doses) is determined on the basis of a quantitative indicator – the cumulation coefficient. Before carrying out chronic toxicological experiments, it is necessary to determine the cumulation index of the pharmacological substance – the ratio of LD50 with a single administration to LD50 with multiple administration. According to the Lim method, the cumulative properties of the drug Delcid 7,5® were studied, the cumulation coefficient of the drug was Kkum = 1,09. In accordance with the classification of chemicals, including pesticides by L.I. For a bear, the drug belongs to a group of substances with pronounced cumulation.

CORRELATION BETWEEN ANTONYMS AND OTHER LEXICAL AND SEMANTIC CATEGORIES

2021 ◽  
pp. 108-118
Author(s):  
D. V. Movchan
Keyword(s):  
General Scheme ◽  
Practical Implementation ◽  
Figurative Meaning ◽  
Quantitative Indicator ◽  
Semantic Categories ◽  
Polynomial Structure ◽  
Common Concept ◽  
Polysemous Words

The article argues that antonymous words are not isolated in the language but are part of the general scheme of thematic classification of the vocabulary, entering into close ties with representatives of synonymous and polysemantic groups. Proof of this position is the availability of antonymous-synonymous blocks and paradigms of meanings of antonymous words-polysemants in the language. This fact serves to understand the antonymy of lexical as a relationship between members of opposing dichotomous series, as well as expands the boundaries of closed binary structures, which are traditionally used to make antonymous connections. Antonymous relations are established to connect two opposites in pairs, as well as to combine several units into one polynomial structure. Words are found to have more antonyms than the corresponding number of meanings. This proves that some semes of one word are opposed by two or more synonymous antonyms. From the above-mentioned, it follows that the antonyms of polysemous words can be stated only within one family. Such a framework can be defined by limiting the range of antonymous units to a third common concept, under which two antonyms are summed up; establishing the antonyms of polysemous words through the contextual indicative minimum; distinguishing between the direct and figurative meaning of the word. The antonymous connections within the framework of the synonymous-antonymous paradigm are established to demonstrate a qualitatively heterogeneous character, differ in the strength of the manifestation of the relations of opposites and the frequency of practical implementation. The analysis of the manifestations of antonyms between the members of the dichotomous synonymous series allows distinguishing the following types: radial, linear, and cross radial. It is proved that the quantitative indicator of the formation of certain antonymous pairs from among the members of synonymous series depends on the volume of the synonymous series being compared, from the nature of semantic differences of the words of each series, from the emotional, evaluative, and stylistic characteristics of the members of the series, and the distribution of the words with relatively opposite meanings.

Effects of Chaihu-Guizhi-Ganji on the Levels of Monoamines and Their Related Substances, and Acetylcholine in Discrete Brain Regions of Mice

1996 ◽  
Vol 24 (01) ◽  
pp. 53-64 ◽  
Author(s):  
Tadanobu ltoh ◽  
Seisuke Michijiri ◽  
Shigeo Murai ◽  
Hiroko Saito ◽  
Hiroshi Saito ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Mouse Brain ◽  
Corpus Striatum ◽  
Repeated Administration ◽  
Brain Regions ◽  
Single Administration ◽  
Nervous Systems ◽  
Related Substances

The effects of the extract powder (CggT) from Chaihu-Guizhi-Gajiang-Tang (Saiko-keishi-kankyo-to, in Japanese) on the monoamines and their related substances and the acetylcholine in mouse brain were examined. 1) A single administration of CggT significantly increased the levels of HVA and 5-HIAA in the cerebral cortex, hypothalamus, corpus striatum and hippocampus at 75 mg/kg, and those in the hypothalamus, corpus striatum and hippocampus at 750 mg/kg. 2) The repeated administration of CggT significantly increased the level of 5-HT in the hippocampus at 75 mg/kg, and the levels of 5-HT in the corpus striatum and of NE and 5-HT in the hippocampus at 750 mg/kg. 3) The level of ACh was significantly increased in the hypothalamus alone after single administration of CggT. These findings suggest that CggT stimulates function of the dopaminergic and serotonergic nervous systems in mice, but not most of the NEnergic and cholinergic nervous systems.

scholarly journals Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration

2018 ◽  
Vol 6 (9) ◽  
pp. 1581-1587
Author(s):  
Sergey A. Zhuchkov ◽  
Alexandr S. Kinzirsky ◽  
Irina V. Koroleva ◽  
Yuriy B. Vicharev
Keyword(s):  
Toxic Effect ◽  
Adrenal Glands ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Repeated Administration ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Pharmacological Substance ◽  
Effect Level

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

scholarly journals N-Methyl-3,4-methylenedioxyamphetamine-induced hepatotoxicity in rats: Oxidative stress after acute and chronic administration

2004 ◽  
Vol 61 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Milica Ninkovic ◽  
Zivorad Malicevic ◽  
Vesna Selakovic ◽  
Ivan Simic ◽  
Ivana Vasiljevic
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Reduced Glutathione ◽  
Chronic Administration ◽  
Repeated Administration ◽  
Dependent Manner ◽  
Single Administration ◽  
Sod Activity ◽  
Orogastric Tube ◽  
Mitochondrial Fractions

Background. The underlying mechanisms of N-Methyl-3,4-methylenedioxyamphetamine-MDMA-induced hepatotoxicity are still unknown. The aim of this study was to evaluate hepatic oxido-reductive status in the rats liver after the single and repeated administration of MDMA. Methods. MDMA was dissolved in distilled water and administered in the doses of 5 mg, 10 mg, 20 mg, and 40 mg/kg. The animals from the acute experiment were treated per os with the single dose of the appropriate solution, through the orogastric tube. The animals from the chronic experiment were treated per os, with the doses of 5, 10, or 20 mg/kg of MDMA every day during 14 days. The control groups were treated with water only. Eight hours after the last dose, the animals were sacrificed, dissected their livers were rapidly removed, frozen and stored at -70?C until the moment of analysis. The parameters of oxidative stress in the crude mitochondrial fractions of the livers were analyzed. Results. Superoxide dismutase (SOD) activity increased in the livers of the animals that were treated with single doses of MDMA. Chronically treated animals showed the increased SOD activity only after the highest dose (20 mg/kg). The content of reduced glutathione decreased in both groups, but the depletion was much more expressed after the single administration. Lipid peroxidation index increased in dose-dependent manner in both groups, being much higher after the single administration. Conclusion. The increased index of lipid peroxidation and the decreased reduced glutathione levels suggested that MDMA application induced the state of oxidative stress in the liver. These changes were much more expressed after the single administration of MDMA.

EVALUATION OF THE GENERAL TOXIC PROPERTIES OF A NEW ANTISEPTIC AND DISINFECTANT FOR VETERINARY USE

2021 ◽  
Vol 1 (4) ◽  
pp. 487-494
Author(s):  
Marina P. Marinicheva ◽  
◽  
Vladimir V. Strogov ◽  
Vasiliy I. Dorozhkin ◽  
◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Repeated Administration ◽  
The Body ◽  
Male Rats ◽  
Intragastric Administration ◽  
Male Mice ◽  
Hazard Class ◽  
Propyl Ketone ◽  
Series Of Experiments

The article presents data on the toxicological properties of the disinfectant, which includes alkyldimethylammonium propyl ketone chloride, glutaraldehyde, glyoxal. Based on the results of a series of experiments, the main parameters of the toxicity of the disinfectant were determined. For male mice, the acute toxicity LD50 was 325±14.5 mg / kg, for male rats – 350±50 mg/kg, according to the classification of GOST 12.1.007-76, the agent belongs to the 3rd hazard class. The LD50 with repeated administration of the drug was 217±13.5 mg/kg of animal weight, the cumulation coefficient was 0.67, which indicates the ability of the drug with repeated intragastric administration to accumulate in the body of animals.

scholarly journals Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

2021 ◽  
Vol 12 ◽  
Author(s):  
Cato M. H. de Vos ◽  
Natasha L. Mason ◽  
Kim P. C. Kuypers
Keyword(s):  
Clinical Studies ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Repeated Administration ◽  
Clinical Effects ◽  
Mrna Levels ◽  
Single Administration ◽  
Bdnf Mrna ◽  
Behavioral Parameters ◽  
Single And Repeated Administration

Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies (n = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.

Regulatory Effect of Danggui-Shaoyao-San on Central Cholinergic Nervous System Dysfunction in Mice

1996 ◽  
Vol 24 (03n04) ◽  
pp. 205-217 ◽  
Author(s):  
Tadanobu Itoh ◽  
Seisuke Michijiri ◽  
Shigeo Murai ◽  
Hiroko Saito ◽  
Keiko Nakamura ◽  
...  
Keyword(s):  
Nervous System ◽  
Therapeutic Agent ◽  
Corpus Striatum ◽  
Senile Dementia ◽  
Repeated Administration ◽  
Single Administration ◽  
Regulatory Effect ◽  
Step Down ◽  
Locomotor Activities ◽  
The Brain

Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki-shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in the brain, the present study examined the effect of TSS on the central cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was suspended in a 5% carboxymethylcellulose solution and mice were orally given single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500 mg/kg. Results on spontaneous locomotor activity showed that (I) single administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited vertical and horizontal locomotor activities, while repeated administration of TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated with scopolamine, repeated administration of TSS at 500 mg/kg significantly inhibited the scopolamine-induced increase in locomotor activities, whereas in mice treated with mecamylamine, single or repeated administration of TSS at 50 and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in locomotor activities. Regarding the step-down passive avoidance responses: single administration, but not repeated administration, of TSS at 50 and 500 mg/kg significantly inhibited scopolamine-induced shortening of step-down latency. In mice treated with mecamylamine, TSS did not exert any influence on the step-down latency. As for ACh contents, single or repeated administration of TSS at 50 or 500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice treated with scopolamine showed a decrease and a single administration of TSS at 500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh levels. These results indicate that TSS ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels in mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests that TSS may be a useful therapeutic agent in Alzheimer's disease and senile dementia.

scholarly journals Hypoglycemic and Hypolipidemic Effects of Ethanolic Extract ofMirabilis jalapaL. Root on Normal and Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ji-Yin Zhou ◽  
Shi-Wen Zhou ◽  
Sheng-Ya Zeng ◽  
Jian-Yun Zhou ◽  
Ming-Jin Jiang ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Serum Insulin ◽  
Ethanolic Extract ◽  
Insulin Level ◽  
Repeated Administration ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Single Administration ◽  
Diabetic Mice

The present study investigated the insulin sensitivity, hypoglycemic, and hypolipidemic activities of ethanolic extract ofMirabilis jalapaL. root (EEM) in normal and diabetic mice. After induction of diabetes with streptozotocin, both normal and diabetic mice were singly or repeatedly for 28 days administrated with EEM at doses of 2, 4, 8 g/kg, respectively. Before induction of diabetes, mice were administrated with EEM at doses of 2, 4, 8 g/kg for 14 days and were injected with streptozotocin and continued on EEM administration for another 28 days. Both after and before induction of diabetes, repeated administration with 4, 8 g/kg EEM continually lowered blood glucose level, decreased serum insulin level and improved insulin sensitivity index, and lowered serum total cholesterol, triglyceride levels and triglyceride content in liver and skeletal muscle, and increased glycogen content in these tissues; but repeated administration had no influence on those indexes of normal mice. Single administration with EEM (4, 8 g/kg) showed hypoglycemic effect in oral glucose tolerance test in normal and diabetic mice. Single administration with EEM had no hypoglycemic and hypolipidemic effects on normal and diabetic mice. These results suggest that EEM possesses both potential insulin sensitivity, hypoglycemic, and hypolipidemic effects on diabetes.

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