scholarly journals ACUTE CHRONICAL TOXICITY AND INTOLERANCE OF SM - COMPLEX

Author(s):  
A. V. Mifatkhudinov ◽  
A. S. Aleshina

The researchers elaborated pharmacological complex of SM at the Chair of Morphology, Physiology and Pharmacology atSouth-UralStateAgrarianUniversity. The complex contains butafosfan, vitamins, vitamin-like substances, selected on the basis of synergistic effect on the body. The parameters of acute toxicity of the SM-complex were explored in the experiment on clinically healthy adult white mice of both genders by a single injection of the solution in the maximum permissible dose according to GOST 31926-2013. Intolerance on the skin of animals was detected in line with GOST R ISO 10993.10-2009. GOST R ISO 10993.10-99 became a guideline for evaluating SM-complex intolerance on the eye conjunctiva. Chronic toxicity was investigated on non-linear rats; the rates were divided into 4 groups of 6. The first group became a control group, the second group received the SM-complex in a therapeutic dose (255mg/kg), the third group - in a 5 -fold therapeutic dose (1275mg/kg), the fourth group - in a 10-fold dose (2550mg/kg). Pharmacological substance was applied through the probe in the form of an aqueous solution for 30 days. The researchers found out that at single oral introduction of SM-complex in the maximum possible doses it does not affect mice organism and it is referred to the 4th class of danger according to GOST 12.1.007-76. Local application in the form of applications on the skin and mucous membranes of rabbits, the complex does not have a local irritant effect. Long-term application of pharmacological composition (30 days) in high doses causes functional and morphological changes of the liver in the form of gray foci and flabbiness, as well as it increases the volume of the organ. Due to the fact that the therapeutic doses are 5 and 10 times lower than the toxic ones and the period of application does not exceed 7-14 days, the authors make a conclusion that SM-complex is safe and secure and can be used in the recommended doses.

2016 ◽  
Vol 3 (4) ◽  
pp. 547-553
Author(s):  
Демин ◽  
A. Demin ◽  
Арисов ◽  
M. Arisov ◽  
Гламаздин ◽  
...  

Objective of research: To evaluate the tolerability of the drug, “Inspector Collar” based on Fipronil, Pyriproxyfen and Ivermectin in dogs and cats applied at a therapeutic dose and double increased therapeutic doses. Materials and methods: Research was conducted at the shelter for dogs and cats «Bano Eco» (Moscow). Effect of drug “Inspector Collar” was studied on 15 clinically healthy outbreed dogs between 2 and 6 years with the body mass of 10–14 kg and 15 clinically healthy outbreed cats between 2 and 4 years with the body mass of 2–3,5 kg, receiving complete and balanced nutrition. Animals were divided into six groups (three groups of dogs and three of cats) five animals in each group. Dogs and cats from the first experimental group had put on one collar (equivalent of single therapeutic dose) for 45 days. The second experimental group had put two collars (double therapeutic dose) for 45 days. Animals from the third (control) group did not carry collars. During the experiment, daily supervision of animals was conducted; their general health status, behavior, appetite were observed, body mass and temperature estimated. Before and 15 and 30 days after the beginning of drug application, blood and urine tests were performed to study morphological and biochemical parameters. Statistical processing of data were carried out using Student’s t-test. Results and discussion: The research results showed that the drug “Inspector Collar” is well tolerated even at double therapeutic dose. All observed indicators remained within the physiological norm.


Author(s):  
M. S. Bugaeva ◽  
O. I. Bondarev ◽  
N. N. Mikhailova ◽  
L. G. Gorokhova

Introduction. The impact on the body of such factors of the production environment as coal-rock dust and fluorine compounds leads to certain shift s in strict indicators of homeostasis at the system level. Maintaining the relative constancy of the internal environment of the body is provided by the functional consistency of all organs and systems, the leading of which is the liver. Organ repair plays a crucial role in restoring the structure of genetic material and maintaining normal cell viability. When this mechanism is damaged, the compensatory capabilities of the organ are disrupted, homeostasis is disrupted at the cellular and organizational levels, and the development of the main pathological processes is noted.The aim of the study is to compare the morphological mechanisms of maintaining structural homeostasis of the liver in the dynamics of the impact on the body of coal-rock dust and sodium fluoride.Materials and methods. Experimental studies were conducted on adult white male laboratory rats. Features of morphological mechanisms for maintaining structural homeostasis of the liver in the dynamics of exposure to coal-rock dust and sodium fluoride were studied on experimental models of pneumoconiosis and fluoride intoxication. For histological examination in experimental animals, liver sampling was performed after 1, 3, 6, 9, 12 weeks of the experiment.Results. The specificity of morphological changes in the liver depending on the harmful production factor was revealed. It is shown that chronic exposure to coal-rock dust and sodium fluoride is characterized by the development of similar morphological changes in the liver and its vessels from the predominance of the initial compensatory-adaptive to pronounced violations of the stromal and parenchymal components. Long-term inhalation of coal-rock dust at 1–3 weeks of seeding triggers adaptive mechanisms in the liver in the form of increased functional activity of cells, formation of double-core hepatocytes, activation of immunocompetent cells and endotheliocytes, ensuring the preservation of the parenchyma and the general morphostructure of the organ until the 12th week of the experiment. Exposure to sodium fluoride leads to early disruption of liver compensatory mechanisms and the development of dystrophic changes in the parenchyma with the formation of necrosis foci as early as the 6th week of the experiment.Conclusions. The study of mechanisms for compensating the liver structure in conditions of long-term exposure to coal-rock dust and sodium fluoride, as well as processes that indicate their failure, and the timing of their occurrence, is of theoretical and practical importance for developing recommendations for the timely prevention and correction of pathological conditions developing in employees of the aluminum and coal industry.The authors declare no conflict of interests.


1988 ◽  
Vol 18 (2) ◽  
pp. 365-374 ◽  
Author(s):  
Susan Golombok ◽  
Parimala Moodley ◽  
Malcolm Lader

SynopsisIn view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in longterm benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function.


2021 ◽  
Author(s):  
Fei Xie ◽  
Xue Jiang ◽  
Yang Yi ◽  
Zi-Jia Liu ◽  
Chen Ma ◽  
...  

Abstract The potential for preventive and therapeutic applications of H2 have now been confirmed in various disease. However, the effects of H2 on health status have not been fully elucidated. Our previous study reported changes in the body weight and 13 serum biochemical parameters during the six-month hydrogen intervention. To obtain a more comprehensive understanding of the effects of long-term hydrogen consumption, the plasma metabolome and gut microbiota were investigated in this study. Compared with the control group, 14 and 10 differential metabolites (DMs) were identified in hydrogen-rich water (HRW) and hydrogen inhalation (HI) group, respectively. Pathway enrichment analysis showed that HRW intake mainly affected starch and sucrose metabolism, and DMs in HI group were mainly enriched in arginine biosynthesis. 16S rRNA gene sequencing showed that HRW intake induced significant changes in the structure of gut microbiota, while no marked bacterial community differences was observed in HI group. HRW intake mainly induced significant increase in the abundance of Lactobacillus, Ruminococcus, Clostridium XI, and decrease in Bacteroides. HI mainly induced decreased abundances of Blautia and Paraprevotella. The results of this study provide basic data for further research on hydrogen medicine. Determination of the effects of hydrogen intervention on microbiota profiles could also shed light on identification of mechanism underlying the biological effects of molecular hydrogen.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Viswanathan Saraswathi ◽  
Curtis Perriotte-Olson ◽  
Robert D Heineman ◽  
Cyrus V Desouza

Introduction: Dyslipidemia is a prevalent condition in obesity and type 2 diabetes. Although fish oil rich in omega-3 fatty acids (ω-3) is a widely used hypolipidemic agent, it is often required at high doses. At high doses, these fatty acids can induce oxidative stress or endothelial activation and therefore, strategies to improve their beneficial effects are needed. We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in low density lipoprotein receptor knock-out mice. Here, we sought to determine the effects of ω-3 fatty acids in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in subcutaneous adipose tissue (scAT) in humans. Methods: Obese dyslipidemic patients were randomly assigned to receive one of these interventions (n=8/group) for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 (2 g twice daily), 3) NX (220 mg twice daily), and 4) ω-3 (2 g twice daily) + NX (220 mg twice daily). Results: The body mass index, HOMA-IR, and plasma total, LDL, and HDL cholesterol levels were not altered significantly in any of the groups. The percent change in plasma triglycerides (TG) from baseline was 75% ( P <0.1) and 68% ( P <0.05) in ω-3 and ω3 + NX-treated subjects, respectively. Notably, 25% of subjects who received ω-3s alone did not show a reduction in TG whereas all the patients that received ω-3 + NX showed a reduction in TG. Realtime PCR analysis of scAT showed that the expression of glucose transporter 4 (GLUT-4), a marker of glucose uptake and a key regulator of glucose homeostasis was significantly reduced in ω-3 compared to control group ( P <0.01). However, combining NX with ω-3 abolished this effect. Moreover, the expression of MCP-1 and VCAM-1, markers of inflammatory response or endothelial activation, was significantly increased in ω-3 but not in ω-3 + NX group. The plasma levels of MCP-1 and E-selectin did not vary significantly in any of the groups. Conclusions: Our data reveal previously unrecognized effects of fish oil in scAT. Our data suggest that combining NX with ω-3 fatty acids will increase their effectiveness in reducing plasma TG and improve the benefits of ω-3 supplements by favorably altering gene expression in scAT.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yangyang Miao ◽  
Shugeng Chen ◽  
Xinru Zhang ◽  
Jing Jin ◽  
Ren Xu ◽  
...  

Background. Stroke is the leading cause of serious and long-term disability worldwide. Survivors may recover some motor functions after rehabilitation therapy. However, many stroke patients missed the best time period for recovery and entered into the sequela stage of chronic stroke. Method. Studies have shown that motor imagery- (MI-) based brain-computer interface (BCI) has a positive effect on poststroke rehabilitation. This study used both virtual limbs and functional electrical stimulation (FES) as feedback to provide patients with a closed-loop sensorimotor integration for motor rehabilitation. An MI-based BCI system acquired, analyzed, and classified motor attempts from electroencephalogram (EEG) signals. The FES system would be activated if the BCI detected that the user was imagining wrist dorsiflexion on the instructed side of the body. Sixteen stroke patients in the sequela stage were randomly assigned to a BCI group and a control group. All of them participated in rehabilitation training for four weeks and were assessed by the Fugl-Meyer Assessment (FMA) of motor function. Results. The average improvement score of the BCI group was 3.5, which was higher than that of the control group (0.9). The active EEG patterns of the four patients in the BCI group whose FMA scores increased gradually became centralized and shifted to sensorimotor areas and premotor areas throughout the study. Conclusions. Study results showed evidence that patients in the BCI group achieved larger functional improvements than those in the control group and that the BCI-FES system is effective in restoring motor function to upper extremities in stroke patients. This study provides a more autonomous approach than traditional treatments used in stroke rehabilitation.


2010 ◽  
Vol 25 (6) ◽  
pp. 525-528 ◽  
Author(s):  
Flavia de Oliveira ◽  
Luci Rezende Bevilacqua ◽  
Carlos Alberto Anaruma ◽  
Silvia de Campos Boldrini ◽  
Edson Aparecido Liberti

PURPOSE: Thermal injury causes catabolic processes as the body attempts to repair the damaged area. This study evaluated the effects of a scald injury on the morphology of muscle fibers belonging to a muscle distant from the lesion. METHODS: Thirty Wistar rats were divided into control (C) and scalded (S) groups. Group S was scalded over 45% of the body surface, standardized by body weight. Rats in both groups were euthanized at four, seven and 14 days following the injury. The middle portions of the medial gastrocnemius muscles were sectioned, stained with hematoxylin and eosin and Picrosirius, and submitted to histological analysis. RESULTS: Control group sections exhibited equidistantly distributed polygonal muscle fibers with peripheral nuclei, characteristic of normal muscle. The injured group sections did not consistently show these characteristics; many fibers in these sections exhibited a rounded contour, variable stain intensities, and greater interfiber distances. A substantially increased amount of connective tissue was also observed on the injured group sections. CONCLUSION: This experimental model found a morphological change in muscle distant from the site of thermal injury covering 45% of the body surface.


Author(s):  
Nisharani Jadhav ◽  
Ravikumar Baradol ◽  
Manisha Bhosale

Background: The aim of the study was to evaluate the seizure modifying potential of Ondansetron in experimental models of seizures in mice.Methods: Mice were treated with three different doses of ondansetron i.p., at 3mg/kg, 6mg/kg and 8mg/kg and control group received normal saline 0.1 ml i.p. for 3 days. On 3rd day, mice were subjected to MES, of different strength half an hour after ondansetron administration and findings were recorded. The minimum threshold current at which tonic hind limb extension occurred was recorded. Each animal was observed for incidence and duration of tonic hind limb extension and the strength of current was noted. In PTZ model, mice were subjected to subconvulsive dose of PTZ 45mg/kg and convulsive dose of PTZ 60mg/kg. The incidence and onset of convulsion at 45 and 60mg/kg dose of PTZ were recorded.Results: Mice receiving ondansetron 3mg/kg, showed significant decrease in duration of tonic hind limb extension at convulsive current strength of 50mA (p<0.001). While group receiving 6mg/kg, showed decrease in seizure threshold. (40mA current strength) Mice receiving 3mg/kg, showed significant increase in onset of seizures (p<0.001) at convulsive 60mg/kg dose of PTZ. While mice receiving 6mg/kg showed decrease in seizure threshold at sub convulsive 45mg/kg dose of PTZ. Group receiving 8mg/kg ondansetron, showed 100% mortality due to convulsions caused by ondansetron.Conclusions: Ondansetron at low therapeutic dose (3mg/kg) has an anticonvulsant action, while it has a proconvulsant action at a high therapeutic dose (6mg/kg). Ondansetron causes convulsions at toxic dose (8mg/kg). So, care should be taken while giving ondansettron in high doses to prevent chemotherapy induced emesis.


Author(s):  
Said Abdul Ghafour Saeedy ◽  
Ahmad Faisal Faiz ◽  
Marjan Nikbakhtzadeh ◽  
Bagher Minaei Zangi ◽  
Mansoor Keshavarz

Drinking ice-cold water is prohibited in Avicenna’s “The Canon of Medicine” book in which he emphasized that ice-cold water drinking was hazardous for the body organs such as the liver. Little information can be found regarding the effects of ice-cold fluid drinks on liver and its probable sequels on this vital organ. Accordingly, we investigated the effects of long-term ice-cold water drink on the rat liver function and histology. Eighteen male Wistar rats, weighing 180±20 g, were randomly divided into three groups of six as two months ice-cold water drink, CW2M; three months ice-cold water drink, CW3M; and three months room temperature water drink; control group. Upon completion of the care period, a blood sample has been taken for liver enzymes and lipid profile assessment. Liver tissue has also been used for histological studies of H&E staining and microscopic examination. Histological findings showed hepatocellular micro-vesicle formation, necrosis and derangement of the cellular cords and infiltration of Kupffer cells in ice-cold water taken animals. Serum TGs, VLDL-C and ALP significantly increased with sound decrease in FBS and LDL-C in ice-cold water taken animals. It seems that long-term ice-cold water has deleterious functional and structural effects on the liver.


Author(s):  
U. І. Теsarinska ◽  
R. S. Fedoruk ◽  
S. Ya. Маrtynyk ◽  
Т. V. Yurynec ◽  
V. А. Smuk ◽  
...  

The paper considers the effect on rats of long-term feeding of an aqueous solution of citric acid (C6H12O6 x H2O, "chemically pure.") in the amount of 8 mg/l. The study was performed on 10 laboratory female rats F1 of the Wistar line, obtained from F0 females. Two groups were set up: control and experimental, 5 animals in each. Animals were under standard conditions with natural light regime day/night, aqueous solutions of citrate, water, and feed received ad libitum. Were determined the morphological composition and biochemical parameters of the blood of female F1 rats. The results of the study indicate the absence of an unfavorable effect of citric acid on red blood cells. Concerning white blood, there is a decrease in the number of leukocytes, which may be due to the development of an adaptive response of the body to citric acid or the inhibition of citric acid's immune response to long-term adaptive action. There is a significant increase in the relative content of eosinophils in females F1, which probably may be due to the action of citric acid. The analysis of the obtained results of blood biochemical parameters indicates a certain tendency to decrease, in terms of control, the content of serum iron, as well as its total and unsaturated Fe-binding capacity. Ferrum saturation of serum transferrin was present at the level of animals in the control group. Analysis of the study results indicates no changes in control in the activity of enzymes: Alkaline phosphatase ALT and AST, also have no statistically significant confirmation of differences in the control group. The level of urea was statistically not significantly higher in terms of control. Thus, long-term watering of citric acid to female rats in the generation F0 and F1 during their physiological and sexual gestation and pregnancy reveal un-favorable effects in female rats F1. However, there was distinguished the adaptive immune-biological response of the animals organism. The immunological response was supported by a decrease in the number of leukocytes and a significant increase in the relative content of eosinophils. The results of biochemical studies of serum indicate the absence of statistically significant differences in animals of the control group.


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