PRECLINICAL STUDY OF THE VETERINARY DRUGS TOXICITY

1970 ◽  
pp. 61-64
Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov
Keyword(s):  
Lethal Dose ◽  
Clinical Manifestations ◽  
Preclinical Study ◽  
Veterinary Drugs ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Therapeutic Effects ◽  
Significant Information ◽  
Important Indicator ◽  
Organ Systems

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.

scholarly journals CHEMOTHERAPY OF TRYPANOSOME AND SPIROCHETE INFECTIONS

1919 ◽  
Vol 30 (5) ◽  
pp. 417-436 ◽  
Author(s):  
Wade H. Brown ◽  
Louise Pearce
Keyword(s):  
Animal Species ◽  
Lethal Dose ◽  
Normal Animal ◽  
Repeated Administration ◽  
Toxic Effects ◽  
Laboratory Animals ◽  
Short Intervals ◽  
Arsonic Acid ◽  
Minimum Lethal Dose

The essential facts to be gathered from these studies of the toxicologic action of N-phenylglycineamide-p-arsonic acid may be summarized very briefly. The substance is one which lends itself well to almost any method of administration and can be given to animals in very large doses. The tolerance of different animal species varies rather widely but with one exception the reaction of laboratory animals to toxic doses of the drug is of favorable character. That is, toxic effects are confined to doses relatively close to the minimum lethal dose and the recovery of animals from sublethal intoxications is remarkably rapid and complete. This feature of the action of the drug makes possible the repeated administration of even very large doses at comparatively short intervals of time without incurring the dangers incident to cumulative action or to superposition of toxic effects. On the contrary, by taking advantage of this peculiarity of action, it is possible to develop such a degree of tolerance on the part of animals that the dose of the drug administered can be progressively increased to a point well above that which is fatal to the normal animal, and this stands out as the feature of the toxicologic action of N-phenylglycineamide-p-arsonic acid which is of greatest significance in the use of the drug for therapeutic purposes.

scholarly journals Effect of the Route of Administration of the Vaccinia Virus Strain LIVP to Mice on Its Virulence and Immunogenicity

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 795
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Alexander A. Sergeev ◽  
Alexei S. Kabanov ◽  
Tatiana V. Bauer ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Vaccinia Virus ◽  
Vaccination Campaign ◽  
Lethal Dose ◽  
Clinical Manifestations ◽  
Immune Defense ◽  
Smallpox Vaccination ◽  
Laboratory Animals ◽  
Optimal Method ◽  
Clonal Variant

The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.

scholarly journals Experimental Modeling Of Hypothyroidism: Principles, Methods, Several Advanced Research Directions In Cardiology

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Aleksey M. Chaulin ◽  
Julia V. Grigorieva ◽  
Galina N. Suvorova ◽  
Dmitry V. Duplyakov
Keyword(s):  
Thyroid Hormones ◽  
Clinical Manifestations ◽  
Preclinical Study ◽  
Experimental Models ◽  
Laboratory Animals ◽  
Research Directions ◽  
Advantages And Disadvantages ◽  
Pathological Conditions ◽  
Effective Models ◽  
Goals And Objectives

Hypothyroidism is one of the most common pathological conditions in modern clinical practice. Due to the fact that the targets of thyroid hormones are virtually all organs and tissues, the morphological and clinical manifestations arising with a deficiency of thyroid hormones are quite diverse. Experimental models of hypothyroidism in laboratory animals are widely used for preclinical study of the fundamental pathophysiological mechanisms underlying hypothyroidism, as well as for assessing the effectiveness of treatment-and-prophylactic effects. Currently, several groups of effective models of hypothyroidism have been developed: dietary, surgical, medicamentous, genetic, radioactive and immunological. Each of the specified models is based on different principles, has advantages and disadvantages, and can be used depending on the goals and objectives of the experiment. In this review, we will consistently consider hypothyroidism modeling methods and indicate some promising areas of their use in cardiology.

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

In vitro and in vivo Assessment of Silver Nanoparticles Against Clostridium botulinum Type A Botulinum

2019 ◽  
Vol 16 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Mohammad Aminianfar ◽  
Siavash Parvardeh ◽  
Mohsen Soleimani
Keyword(s):  
Silver Nanoparticles ◽  
Botulinum Toxin ◽  
Clostridium Botulinum ◽  
Lethal Dose ◽  
Type A ◽  
Positive Control ◽  
Negative Control ◽  
Laboratory Animals ◽  
Control Group ◽  
Nano Silver

Background: Clostridium botulinum causes botulism, a serious paralytic illness that results from the ingestion of a botulinum toxin. Because silver nanoparticle products exhibit strong antimicrobial activity, applications for silver nanoparticles in healthcare have expanded. Therefore, the objective of the current study was to assess a therapeutic strategy for the treatment of botulism toxicity using silver nanoparticles. Methods: A preliminary test was conducted using doses that produce illness in laboratory animals to determine the absolute lethal dose (LD100) of botulinum toxin type A (BoNT/A) in mice. Next, the test animals were divided into six groups containing six mice each. Groups I, II and III were the negative control (botulinum toxin only), positive control-1 (nano-silver only) and positive control-2 (no treatment), respectively. The remaining groups were allocated to the toxin that was supplemented with three nano-silver treatments. Results: The mortality rates of mice caused by BoNT/A significantly reduced in the treatment groups with different doses and injection intervals of nano-silver when compared to the negative control group. BoNT/A toxicity induced by intraperitoneal injection of the toxin of Clostridium botulinum causes rapid death while when coupled with nano-osilver results in delayed death in mice. Conclusion: These results, while open to future improvement, represent a preliminary step towards the satisfactory control of BoNT/A with the use of silver nanoparticles for human protection against this bioterrorism threat. Further study in this area can elucidate the underlying mechanism for detoxifying BoNT/A by silver nanoparticles.

Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohamad Reza Nikouei Moghaddam ◽  
Monireh Movahedi ◽  
Maryam Bananej ◽  
Soheil Najafi ◽  
Nahid Beladi Moghadam ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Uric Acid ◽  
Vitamin D3 ◽  
Chronic Inflammatory Disease ◽  
Toxic Effects ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mannuronic Acid ◽  
Anti Inflammatory ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

Lupus myocarditis: a single center experience and a comparative analysis of observational cohort studies

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1296-1302 ◽  
Author(s):  
J Tanwani ◽  
K Tselios ◽  
D D Gladman ◽  
J Su ◽  
M B Urowitz
Keyword(s):  
Comparative Analysis ◽  
Cohort Studies ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Data Retrieval ◽  
Complete Recovery ◽  
University Of Toronto ◽  
Single Center Experience ◽  
Organ Systems ◽  
Lupus Myocarditis

Background Lupus myocarditis (LM) is reported in 3–9% of patients with systemic lupus erythematosus (SLE) but limited evidence exists regarding optimal treatment and prognosis. This study aims to describe LM in a defined lupus cohort as compared with the existing literature. Patients and methods Patients with LM were identified from the University of Toronto Lupus Clinic database. Diagnosis was based on clinical manifestations and electrocardiographic, imaging, and biochemical criteria. Demographic, clinical, diagnostic and therapeutic variables and outcomes were collected in a standardized data retrieval form. A literature review was performed to identify cohort studies reporting on LM treatment and outcome. A comparative analysis was conducted between our patients and the combined cohort of the existing studies. Results Thirty patients were diagnosed with LM (prevalence 1.6%) and compared with a cumulative cohort of 117 patients from five distinct studies. No significant differences were found regarding the age at diagnosis (32.6 ± 13.4 years) and SLE duration (2.5 years median). Concomitant lupus activity from other organ systems was observed in 97% of the patients. Chest pain was more frequently reported in our cohort whereas dyspnea was more prominent in the other studies. Diagnostic criteria were similar across studies. Therapeutic approach was comparable and consisted of glucocorticosteroids (96.6%) and immunosuppressives (70%). Mortality was approximately 20% whereas another 20% of the patients achieved partial and 60% complete recovery. Conclusions LM usually occurs early in the disease course and in the context of generalized lupus activity. Despite aggressive therapy, approximately 40% of the patients died or had residual heart damage.

Features of Bioaccumulation and Toxic Effects of Copper (II) Oxide Nanoparticles Under Repeated Oral Exposure in Rats

2021 ◽  
Vol 09 ◽  
Author(s):  
Mark Sergeevich Stepankov ◽  
Marina Aleksandrovna Zemlyanova ◽  
Nina Vladimirovna Zaitseva ◽  
Anna Mikhailovna Ignatova ◽  
Alena Evgenievna Nikolaeva
Keyword(s):  
Surface Area ◽  
Pore Volume ◽  
Mesangial Cells ◽  
Lethal Dose ◽  
Toxic Effects ◽  
Oral Exposure ◽  
Oxide Nanoparticles ◽  
Brown Pigment ◽  
Cuo Nps ◽  
Hematological Analysis

Background: Currently, the range of copper (II) oxide nanoparticles’ (CuO NPs) applications is expanding and the global production of CuO NPs is increasing. In this regard, the risk of exposure of the population to this nanomaterial increases. Objective: The aim of the study is to investigate the patterns of bioaccumulation and toxic effects of CuO NPs after multiple oral exposures. Methods: The particle size was determined by scanning electron microscopy and dynamic laser light scattering. Specific surface area was measured by the method of Brunauer, Emmett, Teller. Total pore volume - by the method of Barrett, Joyner, Khalenda. Twenty-four hours after the final exposure, blood samples were taken for biochemical and hematological analysis, and internal organs were taken to determine their mass, copper concentration and histological analysis. The study was carried out in comparison with copper (II) oxide microparticles (CuO MPs). Results: In terms of size, surface area, and pore volume, the studied copper (II) oxide sample is a nanomaterial. The median lethal dose of CuO NPs was 13187.5 mg/kg of body weight. Bioaccumulation occurs in the stomach, blood, intestines, liver, lungs, kidneys and brain. Pathomorphological changes in the liver are manifested in the form of necrosis, degeneration, hepatitis; kidney - proliferation of mesangial cells, dystrophy; stomach - gastritis; small intestine - hyperplasia, enteritis; large intestine - colitis; lungs - hyperplasia, abscess, pneumonia, bronchitis, vasculitis. Clumps of brown pigment were detected in the kidneys, stomach and lungs. The mass of the stomach and intestines increased, the mass of the liver, kidneys and lungs decreased. Pathomorphological changes in organs are likely to cause an increase in the levels of activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, amylase, malondialdehyde concentration and a decrease in plasma antioxidant activity. The proportion of segmented neutrophils, the number of leukocytes are raised, the proportion of lymphocytes is reduced. Conclusion: The degree of bioaccumulation and toxicity of CuO NPs are more expressed in relation to CuO MPs.

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 ◽  
...  
Keyword(s):  
Laboratory Animals ◽  
Therapeutic Effects ◽  
Early Sepsis
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