Using the developed model of unpredictable mild chronic stress in rats, the time to the development of an anxious condition without severe depressive disorders were determined. A combination of stressors to achieve this condition is proposed: individual housing, food and water deprivation, forced swimming in cold (4°C) water, keeping on wet bedding and without bedding, under bright lighting, and at 45°C, light/dark cycle alterations, and 45° cage tilting. The condition of the animals was analyzed by changes in body weight, fructose consumption, coat state, as well as by the parameters of open field and forced swimming tests and nest building. These methods can be used in the study and search for new drugs for the treatment and prevention of anxiety- and depression-like conditions.

Poloxamer 188 is a polymer that is used as a carrier and stabilizer of pharmacological agents. It has been demonstrated to enhance red blood cell and hemoglobin levels in healthy animals and in select clinical cases. The objective of this study was to assess the efficacy of Poloxamer 188 in CBA mice when administered repeatedly in the carboplatin-induced myelosuppression model. The mice were administered carboplatin once at a dose of 100 mg/kg, and then Poloxamer 188 was orally administered daily at doses of 10 mg/kg, 100 mg/kg, 500 mg/kg, and 1000 mg/kg for 7 and 21 days. Poloxamer 188 at a dose of 1000 mg/kg was found to bring the level of 2,3-bisphosphoglycerate in red blood cells close to control level (p = 0.1331 for the control group compared to Poloxamer at a dose 1000 mg/kg) already from day 8 of the study and in bone marrow resulted in regulation of genes responsible for hematopoiesis. G-GSF at day 8 and TNFα at day 22 gene expression was significantly decreased by 54% (p = 0.012) and 16% (p = 0.024), respectively, with Poloxamer 188 administration at a dose of 100 mg/kg. Additionally, in the bone marrow, the treatment was seen to exert a positive regulatory effect on the genes responsible for hematopoiesis. These findings are consistent with the observed increase in red blood cell by 6.7% (p = 0.001), hemoglobin by 4.7% (p = 0.0053), and reticulocyte percentage by 53.6% (p < 0.0001) following Poloxamer 188 administration at a dose of 1000 mg/kg in CBA mice with myelosuppression.

Poloxamer 188 (P188) was tested for effect on medullary hematopoiesis in aplastic anemia. P188 was administered to CBA mice with developing anemia via oral gavage at doses of 10, 100, and 500 mg/kg. A dose-dependent effect was observed, including an increase in erythrocyte count, hemoglobin, and reticulocyte count. The parameters remained low and suggested mild anemia on day 21 in a group treated with carboplatin. P188 was assumed to exert a beneficial effect on the blood cell composition, which is distorted by cytostatic drugs.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

Type 2 diabetes mellitus develops due to a combination of genetic and environmental factors. C57BL/6 mice prone to obesity and leptin resistance were kept on a high-fat diet for 21 weeks. The animals showed a significant increase in fasting and postprandial glucose levels and body weight, the development of insulin resistance, and by week 18, an increase in the serum TNFα level. Metformin therapy at a dose of 250 mg/kg was effective against the background of disturbances in carbohydrate metabolism: animals showed a significant decrease in insulin resistance and TNFα level.

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

A common method of modeling urolithiasis is the use of 1 and 0.75% ethylene glycol, or a combination of ethylene glycol with other lithogens, but too rapid progression of the disease and multiple organ toxicity have been reported. We developed a urolithiasis model in Sprague-Dawley rats, in which the animals received a relatively low concentration of ethylene glycol (0.5%), but for a long-term period (6 weeks) followed by animal observation during the 6-week recovery period. In urine samples, signs of the urolithiasis development were observed starting from the sixth week: the presence of ketones, decrease in diuresis and urine pH; in the blood, urea, protein, and hematocrit were elevated. However, no leukocytes were detected in the urine; in the blood, no shifts in differential leukocyte count and no elevation in ALT, creatinine, cholesterol, and triglycerides were observed, which indicates the absence of multiple organ failure while using 1% ethylene glycol. In addition, the animals receiving 0.5% ethylene glycol were followed up to 12 weeks in contrast to animals receiving 1% ethylene glycol (the experiment in this case was stopped during the third week for ethical reasons).

The aim of the study was to investigate the effect of AMP-activated protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) on the consequences of metabolic syndrome and type 2 diabetes induced by the consumption of a high-fat diet (HFD) in male C57Bl/6 mice. Additionally, the animals from group 6 were administered Methotrexate (MTX) at a dose of 1 mg/kg in parallel with AICAR, which slows down the metabolism of AICAR. The animals were recorded with signs of metabolic syndrome and type 2 diabetes mellitus by recording their body weights, glucose and insulin levels, and the calculating HOMA-IRs. At the end of the study, at the end of the 13th week, during necropsy, the internal organs were assessed, the masses of the organs were recorded, and special attention was paid to visceral fat, assessing its amount and the mass of the fat surrounding epididymis. The biochemical parameters and histology of the internal organs and tissues were assessed. The animals showed signs of metabolic syndrome and type 2 diabetes, namely, weight gain, hyperglycemia, hyperinsulinemia, an increase in the amount and mass of abdominal fat, and metabolic disorders, all expressed in a pathological change in biochemical parameters and pathological changes in internal organs. The AICAR treatment led to a decrease in body weight, a decrease in the amount and mass of abdominal fat, and an improvement in the pathomorphological picture of internal organs. However, some hepatotoxic effects were observed when the animals, on a received standard diet (STD), were treated with AICAR starting from the first day of the study. The additional administration of MTX, an AICAR metabolic inhibitor, did not improve its efficacy. Thus, AICAR has therapeutic potential for the treatment of metabolic syndrome and type 2 diabetes.

CO2 inhalation is currently the most common method of euthanasia for laboratory rats and mice, and it is often used for further terminal blood sampling for clinical biochemical assays. Lately, this method has been criticized due to animal welfare issues associated with some processes that develop after CO2 inhalation. The stress reaction and the value of the clinical laboratory parameters significantly depend on the used anesthetics, method, and the site of blood sampling. Especially in small rodents, an acute terminal state followed by a cascade of metabolic reactions that can affect the studied biochemical profile may develop and cause unnecessary suffering of animals. The aim of this study was to compare the stability of biochemical parameters of outbred Sprague Dawley rats and CD-1 mice serum collected after CO2 inhalation or the intramuscular injection of tiletamine–zolazepam–xylazine (TZX). The serum content of total protein and albumin, cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotr ansferase (ALT), alkaline phosphatase (ALP), total bilirubin, and creatinine was decreased by the injection of TZX in comparison with CO2 inhalation. In addition, the levels of calcium, phosphates, chlorides and potassium were lowered by TZX vs. CO2 administration, while the level of sodium increased. Finally, the level of the majority of serum clinical biochemical parameters in rats and mice tend to be overestimated after CO2 inhalation, which may lead to masking the possible effect of anti-inflammatory drugs in animal tests. Injection anesthesia for small rodents with TZX is a more feasible method for terminal blood sampling, which also reduces the suffering of animals.

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

The paper provides characteristics of diagnostic methods, treatment and preventive measures for staphylococcal infection in dogs. Staphylococcal infection in dogs is an infectious disease caused primarily by staphylococcus virulent strains, characterized by various clinical forms, and it affects the dogs having defects in their immune system. Staphylococci produce a great number of pathogenicity factors (including toxins able to act independently). Therefore, it is rather difficult to apply tools of specific protection and prophylaxis. Skin and mucosa inflammation is the most common pathological condition observed in dogs. Clinical signs include: chronic septic condition with internal abscesses, different skin lesions accompanied by conjunctivitis, otitis, vulvitis, posthitis, rhinitis, sinusitis, cystitis, phlegmon, abscesses, pyometra, wound abscess, polyarthritis, gingivitis. In addition to the pathological agent, the following extra factors are needed for the disease clinical manifestation: immune deficiency, metabolic disorder, parasitic disease, manipulations resulting in damage to the skin and mucosa integrity. The fact that domestic animals can be a source of infection for people can be another reason behind an increasing interest in staphylococcal infection. A comprehensive approach is required to diagnose this disease. In addition to clinical examination, the following tests are needed biochemical blood test, bacteriological tests of biomaterials from animals, isolation of pure agent cultures and determination of sensitivity to antibacterial preparations in every particular case. Bacteriological tests are mandatory to make the final diagnosis. Treatment of dogs also requires a comprehensive approach including specific immunotherapy (active, with the use of anatoxins and antigens and passive with antistaphylococcal hyperimmune sera). Timely prevention and new approaches to treatment are crucial elements.

Preclinical studies on systemic toxicity and allergenic properties of amide form of HLDF-6 peptide in order to study the safety of its use as a drug with nootropic activity when administered intranasally were conducted. Studies were performed on male and female SD (Sprague Dawley) rats and CD-1 mice. Test results have demonstrated a lack of toxic effects of the study drug at the doses used in this rote of administration.

The paper provides characteristics of diagnostic methods, treatment and preventive measures for staphylococcal infection in dogs. Staphylococcal infection in dogs is an infectious disease caused primarily by staphylococcus virulent strains, characterized by various clinical forms, and it affects the dogs having defects in their immune system. Staphylococci produce a great number of pathogenicity factors (including toxins able to act independently). Therefore, it is rather difficult to apply tools of specific protection and prophylaxis. Skin and mucosa inflammation is the most common pathological condition observed in dogs. Clinical signs include: chronic septic condition with internal abscesses, different skin lesions accompanied by conjunctivitis, otitis, vulvitis, posthitis, rhinitis, sinusitis, cystitis, phlegmon, abscesses, pyometra, wound abscess, polyarthritis, gingivitis. In addition to the pathological agent, the following extra factors are needed for the disease clinical manifestation: immune deficiency, metabolic disorder, parasitic disease, manipulations resulting in damage to the skin and mucosa integrity. The fact that domestic animals can be a source of infection for people can be another reason behind an increasing interest in staphylococcal infection. A comprehensive approach is required to diagnose this disease. In addition to clinical examination, the following tests are needed biochemical blood test, bacteriological tests of biomaterials from animals, isolation of pure agent cultures and determination of sensitivity to antibacterial preparations in every particular case. Bacteriological tests are mandatory to make the final diagnosis. Treatment of dogs also requires a comprehensive approach including specific immunotherapy (active, with the use of anatoxins and antigens and passive with antistaphylococcal hyperimmune sera). Timely prevention and new approaches to treatment are crucial elements.

Introduction: It is important that the method of anesthesia of mice does not considerably alter the animal's physiological and metabolic status before terminal blood sampling taken in order to analyze clinical pathology parameters.Methods: Hematology, hemostasis, and clinical chemistry parameters were compared in male and female BALB/c mice exposed to either tiletamine-zolazepam-xylazine (TZX) anesthesia or euthanasia in carbon dioxide (CO2) chamber to reveal an alternative method of anesthesia vs. the recommended CO2 inhalation. Blood samples were taken from the inferior vena cava.Results: Clinical blood parameters in mice exposed to CO2 inhalation or TZX anesthesia proved to be substantially different. The TZX group had lower activated partial thromboplastin time (APTT) and fibrinogen (statistically in males and tending in females) and lower platelets (PLT), red blood cells (RBC), hemoglobin (HGB), and white blood cells (WBC) in both sexes. TZX anesthesia resulted in lower blood serum concentrations of total protein, albumin and globulins, creatinine in males (higher in females); cholesterol, triglycerides, alanine aminotransferase (ALT) and alkaline phosphatase (AP) in both sexes, and bilirubin in males. The calcium level decreased in TZX-anesthetized males and females while the phosphates decreased only in females. The volume of serum obtained from females of TZX group was approximately two times higher than in the CO2-anesthetized group, with the degree of hemolysis tending to decrease.Discussion: The studied method of mouse anesthesia, followed by terminal blood sampling and analysis of clinical pathology parameters, suggests that TZX is a good alternative to CO2 inhalation in toxicological and other non-clinical studies. The differences in hemostasis, hematology, and clinical chemistry parameters between these groups are supposedly associated with alterations in physiological and metabolic status of mice under conditions of increasing hypoxia, respiratory standstill, and circulatory arrest after CO2 inhalation. (C) 2016 Elsevier Inc. All rights reserved.

The historical blood test data of control CD (Sprague-Dawley) rats having SPF category (pathogenic flora free) are presented. The data have been received by using hematological analyzers. The comparison of the results of rat' 3-part white blood cells differential leukogram with the data of microscopic studying revealed the difference in the quantitative formula of leukocyte subpopulations.