Increased Alanine Aminotransferase Activity Research Articles

Influence of chronic immobilization stress on vitamin status in rats fed different diets

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.

PROGNOSTIC SIGNS OF HEPATOPATHY FORMATION IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

Introduction. The incidence of diabetes mellitus in the world among children is steadily increasing. The main striking factor in type 1 diabetes mellitus (T1DM) is hyperglycemia, which affects the formation of liver complications such as glycogenic hepatopathy and non-alcoholic fatty liver disease (NAFLD).&#x0D; The aim of the study is to determine the prognostic signs of hepatopathy formation in adolescents with type 1 diabetes mellitus.&#x0D; Materials and methods. Clinical-anamnestic and laboratory-instrumental examination: glycosylated hemoglobin (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and its fractions, lipidogram. According to the results of ultrasound of the hepatobiliary system, girls and boys with T1DM were divided into groups taking into account the size of the liver. The study included 87 girls and 86 boys aged 8-18 years. Methods of mathematical statistics, system-information analysis, Wald’s heterogeneous sequential statistical procedure with Kulbak’s information measure were used.&#x0D; Results. A comprehensive examination of adolescents with T1DM revealed that 70% of patients had digestive system disorders in the form of pain and dyspeptic syndromes. In 88% of boys and 68% of girls, palpation and ultrasound revealed liver enlargement (χ2 &lt; 0,05). Atherogenic orientation of lipidogram was determined in all adolescents with T1DM. In girls, the difference in β-lipoprotein level and atherogenicity coefficient reached statistical significance compared with boys. In most adolescents, the content of high-density lipoprotein cholesterol was within normal limits, but the frequency of its decrease in boys with liver enlargement was greater compared with girls with liver enlargement (32% and 24%, respectively, χ2 &lt; 0,05). ALT activity significantly exceeded the upper limit of normal only in the group of girls with liver enlargement. Increased ALT activity in girls with enlarged liver appeared 1.5 times more often than in boys of the similar group (respectively 68% and 43%, χ2 &lt; 0,05).&#x0D; Conclusions. In boys with T1DM, significant informative prognostic factors for the formation of hepatopathy are the duration of the disease, increased levels of HbA1c, atherogenic lipoprotein fractions, and ALT activity. In girls with T1DM, the most significant prognostic factor was an increase in ALT activity; the overall informativeness of lipid profile parameters in girls was three times lower compared with boys. The duration of the disease and the degree of compensation were less significant for the formation of hepatopathy in girls.

Tryptophan Prevents the Development of Non-Alcoholic Fatty Liver Disease.

The main aim of this research is to study the protective effects of tryptophan on the histomorphological and biochemical abnormalities in the liver caused by a high-calorie diet (HCD), as well as its ability to normalize mitochondrial functions in order to prevent the development of non-alcoholic fatty liver disease (NAFLD). The study was conducted in male Wistar rats aged 3 months at the start of the experiment. Control animals (group I) were fed a standard diet. Group II experimental animals were fed a diet with an excess of fat (45%) and carbohydrates (31%) for 12 weeks. Group III experimental animals also received L-tryptophan at a dose of 80 mg/kg body weight in addition to the HCD. The presence of NAFLD, functional activity, physiological regeneration, and the state of the liver parenchyma and connective tissue were assessed using physiological, morphological, histo-morphometric, biochemical, and biophysical research methods. HCD induced the development of NAFLD, which is characterized by an increase in liver weight, hypertrophy of hepatocytes and an increase in the concentration of lipids, cholesterol and triglycerides in liver tissue. Increased alanine aminotransferase activity in the liver of obese rats also confirm hepatocytes damage. Tryptophan added to the diet lowered the severity of NAFLD by reducing fat accumulation and violations of bioelectric properties, and prevented a decrease in mitochondrial ATP synthesis. The addition of tryptophan can have a potential positive effect on the liver, reducing the severity of structural, biochemical, mitochondrial and bioelectric damage caused by HCD.

Gender peculiarities of hepatopathy manifestation in adolescents with type 1 diabetes

The incidence of diabetes mellitus is steadily increasing worldwide, including in the pediatric population. Type 1 diabetes is a disease that is often accompanied by liver damage in the form of glycogenosis, steatosis, and fibrosis. However, there is paucity of research devoted to this problem.&#x0D; Objective — to determine the gender characteristics of the clinical course of hepatopathy in adolescents with type 1 diabetes.&#x0D; Materials and methods. The study included 86 boys and 87 girls aged 8 to 18 years (school-age children in the period of hormonal puberty adjustment), suffering from type 1 diabetes. Clinical and anamnestic, laboratory and instrumental examinations were carried out in accordance with the current standards. Blood biochemistry examinations included determining the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and its fractions, total cholesterol, triglycerides, high density lipoprotein, β­lipoproteins. According to the results of ultrasound examinations, adolescents with type 1 diabetes were divided into groups based on the liver size.&#x0D; Results and discussion. The groups did not differ significantly by the nature of dyspeptic complaints. During ultrasound examinations, an increase in the liver size was determined more often in boys; the frequency of steatosis signs did not depend on gender. Absence of positive dynamics of these signs was established in 50 % of patients, regardless of the state of glycemic control. Regardless of gender, functional disorders of the biliary tract were found in almost all of them. The indicators of the lipid panel in girls were slightly higher than in boys, and the difference in β­lipoproteins level was significant. In most adolescents, levels of high density lipoprotein were within the normal ranges, but the frequency of its decrease in boys with enlarged liver was higher compared to girls. ALT activity significantly increased only in girls with enlarged liver, and in boys it only tended to increase; the frequency of increased ALT activity in girls with enlarged liver was 1.5 times higher compared to boys. The AST/ALT ratio in every fifth patient, regardless of gender and liver size, was ≥ 1.3 (a marker of fibrosis formation).&#x0D; Conclusions. The performed investigation revealed the gender peculiarities of clinical, ultrasound and biochemical manifestations of hepatopathy in adolescents with type 1 diabetes, which can be the basis for the administration of patient oriented therapeutic, preventive and rehabilitation measures.

Effect of different concentration of Single and Multi -Walled Carbon Nanotubes in liver texture and hepatic enzymes in the New Zealand white rabbit

The aim of the present study was to investigate the effect of variable doses of single and multiwalled carbon nanotubes (SWCNTs and MWCNTs) instilled intratracheally on texture of liver and hepatic enzymes ,alanine amino transferase (ALT) and aspartate amino transferase (AST) in New Zealand white rabbits. In this study was used 70 males New Zealand white rabbits, their ages range between (12-18 months) divided into seven groups, ten for each group which instilled with Nanoparticles, At days 7 and 90 post exposure, The blood and tissue samples were collected for each group.&#x0D; Instillation of SWCNTs ( 1 or 5 mg/ml/kg (b.w) or MWCNTs (1,3or 5 mg/ml/kg b.w) in the trachea of rabbits induced a significant increase in activity of ALT and AST.&#x0D; Translocation of carbon nanotubes was seen from the lungs to the liver. It was concluded that: SWCNTs and MWCNTs induced hepatic injuries through its effect in activity of hepatic enzyme and the nanotubes translocated from the lung to the liver and pleura.&#x0D; &#x0D;

Biochemical parameters of blood in cats with cardiogenic arterial thromboembolism and acute heart failure

Investigating the impact of vascular blockage on blood biochemical parameters, particularly in the context of acute heart failure, is crucial for understanding the underlying mechanisms of arterial thromboembolism in animals. The purpose of the study is to investigate the effect of vascular occlusion on the biochemical parameters of blood in cats with cardiogenic arterial thromboembolism. The study involved 12 cats and formed two groups: the first – animals with acute heart failure and the second – animals with arterial thromboembolism. Anamnesis data were collected for experimental animals, clinical examination, echocardiography, and biochemical examination of blood samples were performed. The activity of alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase, the concentration of glucose, creatinine, urea, potassium, calcium, total and inorganic phosphorus were determined spectrophotometrically in blood serum. It was found that in cats with acute heart failure, the average value of serum aspartate aminotransferase activity increased by 2.8 times, and the creatinine concentration by 1.9 times compared to the upper limit of reference values. This indicates functional changes in the myocardium and kidneys in this pathology. In cats affected by arterial thromboembolism, the blood serum shows a significant elevation in various biochemical parameters compared to the upper limit of the corresponding reference intervals. Specifically, there is a 4.4-fold increase in alanine aminotransferase activity, a 4.3-fold increase in aspartate aminotransferase activity, a 1.4- fold increase in glucose concentration, a 1.8-fold increase in creatinine levels, a 2.0-fold increase in urea levels, and a 1.3-fold increase in inorganic phosphorus levels. The changes in biochemical parameters for feline thromboembolism may be a consequence of functional renal failure, ischemia, and muscle necrosis. Moreover, it was established that in most cats with acute heart failure, the urinary system is primarily affected, and with arterial thromboembolism, changes in muscle tissue also occur. The results obtained are of practical value for veterinary doctors when choosing a therapeutic strategy and prescribing additional diagnostic examinations

Safety and pharmacokinetics of thalidomide in tumor-bearing dogs.

Thalidomide, an angiogenesis inhibitor, has recently been used to treat malignant canine tumors. This study retrospectively investigated the adverse events (AEs) of thalidomide administered to tumor-bearing dogs. We investigated the pharmacokinetics of thalidomide after administration and the rate of body weight change before and after administration. The initial thalidomide dose was 5 mg/kg per os once daily, which was increased to 10 mg/kg once daily in dogs with no significant AEs. Pharmacokinetics were measured in four dogs after the 5 mg/kg or 10 mg/kg dose. We evaluated AEs related to clinical signs in 51 patients; 9/51 had lethargy, 6/51 had tremor, 4/51 had dizziness, 31/51 had decreased appetite, 8/51 had vomiting, and 16/49 had soft stool/diarrhea. We evaluated hematologic toxicity in 44 patients with grade 3 or higher adverse events; 1/44 had thrombocytopenia, 1/44 had increased blood urea nitrogen concentrations, and 5/44 had increased alanine aminotransferase activities. The mean thalidomide blood levels were Cmax=1.4 ± 0.7 μg/mL (Area under the curve [AUC]0-24=8.5 ± 4.7 μg•hr /mL) and Cmax=3.2 ± 2.1 μg/mL (AUC0-24=22.0 ± 14.7 μg•hr/mL) in the 5 mg/kg and 10 mg/kg groups, respectively. The Cmax and AUC in the 10 mg/kg group were comparable to the effective blood concentrations seen in humans administered thalidomide. The weight fluctuation rates were assessed in 24 dogs approximately 1 month after the start of thalidomide administration; more than half showed weight maintenance or gain. Most AEs were clinically acceptable; however, peripheral nerve signs were seen in some dogs.

Leptospira spp. Prevalence in Cats from Southern Italy with Evaluation of Risk Factors for Exposure and Clinical Findings in Infected Cats.

Leptospirosis is a worldwide zoonotic disease, but feline leptospirosis is rarely reported. This study aimed at investigating Leptospira spp. prevalence in cats from southern Italy, evaluating risk factors, clinical findings and laboratory data associated with infection. The serum of 112 cats was investigated by microscopic agglutination test (MAT), detecting anti-Leptospira antibodies against 14 pathogenic serovars. Blood and urine samples were tested by a real-time polymerase chain reaction targeting the lipL32 gene of pathogenic Leptospira. Antibodies against serovars Poi, Bratislava, Arborea, Ballum, Pomona and Lora were detected in 15.3% (17/111) of cats (titers range: 20–320). Leptospira spp. DNA was found in 3% (4/109) of blood and 9% (10/111) of urine samples. The spring season was the only risk factor for urinary Leptospira DNA shedding. Laboratory abnormalities significantly associated and/or correlated with Leptospira spp. positivity were anemia, monocytosis, neutrophilia, eosinopenia, increased alanine aminotransferase activity, hypoalbuminemia and hyperglobulinemia. In the investigated areas, cats are frequently infected by Leptospira spp. and can represent an additional reservoir or sentinel for a risk of infection. Moreover, some laboratory changes could be compatible with a pathogenic effect of Leptospira spp. in the feline host.

Investigation of a relationship between serum concentrations of microRNA-122 and alanine aminotransferase activity in hospitalised cats.

ObjectivesCurrent blood tests to diagnose feline liver diseases are suboptimal. Serum concentrations of microRNA (miR)-122 have been shown in humans, dogs and rodents to be a sensitive and specific biomarker for liver injury. To explore the potential diagnostic utility of measuring serum concentrations of miR-122 in cats, miR-122 was measured in a cohort of ill, hospitalised cats with known serum alanine aminotransferase (ALT) activity.MethodsIn this retrospective study, cats were grouped into those with an ALT activity within the reference interval (0–83 U/l; n = 38) and those with an abnormal ALT activity (>84 U/l; n = 25). Serum concentrations of miR-122 were measured by real-time quantitative PCR and the relationship between miR-122 and ALT was examined.ResultsmiR-122 was significantly higher in the group with high ALT activity than the ALT group, within normal reference limits (P <0.0004). There was also a moderately positive correlation between serum ALT activity and miR-122 concentrations (P <0.001; r = 0.52).Conclusions and relevanceConcentrations of miR-122 were reliably quantified in feline serum and were higher in a cohort of cats with increased ALT activity than in cats with normal ALT activity. This work highlights the potential diagnostic utility of miR-122 as a biomarker of liver damage in cats and encourages further investigation to determine the sensitivity and specificity of miR-122 as a biomarker of hepatocellular injury in this species.

Subchronic Toxicity of Ivermectin and Butaphosphan in Layer Chickens

The development of new veterinary drugs to treat and prevent poultry parasitic infections, as well as the study of their safety is a hot topic for modern parasitology. The purpose of this research was to study the subchronic toxicity of the ivermectin and butaphosphan-based drugs at a therapeutic and threefold therapeutic dose during a seven-day oral administration to the Hisex White chickens. The provisional name of the drug is Iverbutan. The chickens from the first experimental group were given the drug at a threefold therapeutic dose of 3 mL of the drug per one liter of drinking water. The chickens from the second experimental group were given the drug at a therapeutic dose of 1 mL of Iverbutan per one liter of drinking water. The chickens from the control group received water without the drug. The chickens were weighed, and then the body temperature and blood samples from the axillary vein were measured on days 1, 8, and 17 of the experiment before the morning feeding. On day 8 of the study, the chickens from the first experimental group showed a 7.4% decrease in body weight and increase in body temperature by 0.8%, an increase in alanine aminotransferase activity by 2.1 times, aspartate aminotransferase activity by 1.6 times, and bile acids by 1.4 times. Moreover, there was a 4.6% decrease in glucose concentration, a 3.5% increase in lactate dehydrogenase activity, a 7.3% decrease in triglycerides, as well as a decrease in hemoglobin by 3.2% and erythrocytes by 10.6% in the first experimental group, compared to the control group. On day 17 of the experiment, the above blood parameters in the chickens from the first experimental group did not significantly differ from the control group, indicating the reversibility of the hepatotoxic effect. In this regard, a three-fold therapeutic dose can be considered a threshold. The chickens from the second experimental group showed no changes in their physiological status as compared to the control. Thus, the study results confirm the safety of the drug in the recommended dosage regimen.

Spontaneous abdominal effusion in dogs with presumed anaphylaxis.

To describe patient characteristics of dogs developing spontaneous abdominal effusion in association with anaphylaxis. Retrospective study between 2010 and 2018. University teaching hospital and referral specialty private practice emergency departments. Sixteen dogs presenting to the emergency department for clinical signs suggestive of anaphylaxis with peritoneal effusion documented via ultrasonography. None. Dogs presented with clinical signs of anaphylaxis including vomiting 12 of 16 (75%), diarrhea 9 of 16 (56%), and collapse 7 of 16 (44%). Physical examination findings included altered mentation 14 of 16 (88%), erythema 2 of 16 (13%), and urticaria 2 of 16 (13%). Historically, 3 of 16 (19%) had just recently been vaccinated, 1 of 16 (6%) had known contact with an insect, and 8 of 16 (50%) had been outdoors prior to the onset of clinical signs, whereas 5 of 16 (31%) had no known triggering event. At presentation, median systolic arterial pressure was 70mm Hg (range, 30-210mm Hg). Venous blood gas revealed an acidemia with a mean pH of 7.24 ± 0.09, a base deficit of 7.15 ± 7.7mmol/L, and an increased plasma lactate with a mean of 7.35 ± 2.09mmol/L. Bloodwork abnormalities included an increased alanine aminotransferase activity with a mean of 439.2 ± 404.5U/L and an increased gamma-glutamyl transferase activity with a mean concentration of 7.29 ± 4.1U/L. Twelve patients (75%) had gallbladder wall abnormalities on ultrasonography. Eight patients (50%) had abdominocentesis performed. The median PCV of the effusion was 0.29 L/L (29%; range, 4-41) and total plasma protein was 38g/L (3.8g/dL; range, 2.4-6.5). Two dogs (12.5%) were euthanized. The remaining 14 dogs (87.5%) survived to discharge, with a mean hospitalization time of 23.7 ± 16.7hours. Abdominal effusion should be considered a potential sequela of anaphylaxis in dogs. Therefore, serial monitoring for presence or development of spontaneous abdominal effusion should be considered.

Mitigation Effects of Bentonite and Yeast Cell Wall Binders on AFB1, DON, and OTA Induced Changes in Laying Hen Performance, Egg Quality, and Health.

The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying hens were randomly allocated into four experimental groups with 10 replicates of nine birds each. The four groups received either a basal diet (BD; Control), a BD supplemented with 0.15 mg/kg AFB1 + 1.5 mg/kg DON + 0.12 mg/kg OTA (Toxins), a BD + Toxins with Toxo-HP binder (Toxins + HP), or a BD + Toxins with TOXO XL binder (Toxins + XL) for 12 weeks. Compared to the control, dietary supplementation of mycotoxins decreased (P < 0.10) total feed intake, total egg weight, and egg-laying rate, but increased feed/egg ratio by 2.5–6.1% and mortality during various experimental periods. These alterations induced by mycotoxins were alleviated by supplementation with both TOXO HP and XL binders (P < 0.10). Furthermore, dietary mycotoxins reduced (P < 0.05) eggshell strength by 12.3% and caused an accumulation of 249 μg/kg of DON in eggs at week 12, while dietary supplementation with TOXO HP or XL mitigated DON-induced changes on eggshell strength and prevented accumulation of DON in eggs (P < 0.05). Moreover, dietary mycotoxins increased relative liver weight, but decreased spleen and proventriculus relative weights by 11.6–22.4% (P < 0.05). Mycotoxin exposure also increased alanine aminotransferase activity and reduced immunoglobulin (Ig) A, IgM, and IgG concentrations in serum by 9.2–26.1% (P < 0.05). Additionally, mycotoxin exposure induced histopathological damage and reduced villus height, villus height/crypt depth, and crypt depth in duodenum, jejunum and (or) ileum (P < 0.05). Notably, most of these histological changes were mitigated by supplementation with both TOXO HP and XL (P < 0.05). In conclusion, the present study demonstrated that the mycotoxin binders TOXO HP and XL can help to mitigate the combined effects of AFB1, DON, and OTA on laying hen performance, egg quality, and health.

A retrospective evaluation of eastern coral snake envenomation and antivenom administration in cats: 30 cases (2012–2019)

Thirty cats were identified to be have been suspected to have a potential coral snake envenomation after searching medical records from 2012 to 2019 at a university teaching hospital. The records were reviewed and evaluated for signalment, date and time of the snake encounter, elapsed time between encounter and hospital examination, presenting complaint, initial physical examination findings, initial laboratory findings, antivenom dose and duration of administration, adverse reactions to antivenom, additional treatments administered, progression of clinical signs, length of hospitalization, and outcome. Thirteen cats presented with clinical signs consistent with envenomation while 17 cats were treated for possible asymptomatic envenomation, as defined by the owner discovering a live or dead coral snake in their home or on their property. Initial physical examination findings included tachypnea with short shallow breaths and use of accessory muscles; tetraparesis with normal or decreased to absent spinal reflexes; cranial nerve deficits including decreased to absent gag, slow pupillary light reflexes, and absent physiologic nystagmus; and normal or altered mentation. Laboratory findings included hypercapnia, hyperglycemia, hypokalemia, increased aspartate aminotransferase activity, increased alanine aminotransferase activity, echinocytosis, leukocytosis, azotemia, and hyperlactatemia. Twenty-eight cats received antivenom; two cats received two vials while twenty-six cats received one vial. Antivenom reaction was suspected in one cat that developed facial swelling during administration of the drug. Average length of hospitalization was 1 day for cats without clinical signs and 3 days for cats with clinical signs. Twenty-nine cats survived to discharge. Due to the inclusion criteria of the study, cats euthanized on presentation or discharged without receiving antivenom may have been unintentionally excluded from the study.Diagnosis of eastern coral snake envenomation should be suspected in the cat that has acute onset of lower motor neuron neuropathy. Prognosis with treatment is considered good with 97% of cats surviving to discharge. Antivenom reaction occurred in 3.5% of administrations with none being fatal. Monitoring of hypercapnia was critical in making the decision to mechanically ventilate patients. Supportive care that includes antivenom administration, recumbency care, and mechanical ventilation if needed are the mainstays of therapy.

Resveratrol Improves Hepatic Redox Status and Lipid Balance of Neonates with Intrauterine Growth Retardation in a Piglet Model.

Abnormal lipid metabolism, oxidative stress (OS), and inflammation play a pivotal role in the increased susceptibility to neonatal fatty liver diseases associated with intrauterine growth retardation (IUGR). This study was firstly conducted to investigate whether resveratrol could alleviate IUGR-induced hepatic lipid accumulation, alteration of redox and immune status in a sucking piglet model and explore the possible mechanisms at transcriptional levels. A total of 36 pairs of 7 d old male normal birth weight (NBW) and IUGR piglets were orally fed with either 80 mg resveratrol/kg body weight/d or 0.5% carboxymethylcellulose sodium for a period of 14 days, respectively. Compared with the NBW piglets, the IUGR piglets displayed compromised growth performance and liver weight, reduced plasma free fatty acid (FFA) level, increased hepatic OS, abnormal hepatic lipid accumulation and weakened hepatic immune function, and hepatic aberrant transcriptional expression of some genes such as heme oxygenase 1, superoxide dismutase 1, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, liver fatty acid-binding proteins 1, toll-like receptor 4, and tumor necrosis factor alpha (TNF-α). Oral administration of resveratrol to piglets decreased the levels of FFA and total triglycerides (TG) in the plasma and hepatic TNF-α concentration, and increased glutathione reductase activity and reduced glutathione level in the liver. Resveratrol restored the increased alanine aminotransferase activity in the plasma of IUGR piglets. Treatment with resveratrol ameliorated the increased hepatic malondialdehyde, protein carbonyl, TG, and FFA concentrations induced by IUGR. Resveratrol treatment alleviated the reduced lipoprotein lipase activity and its mRNA expression as well as TNF-α gene expression in the liver of IUGR piglets. Hepatic glutathione peroxidase 1 and monocyte chemotactic protein 1 genes expression of piglets was upregulated by oral resveratrol administration. In conclusion, resveratrol administration plays a beneficial role in hepatic redox status and lipid balance of the IUGR piglets.

Hepatotoxic Effects of Hexafluoropropylene Oxide Trimer Acid (HFPO-TA), A Novel Perfluorooctanoic Acid (PFOA) Alternative, on Mice.

As an alternative to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been increasingly used for fluoropolymer manufacture in recent years. Its growing detection in environmental matrices and wildlife raises considerable concern about its potential health risks. Here we investigated the effects of HFPO-TA on mouse liver following 28 days of exposure to 0.02, 0.1, or 0.5 mg/kg/d of HFPO-TA via oral gavage. Results showed that HFPO-TA concentrations increased to 1.14, 4.48, and 30.8 μg/mL in serum and 12.0, 32.2, and 100 μg/g in liver, respectively. Liver injury, including hepatomegaly, necrosis, and increase in alanine aminotransferase activity, was observed. Furthermore, total cholesterol and triglycerides decreased in the liver in a dose-dependent manner. Liver transcriptome analysis revealed that 281, 1001, and 2491 genes were differentially expressed (fold change ≥2 and FDR < 0.05) in the three treated groups, respectively, compared with the control group. KEGG enrichment analysis highlighted the PPAR and chemical carcinogenesis pathways in all three treatment groups. Protein levels of genes involved in carcinogenesis, such as AFP, p21, Sirt1 C-MYC, and PCNA, were significantly increased. Compared with previously published toxicological data of PFOA, HFPO-TA showed higher bioaccumulation potential and more serious hepatotoxicity. Taken together, HFPO-TA does not appear to be a safer alternative to PFOA.

Anticancer redox activity of gallium nanoparticles accompanied with low dose of gamma radiation in female mice.

Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC50 of 8.0 μg. Gallium nanoparticles (0.1 mg/kg body weight) were injected intraperitoneally daily on the seventh day of Ehrlich carcinoma cells inoculation. Whole-body γ-radiation was carried out at a single dose of 0.25 Gy on eighth day after tumor inoculation. Biochemical analysis showed that solid Ehrlich carcinoma induced a significant increase in alanine aminotransferase activity and creatinine level in serum, calcium, and iron concentrations in liver tissue compared to normal control. Treatment of Ehrlich carcinoma-bearing mice with gallium nanoparticles and/or low dose of γ-radiation exposure significantly reduced tumor volume, decreased alanine aminotransferase and creatinine levels in serum, increased lipid peroxidation, and decreased glutathione content as well as calcium and iron concentrations in liver and tumor tissues with intense DNA fragmentation accompanied compared to untreated tumor cells. Moreover, mitochondria in the treated groups displayed a significant increase in Na+/K+-ATPase, complexes II and III with significant reduction in CYP450 gene expression, which may indicate a synergistic effect of gallium nanoparticles and/or low dose of γ-radiation combination against Ehrlich carcinoma injury, and this results were well appreciated with the histopathological findings in the tumor tissue. We conclude that combined treatment of gallium nanoparticles and low dose of gamma-radiation resulted in suppressive induction of cytotoxic effects on cancer cells.

Analysis of blood serum biochemical parameters during the treatment with sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate

Topicality. The search of new biologically active compounds among 1,2,4-triazole furan substituted is subject of publications. Each researcher reasonably proves the usage prospects of this particular class of synthetic derivatives as potential pharmacologically active substances. Thus, today we can confidently assert the facts of very successful combination of presented heterocyclic systems to create an individual promising scientific field of synthetic research. Aim . To present and to analyze the serum biochemical parameters of experimental rats on the background of introduction the sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate, to make certain conclusions for future pharmacological implementations of the compound. Materials and methods . The material of the study was 1 % aqueous solution of sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate. Laboratory animals - white rats weighing 130-150 g were used for the study. Results and discussion . The use of sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate 1 % aqueous solution leads to increase of alanine aminotransferase activity and partly to reduce of aspartate aminotransferase activity. Regarding to gamma glutamyl transpeptidase its level naturally decreases. There is a tendency to reduce the lactate dehydrogenase activity. Compared with the control group the use of sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate 1% aqueous solution leads to increase of glucose level. It should be also noted the trend towards reduction of cholesterol level, significant decrease of triacylglyceride and concentration of uric acid. As for the second group of animals it is marked the tendency to increase the seromucoid level in blood serum. These parameters of blood serum as alkaline phosphatase, urea, α-amylase, bilirubin, inorganic phosphorus and calcium had no significant fluctuations after application of the solutions in the two test groups. Conclusions . Analysis of biochemical studies may show a high probability of the use of sodium 2-(4-amino-5-(furan-2-yl)-1,2,4-triazole-3-ylthio)acetate 1 % aqueous solution in the future as a potential antioxidant and immune-modulating agent.

Changes of ammonia, urea contents and transaminase activity in the body during aerial exposure and ammonia loading in Chinese loach Paramisgurnus dabryanus.

The Paramisgurnus dabryanus was exposed to 30mmolL-1 NH4Cl solution and air to assessing the change of body ammonia and urea contents and the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST). After 48h of ammonia exposure, ammonia concentration in the plasma, brain, liver and muscle were 3.3-fold, 5.6-fold, 3.5-fold and 4.2-fold, respectively, those of the control values. Plasma, brain, liver and muscle ammonia concentrations increased to 2.2-fold, 3.3-fold, 2.5-fold and 2.9-fold, respectively, those of control values in response to 48h of aerial exposure. Within the given treatment (ammonia or aerial exposure), there was no change in plasma, brain and liver urea concentrations between exposure durations. The plasma ALT activity was significantly affected by exposure time during aerial exposure, while the liver ALT activity was not affected by ammonia or aerial exposure. Exposure to NH4Cl or air had no effect on either plasma or liver AST activity. Our results suggested that P. dabryanus could accumulate quite high level of internal ammonia because of the high ammonia tolerance in its cells and tissues, and NH3 volatilization would be a possible ammonia detoxification strategy in P. dabryanus. Urea synthesis was not an effective mechanism to deal with environmental or internal ammonia problem. The significant increase of ALT activity in plasma during aerial exposure, indicating that alanine synthesis through certain amino acid catabolism may be subsistent in P. dabryanus.

Evaluation of tissue metal and trace element content in a rat model of non-alcoholic fatty liver disease using ICP-DRC-MS

The primary objective of the study was to assess the level of metals and trace elements in liver, serum, and hair of rats with diet-induced non-alcoholic fatty liver disease (NAFLD) using inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS). 56 female 3-months-old Wistar rats divided into two equal groups were fed either standard (10% calories from fat) or high-fat high-carbohydrate diet (60% calories from fat in chow and 10% sucrose solution) for 6 weeks. Serum was examined for insulin resistance markers, lipid profile, and alanine aminotransferase (ALT) activity. Liver histology was assessed after hematoxylin and eosin staining. Metal and trace element concentrations were assessed by means of ICP-DRC-MS. Overfed animals were characterized by higher values of morphometric parameters. Liver examination revealed large and small droplet steatosis, hepatocyte ballooning and necrosis, being characteristic for NAFLD. Animals with NAFLD were characterized by insulin resistance, atherogenic changes of lipid profile and increased ALT activity. Significantly decreased hepatic Co, Cu, I, Li, Mn, Se, Zn levels were observed in rats with NAFLD. At the same time, only hepatic Mn and Se levels remained decreased after adjustment for total protein. Overfed animals were characterized by significantly lower I, Li, and Mn levels in blood serum, whereas concentration of Co, Se, V, and Sr exceeded the control values. In general, the results of the study demonstrate that NAFLD significantly affects metal and trace element status in experimental animals.

Investigation of activity of jnk kinases new potential inhibitors

JNK kinase - group stress-activated kinases that are involved in apoptosis, growth, development and differentiation of cells. JNK kinase activation is observed in the development of inflammatory processes, neurodegenerative disorders, insulin resistance, some types of cancer. Therefore, the search for new inhibitors of kinases JNK is an important and urgent problem. The purpose of this study was to investigate the activity of the new compounds, potential inhibitors of JNK kinases. Experiments were performed on isolated rat hepatocytes. It was determined the content of JNK and its active phosphorylated form (p-JNK), the activity of glycogen synthetase (GS) and alanine aminotransferase (ALT). It was found that substances G0003, G0004, G0006 and G0007 inhibited the activity of JNK, reducing the content of p-JNK, decreased GS activity and increased ALT activity. We have found that substances G0006 and G0007 showed the highest activity.