The metabolic response to norepinephrine in carbon tetrachloride poisoned sheep

The intraruminal administration of carbon tetrachloride to healthy sheep caused a sharp rise in the serum OCT levels. The plasma concentration of non-esterified fatty acids (NEFA) increased, while blood glucose remained unaffected. The glucose response to the intravenous injection of norepinephrine was greatly reduced after carbon tetrachloride administration, indicating a depletion of the liver glycogen. The NEFA response was not altered. As the increase in NEFA caused by carbon tetrachloride was only moderate, a block in lipoproteinsynthesis is discussed as the main factor in the development of the fatty liver.     

The Effect of Cyclic Adenosine 3', 5' Monophosphate,Methyl Xanthines and Nicotinic Acid on Plasma Nonesterified Fatty Acids in Sheep

The intravenous injection of 3'', 5'' AMP, 10 mg/kg, caused an immediate rise in blood glucose in normal sheep. In sheep where liver glycogen was depleted by pretreatment with 100 mg/kg of nicotinic acid, the blood glucose response was greatly reduced. The glycogenolytic effect of 3'', 5'' AMP was thus easily demonstrated. The injection of 3'', 5'' AMP was followed by an immediate rise in NEFA, which was most pronounced in the pretreated animals. After the initial increase there was a fall in NEFA in both the normal and the pretreated animals. The role of hyperglycemia for the NEFA response to exogenous 3'', 5'' AMP was discussed. It seemed possible that hyperglycemia may modify the initial increase in NEFA. The later fall in NEFA was discussed as a complex response, which may be the result of the action of several hormones, which may be released by 3'', 5'' AMP injection. Nicotinic acid and pyridyl-3-acetic acid showed a potent antilipolytic activity. Nicotinic acid caused a rebound elevation of NEFA. No rebound was observed after pyridyl-3-acetic acid. Pyridyl-3-acetic acid, however, did not change NEFA when administered orally. Pyridyl-2-acetic acid had no antilipolytic effect. Of the methyl xanthines caffeine and theophylline showed about the same lipolytic activity. Theobromine was quite ineffective.     

Subacute butyric acid burden in cattle. 1. Clinical results and effects on the carbohydrate-fat metabolism and the liver function of young fattening bulls

Daily butyric acid doses of 0.5 g/kg body weight or 1.0 g/kg were intraruminally applied to 8 young fattening bulls together with regular feed rations, for 19 days, following an initial phase for adaptation. Indigestion phenomena were recordable from 30% of the animals, primarily on the early days of the experiment. Both doses produced sinusoidal beta-OH butyrate curves without major dose-dependent deviations. The concentrations of glucose and free fatty acids were indicative of temporary subclinical ketosis. Neither ASAT, ALAT, and gamma-glutamyltransferase nor bilirubin nor liver glycogen were indicative of liver damage. The lower dose of 0.5 g/kg was widely tolerated, but clearly discernible disorders developed in response to the higher dose of 1.0 g/kg of butyric acid.     

The Glycogenic Properties of Butyric Acid

When butyric acid was injected intravenously at an amount of 2.5 mM/kg, blood glucose rose markedly in normal sheep. In a ewe with pregnancy toxemia blood glucose did not change. When the same amount was injected intraruminally to sheep and cows, the plasma level of non-esterified fatty acids, NEFA, was in most cases decreased by about 30—50 %, while blood glucose remained almost unchanged. The same results were obtained when the double amount, 5 mM/kg, was used. The depressant effect of butyric acid on NEFA after intravenous and intraruminal administration is discussed. When butyrate occurs in the circulating blood a breakdown of liver glycogen is induced and the resulting hyperglycemia causes a decrease in the NEFA level. The butyric acid which is infused into or produced in the rumen is probably completely metabolized to ketone bodies in the rumen epithelium and depresses NEFA indirectly by increasing the production of insulin.     

Propionate loading test for liver function during experimental liver necrosis in sheep

The first objective of this work was to study the conversion of propionate to glucose by liver of the sheep during experimentally induced liver necrosis. An additional objective was to determine the most appropriate sampling time after a propionate load has been given to use glucose concentration as an aid in the diagnosis of disturbed liver function. Sodium propionate (3 mmol/kg) was injected IV into 6 healthy sheep before and after they were given carbon tetrachloride (20% CCl4 in mineral oil; 0.25 ml of CCl4/kg, orally). To differentiate the effects of liver necrosis from the effects of decrease in food intake after CCl4 administration, 5 sheep which were fasted for 2 days, but not given CCl4, were studied. Microscopically, liver necrosis was observed, as well as an increase of fatty infiltration in nonnecrotic liver tissue. After sheep were given CCl4, the plasma liver-specific enzyme activities (namely, those of iditol dehydrogenase and gamma-glutamyl-transferase) were elevated. Microscopic and enzymatic changes were not observed in fasted animals. Serum sulfobromophthalein (BSP) half-life (t1/2) was markedly increased in the sheep given CCl4 treatment (t1/2 = 22.8 +/- 11 minutes) when compared with the t1/2 before treatment (t1/2 = 2.5 +/- 0.2 minutes). The BSP t1/2 did not differ between fed and fasted sheep. The t1/2 of the IV propionate load increased significantly, from 6.9 +/- 0.4 minutes in the control sheep to 12.8 +/- 2 minutes in the CCl4-treated sheep, whereas an insignificant increase was seen after fasting (6.8 +/- 1 minutes to 8.3 +/- 1 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cyromazine pour-on for the prevention of cutaneous myiasis of sheep

The results of trials on eight farms to assess the efficacy of two pour-on formulations containing cyromazine for the prevention of cutaneous myiasis of sheep are presented; data from trials on sheep with larval implants and on sheep kept in cages with adult flies are also reported. The incidence of cutaneous myiasis was reduced by between 87 per cent and 100 per cent for eight weeks when a formulation containing 6 per cent w/v cyromazine was used at an application rate of 60 to 85 mg of active ingredient/kg bodyweight. When a formulation containing 10 per cent w/v was used at an application rate of 50 to 100 mg/kg, the incidence of the condition was reduced by between 90 per cent and 100 per cent for eight weeks. Studies of sheep with larval implants, using the formulation containing 10 per cent w/v cyromazine at 50, 100 and 150 mg/kg bodyweight gave variable results with some animals at each dose rate having lost protection by the seventh week. When sheep were treated with the formulation containing 10 per cent w/v cyromazine at 50 or 100 mg/kg and exposed to adult flies in fly-proof cages they were completely protected for nine and eight weeks, respectively.     

The effect of cadmium poisoning on glucose transformation in skeletal muscles

Long-time effects of Cd on carbohydrate metabolism were investigated in male Wistar rats. A dose of 0.3 mg/kg body weight of Cd in acetate form was subcutaneously injected to the experimental animals twice a week through 3 months. Selected enzyme activities of glycolysis as well as concentrations of glycogen, glucose, pyruvate, lactate, triglycerides, and free fatty acids (FFA) were determined in blood serum, muscles, liver, and fatty tissues. The experimental animals differed from the control group, in that Cd intoxication was followed by decline in the blood serum only of pyruvate kinase and lactate dehydrogenase activities. In the liver, however, all enzyme activities were reduced. Glycogen glucose and FFA levels were increased. Intramuscular alterations were found to depend on the fibre type. The severest disturbance of glycolysis was recordable from red long fibres, whereas rapid white fibres were more resistant. The change in FFA concentration may be interpreted as some compensation for the impairment of carbohydrate metabolism in the energy balance.     

Plasma bile acid elevation following CCI4 induced liver damage in dogs, sheep, calves and ponies.

Plasma bile acid concentration was determined in normal dogs,sheep, calves and ponies for three days before and six days after liver damage, induced by carbon tetrachloride. In all species, a significant increase in plasma bile acid concentration was associated with a concomitant significant increase in plasma sorbitol dehydrogenase and transferase activity. Plasma bilirubin also significantly increased in all animals except the dogs. Results suggested that plasma bile acid levels could be used to test liver function in domestic animals.     

Subacute butyric acid exposure in cattle. 4. Clinical influence and effect on the carbohydrate-fat metabolism and liver function of cows

Eleven cows in late lactation were exposed to butyric acid for three weeks and were compared to five controls. Two intraruminal doses were daily applied, that is 1.0 g/kg B.W. of butyric acid to six animals and 1.0 g/kg B.W. of sodium butyrate to another five. Decline in milk yield was clinically recorded in response to butyric acid, while muscle tremor and diarrhoea resulted additionally from sodium butyrate. Behaviours of the clinico-chemical parameters of beta-OH-butyrate, glucose, free fatty acids, bilirubin, ASAT, gamma-GT, AP, and cholesterol were comparable to those in fattening bulls. Liver damage was not safely established. Some of the clinico-chemical alterations were more strongly pronounced after administration of sodium butyrate. One cow fell ill with ketosis under butyric acid load.     

THE EFFICIENCY OF CLIOXANIDE AND RAFOXANIDE AGAINST FASCIOLA HEPATICA IN SHEEP BY DIFFERENT ROUTES OF ADMINISTRATION

Groups of sheep were infected with 100 viable metacercariae of Fasciola hepatica. The efficiencies of clioxanide and rafoxanide were evaluated against infections aged 6 and 12 weeks, by using 3 dose rates of each compound by each of 3 routes of administration. Clioxanide, at 40 mg/kg, administered orally and intra-ruminally against 6-week-old liver fluke was 85 and 90% efficient respectively. At 80 mg/kg intra-abomasally its efficiency was 43%. Clioxanide at 20 mg/kg was 96% efficient against 12-week-old liver fluke when given orally or intra-ruminally and 82% efficient when given intra-abomasally. Because of its lower efficiency intra-abomasally, clioxanide may be unsatisfactory in a proportion of sheep, for use against immature liver fluke at a dose rate of 40 mg/kg. It may be expected to give a moderate to high efficiency against mature infections at 20 mg/kg.     

Effects of low dose rates of sporidesmin given orally to sheep

AIM: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. METHODS: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. RESULTS: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. CONCLUSIONS: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals. These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

大蒜多糖对ConA致小鼠肝损伤保护作用组织学观察

探讨大蒜多糖（GPA）对刀豆蛋白A（ConA）诱导的小鼠免疫性肝损伤的保护作用和对肝糖原的影响。将40只小鼠随机分为5组,即空白对照组、模型组、不同剂量多糖组（100、200、400mg／kg）。空白对照组和模型组小鼠灌胃生理盐水,多糖组小鼠分别以相应剂量灌胃,至第7天处死前8h,除空白对照组外所有小鼠尾静脉注射ConA,以制造急性免疫性肝损伤,取肝组织,进行病理学观察。结果模型组小鼠肝组织变性、坏死、瘀血等损伤严重,细胞界线与细胞核模糊不清,肝糖原含量减少,多糖组小鼠肝组织损伤均明显较轻,肝细胞界线清晰,糖原含量减少不显著,100mg／kg多糖组接近正常水平。研究表明,大蒜多糖能够促进肝糖原合成和储存,对小鼠免疫性肝损伤有良好的保护作用。     

Effects of low dose rates of sporidesmin given orally to sheep

Aim: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days.

Methods: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded.

Results: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease.

Conclusions: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals.These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.     

Pharmacokinetics, safety and tissue residues of sustained-release sulfamethazine in sheep

Concentration-time profiles and the rates of absorption, extent of distribution and half-lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained-release formulation (CalfSpan) were determined in 10 healthy sheep. The geometric mean half-life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained-release preparation (CalfSpan) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 micrograms/ml for more than 48 h for CalfSpan, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.o./AUCi.v.). The estimated bioavailability of the CalfSpan preparation was 52.5%. The safety of the sustained-release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18-day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.     

Effect of high-carbohydrate diet in the form of sugar beet on glucose and ketone body levels in the blood serum of highly pregnant and freshly lactating cows

In an experiment using 24 high-yielding cows (3rd and 6th lactations), group II was fed sugar beet as carbohydrate source (2 kg DM per animal and day) for 4 weeks before and for 4 weeks after parturition, whilst group I was given the equivalent amount of dried spent beet pulp. Sugar beet feeding during the dry period caused the glucose level in the blood to rise significantly from 48 to 55 mg/100 ml. On the 21st day of lactation the glucose concentration in group II (27 mg) had declined more strongly than in group I (37 mg). Feeding large amounts of easily soluble carbohydrates during the dry period obviously inhibits gluconeogenesis during early lactation. The ketone body level of group II was found to rise to 14 mg/100 ml by the 21st day of lactation (group I--4 mg), a level indicative of ketosis. The ketogenous action (strong formation of butyric acid in the rumen) of sugar beet enhances this effect, too. The daily milk yield did not vary much coming to 26.8 and 27.8 kg in the control and in the experimental group, respectively. The results allow to conclude that feeding fresh sugar beet to high-yielding cows just before and shortly after parturition is not advisable.     

The effect of niclofolan on desert sheep experimentally infected with immature Fasciola gigantica

Eight desert sheep were each infected orally with 500 metacercariae of Fasciola gigantica and, after 4 weeks, four of the animals were given niclofolan orally at the recommended therapeutic dose rate of 7 mg/kg, the other four remaining as controls. One week later, the animals were slaughtered and the fasciocidal effect of the drug was evaluated on the basis of worm burden, haemogram, some plasma constituents, and gross and histopathological lesions of the liver, as indicators of efficacy. The treatment was found to be ineffective, the degree of infection remaining the same as in the untreated control group. The experiment was repeated using eight infected sheep: four were given the drug orally at a dose rate of 10.5 mg/kg, i.e., 1.5 times the recommended dose; and the same parameters were measured as described above. The drug failed to cure the infected sheep, and caused depression, anorexia and weakness. In a third experiment six sheep were infected as before and three were treated with niclofolan by deep i.m. injection at the recommended therapeutic dose of 2 mg/kg. A week later the animals were killed and examined as before. The drug was effective in treating the infection and produced no untoward effects except for transient signs of pain at the site of injection. It seems possible that the oral dose, unlike the i.m. dose, of niclofolan is not absorbed and/or metabolized sufficiently to prevent elimination of the infection.     

Evaluation of a fibrate,specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator‐activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty‐three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2‐methyl‐2‐phenoxy‐propionic acid; 10 mg/kg of 2‐methyl‐2‐phenoxy‐propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum β‐hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2‐methyl‐2‐phenoxy‐propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2‐methyl‐2‐phenoxy‐propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.     

The effect of polychlorinated biphenyls on the vitamin A, vitamin E, and ascorbic acid status in young pigs

Admixture for 14 to 26 days of concentrations between 1 mg/kg to 250 mg/kg of polychlorinated biphenyls, Delor 103, 105, and 106 (Chemko, Strázeke) to ready-mixed feedstuffs was studied in 5 experiments for its effects on 71 piglets and store pigs. Neither growth nor general health were in any way impaired. Polychlorinated biphenyls produced different effects upon vitamin A, vitamin E, and ascorbic acid levels in different organs. Vitamin A concentrations in blood serum, for example were reduced by 100 mg/kg and 250 mg/kg of Delor 105 as well as by 250 mg/kg of Delor 103. Liver levels were not significantly depressed. No changes were recordable from vitamin E levels in blood serum and liver. Ascorbic acid saturation of the organism was positively affected. Its concentrations and overall levels in the liver in all experimental groups were higher than those in all controls. Significant rise of ascorbic acid concentrations in blood serum, urine, and kidneys occurred merely in response to 100 mg/kg and 250 mg/kg of Delor 105 as well as to 250 mg/kg of Delor 103. No adverse effect of tissue-borne residues of polychlorinated biphenyls on the status of administered vitamins was recordable 1 to 4 months after termination of experimental supply. Feed intake with 1 mg/kg of Delor 105, which was equivalent to increased natural contamination, did not cause any negative phenomena in any of the probands.     

Glucose tolerance in the toad Bufo gutturalis (Power)

Some aspects of glucose homeostasis were investigated in the toad Bufo gutturalis. Normal blood glucose and liver glycogen levels were determined and glucose tolerance tests were performed on laboratory acclimatized toads. The mean blood glucose concentration in such animals fasted for 48 h was 2,94 ± 0,65 mmol/l and 8,8 ± 2,62% of the wet mass of the liver consisted of glycogen. The rate of removal of glucose from the blood was directly dependent on the dose of glucose administered; the greater the dose the faster the removal rate. The renal threshold for glucose is between 3,22 and 5,64 mmol/l blood glucose.     

Hepatic serine and alanine metabolism during endotoxin-induced fever in sheep.

Time course changes in plasma amino acid concentrations and the hepatic metabolism of serine and alanine were measured in six mature wethers during endotoxin-induced fever. In separate trials, the animals' responses to injections of saline and endotoxin were measured. The endotoxin was from Escherichia coli serotype 055:B5 and was injected intravenously (4 micrograms/kg body weight). Liver biopsies were obtained from the sheep at 6 h postinjection during both endotoxin and saline injection trials. Rectal temperature in the endotoxin treated animals was increased (P less than 0.05, above that in control animals from 4.25 h to 9 h postinjection, with a maximum rise of 2.43 degrees C at 5.5 h postinjection. Glucose concentration in jugular plasma decreased (P less than 0.05) by 3 h postinjection and remained depressed throughout the 24 h postinjection sampling period. Plasma serine concentration was decreased (P less than 0.05) by 3 h postinjection. Plasma alanine concentration was decreased significantly (P less than 0.05) only at 24 h postinjection. Endotoxin injection increased (P less than 0.05) hepatic oxidation of 14C-serine (162%) and the net incorporation of 14C-serine carbon into hepatic protein (173%) and glycogen (275%). The net incorporation of 14C-alanine carbon into hepatic protein (172%) and glycogen (323%) were increased (P less than 0.05) by endotoxin injection, while alanine oxidation was not affected by endotoxin treatment (P greater than 0.05). The increased hepatic use of serine may explain, in part, the dramatic decrease in plasma concentrations of this amino acid following endotoxin injection into sheep.