The efficacy of 4-methylpyrazole (4-MP) and ethanol as treatment for ethylene glycol (EG) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-MP; those of another experimental group were given only EG. Cats of 3 experimental groups were intoxicated with EG and given 4-MP at 0 hour or 2 or 3 hours after EG ingestion, and those of 1 experimental group were given EG and treated with ethanol 3 hours after EG ingestion. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after EG ingestion, or 4-MP treatment in cats of the 4-MP only group. The half-life of EG and percentage of ingested EG excreted unchanged were determined for each group. 4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of EG. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after EG ingestion. Ethanol given 3 hours after EG ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after EG ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized. 4-Methylpyrazol given 2 or 3 hours after EG ingestion was less effective in preventing EG metabolism than was ethanol given 3 hours after EG ingestion. Therefore 4-MP, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of EG intoxication in cats.

Canine erythrocytes were loaded with the antineoplastic drug doxorubicin and then treated with 0.16% glutaraldehyde. This procedure has been previously shown to slow down the efflux of doxorubicin from erythrocytes and to result in the selective targeting of the carrier erythrocytes to liver. Three dogs were treated each with 2 different schedules of IV bolus administration of doxorubicin (0.4 mg/kg of body weight): free drug and doxorubicin encapsulated in glutaraldehyde-treated erythrocytes. The 2 treatments yielded consistent differences in the plasma pharmacokinetic properties of doxorubicin and of its only metabolite, doxorubicinol. A triphasic exponential decay of doxorubicin plasma concentrations was observed on injection of the free drug. Conversely, in the case of erythrocyte-encapsulated doxorubicin, 4 phases of plasma concentrations of doxorubicin were found. The plasma concentrations of doxorubicinol, after a steady increase during the first hour, followed patterns of decay comparable to those of the parent drug. On the basis of the kinetic variables calculated with the 2 administration schedules, area under curve concentrations of plasma doxorubicin were 136 microgram.h/L (free infusion) and 734 microgram.h/L erythrocyte-encapsulated drug). Significant alterations of hematologic and hematochemical factors were not observed in the 3 dogs during and after the 2 treatments. On the basis of our findings, doxorubicin-loaded and glutaraldehyde-treated erythrocytes may potentially be used in the treatment of systemic and hepatic tumors in dogs.

Canine circulating neutrophils, isolated by a blood lysing technique, were incubated with 7-S nerve growth factor (NGF), at final concentrations between 12.5 and 800 ng/ml, for 30 minutes at 37 C. Neutrophil cytosolic H2O2 production, measured by flow cytometry, after 7-S NGF incubation was not significantly different from that produced at 37 C (baseline temperature controls) alone. Phorbol myristate acetate (PMA; 100 ng/ml) stimulation of neutrophils produced cytosolic H2O2 concentrations almost 13 times that of baseline temperature control neutrophils. Preincubation of neutrophils with 7-S NGF (100 to 800 ng/ml, 30 minutes, 37 C) and subsequent stimulation by PMA resulted in augmented H2O2 production in excess of twice that of neutrophils treated with PMA alone, and almost 30 times that of baseline temperature controls.

Glutamine has been shown to be an important metabolic substrate of enterocytes in many animals, including cats, dogs, hamsters, human beings, monkeys, rabbits, rats, and sheep. To determine whether glutamine is important in the metabolism of cells of the equine gastrointestinal tract, we examined transintestinal differences in glutamine concentrations in the arterial and venous circulation, and measured activity of the major glutamine catabolizing enzyme, glutaminase. Arteriovenous differences provide an index of the amount of a given substrate removed by the tissue across which the measurements are made, and commonly are expressed as a percentage of substrate removed, or percent extraction. Arteriovenous differences for glutamine were determined in 7 anesthetized adult horses (weight, 450 to 500 kg) before and after an IV glutamine infusion. The mean baseline arterial glutamine concentration (+/- SEM) was 572 +/- 24 microM; this concentration quadrupled (to 2,167 +/- 135 microM, P < 0.01) 1 minute after IV bolus infusion of a 17.5-g glutamine load. Baseline extraction by the portal-drained viscera was 7.5 +/- 1.5%; this value increased to 18 +/- 2% at 1 minute (P < 0.01) and had returned to baseline values 60 minutes later. Arteriovenous differences were greatest across the jejunum (11.8 +/- 1.8% in the baseline period vs 33.1 +/- 3.1% at 1 minute, P < 0.001), with smaller differences across the colon, suggesting that the jejunum was the more avid utilizer of glutamine. Glutaminase activity was 4.38 +/- 0.16 and 4.00 +/- 0.60 micromol/mg of protein/h under standard conditions in jejunal and ileal mucosa, respectively. Kinetic studies of jejunal glutaminase revealed the enzyme to have a Km of 3.81 +/- 0.35 mM and a Vmax of 8.08 +/- 0.54 micromol/mg of protein/h, suggesting that the small intestine of horses has a high capacity to extract and metabolize circulating glutamine.

Six primiparous Holstein cows were fed a Se-deficient diet, beginning at least 90 days before their first calving, and 6 other primiparous cows were given the same diet plus a supplement of 2 mg of Se/cow/d as sodium selenite. All cows were fed their diets for the duration of the experimental period. One uninfected quarter of each cow was injected with 25 microgram of Escherichia coli endotoxin at postpartum week 5. Leukocytes were isolated by centrifugation from milk collected at postinjection hour 16. Isolated cells were 92 +/- 3% neutrophils and were incubated with Staphylococcus aureus or E coli in a 1:300 ratio. Phagocytosis and intracellular killing by neutrophils were assessed after 0, 30, 60, and 90 minutes by a fluorochrome assay, using acridine orange. Viability of neutrophils was assessed by use of trypan blue. Superoxide anion production and hydrogen peroxide production by neutrophils also were determined. Cows fed Se-deficient diets had significantly (P < 0.05) lower blood Se concentration and blood glutathione peroxidase activity than cows fed Se-supplemented diets. Selenium status had no effect on the phagocytic capacity of neutrophils. Neutrophils obtained from cows fed Se-supplemented diets killed a significantly (P < 0.05) higher percentage of ingested bacteria than did neutrophils from cows fed the Se-deficient diet. Viability was significantly (P < 0.05) reduced by incubation with S aureus in neutrophils from both groups of cows, with neutrophils from Se-deficient cows having lower viability. Superoxide anion production did not differ significantly between neutrophils from the 2 groups, but extracellular hydrogen peroxide concentration was significantly (P < 0.05) higher in neutrophils harvested from milk of cows fed the Se-deficient diet.

The insulin-like growth factor-I(IGF-I) is an important metabolic factor involved in cell growth and metabolism. Although secretion of IGF-I in rat liver is regulated by growth hormone, the effects of forskolin, adenylate cyclase activator, on secretion of IGF-I have not been reported. Therefore, a modified perfused rat liver model was used to investigate the regulatory effects of forskolin on IGF-I secretion in this experiment. The results were summerized as follows: 1. Modified perfused rat liver model was not changed to aspartate aminotransferase(AST), alanine aminotransferase(ALT) and lactic dehydrogenase(LDH) secretion in time. 2. The IGF-I secretion in hepatic cell was increased by forskolin(10-5, 10-6 and 10-7M) in a dose-dependent manner as compared with those of the controls, and significantly increased by 10-5 and 10-6M forskolin(p0.05). 3. Secretion of glucose in hepatic cell significantly was decreased by 10-5M forskolin as compared with those of controls(p0.05). These results suggest that forskolin may be involved in the regulation of IGF-I secretion in the perfused rat liver.

As micotoxicoses são grandes causadoras de perdas produtivas em ruminantes, sendo aflatoxina (AFLA) e zearalenona (ZEA) as principais micotoxinas encontradas em alimentos conservados. Estas micotoxinas apresentam efeito sobre o metabolismo animal, através da ação anabólica de metabólitos da ZEA, bem como pelas lesões hepáticas causadas pela AFLA. O objetivo deste estudo foi determinar a influência do adsorvente glucomanano modificado sobre parâmetros metabólicos de ovelhas submetidas a dietas contendo AFLA e ZEA. Foram utilizadas 34 fêmeas divididas em 6 grupos (ZEA; ZEA + ADS; AFLA; AFLA + ADS; CONTROLE + ADS; CONTROLE), recebendo 1,0 mg/kg de ZEA, 1,5 mg/kg de AFLA e/ou 2 kg/ton de adsorvente. A ZEA diminuiu os níveis séricos de glicose, em relação ao CONTROLE (p < 0,05), porém, o adsorvente não influenciou os níveis de glicose, não havendo diferença entre os grupos ZEA e ZEA + ADS. A ZEA aumentou os níveis de AST e GGT em relação ao grupo CONTROLE (p < 0,05), sendo que os níveis de AST foram superiores no grupo ZEA (p < 0,05), quando comparado ao grupo ZEA + ADS. Ainda, a aflatoxina causou uma redução nos níveis de albumina, em relação aos valores fisiológicos de ovinos. Assim, a partir destes resultados pode-se concluir que a ZEA causou alterações metabólicas em ovinos, bem como o glucomanano modificado foi eficiente em reduzir a possível agressão hepática causada por esta micotoxina, demonstrada pela diminuição nos níveis de AST.

As micotoxicoses são grandes causadoras de perdas produtivas em ruminantes, sendo aflatoxina (AFLA) e zearalenona (ZEA) as principais micotoxinas encontradas em alimentos conservados. Estas micotoxinas apresentam efeito sobre o metabolismo animal, através da ação anabólica de metabólitos da ZEA, bem como pelas lesões hepáticas causadas pela AFLA. O objetivo deste estudo foi determinar a influência do adsorvente glucomanano modificado sobre parâmetros metabólicos de ovelhas submetidas a dietas contendo AFLA e ZEA. Foram utilizadas 34 fêmeas divididas em 6 grupos (ZEA; ZEA + ADS; AFLA; AFLA + ADS; CONTROLE + ADS; CONTROLE), recebendo 1,0 mg/kg de ZEA, 1,5 mg/kg de AFLA e/ou 2 kg/ton de adsorvente. A ZEA diminuiu os níveis séricos de glicose, em relação ao CONTROLE (p &lt; 0,05), porém, o adsorvente não influenciou os níveis de glicose, não havendo diferença entre os grupos ZEA e ZEA + ADS. A ZEA aumentou os níveis de AST e GGT em relação ao grupo CONTROLE (p &lt; 0,05), sendo que os níveis de AST foram superiores no grupo ZEA (p &lt; 0,05), quando comparado ao grupo ZEA + ADS. Ainda, a aflatoxina causou uma redução nos níveis de albumina, em relação aos valores fisiológicos de ovinos. Assim, a partir destes resultados pode-se concluir que a ZEA causou alterações metabólicas em ovinos, bem como o glucomanano modificado foi eficiente em reduzir a possível agressão hepática causada por esta micotoxina, demonstrada pela diminuição nos níveis de AST. | The micotoxicoses are causing great losses of production in ruminants, being aflatoxin (AFLA) and zearalenone (ZEA) the major mycotoxins found in foods preserved. These mycotoxins have effect on the metabolism animal through the anabolic action of metabolites of the ZEA, and the liver injury caused by AFLA. The purpose of this study was to determine the influence of the sorbent modified glucomannan on metabolic parameters of sheep submitted to diets containing AFLA and ZEA. For this, 34 females were used and they were divided into 6 groups (ZEA; ZEA + ADS; AFLA; AFLA + ADS; CONTROL + ADS; CONTROL), receiving 1.0 mg/kg of ZEA, 1.5 mg/kg of AFLA and/or 2 kg/ton of sorbent. The ZEA decreased serum levels of glucose, for the CONTROL (p < 0.05), however, the sorbent not influence the levels of glucose, with no difference between groups ZEA and ZEA + ADS. The ZEA increased levels of AST and GGT compared to group CONTROL (p < 0.05), whereas the levels of AST were higher in the group ZEA (p < 0.05) when compared to the group ZEA+ADS. Still, the aflatoxin caused a reduction in the levels of albumin, for physiological values of sheep. Thus, from these results it was concluded that ZEA caused metabolic alterations in sheep, and the modified glucomannan was effective in reducing the possible liver aggression caused by this mycotoxin, shown by the decrease in the levels of AST.