Effect of N‐Acetylcysteine Supplementation on Intracellular Glutathione,Urine Isoprostanes,Clinical Score,and Survival in Hospitalized Ill Dogs

Background

Antioxidant depletion and lipid peroxidation have been correlated with disease severity and associated with poor outcomes.

Hypothesis/Objectives

Supplementing dogs with N‐acetylcysteine (NAC) during the first 48 hours of hospitalization will increase cysteine, normalize glutathione concentrations, and decrease the degree of lipid peroxidation associated with illness.

Animals

Sixty systemically ill hospitalized client‐owned dogs and 14 healthy control dogs.

Methods

Randomized investigator‐blinded, placebo‐controlled prospective study. Dogs were randomized to treatment with NAC (n = 30) versus placebo (n = 30). Antioxidants, urine 8‐isoprostane/creatinine (IP/Cr), and clinical score were determined before and after treatment with NAC. Glutathione, cysteine, and vitamin E concentrations were quantified using high‐performance liquid chromatography. Atomic absorption spectroscopy and enzyme‐linked immunosorbent assays were used to quantify selenium and isoprostane concentrations, respectively.

Results

Ill dogs had significantly lower vitamin E concentrations (27 versus 55 μg/mL; P = .0005) as well as elevated IP/Cr ratios (872 versus 399 pg/mg; P = .0007) versus healthy dogs. NAC supplementation significantly increased plasma cysteine (8.67 versus 15.1 μM; P < .0001) while maintaining glutathione concentrations. Dogs in the placebo group experienced a statistically significant decrease in glutathione concentrations (1.49 versus 1.44 mM; P = .0463). Illness severity and survival were unchanged after short duration NAC supplementation.

Conclusions

Ill dogs experience systemic oxidative stress. Supplementation with NAC during the first 48 hours of hospitalization stabilized erythrocyte glutathione concentrations. The clinical impact of this supplementation and glutathione concentration stabilization was undetermined.     

Glutathione Peroxidase Activity,Plasma Total Antioxidant Capacity,and Urinary F2‐ Isoprostanes as Markers of Oxidative Stress in Anemic Dogs

Background

Oxidative stress plays a role in the pathophysiology of several diseases and has been documented as a contributor to disease in both the human and veterinary literature. One at‐risk cell is the erythrocyte, however, the role of oxidative stress in anemia in dogs has not been widely investigated.

Hypothesis/Objective

Anemic dogs will have an alteration in the activity of glutathione peroxidase (GPx), a decrease in of total antioxidant capacity (TAC), and an increased concentration of urinary 15‐F₂‐isoprostanes (F₂‐IsoP) when compared to healthy dogs.

Animals

40 client‐owned dogs with anemia (PCV <30%) age‐matched to 40 client‐owned healthy control dogs.

Methods

Prospective, cross‐sectional study. Whole blood GPx activity, plasma TAC, and urinary F₂‐isoprostane concentrations were evaluated in each dog and compared between groups.

Results

Anemic dogs had significantly lower GPx activity (43.1 × 10³ +/‐ 1.6 × 10³ U/L) than did dogs in the control group (75.8 × 10³ +/‐ 2.0 × 10³ U/L; P < 0.0001). The GPx activity in dogs with hemolysis (10³ +/‐ 0.8 × 10³ U/L) was not significantly different (P = 0.57) than in dogs with nonhemolytic anemia (43.5 × 10³ +/‐ 1.1 × 10³ U/L). The TAC concentrations (P = 0.15) and urinary F₂‐isoprostanes (P = 0.73) did not significantly differ between groups.

Conclusions and Clinical Importance

Glutathione peroxidase activity was significantly decreased in anemic dogs indicating oxidative stress. Additional studies are warranted to determine if antioxidant supplementation would improve survival and overall outcome as part of a therapeutic regimen for anemic dogs.     

Fibronectin Concentrations in Pleural and Abdominal Effusions in Dogs and Cats

A commercial nephelometric test kit for human fibronectin (FN) was found suitable for the estimation if fibronectin concentration in body effusions of cats and dogs. The FN measurements were set in relation to the FN concentration of plasma pools in cats and dogs. A discrimination line of 31.5% completely separated malignant from cardiogenic pleural effusions in cats. For the diagnosis of a malignant pleural effusion, sensitivity was 100% and specificity was 57%. Pleuritis also resulted in high FN concentrations. The FN concentration in malignant pleural effusions in dogs differed significantly ( P < .02) from that in cardiogenic effusions. There were no clinically useful differences in the FN concentration in peritoneal effusions in cats and dogs. The FN/albumin ratio was significantly higher ( P < .02) in dogs with neoplastic abdominal effusion than in those with congestive heart failure.     

Oxidative Stress and Neutrophil Function in Cats with Chronic Renal Failure

Background: Oxidative stress is an important component in the progression of chronic renal failure (CRF) and neutrophil function may be impaired by oxidative stress. Hypothesis: Cats with CRF have increased oxidative stress and decreased neutrophil function compared with control cats. Animals: Twenty cats with previously diagnosed renal failure were compared with 10 age‐matched control cats. Methods: A biochemical profile, CBC, urinalysis, antioxidant capacity, superoxide dismutase (SOD) enzyme activity, reduced to oxidized glutathione ratio (GSH : GSSG), and neutrophil phagocytosis and oxidative burst were measured. Statistical comparisons (2‐tailed t‐test) were reported as mean ± standard deviation. Results: The CRF cats had significantly higher serum blood urea nitrogen, creatinine, and phosphorus concentrations than control cats, and significantly lower PCV and urine specific gravity than control cats. The GSH : GSSG ratio was significantly higher in the CRF group (177.6 ± 197, 61.7 ± 33; P < .02) whereas the antioxidant capacity was significantly less in the CRF group (0.56 ± 0.21, 0.81 ± 0.13 Trolox units; P < .005). SOD activity was the same in control and CRF cats. Neutrophil oxidative burst after Escherichia coli phagocytosis, measured as an increase in mean fluorescence intensity, was significantly higher in CRF cats than controls (732 ± 253, 524 ± 54; P < .05). Conclusions: The higher GSH : GSSG ratio and lower antioxidant capacity in CRF cats is consistent with activation of antioxidant defense mechanisms. It remains to be determined if supplementation with antioxidants such as SOD beyond the level of control cats would be of benefit in cats with CRF.     

Serum Erythropoietin Concentrations Measured by Radioimmunoassay in Normal, Polycythemic, and Anemic Dogs and Cats

Serum erythropoietin (Epo) concentrations were measured by radioimmunoassay (RIA) in normal, polycythemic, and anemic dogs and cats. The serum Epo concentration in normal dogs ( n = 25) ranged from 7 to 37 mU/mL (median, 20 mU/mL); and in normal cats ( n = 11) ranged from 9 to 38 mU/mL (median, 18 mU/mL). Polycythemic animals (PCV < 55% in dogs, > 45% in cats) were classified as those with primary (polycythemia vera), secondary, or polycythemia of uncertain etiology. Dogs with polycythemia vera (PV, n = 8) had a median serum Epo concentration in the normal range (17 mU/mL); cats with PV ( n = 7) also had a median serum Epo concentration that was within the normal range (10 mU/mL). In the category of secondary polycythemias, dogs ( n = 7) (median, 30.7 mU/mL) and cats ( n = 2) had normal Epo concentrations. The median serum Epoconcentration was significantly decreased ( P > .05) in dogs with PV compared with dogs with secondary polycythemias. The median serum Epo concentrations in dogs ( n = 13) and cats ( n = 5) with anemias not due to chronic renal disease were significantly increased ( P > .05) compared with normal dogs and cats. In cats with anemias due to chronic renal disease ( n = 5) the median serum Epo concentration was not significantly different from normal cats. The measurement of the serum EPO concentration may be useful in assessment of anemia or polycythemia but the overlap of values with the normal range in all groups evaluated limit its diagnostic use.     

A Comparison of the Plasma Fructose Concentrations in Dogs and Cats and Changes in the Fructose Concentrations in Dogs Following Intravenous Administration of Fructose

The plasma concentrations of fructose, glucose, free fatty acids (FFA) and triglycerides (TG) were measured in dogs and cats. Changes in these concentrations were investigated in dogs by an intravenous fructose tolerance test (IVFTT) at a dose of 0.1 g/kg body weight. Fructose concentrations in the plasma of dogs were significantly higher than those of cats. There was no significant difference in plasma glucose concentrations between dogs and cats. Plasma FFA concentrations decreased and TG concentrations increased after feeding in both dogs and cats. During the IVFTT, the plasma fructose concentrations in the dogs increased rapidly to a peak by 2 min and then decreased to half of the peak by 5 min after the administration of fructose. Administration of fructose resulted in an increase in the plasma TG concentrations and reduced plasma FFA concentrations in the dogs. Only 4% of the administered fructose was detected in the urine of dogs following IVFTT. Plasma fructose was considered to be rapidly absorbed and metabolized in both dogs and cats. However, as with glucose metabolism, there appear to be some differences in fructose metabolism between dogs and cats.     

植物抗氧化剂谷胱甘肽研究进展

谷胱甘肽(glutathione,GSH)是植物体内一种重要的抗氧化剂,可以清除细胞代谢过程中产生的多余活性氧自由基,减少由于膜脂过氧化作用而对细胞造成的伤害,在植物抵抗逆境胁迫中起着非常重要的作用.本文主要从植物体内GSH的种类、GSH对植物细胞保护的生理机制(清除细胞内自由基、与有毒重金属物质结合形成无毒化合物、吸收和转运氨基酸)和GSH对逆境胁迫(温度胁迫、干旱胁迫、重金属胁迫和盐胁迫)植物的保护作用等方面进行了总结分析.GSH的研究对于深入了解和认识植物抗氧化剂在代谢过程中的生理作用及清除活性氧自由基的机理具有积极作用,对研究植物抗逆性具有重要的意义.     

Peripheral and Central Venous Blood Glucose Concentrations in Dogs and Cats with Acute Arterial Thromboembolism

Background

Acute limb paralysis because of arterial thromboembolism (ATE) occurs in cats and less commonly in dogs. ATE is diagnosed based on physical examination findings and, occasionally, advanced imaging.

Hypothesis/Objectives

Peripheral, affected limb venous glucose concentration is decreased in ATE, whereas its systemic concentration is within or above reference interval.

Animals

Client‐owned cats and dogs were divided into 3 respective groups: acute limb paralysis because of ATE (22 cats and 9 dogs); acute limb paralysis secondary to orthopedic or neurologic conditions (nonambulatory controls; 10 cats and 11 dogs); ambulatory animals presented because of various diseases (ambulatory controls; 10 cats and 9 dogs).

Methods

Prospective observational, clinical study. Systemic and local (affected limb) blood glucose concentrations were measured. Their absolute and relative differences (ΔGlu and %ΔGlu, respectively) were compared among groups.

Results

ΔGlu and %ΔGlu were significantly higher in the ATE cats and dogs groups, compared to both of their respective controls (P < .0001 and P < .001, respectively). No significant differences were observed between the control groups. Receiver operator characteristics analysis of ΔGlu and %ΔGlu as predictors of ATE had area under the curve of 0.96 and 0.99 in cats, respectively, and 1.00 and 1.00, in dogs, respectively. ΔGlu cutoffs of 30 mg/dL and 16 mg/dL, in cats and dogs, respectively, corresponded to sensitivity and specificity of 100% and 90% in cats, respectively, and 100% in dogs.

Conclusions and Clinical Importance

ΔGlu and %ΔGlu are accurate, readily available, diagnostic markers of acute ATE in paralyzed cats and dogs.     

Cardiac Troponins in Dogs and Cats

Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conventionally, the cardiac troponins have been used for diagnosis of acute myocardial infarction in humans and have become the gold standard biomarkers for this indication. They have become increasingly recognized as an objective measure of cardiomyocyte status in both cardiac and noncardiac disease, supplying additional information to that provided by echocardiography and ECG. Injury to cardiomyocytes can occur through a variety of mechanisms with subsequent release of troponins. Independent of the underlying disease or the mechanism of troponin release, the presence of myocardial injury is associated with an increased risk of death. As increasingly sensitive assays are introduced, the frequent occurrence of myocardial injury is becoming apparent, and our understanding of its causes and importance is constantly evolving. Presently troponins are valuable for detecting a subgroup of patients with higher risk of death. Future research is needed to clarify whether troponins can serve as monitoring tools guiding treatment, whether administering more aggressive treatment to patients with evidence of myocardial injury is beneficial, and whether normalizing of troponin concentrations in patients presenting with evidence of myocardial injury is associated with reduced risk of death.     

Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.