Antioxidant supplementation during illness in dogs: effect on oxidative stress and outcome, an exploratory study.

OBJECTIVES: To assess whether combination antioxidant supplementation for 30 days in systemically ill dogs alters antioxidant status, degree of lipid peroxidation, clinical score and survival. MATERIALS AND METHODS: Forty client-owned systemically-ill hospitalised dogs were eligible for inclusion. Dogs were randomised to no supplementation (NS; n=19) or supplementation with N-acetylcysteine/S-adenosylmethionine/silybin and vitamin E (AS; n=20) for 30 days. Clinical score and oxidative biomarkers including glutathione, cysteine, vitamin E, selenium and urine isoprostanes/creatinine (F2 -IsoPs/Cr) were determined on days 0 and 30. Glutathione, cysteine, vitamin E and urine F2 -IsoPs/Cr were quantified by high-performance liquid chromatography, and selenium concentrations determined using atomic absorption spectroscopy. RESULTS: Thirty-two dogs completed the study (NS, n=16; AS, n=16). Vitamin E concentrations were significantly greater in the supplemented compared to the non-supplemented group. No other markers of oxidative stress significantly changed with supplementation. There was no difference in Day 30 clinical scores or survival between the two groups. CLINICAL SIGNIFICANCE: In this population of systemically-ill hospitalised dogs, combination antioxidant supplementation did not alter redox state or clinical outcome.

Serum Cobalamin and Methylmalonic Acid Concentrations in Hyperthyroid Cats Before and After Radioiodine Treatment.

BACKGROUND: Hyperthyroidism, the most common endocrine disorder in cats, has been associated with low serum cobalamin concentrations. Whether this is a functional cobalamin deficiency of clinical importance has not been assessed. HYPOTHESIS/OBJECTIVES: Cats with hyperthyroidism experience a functional cobalamin deficiency which correlates with their clinical catabolic state and is reversible with return of the euthyroid state. ANIMALS: Thirty-nine client-owned hyperthyroid cats. METHODS: Prospective observational study. Serum cobalamin, methylmalonic acid, and clinical scores were determined in each hyperthyroid cat at enrollment and when euthyroid (60 days after radioiodine treatment). RESULTS: Five of the 39 hyperthyroid cats (13%) had a low serum cobalamin concentration ranging from <150 to 290 ng/L. Serum cobalamin concentrations normalized to >350 ng/L in 2 of the hypocobalaminemic cats once euthyroid. None of the hyperthyroid/hypocobalaminemic cats had increased serum methylmalonic acid concentrations (175-601 nmol/L). In cats with clinical and biochemical hyperthyroidism, there was no correlation between serum cobalamin concentrations with total T4 concentration (P = .12) or clinical scores including body weight (P = .11) and BCS (P = .54). CONCLUSIONS AND CLINICAL IMPORTANCE: In this population of hyperthyroid cats, the prevalence of hypocobalaminemia was low. Specifically, hyperthyroid cats, in which concurrent gastrointestinal disease is unlikely. Hypocobalaminemia is not a functional deficiency requiring supplementation in hyperthyroid cats without gastrointestinal disease.

The dependence of motion repulsion and rivalry on the distance between moving elements.

We investigated the extent to which motion repulsion and binocular motion rivalry depend on the distance between moving elements. The stimuli consisted of two sets of spatially intermingled, finite-life random dots that moved across each other. The distance between the dots moving in different directions was manipulated by spatially pairing the dot trajectories with various precisions. Data from experiment 1 indicated that motion repulsion occurred reliably only when the average distance between orthogonally moving elements was at least 21.0 arc min. When the dots were precisely paired, a single global direction intermediate to the two actual directions was perceived. This result suggests that, at a relatively small spatial scale, interaction between different directions favors motion attraction or coherence, while interaction at a somewhat larger scale generates motion repulsion. Similarly, data from experiment 2 indicated that binocular motion rivalry was significantly diminished by spatially pairing the dots, which moved in opposite directions in the two eyes. This supports the recent proposal that rivalry occurs at or after the stage of binocular convergence, since monocular cells could not have directly responded to our interocular pairing manipulation. Together, these findings suggest that the neural mechanisms underlying motion perception are highly sensitive to the fine spatial relationship between moving elements.

Perceptual learning on orientation and direction discrimination.

Two experiments were conducted to determine the extent to which perceptual learning transfers between orientation and direction discrimination. Naive observers were trained to discriminate orientation differences between two single-line stimuli, and direction differences between two single-moving-dot stimuli. In the first experiment, observers practiced the orientation and direction tasks along orthogonal axes in the fronto-parallel plane. In the second experiment, a different group of observers practiced both tasks along a single axis. Perceptual learning was observed on both tasks in both experiments. Under the same-axis condition, the observers' orientation sensitivity was found to be significantly elevated after the direction training, indicating a transfer of learning from direction to orientation. There was no evidence of transfer in any other cases tested. In addition, the rate of learning on the orientation task was much higher than the rate on the direction task. The implications of these findings on the neural mechanisms subserving orientation and direction discrimination are discussed.

The effect of complex motion pattern on speed perception.

We recently reported a new motion illusion where dots in expanding random dot patterns appear to move faster than those in rotation patterns despite having the same physical speed distributions. In the current paper, we compared expansion and rotation motion to translational motion and found that the perceived dot speed in translation patterns was between that of expansion and rotation. We also explored contraction motion and found subjects perceived dots in contracting patterns as moving slightly faster than those in expanding patterns and much faster than those in rotating patterns. Finally, we found that stimulus presentation order in a trial plays an important role in determining the magnitude of the speed illusion--the effect is greater when the subjectively faster stimulus is viewed second (e.g., expansion after rotation). The dependence on stimulus order is greatest when comparing complex motion patterns with large subjective speed differences. This phenomenon is unlikely to be explained in terms of channel fatigue or adaptation.

Maps of complex motion selectivity in the superior temporal cortex of the alert macaque monkey: a double-label 2-deoxyglucose study.

The superior temporal sulcus (STS) of the macaque monkey contains multiple visual areas. Many neurons within these regions respond selectively to motion direction and to more complex motion patterns, such as expansion, contraction and rotation. Single-unit recording and optical recording studies in MT/MST suggest that cells with similar tuning properties are clustered into columns extending through multiple cortical layers. In this study, we used a double-label 2-deoxyglucose technique in awake, behaving macaque monkeys to clarify this functional organization. This technique allowed us to label, in a single animal, two populations of neurons responding to two different visual stimuli. In one monkey we compared expansion with contraction; in a second monkey we compared expansion with clockwise rotation. Within the STS we found a patchy arrangement of cortical columns with alternating stimulus selectivity: columns of neurons preferring expansion versus contraction were more widely separated than those selective for expansion versus rotation. This mosaic of interdigitating columns on the floor and posterior bank of the STS included area MT and some neighboring regions of cortex, perhaps including area MST.

A novel speed illusion involving expansion and rotation patterns.

Using random dot stimuli well controlled for dot speed, we found that the moving features in expanding patterns appear to move faster than those in rotating patterns. The illusion is well correlated with the strength of the global motion signal. For example, in displays where the number of motion directions defining the patterns is reduced, the magnitude of the illusion decreases. Similarly, the strength of the effect diminishes as dot density is reduced. In patterns where only wedge-shaped segments of the stimuli are left exposed, the difference in perceived speed increases with the angular size of the wedge. Stimulus placement relative to the fixation point has little effect on the persistence of this phenomenon-expansion patterns appear to contain elements of greater speed, independent of stimulus eccentricity. These results argue against a local explanation for this perceptual illusion, suggesting that the global motion pattern of the stimulus, per se, is responsible.

The analysis of complex motion patterns by form/cue invariant MSTd neurons.

Several groups have proposed that area MSTd of the macaque monkey has a role in processing optical flow information used in the analysis of self motion, based on its neurons' selectivity for large-field motion patterns such as expansion, contraction, and rotation. It has also been suggested that this cortical region may be important in analyzing the complex motions of objects. More generally, MSTd could be involved in the generic function of complex motion pattern representation, with its cells responsible for integrating local motion signals sent forward from area MT into a more unified representation. If MSTd is extracting generic motion pattern signals, it would be important that the preferred tuning of MSTd neurons not depend on the particular features and cues that allow these motions to be represented. To test this idea, we examined the diversity of stimulus features and cues over which MSTd cells can extract information about motion patterns such as expansion, contraction, rotation, and spirals. The different classes of stimuli included: coherently moving random dot patterns, solid squares, outlines of squares, a square aperture moving in front of an underlying stationary pattern of random dots, a square composed entirely of flicker, and a square of nonFourier motion. When a unit was tuned with respect to motion pattern producing the most vigorous response in a neuron was nearly the same for each class. Although preferred tuning was invariant, the magnitude and width of the tuning curves often varied between classes. Thus, MSTd is form/cue invariant for complex motions, making it an appropriate candidate for analysis of object motion as well as motion introduced by observer translation.

Effects of multiple injections of HCG on testis blood flow.

In attempting to determine whether or not multiple injections of human chorionic gonadotropin (hCG) augment testis blood flow, adult male rats were injected with three doses of 10 IU of hCG every other day and testis blood flow was determined on day 5, the day of the final injection. Testis blood flow (mL/100 g testis tissue/min +/- SEM) as measured by the 133Xe washout method increased from 10.8 +/- 1.3 to 20.4 +/- 4.5 (p less than 0.05) after the three doses of hCG. These observations suggest that multiple injections of hCG appear to have the same effect as a single dose of hCG in increasing testis blood flow. This supports the hypothesis that hCG should be administered to all patients undergoing orchiopexy in the hope that the increased perfusion of the gonad will make it less susceptible to ischemia during the surgical procedure.

Effect of the antiandrogen, WIN 49,596, on the descent of the testis in the male rat.

Testicular descent in the male rat is believed to be an androgen dependent event with dihydrotestosterone the most likely active androgen. To provide further insight into the endocrinology of this important physiological event, we treated male rats with the antiandrogen, WIN 49596 (50 mg./kg./day), from day 1 to day 27 of age and evaluated its effect on the post-natal androgen-dependent events in this animal model. It was determined that while treatment with WIN inhibited the weights of the ventral prostate, seminal vesicles and penis when compared to those seen in castrate animals, the drug only caused a 19% (3/16) inhibition in the descent of the testes when compared to the control group (0/16; p = 0.112). These data together with those previously obtained in animals exposed to selective inhibitors of the 5-alpha reductase enzyme suggest that other factors possibly working in tandem with androgens play a predominant role in testicular descent in the rat.

Kinetics of cyclosporine A-induced inhibition of succinate-coenzyme Q dehydrogenase in rat renal cortical mitochondria.

The kinetic mechanism of succinate-coenzyme Q dehydrogenase (Complex II) inhibition by cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS showed two modes of inhibition of Complex II of the mitochondrial electron transport system: (a) a mixed linear noncompetitive inhibition of resting succinate-limited and ADP-stimulated respirations suggesting that CS binds to Complex II at a different site than the substrate, affecting the dissociation constant for the enzyme-substrate complex and (b) a competitive inhibition of the DNP-stimulated electron transport system suggesting competition with the oxidized form of a component of Complex II. CS action to renal mitochondrial Complex II limits its function, an effect which may be related to CS nephrotoxicity.

Cyclosporine augments renal mitochondrial function in vivo and reduces renal blood flow.

The in vivo action of cyclosporine A (CS) on rat renal cortical mitochondria was investigated. CS (30 mg.kg-1.day-1) given orally to rats for 30 days caused an augmentation of renal mitochondrial oxidative phosphorylation. The ADP-stimulated respiratory rate was increased by 37.0% with glutamate plus malate as respiratory substrates (P less than 0.025) but not with succinate-supported respiration, indicating enhancement of mitochondrial complex I activity. This reaction may be a response to the 32.5% reduction of renal blood (P less than 0.005) in the CS-treated group, possibly serving to maximize ATP synthesis during ischemia. Ligation-induced decreases in renal blood flow also resulted in enhancement of mitochondrial complex I activity.