3-Acetylpyridine neurotoxicity in mice.

3-acetylpyridine (3-AP) is a metabolic antagonist used in research to decrease levels of nicotinamide (niacinamide) in laboratory animals. The administration of 3-AP followed by nicotinamide to rats leads to the selective destruction of neurons in the medial inferior olive, resulting in a loss of climbing fibers innervating cerebellar Purkinje cells and a consequent ataxia manifest by alterations in both balance and gait. Although 3-AP has also been administered to mice to destroy neurons in the inferior olive, there are limited studies quantifying the consequent effects on balance, and no studies on gait. Further, the relationship between 3-AP-induced lesions of the inferior olive and behavior has not been elucidated. Because 3-AP continues to be used for experiments involving mice, this study characterized the effects of this toxin on both balance and gait, and on the neuronal integrity of several brain regions involved in motor coordination. Results indicate that C57BL/6 mice are less sensitive to the neurotoxic effects of 3-AP than rats, and a dose more than 6.5 times that used for rats produces deficits in both balance and gait comparable to those in rats. This dose led to a significant (p<0.05) loss of NeuN(+) neurons in several subregions of the inferior olive including the rostral medial nucleus, dorsomedial cell column, ventrolateral protrusion, and cap of Kooy. Further, the number of NeuN(+) neurons in these subregions, with the exception of the dorsomedial cell column, was significantly (p<0.05) related to rotorod performance, implicating their involvement in this behavior.

Effect of age and severity of cognitive dysfunction on two simple tasks in pet dogs.

Dogs exhibit age-dependent losses in learning and memory as well as a progressive accumulation of neuropathology that parallels that observed in normal human aging and early Alzheimer's disease. These deficits have been extensively studied using a number of standard cognitive tasks in the laboratory; however, appropriate tools for their assessment in veterinary clinics are still lacking. The aim of this study was to evaluate the effect of age and the severity of cognitive dysfunction syndrome (CDS) on two simple tests conducted in a clinical setting. A food searching (FS) task and a problem-solving (PS) task were administered to young (1-4 years, n=9), middle-aged (5-8 years, n=10), cognitively unimpaired aged (≥9 years, n=31), and cognitively impaired aged (≥ 9 years, n=37) dogs. Cognitive status was classified using an owner-based questionnaire, and in the impaired group, dogs were categorized as having either mild or severe CDS. During the FS task, younger dogs (<9 years) were able to locate the food more quickly and with more success than the aged groups (≥9 years). Dogs with severe CDS exhibited poorer performance than those with mild CDS or their healthy counterparts. In the PS task, younger dogs performed better than the aged dogs in obtaining food, but there were no differences related to CDS severity. The FS task might help to better characterize cognitively affected dogs in the clinical setting than the PS task. These and similar tasks require further investigations in the field.

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 1: locomotor and exploratory behaviour.

Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs. An open-field (OF) test and a curiosity test were administered at baseline and 6 months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively unimpaired aged (≥ 9 years, n=31), and cognitively impaired aged ( ≥ 9 years, n=36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed. The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6 months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals.

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 2: social responsiveness.

Changes in social interactions with owners and other dogs are frequently observed in dogs with cognitive dysfunction syndrome (CDS). The aim of this work was to assess the effect of age and severity of CDS on social responsiveness. This is the second part of a 2-part report on spontaneous activity in pet dogs. A human interaction test and a mirror test were administered at baseline and 6 months later to assess social responses to humans and conspecifics, respectively, to four groups of privately-owned dogs: young (n=9), middle-aged (n=9), cognitively unimpaired aged (n=31), and cognitively impaired aged (n=36). The severity of cognitive impairment was considered in the last group and dogs were categorised as having either mild or severe CDS. The influence of the person and the mirror on locomotion and exploratory behaviour was also studied. Dogs were recorded in a testing room and the video recordings were subsequently analysed. Young dogs displayed more interactions involving physical contact with a person. Young and middle-aged dogs showed more vocalisations in response to social isolation. In contrast, aged animals spent more time in front of the mirror. Changes in social responsiveness associated with severe CDS included decreased response to social isolation and human interaction and increased time in front of the mirror, suggesting a deficit in habituation. Testing of spontaneous activity might help to characterise CDS in aged dogs, a condition increasingly diagnosed in veterinary clinics and a potentially useful natural model of Alzheimer's disease in humans.

Effect of fluoxetine on blood concentrations of serotonin, cortisol and dehydroepiandrosterone in canine aggression.

Canine aggression directed towards people is the most frequent reason for referral to behaviour practices. The serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis are believed to play an important role in controlling aggression. The selective serotonin reuptake inhibitor fluoxetine is the most commonly used drug in canine aggression. The aim of the present study was to assess the effect of a 30-day-long fluoxetine treatment on the peripheral serotonergic system and the HPA axis in canine aggression. To this end, the concentrations of serum serotonin (5-HT) and plasma cortisol and dehydroepiandrosterone (DHEA) were analysed in a group of aggressive (n = 22) and nonaggressive dogs (n = 9) during pre- (day 0) and posttreatment (day 30) conditions. Treatment caused a significant decrease in 5-HT concentrations (46% in the aggressive group and 32% in the control group). There was a trend towards a rise of DHEA/cortisol ratio values after treatment both in the aggressive and the control group. The determination of blood 5-HT and the DHEA/cortisol ratio could have important clinical applications in the future for deciding which animals might benefit from a given treatment as well as for monitoring the response. Further large-scale studies with this aim should be carried out to obtain sound conclusions.

Papel del eje corticotropo en la agresividad canina / No disponible

No disponible

Effects of estradiol metabolites on cAMP production and degradation.

(Full text is available at http://www.manu.edu.mk/prilozi). 17beta-Estradiol is metabolized to 2-hydroxyestradiol, and 2-hydroxyestradiol is converted to 2-methoxyestradiol. These steroids reduce proliferation of, migration of and collagen production by vascular smooth muscle cells with an order of potency of 2-methoxyestradiol > 2-hydroxyestradiol > 17beta-estradiol, i.e. the converse of their estrogenic potency. Since cAMP also inhibits cell growth, it is conceivable that these steroids alter cAMP synthesis or degradation, and this hypothesis was addressed in this study. In cultured preglomerular vascular smooth muscle cells pretreated with a high concentration of a broad spectrum phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine, 1 mM) to eliminate phosphodiesterase activity as a confounding variable, high (100 microM), but not low (10 microM), concentrations of 17beta-estradiol, 2-hydroxyestradiol and 2-methoxyestradiol attenuated isoproterenol-induced cAMP by 15%, 19% and 55%, respectively. 2-Hydroxyestradiol (100 microM) also attenuated forskolin-induced cAMP by 31% in cells treated with 3-isobutyl-1-methylxanthine. In cells not pretreated with 3-isobutyl-1-methylxanthine and using concentrations of steroids (10 microM) that did not interfere with adenylyl cyclase, 17beta-estradiol decreased by 34%, 2-hydroxyestradiol did not alter and 2-methoxyestradiol increased by 60% isoproterenol-induced cAMP. These results indicate that in preglomerular vascular smooth muscle cells, high concentrations of 2-hydrxoyestradiol markedly inhibit adenylyl cyclase whereas 17beta-estradiol and 2-methoxestradiol only modestly inhibit adenylyl cyclase even at high concentrations. Our results also indicate that lower concentrations of 17beta-estradiol, 2-hydroxyestradiol and 2-methoxyestradiol activate, have no effect on and inhibit, respectively, phosphordiesterase activity. The effects of these compounds on phosphodiesterase activity may account in part for the greater potency of 2-methoxyestradiol as an anti-growth compound compared with 17beta-estradiol and 2-hydroxyestradiol. Key words: Estradiol, Estradiol metabolites, 2-Methoxyestradiol, Cyclic adenosine monophosphate.

Prevalence and risk factors of behavioural changes associated with age-related cognitive impairment in geriatric dogs.

OBJECTIVES: The aim of this study was to describe the prevalence and severity of behavioural changes associated with age and their relationship to risk factors such as sex, reproductive status, bodyweight and age. METHODS: A cross-sectional study design was chosen. A total of 325 geriatric dogs were included. Owners of dogs older than nine years were interviewed by a veterinary behaviourist. Structured phone interviews were used to gather information about four behavioural categories related to cognitive impairment: sleep/wake cycles, social interaction, learning and house training and signs of disorientation. RESULTS: Signs of cognitive impairment showed a prevalence of 22.5 per cent in geriatric dogs. Sex and age emerged as significant predictor variables. Females and neutered dogs were significantly more affected than males and entire dogs, respectively. Prevalence and severity increased with age. Although weight was not a statistically significant predictor variable, smaller animals had greater odds of showing age-related cognitive impairment. The most impaired behavioural categories were social interaction and house training. CLINICAL SIGNIFICANCE: Age-related behavioural changes should be considered by practicing veterinarians because of their relative high prevalence among geriatric dogs, especially in females.

[Malignant hyperthermia in a pig anesthesized with desflurane]. / Hipertermia maligna en un cerdo anestesiado con desflurano.

A large-white pig that had not been genetically selected to develop malignant hyperthermia (MH) during anesthesia nevertheless suffered an episode of severe MH after repeated exposure to increasing concentrations of desflurane. MH is a hypermetabolic alteration that may develop in susceptible patients who have inhaled certain drugs or agents that act as triggers. Early identification and appropriate treatment are essential to reduce the likelihood of death associated with this severe alteration. We report a case of late-developing MH triggered by low concentrations of inhaled desflurane.

Hipertermia maligna en un cerdo anestesiado con desflurano / Malignant hyperthermia in a pig anesthestized with desflurane

Un cerdo de la raza Large-White, no seleccionado genéticamente para desarrollar hipertermia maligna (HM) durante la anestesia, presentó un episodio de hipertermia maligna grave tras la exposición repetida a concentraciones crecientes con desflurano.La hipertermia maligna es una alteración hipermetabólica que se puede presentar en pacientes susceptibles a los que se le administran ciertos fármacos o agentes inhalatorios que actúan como agentes desencadenantes. La identificación precoz y el tratamiento adecuado son imprescindibles para disminuir la mortalidad asociada a tan grave alteración.Este caso de hipertermia maligna desencadenado por desflurano se caracterizó por una presentación tardía y por desarrollarse con una concentración mínima de agente inhalatorio (AU)

Diagnóstico diferencial de meningitis postoperatoria tras anestesia subaracnoidea / Differential diagnosis of postoperative meningitis following subaracnoid anesthesia

No disponible

[Transfusion needs during intraoperative and immediate postoperative periods in arthroplasty of the hip and knee]. / Necesidades transfusionales durante el intra y postoperatorio inmediato de la artroplastia de cadera y rodilla. Incidencia y factores asociados.

OBJECTIVES: To determine the factors associated with immediate perioperative transfusion requirements of hip or knee arthroplasty patients who have not been enrolled in a blood salvage program. PATIENTS AND METHODS: This prospective study collected demographic (age, sex, weight, height, etc.), physiological (hemoglobin levels, coagulation times, preoperative platelet counts, etc.), clinical history and anesthetic and surgical data (type of anesthesia, surgical diagnosis, duration of procedure) in 112 patients undergoing orthopedic surgery: 19 cases of primary knee arthroplasty, 77 cases of hip arthroplasty and 16 replacements of hip arthroplasty. Logistic regression analysis of the aforementioned variables was performed to search for factors related to transfusional needs during and after hip arthroplasty or after knee arthroplasty, which was performed with a tourniquet applied to render intraoperative transfusion unnecessary. RESULTS: The variables that increased the risk of transfusion during surgery were duration of procedure exceeding 120 min (OR 15.24; p = 0.01) and loss of over 500 ml of blood during surgery (OR 11.4; p = 0.02). The variables associated with perioperative transfusion were loss of over 500 ml in the postanesthetic recovery room (OR 12.6; p < 0.0001), hypotensive episodes during recovery (OR 11.7; p = 0.0001), prosthetic replacement (OR 6.33; p = 0.005), height < 160 cm (OR 5.03; p = 0.02), preoperative hemoglobin level < 13.5 g/dl (OR 4.97; p = 0.02), and surgery for reasons other than osteoarthritis (arthritis, pathological fractures, etc.) (OR 4.60; p = 0.04). Variables associated with transfusion of over two units of packed red cells were a history of neoplastic disease unrelated to arthroplasty (OR 378.67; p = 0.005), prosthetic replacement (OR 49.71; p = 0.009), diabetes (OR 36.49; p = 0.02) and a hypotensive event while in the postanesthetic recovery room (OR 29.12; p = 0.02). CONCLUSION: These results suggest that certain modifiable factors increase the risk of blood transfusion in knee and hip arthroplasty. Specifically, they are duration of surgery, intra- and postoperative bleeding, preoperative hemoglobin level and instances of perioperative hypotension. Other factors outside our control are height or patient clinical history.