Rats move nesting materials to create different functional areas: Short report.

Here we document how rats separate their living space into different functional regions. Five groups of four female Sprague Dawley rats were housed in caging systems that consisted of two standard cages connected by a tube. Both cages were provided with the same amount of bedding and nesting materials, but only one contained food and water. Nesting cover and weight of each cage were measured once a week for five weeks during cage cleaning. We found that the cages with food and water had 9% less nesting material coverage but had gained 90% more weight when compared with cages where food and water were absent. These results indicate that, when provided with separate spaces, rats move nesting materials away from the cage containing food and water sources, but preferentially excrete in the cage with water and food.

Effects of personality on assessments of anxiety and cognition.

Individual variation in responses to commonly used tests of anxiety and spatial memory is often reported. While this variation is frequently considered to be 'noise', evidence suggests that it is, at least partially, related to consistent individual differences in behavioral responses (i.e., personality). The same tests used to assess anxiety are often used to profile personality traits, but personality differences are rarely considered when testing treatment differences in anxiety. Focusing on the rat literature, we describe fundamental principles involved in anxiety and spatial memory tests and we discuss how personality differences and housing conditions can influence behavioral responses in these tests. We propose that an opportunity exists to increase stress resiliency in environmentally sensitive individuals by providing environmental enrichment. We conclude by discussing different approaches to incorporating personality measures into the design and analysis of future studies; given the potential that variation masks research outcomes, we suggest that a strategy which considers the individual and its housing can contribute to improving research reproducibility.

Individual differences in rat sensitivity to CO2.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in aversion may reflect CO2 sensitivity, but other personality traits could also account for individual differences in aversion. The aims of this study were to 1) assess the stability of individual differences in rat aversion to CO2, 2) determine if individual differences in sweet reward motivation are associated with variation in aversion to CO2, and 3) assess whether variation in aversion to CO2 is related to individual differences in motivation to approach gains (promotion focus) or maintain safety (prevention focus). Twelve female Sprague Dawley rats were exposed multiple times at three different ages (3, 9 and 16 months old) to CO2 in approach-avoidance testing to assess motivation to avoid CO2 against motivation to gain sweet rewards. Rats were also tested for motivation to find hidden sweet rewards, and for their motivation to approach rewards or darkness. Tolerance to CO2 increased with repeated exposures and was higher at older ages. Individual differences in aversion to CO2 were highly repeatable but unrelated to motivation for sweet rewards or the strength of promotion and prevention focus. These results indicate that individual differences in aversion to CO2 reflect variation in CO2 sensitivity.

Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement over CO2 but are not widely adopted. We conducted an online survey of Canadian and European laboratory animal professionals and researchers (n = 592) to assess their attitudes towards the use of CO2 and alternative methods for rodent euthanasia using quantitative 7-point scale (from 1 (= strongly oppose) to 7 (= strongly favour) and qualitative (open-ended text) responses. CO2 was identified as the most common method used to kill rodents, and attitudes towards this method were variable and on average ambivalent (mean ± SD score on our 7-point scale was 4.4 ± 1.46). Qualitative analysis revealed four themes relating to participant attitude: (a) the animal's experience during gas exposure; (b) practical considerations for humans; (c) compromise between the animal's experience and practical considerations; and (d) technical description of the procedure or policies. Many participants (51%) felt that there were alternatives available that could be considered an improvement over CO2, but perceived barriers to implementing these refinements. Qualitative analysis of these responses revealed five themes: (a) financial constraints; (b) institutional culture; (c) regulatory constraints; (d) research constraints; and (e) safety concerns. In conclusion, concerns regarding the use of CO2 often focused on the animal's experience, but barriers to alternatives related to operational limitations. New research is now required on to how best to overcome these barriers.

Voluntary Oral Ingestion of a Sedative Prior to Euthanasia with CO2: Behavioural Responses of Mice.

Laboratory mice are commonly euthanised with carbon dioxide (CO2); however, there is ample evidence that this gas is aversive. Previous work suggests that sedation achieved via injection with benzodiazepines prior to CO2 administration could reduce aversive behaviours during euthanasia. We explored the potential of using a voluntarily ingested sedative (tiletamine-zolazepam, Zoletil®) prior to euthanasia. Male and female C57BL/6 mice were allocated into one of the five experimental groups, which differed in the dose of Zoletil: 0, 10, 20, 40, 80 or 100 mg/kg. A dose of 20 mg/kg was found to achieve mild sedation prior to euthanasia; mice which received this dose numerically reared and walked on the cage lid less, and showed ataxia, immobility and recumbency for longer than mice that received a lower dose. During euthanasia, mice that received 20 mg/kg showed fewer aversive responses to CO2. Doses of 40 to 100 mg/kg were associated with signs of moderate to severe sedation, but resulted in an incomplete intake of the sedative, which made the interpretation of the aversiveness to CO2 difficult. Voluntary oral administration of a sedative is an effective, affordable, and easy way to minimize the stress of mice to euthanasia with CO2.

Understanding rat emotional responses to CO2.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2 exposure with active and passive defense behaviors. Plasma corticosterone and bradycardia increased in rats exposed to CO2. As with anxiogenic drugs, responses to CO2 are counteracted by the administration of anxiolytics, SRIs, and SSRI's. Human studies reviewed indicate that, when inhaling CO2, humans experience feelings of anxiety fear and panic, and that administration of benzodiazepines, serotonin precursors, and SSRIs ameliorate these feelings. In vivo and in vitro rat studies reviewed show that brain regions, ion channels, and neurotransmitters involved in negative emotional responses are activated by hypercapnia and acidosis associated with CO2 exposure. On the basis of the behavioral, physiological, and neurobiological evidence reviewed, we conclude that CO2 elicits negative emotions in rats.

Evidence for consistent individual differences in rat sensitivity to carbon dioxide.

Carbon dioxide (CO2) gradual-fill is commonly used to kill laboratory rats, but this use remains controversial due to a lack of agreement between studies. Inconsistencies may arise from differences in behaviors measured (e.g. active versus passive behaviors), in how rats cope with threats, or in rat sensitivity to CO2. The aims of the current study were to 1) describe active and passive responses during CO2 forced exposure, 2) determine if these responses are consistent within individuals and across aversive stimuli, 3) assess individual differences in aversion to CO2 in aversion-avoidance and approach-avoidance tests and 4) determine how responses in aversion tests relate to individual differences in behavior during forced exposure. Twelve Sprague Dawley female rats were exposed twice to three treatments: CO2, oxygen (O2), and fox scent, and were exposed to CO2 twice in each aversion test. The change in behavior from baseline was higher for rearing and locomotion when rats were exposed to CO2 than when exposed to O2 and fox scent. Responses varied among rats but were consistent across multiple tests within rats. For example, rearing was consistent within individuals between two exposures to CO2. Similarly, the strength of aversion was consistent within individuals across multiple exposures to CO2 in aversion-avoidance and approach-avoidance testing. Latency to avoid CO2 in aversion-avoidance tests was negatively correlated with rearing during CO2 forced exposure. Collectively, these results indicate that rat responses to CO2 vary between (but are consistent within) individuals, suggesting that rats vary in CO2 sensitivity. However, even the less responsive rats avoided CO2 concentrations far below those necessary to achieve unconsciousness, indicating that all rats likely experience negative states when euthanized with CO2.

Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar to those avoided by rats, and these feelings are diminished by the administration of benzodiazepines. Our aim was to assess the effects of the benzodiazepine midazolam on individual thresholds of rat aversion to CO2. Six female Sprague Dawley rats were repeatedly exposed to CO2 gradual-fill in approach-avoidance testing. The first three exposures were to a control-treatment followed by three exposures to midazolam (0.375 mg/kg). Within each treatment aversion to CO2 was not affected by exposure number; however, tolerance increased from an average of 10.7% CO2 avoided during control sessions, to 15.5% CO2 avoided when treated with midazolam. These results indicate that rats experience anxiety when exposed to CO2, and that variation in rat CO2 sensitivity is driven by individual differences in the onset of these feelings of anxiety. No rat tolerated CO2 concentrations required to induce loss of consciousness.

Virus de inmunodeficiencia humana: ¿estado de hipercoagulabilidad? Presentación de dos casos / Is AIDS a prothrombotic entity? Report of two cases

La infección por VIH ha sido reconocida en la actualidad como una condición protrombótica, reportándose en pacientes con SIDA 10 veces mayor riesgo de desarrollo de eventos tromboembólicos de los sistemas arterial y venoso; la literatura reciente ha estimado una incidencia entre el 0.26% y 7.6 %; dicha incidencia se describe asociada a infecciones. oportunistas y/o malignidades. Una variedad de mecanismos potenciales relacionados con factores del hospedador, el virus y el TARV (tratamiento antiretroviral), están implicados en el estado de hipercoagulabilidad en pacientes con SIDA, cuya fisiopatología conduce a alteraciones en la respuesta inflamatoria y de la cascada de coagulación que no han sido bien dilucidadas; sin embargo, incluye la presencia de anticuerpos anticardiolipinas, disminución de anticoagulantes naturales, y otros factores independientes que en conjunto originan morbi-mortalidad creciente si dicha predisposición a eventos trombóticos no es reconocida por el médico. Los autores de este artículo describen 2 casos de eventos trombóticos en pacientes con síndrome de inmunodeficiencia humana hospitalizados en el Servicio de Medicina Interna de Hospital Universitario de Caracas(AU)

AIDS infection has now been recognized as a prothrombotic condition reported in patients with this disease, and have been found 10 times at greater risk of developing thromboembolic events with systemic involvement. Recent literature has estimated an incidence between 0.26% and 7.6%, also described in association with opportunistic infections and / or malignancies. A variety of potential mechanisms related to host factors, virus and antiretroviral therapy (ART) are implicated in the hypercoagulability status in HIV-positive patients, the pathophysiology leading to alterations in the inflammatory response and the coagulation cascade. It has not been well understood and includes the presence of anticardiolipin antibodies, reduction of natural anticoagulants, and other independent factors that lead to increased morbidity and mortality if such predisposition to thrombotic events is not recognized by the clinician. The authors of this article describe 2 cases of thrombotic events in patients with human immunodeficiency syndrome hospitalized in the Hospital Universitario of Caracas, Venezuela(AU)

Endocarditis infecciosa en el Hospital Vargas de Caracas / Indective endocarditis diagnosis in the Hospital Vargas of Caracas

Se estudiaron en forma retrospectiva las historias clínicas de 64 pacientes que cunplían con los criterios diagnósticos de endocarditis infecciosa (EI) en el Hospital Vargas de Caracas entre enero de 1990 y diciembre de 1995. Se analizó la casuística en base a diagnóstico definitivo o probable de EI, sexo, edad, signos y síntomas más frecuentes, factores predisponentes, hallazgos microbiológicos, ecocardiográficos, evolución clínica, complicaciones y mortalidad durante su hospitalización. De acuerdo al análisis de los resultados, la endocarditis infecciosa no es una patología despreciable en nuestro medio, presentándose la mayoría de los casos entre la segunda y cuarta década de vida en pacientes en su mayoría con valvulopatias subyacentes, con un predominio de Gram positivos como agente causal y una mortalidad superior a la reportada en otras series internacionales, principalmente por complicaciones cardíacas