Contemporary Topics 39 (1)
2000

The effects of housing enrichment on cardiovascular parameters in spontaneously hypertensive rats. Contemporary Topics 39 (1): 9.
This study looked at the effect of various housing situations on multiple cardiovascular parameters in SHR (spontaneously hypertensive rats). Adult male SHR rats were implanted with radiotelemetric transmitters with catheters inserted in the femoral artery. After recovery from surgery, baseline values were recorded. These included mean systolic and diastolic blood pressure, mean heart rate and total activity.
During the first period, individually housed males were compared with pair-housed males. In the second period, each cage was enriched by adding a large piece of plastic drainpipe and several golf balls. In addition, all the animals were placed together daily for 2 hours at the beginning of the dark cycle. During the last period, rats previously individually housed were paired with another rat. Likewise, pair-housed rats were separated to single housing cages. Light cycle values were compared to dark cycle values.
Results confirmed earlier reports that show SHR rats have marked circadian rhythms in blood pressure, heart rate and activity. Pair-housed rats were more active and had higher systolic blood pressure when compared to individually housed rats. This was true with and without enrichment (in the form of manipulata or social enrichment). Finally, animals moved from double to single housing had significantly higher blood pressures and heart rates than rats changed from single to double housing.
Differences in cardiovascular parameters occuring at night between the 2 groups were linked to differences in activity. However, this correlation did not exist during the day. Therefore, the addition of enrichment which resulted in increased blood pressure may indicate that this change was viewed as a stressor. Further work needs to be done in various rat models to eludicate which 'enrichments' result in decreased stress in the animals, and which actually stimulate a neurogenic stress response.
Questions:
1. What is the SHR rat?
2. Name 2 methods for measuring blood pressure.
3. T/F SHR rats have defined circadian rhythms detectable in cardiovascular parameters.
4. T/F Placement of enrichment devices decreases the heart rate and blood pressure in SHR rats.
Answers:
1. Spontaneously hypertensive rat
2. Tail-cuff method (indirect) and arterial cannulation (direct)
3. T
4. F This did not always result in decreases in cardiovascular parameters.

Environmental Enrichment for rhesus macaques: a cost-effective exercise cage. Contemporary Topics 39 (1): 14.
This article discusses a novel method of modifying pre-existing, but outdated caging to serve as a portable excercise cage for environmental enrichment in non-human primates (must see picture of caging in article to appreciate). The newly modified caging serves to curb negative behavioral stereotypes in singly housed macaques as well as providing substantial cost savings. The authors also noted that use of these cages led to decreased self-directed biting, improved food consumption and and increased visual attentiveness by other animals.
Questions:
Q1. What are the recommended caging requirements for rhesus macaques up to 10 kg ( according to the "Guide")?
Q2. What are the recommended requirements for housing two or more animals in the same cage?
Q3. True or False
Type 304 stainless steel is recommended for nonhuman primate caging composed of stainless steel.
Answers:
A1. 32 " high, 4.3 ft sq
A2. The cage floor must be the sum of the space required for both animals and the cage height must be the sum of space required for both animals and the cage height must meet the requirements for the largest animal (exception: mothers with infants less than 6 months
A3. True

Stress produced by gavage administration in the rat. Contemporary Topics 39 (1): 17.
The relationship between gavage administration of various vehicles and induction of the stress response was studied in rats. Increased plasma corticosterone levels were used as the indication of the stress response. Additionally, elicitation of clinical signs of distress and aspiration leading to airway/pulmonary changes were assessed. The following vehicles, commonly used in toxicology studies, were assessed: water, corn oil, 1% methylcellulose/0.2% Tween 80.
After a quarantine and acclimation period to the dosing regime, rats were randomized into vehicle groups at various dosages. An hour after dosing rats, blood samples were collected (for corticosterone levels), then 4 hours after dosing rats, the rats were euthanized by carbon dioxide asphyxiation. Rats were necropsied with the respiratory tract being examined for evidence of aspiration. Lungs were weighed and removed.
Gavage administation of the vehicles at dose levels of greater or equal to 20 ml/kg resulted in clinical signs in rats. Gavage administration of corn oil at greater or equal to 20 mg/kg induced a stress response in a volume-dependent fashion, resulting in elevated plasma corticosterone levels. This response was not seen with water nor 1% methylcellulose / 0.2% Tween 80; however, rats given these agents had evidence of aspiration. The response due to corn oil was also seen after gavage administration of sesame, soybean, and peanut oils. Consequently, gavage dosing of lipid vehicles induces activation of the stress response in a volume-dependent fashion.
QUESTIONS
Q1: How is dose volume determined for administration in gavage studies?
Q2: Which agent induced a stress response in a volume-dependent fashion?
Q3: What is the dose volume limit for gavage administration in the rat (according to this study)?
ANSWERS
A1: solubility of test compound in vehicle
dose level to be administered
stability and homogeneity of dosage formulation
concentration of test compound in vehicle
A2: corn oil
A2: 10 mg/kg

A novel vented microisolation container for caging animals: microenvironmental comfort in a closed-system filter cage. Contemporary Topics 39 (1): 22.
This group designed a closed-system cage with filtered vent ports. The placement of the ports was designed to provide continuous airflow in an occupied cage. The metabolic heat loads of mice provided the driving force for air flow. Upward warm air currents escaped through the top exhaust port, while cool room air entered through the lower intake port. Computational Fluid Dynamics (CFD) and smoke visualization helped design and document a one - pass air circulation in this system. In addition, Hot - film anemometry and smoke test techniques demonstrated adequate ventilation in an occupied cage.
Results: In a room with 0 air changes per hour (ACH)
Cage occupied by 1 mouse: 6 ACH
Cage occupied by 5 mice: 12 ACH; after 1 week the avrg. cage temp
was 0.5C, relative humidity was 34%, and the ammonia concentration was 3ppm higher than the room.
Question:
What is CFD?
Answer:
CFD is the science of determining a numerical solution to the governing equations of fluid flow whilst advancing the solution through space or time to obtain a numerical description of the complete flow field of interest.

A novel approach for assessing the quality and effectiveness of IACUC oversight in investigator compliance. Contemporary Topics 39 (1): 28.
In order to measure the effectiveness of IACUC oversight and evaluation of animal care and use, the author's IACUC retained a management consultant group to design and conduct a survey that could be used to determine how the IACUC could improve the process of aiding researcher compliance with regulation and accreditation standards.
Step 1: In the first stage of the project, the management consultant group conducted confidential interviews with IACUC members and 25 of the facility's principal investigators. Following the interviews, the consultant met with selected IACUC members to review findings which were subsequently used to develop a written survey questionnaire for the second stage of the project.
Step 2: The written survey contained 22 close-ended multiple-choice questions, 5 open-ended questions and appropriate demographic items. Close-ended questions were expressed in a "Strongly agree" to "Strongly disagree" response continuum with a "No opinion" option. Open-ended questions allowed the respondents to express their own opinions. A draft of the written questionnaire was submitted to the IACUC for review and approval prior to distribution. The survey was distributed to the animal-using population including technical staff, vice-presidents, directors, etc. Survey responses were submitted directly to the consultant group in order to maintain confidentiality.
Step 3: Survey results were presented to the IACUC in formal briefing sessions and in a comprehensive Summary Report. Response to the written survey was considered good (34%). Recommendations were made based on the results of both interviews and the written survey.
In an attempt to improve overall IACUC effectiveness with respect to investigator compliance, the IACUC instituted a plan of action that prioritized survey findings. Follow-up surveys will be used to measure the plan's success. The survey was considered an excellent way to assess the quality and effectiveness of IACUC - investigator interactions by determining the level of researcher satisfaction.
Questions:
1.) What approach did the facility's IACUC use for assessing the quality and effectiveness of IACUC oversight in investigator compliance?
2.) How was the content of the written survey gathered?
Answers:
1.) A management consultant group was retained to objectively design and conduct a confidential survey.
2.) The survey questions reflected information that was gathered during the individual interviews.

Therapeutic efficacy of oral lactobacillus preparation for antibiotic-associated enteritis in guinea pigs. Contemporary Topics 39 (1): 32.
Anecdotal evidence exists for the treatment of antibiotic associated enteropathy for mice, hamsters, guinea pigs, and rabbits. Frequently Clostridium difficile is implicated in most rodent species (C. spiriforme is the causative bacterium in rabbits). This phenomenon in the hamster is used as model for pseudomembranous colitis in people. The rational for using lactobacillus preparations to limit disease in affected animals is: the good bacteria will compete with potential pathogens for colonization sites as well as produce lactic acid which is thought to stimulate GI immune function. This study aim to assess the ability of a single dose of clindamycin to induce enteritis in CAMM/Hartley guinea pigs and to evaluate a commercially available lactobacillus formulation (Probiocin) for it^Òs ability to reduce or eliminate the clinical effects of enteritis.
Results: Guinea pigs receiving only Probiocin via gavage BID remained healthy and active. Guinea pigs receiving the antibiotic only or antibiotic with Probiocin treatment developed large bowel edema and congestion, with neutrophillic infiltration of the small and large bowel. No Clostridal enterotoxin type A was detected at any time.
Conclusion: Probiocin was ineffective at preventing anorexia, weight loss, as well as decreased food and water consumption in guinea pigs receiving a single injection of clindamycin. They offer many hypothetical reasons for the failure of the treatment.
Questions:
1. What organism is commonly implicated in antibiotic associated enteritits of hamsters, mice and guinea pigs? Rabbits?
2. How does this organism cause morbidity in animals?
3. T/F Oral administration of lactic acid products to guinea pigs have proven to be very effective at limited the clinical course of enteric disease.
4. Which antibiotic is highly associated with enteric disease in guinea pigs?
Answers:
1. Clostridium difficile, rabbits get C. spiriforme
2. Production of Type A enterotoxin
3. False.
4. clindamycin

Outbreak of Pasteurella pneumotropica in a closed colony of STOCK-Cd28tm1Mak mice. Contemporary Topics 39 (1): 39.
This report of an outbreak of Pasteurella pneumotropica in a group of mice homozygous for a Cd28 gene mutation discusses both evidence for an immunologic basis for susceptibility to this agent, and information about the mouse strain itself. These mice are selectively immunodeficient when homozogous for Cd28 -/-. Nude mice have been shown elsewhere to have an increased incidence to P. pneumotropica, and in this case 20% of homozygous pups (two to three weeks of age) showed periorbital abscesses while only one of the heterozygotes and none of the wild type littermates showed disease.
This strain of mouse shows immunodeficiency toward some agents and normal response to others, thus it is termed "selectively immunodeficient". Interestingly when the homozygote is crossed with NOD mice for which Cd28/B7 interaction is important in the spontaneous autoimmune diabetes in NOD mice, there is more rapid development of diabetes rather than the expected resistance expected in Cd28 negative mice.
Pasteurella pneumotropica can be expected to show the following pathologic changes: conjunctivitis, dacryoadenitis, and panopthalmitis, plus urogenital and subcutaneous infections. There are several variants which can be distinguished through culture media alterations, but this is difficult due to weak and variable phenotypic reactions. PCR of the 16S sequence is currently only available for three types, but is an easier and more definitive method for typing. The organisms in this outbreak showed strong (99.5%) homology to biotype Heyl.
Virulence of the organism appears low since cage mates that were not Cd28 -/- , except for one heterozygote, did not develop signs.
Questions:
1. List three pathologic changes in Pasteurella pneumotropica infection.
2. What is meant by -/- in the name of these mice?
3. Culture is the best method to distinguish variants of P. pneumotropica. T or F
4. What trait is found in NOD mice?
Answers:
1. conjuctivitis, dacryoadenitis, panopthalmitis, uorgenital infections, subcutaneous infections
2. the animal are missing both alleles of the gene , in this case Cd28 gene
3. False, PCR is a more definitive and easier test
4. Spontaneous autoimmune (Type 1) diabetes mellitus

Reverse transcriptase polymerase chain reaction (RT-PCR). Contemporary Topics 39 (1): 42.
This is a technology update illustrating RT-PCR. RT-PCR is like PCR except that it amplifies small pieces of RNA, not DNA. This article illustrates the RNA template, the priming event, the first strand synthesis of cDNA, the removal of the original RNA template and finally the PCR reaction.
Questions:
1) What stain is used to visualize DNA on a gel?
2) What are alternative techniques for RT-PCR?
3) What are the advantages of RT-PCR?
4) What are the disadvantages of RT-PCR?
Answers:
1) Ethidium bromide
2) Northern blot analysis, RNAse protection assay
3) High sensitivity, very specific, can be completed fairly rapidly (1-2 working days)
4) Similar to those of PCR, it detects mRNA and not protein