Laboratory Animal Science 47 (6)
1997
 

Animal Well-Being I.  General Considerations. Laboratory Animal Science 47 (6): 564.
This is the first in a series of papers intended to provide a scientific overview of animal well-being and related topics that will serve as a stimulus for empirical research in this area..
    Currently there is no clear definition of animal well-being. Critical anthropomorphism, which is defined as empathy tempered by objective knowledge of the particular species' life history, behavior and physiology, has usually been employed. Physical well-being, such as freedom from disease and contamination, has mostly been achieved. Psychological well-being on the other hand remains difficult to achieve due to lack of empirical studies and precise definitions.  Research data from a variety of fields, such as animal biology and behavior, stress biology, and psychoneuroimmunology, increasingly support a holistic view of well-being. An animals's state of well-being or homeostasis is determined by a multitude of external (psychosocial and physical stimuli) and internal (mental and biological responses) factors and interacting variables and by other aspects such as ethology, genetics, individual variation, social milieu, experience, learning, perception, coping style, and intensity, duration and frequency of stimuli.
No questions

Animal Well-Being II. Stress and Distress. Laboratory Animal Science 47 (6): 571.
Stress, in general, refers to a state of threatened homeostasis.  Despite 50 years of research, an acceptable universal definition has not been established.
This is largely due to the inability to solve 4 major problems:
1. defining consistent physiological indicators of stress
2. lack of nonspecific stress response characteristics to different stimuli
3. individual response variability
4. failure to correlate stress measures to animal well-being
Stess does not refer to a single factor of bodily reactions, but to a heterogeneous assortment of phenomena.
Kopin's definition of stress:  stress occurs when the expectations, genetic or acquired do not match current or anticipated perceptions of the internal or external environment.
Definitions:
Eustress - good stress, benefits animal comfort, well-being, reproduction and helps maintain a homeostatic state
Neutral Stress - neither helpful nor harmful to the animal
Distress - interferes with animal comfort, well-being, reproduction and helps maintain a homeostatic state
Physiological Stress - harmless, fully adaptive stimulation
Over Stress - initially damaging response, but fully adaptive stimulation
Threats to homeostasis:
- lack of information
- excess stimulation
- inhibition of predetermined response - a captive environment may contribute
- development of acquired needs - could also be a result of captivity
- lack of stimulation
Mechanisms for dealing with stress are derived from either:
1. Phylogeny - species-specific responses (which are difficult to modify)
In captivity when these responses are inhibited they may result in CNS disturbances and psychomotor activities which contribute to psychological disability or disease
2. Ontogeny - individual selection based upon development and learning
Adaption - passive event, animal has little control over, can be manifested at the species level in genetic change or at the individual level in developmental change.
Coping - active process
        - may resist stress rapidly (by fleeing) - involves sympathetic
response (or) may resist slower (by freezing or gradually withdrawing) - involved hypothalamus-pituitary axis (HPA) and parasympathetic response
Habituation - decreased response to repeated stimuli - nonassociative learning
Sensitization - increased response to repeated stimuli - nonassociative learning
    Autonomic System (AS) response involves the sympathetic nervous system, adrenal medulla, and release of catecholamines (fight or flight response). Sudden acute challenge results in release of dopamine, epinephrine (E), and norepinephrine (NE) from the hypothalamus;  E and NE from the adrenal
medulla, and NE from the sympathetic nerve termini
  E and NE inhibit glucose and fatty acid storage and protein synthesis.
  Release of energy substrates (glucose, aa, free fatty acids) from the liver, muscle and fat are stimulated
  The sympathetic nervous system response also facilitates learning and memory.
HPA response - involves the hypothalamus, anterior pituitary gland, adrenal cortex, and glucocorticoid release.
  Response is slower and initially counteracts the AS response inorder to restore homeostasis
  Usually occurs with more severe, persistent and repeated disturbances The AS and HPA are not separate but integrated and complementary
    The brain plays the role of central regulator in stress. It organizes the response to aversive stimuli.
    The neurons in the hypothalamus and brain stem respond to internal (psychochemical) and external (psychosocial and physical) stimuli The limbic system affects the psychological state and feelings and is involved in learning and memory of the stimulus-response association.
   Tonic Immobility - behavioral response characterized by profound motor inhibition and temporary loss of righting reflex (the animal can't flee or fight).
     There are several other bodily systems involved in the response to stress.  Aversive stimuli typically inhibit the parasympathetic system.  Growth hormone and somatomedin production are typically inhibited by noxious stimuli in rodents, whereas in humans the GH levels initially increase, but decrease if the stimulation is prolonged.
Questions:
1. Most closely involved in the  autonomic system's immediate response to an aversive stimuli are:
a. hypothalamus, sympathetic nervous system, adrenal medulla
b. hypothalamas, parasympathetic nervous system, adrenal medulla
c. hypothalamas, sympathetic nervous system, adrenal cortex
d. anterior pituitary gland, sympathetic nervous system, adrenal medulla
e. anterior pituitary gland, sympathetic nervous system, adrenal cortex
2. The following factors (more than one) are released from the hypothalamus in response to an aversive stimuli:
a. dopamine
b. corticotropin releasing hormone (CRH)
c. epinephrine
d. norepinephrine
e. adrenal corticotropic hormone (ACTH)
3. Eustress is:
a. true stress
b. good stress
c. bad stress
d. baseline stress
e. female sheep stress
4. If an animal flees from an aversive stimuli it is:
a. adapting
b. coping
c. habituating
d. counter-averting
5. Which of the following term(s) can be associated with nonassociative learning:
a. limbic system
b. habituation
c. sensitization
d. phylogeny
e. ontogeny
Answers:
1. a) hypothalamus, sympathetic nervous system, adrenal medulla
2.  a, b, c, d)  (ACTH is released from the AP in response to CRH)
3. b) good stress
4.  b) coping
5.  b,c,e)

Animal Well-Being III.  An Overview of Assessment. Laboratory Animal Science 47 (6): 580.
An assessment of animal well-being is a complex issue that should involve a multidisciplinary approach of investigators including vets, ethologist, behaviorist, physiologist, psychologist, epidemiologist and pathologist.  There is a need to evaluate numerous criteria (ie performance, clinical status, mental and biological profiles, neurochemistry, endocrinology, immunology, ethology and morphology)  to compile a complete mental\biological profile  of animals.  Researchers are urged towards determiniing the status of well-being in a captive situation and making appropriate adjustments rather than simply attempting to mimic the animals natural habitat.  An assessment should be made of the prepathological state.  The prepathological state does not necessarily imply that the pathologic state will follow but it represents a threat to well-being. Assessing this prepathological period is also important. More emphasis should be placed on finding ways of refining the existing measures of well-being and deteriming ho
   Some factors that contribute to difficulty in interpretation of well-being data are responses to handling, circadian, population density, training and biological interactions.
   This article was difficult to summarize because it dealt with several key points.  I felt that the above were some of the most important.
No questions

Animal Well-Being IV.  Specific Assessment Criteria. Laboratory Animal Science 47 (6): 586.
This was part of a Special Topic Overview on animal well-being.  A number of factors have potential use as indicators of animal well-being. Classic and practical criteria for assessing animal well-being are a combination of general health status, clinical signs of disease, and performance.  Abnormal behaviors are classified as qualititative (occur in captivity but not in nature) or quantitative (part of the natural reportoire, but ocurring in abnormal context, frequnecy, or duration).  Neurochemical and endocrine factors are involved in an animal's responses to stimuli.  Catecholamines, glucocorticoids, serotonin, and other endogenous compounds can have profound effects on the physiology of an animal, and can cause morphologic and pathologic changes in some tissues.  The lymphosuppressive influence of the hypothalamic-pituitary-adrenal axis on the immune system is well documented.
Questions
1.  T/F  Prolonged aversive stimuli have been shown to cause
        a.              ...morphologic changes in tissue
        b                ...quantitative and qualitative behavior abnormalities
        c.              ...alterations in hormone and neurotransmitter levels
2.  Categorize these abnormal  behaviors as quantitative or qualitative
a.              self-mutilation in a primate
b.              barbering in mice
Answers:
1- abc all True
2. a. Qualitative (not a natural behavior)
        b quantitative (excessive grooming, where grooming is a natural behavior).
(Some behaviors overlap- e.g. repetetive stereopathies may incorporate a normal behavior (flipping) but take it to extremes of frequency.

Spontaneous Osteoarthritis in Dunkin Hartley Guinea Pigs:  Histologic, Radiologic, and Biochemical Changes. Laboratory Animal Science 47 (6): 598.
The Hartley guinea Pigs are animal models of spontaneous osteoarthritis (OA) used to study the pathogenesis of the disease and drug evaluation as a therapeutic model.  Similar to changes in humans with OA, histologic changes in male Dunkin Hartley Guinea Pigs at 22 months of age were characterized by cartilage degradation, cyst formation, marginal osteophytes, and subchodral sclerosis.  Radiographic changes included marginal tibial osteophytes, sclerosis of the subchondral bone of the tibial plateau, cysts in femoral condyles and tibial plateau, and calcification of the collateral ligaments of the knee.  Biochemical changes included increased deposition of proteoglycan in cartilage in the hypertrophic phase of the disease and the increase in collagen fragments in synovial fluid.
Questions:
1- When appear moderate to severe spontaneous osteoarthritis histologic lesions in Hartley guinea Pigs animal models ?
a) 2 months
b) 3 months
c) 8 months
d) 12 months
e) 18 months
f)  22 months
2- T/F.  The increased deposition of proteoglycan in cartilage in the hypertrophic phase of the disease and the increase in collagen fragments observed in synovial fluid can be detected by measuring the changes in the proteoglycan-to-collagen ratio in harvested cartilage and are charateristic of OA.
Answers:
1- e)
2- True

Lack of Reactivation of Shigellosis in Naturally Infected Enrofloxacin-Treated Cynomolgus Monkeys After Exogenous Immunosuppression. Laboratory Animal Science 47 (6): 602.
Four of 60 cynomologous monkeys in quarantine became acutely ill with dysentery. Shigella flexneri was isolated from rectal swabs. All 60 animals were treated with enrofloxacin, 5mg/kg, im, q 24 hrs for 10 days.  The ill animals showed clinical improvement within 24 hours and no new cases appeared.  Rectal swabs were taken weekly for 4 weeks after cessation of antibiotic treatment and were consistently negative for S. flexneri. It is believed that some NHPs can enter an asymptomatic carrier state that can later, possibly in association with stress, revert to active clinical disease and/or shedding of the organism. To test this idea, the investigators attempted to reactivate the disease by immunosuppressing the 4 previously ill animals.  Four months after resolution of clinical signs, the animals were treated with methylprednisolone acetate, 10 mg/kg, im, 2x weekly, for 5 weeks. Immunosuppression was considered successful based on the depressed uptake of tritiated thymidine in a PHA stimulation assay on cultured lymphocytes from the treated animals. During the 5 week treatment period and for 2 weeks thereafter, the animals were regularly observed and examined. No animal developed signs of clinical illness and S. flexneri was not isolated from blood or fecal swabs. These results suggest that treatment with enrofloxaxin eliminated Shigella from the animals. Some caveats to this conclusion were noted. First, S. flexneri can be difficult to isolate and diagnostic polymerase chain reaction techniques might have been more efficient for detecting low numbers of organisms. Secondly the sample size of 4 is small.
Questions:
1. What area of the gastrointestinal tract is most likely to be affected by
a Shigella infection?
a. oral mucosa
b. stomach
c. small intestine
d. colon
2. What role(s) do plasmids play in the pathogenicity of Shigella?
Answer:
1. The answer is d. but lesions have been reported in all of the other choices as well.
2. The genetic information for the production of several virulence factors that enable Shigella organisms to attach and penetrate cells is found on plasmids. Other plasmids or R-factors carry antibiotic-resistance genes.

Pancreatic Exocrine Studies in Intact Animals:  Historic and Current Methods. Laboratory Animal Science 47 (6): 606.
This report presents a review of the historic and current methods for performing pancreatic exocrine studies in intact animals.
    In humans, the major pancreatic duct has a common outlet into the duodenum with the bile duct at the major duodenal papilla and is know as the pancreatic duct. The accessory duct retains its duodenal outlet at the minor duodenal papilla.  In dogs, the main duct is the accessory pancreatic duct, opening into the duodenum at the minor duodenal papilla. The pancreatic duct, which joins the bile duct and forms the major duodenal papilla in man, is small and not always present in the dog. The canine pancreatic duct system, characterized by a major function of the accessory pancreatic duct and a small pancreatic duct that can be ligated without retention of pancreatic secretions, allow acquisition of the whole pure pancreatic secretion without admixture of bile.
    To collect pancreatic secretion in dogs, three animal models have been developed: pancreatic fistulas, duodenal pouches and duodenal fistulas.
    Pancreatic fistulas: With the exception of acute studies in anesthetized animals, pancreatic fistulas were used mainly during the first half of the 20th century and have rather historic significance. The fistulas used may be classified as temporary, semipermanent and permanent.  Temporary pancreatic fistulas were made by cannulating the pancreatic duct in an acute experiment. They were used mainly for physiologic studies with its greatest use in pharmacokinetic studies and studies of humoral agents.  Semipermanent fistulas were made by cannulating the pancreatic duct with a catheter that was exteriorized through the abdominal wall. The authors describe several techniques which were employed. The semipermanent fistulas have mainly historic significance, with only one success. Technical difficulties and chronic pancreatitis secondary to the increasing intraductal pressure in the pancreatic duct caused by the cannula and its fixation were responsible for failure of these procedures. Long-term pancreatic fistulas are the result of transplanting the pancreatic duct or the duodenal papilla into the skin.  Several techniques are described. The main disadvantage of the total pancreatic fistulas is that they cause disturbances in digestion and absorption, disorders in water and electrolyte balance and local irritive lesions.
    Duodenal pouches: A duodenal pouch represents a separated segment of the duodenum containing the pancreatic papilla, which is closed at both ends an into which the pancreas drains. Several techniques are described. The preparation of duodenal pouches is the method of choice for studying the pancreatic secretory response to orally or intragastrically administrated meals, which is impossible to study using duodenal fistulas.
    Duodenal Fistulas: A duodenal fistula allows a method for collecting pancreatic secretion through a permanent duodenal fistula, leaving the pancreas and its ducts in their normal relations to the duodenum and to their nerve and blood supply. Several techniques are described. Advantages of this method are: the duodenal fistula allows collection of total pancreatic secretion; the secretion is not contaminated with bile and duodenal juice and is therefore not activated by the duodenal juice and  duodenal enterokinase; experiments can be performed in conscious dogs; the intra- and postoperative mortality is very low; and a long duration of survival allows several experiments, including control, to be performed in the same animal.
    Rats: The pancreas of the rat is very diffuse. The bile duct is embedded for its distal four-fifths in the pancreatic tissue, The pancreatic ducts vary in number from 15 to 40 and empty into the bile duct. Apparently, none empty directly into the duodenum, so that pancreatic secretion from the gland passes in a mixture with bile into the duodenum. Therefore, a cannula inserted into the proximal fifth of the bile duct, near the liver, will drain bile alone, leaving the pancreatic flow into the intestine undisturbed. Several techniques are described.
    Cats: The feline species has a relationship to the bile duct to the pancreatic duct that is similar to humans. The accessory pancreatic duct is either absent or very small. Several techniques are described.
    Pigs: In the pig the pancreatic duct passes directly into the duodenum, which corresponds embryologically to the accessory pancreatic duct.. No other duct becomes functional, even when the function of the first duct is interrupted.. Several techniques are described.
    Rabbit: In rabbits, a main pancreatic duct enters the ascending duodenum 35 to  40 cm distal to the bile duct entrance; however, it is difficult from he available sources to determine which duct it is. Several techniques are described.
    Cattle: The main advantage of collecting pancreatic secretions from ruminant species over monogastric animals is that bovine species have a greater capacity for homeostasis. The cow may be the species of choice when large quantities of pancreatic secretion are needed.
    Sheep: Only the main pancreatic duct is s present in sheep. It joins the common bile duct before it reaches the duodenum.
    Horses: The equine pancreas is almost invariably drained by two ducts. The main pancreatic duct opens into the hepatopancreatic ampulla alongside the bile duct. The accessory pancreatic duct ends on the minor duodenal papilla opposite the main duct.
No questions - look at pictures

Predictive Value of Several Signs of Infection as Surrogate Markers for Mortality in a Neutropenic Guinea Pig Model of Psuedomonas aeruginosa Sepsis. Laboratory Animal Science 47 (6): 617.
Bloodstream infections in humans due to Pseudomonas aeruginosa have an overall mortality of 33-78% and more effective antipseudomonal therapies are being sought.  Neutropenic mouse and rat models of Pseudomonas sepsis are used to compare efficacies of anti-pseudomonal antibiotics.  These models have been the only experimental paradigms that have been shown to predict the relative efficacies of antibiotics in neutropenic pateints with bacterial sepsis.  In these neutropenic models of sepsis, death is used as an end point (as also occurs in human clinical trials!).  Study was designed to determine premortality end points to be used without decreasing the validity of the experimental findings.  Guinea pigs were used instead of rats or mice because the dehydropeptidase-1 enzyme of humans and guinea pigs does not hydrolyze the antibiotic, meropenem rapidly, whereas this enzyme found in the renal brush border of the mouse and rat does hydrolyze meropenem.  283 female Hartley guinea pigs were made neutropenic by daily injections of cyclophosphamide IP for 6 days to induce a neutrophil count of <500 cell/ml blood.  24 hrs. after the last cyclophosphamide dose, the guinea pigs were injected with P. aeruginosa IP.  Guinea pigs were observed at 8a, noon, 4p, 12p for 8 days.  Various antibiotics were tested by dosing 2 hrs. after P. aeruginosa and every 8 hrs. for 9-12 doses.  The signs of infection that were evaluated as potential markers for mortality included ruffled fur, labored breathing, diarrhea, hunched posture, abnormal movements, lethargy, inappetence for >48 hrs., the inability to ambulate, and the inability of supine animals to stand.  All of the animals that received 10 7 and 10 8 CFU bacteria died within 48 hrs. and 80-90% of those in the lower bacterial inocula died between 1-3 days.  Overall, 31% of the treated guinea pigs survived, and 69% died.  Analysis of signs that occurred in untreated animals was hampered by the fact that these animals died within 24 hrs. of infection.  The inability of standing animals to walk and the inability of animals to rise from a supine position both had a 100% positive predictive value for ensuing death and a specificity of 100%.  In the antibiotic treated group, the inability of animals to rise from a supine position and the inability to ambulate when gently prodded with a gloved finger had 100% positive predictive value for death with death occurring within 8 hrs. and 40 hrs. respectively.  The infections progressed rapidly when it was in its final stages and they admitted they needed more frequent observations.  5% of infected guinea pigs developed nonreducible rectal prolapse during the study and were euthanized.  Therefore, in infected neutropenic treated and untreated animals, the only signs that reliably predicted death were the inability of infected guinea pigs to rise from the supine position and the inability of animals to ambulate with positive predictive value of 100%, and can be used in place of death as an endpoint in models of P. aeruginosa sepsis.  Signs like ruffled fur, lethargy or decreased food and water intake were present in many of the study animals and could not be used to predict death.
Questions:  Which signs in the guinea pig Pseudomonas aeruginosa sepsis model can be used to predict death?
Answer:  In infected neutropenic treated and untreated animals, the only signs that reliably predicted death were the inability of infected guinea pigs to rise from the supine position and the inability of animals to ambulate with positive predictive value of 100%, and can be used in place of death as an endpoint in models of P. aeruginosa sepsis.

Retrospective Evaluation of Cardiopulmonary and Acid-Base Variables During Long-Term Balanced Anesthesia for Experimental Surgery in Dogs. Laboratory Animal Science 47 (6): 624.
Retrospective Evaluation of Cardiopulmonary and Acid-Base Variables During long-term experimental surgical procedures in healthy dogs. The authors did a retrospective study of dogs that were anesthetized between 12.5 and 16.9 hours for experimental bulla osteotomy with implantation of hearing aids. The group reporting this data is from Germany so several of the drugs they used may be unfamiliar to us in the US. They premedicated with propionylpromazine (phenothiazine derivative) and L-methadone (opiod agonist that is 1 to 3 times as potent as morphine), induced with pentobarbital sodium and maintained with halothane in nitrous oxide and oxygen. They analyzed data form 4 hours and 14 hours after induction of anesthesia and found arterial (Pao2) and alveolar (PAo2) oxygen tensions, arterial-to-alveolar oxygen tension ratio (Pao2/PAo2), and arterial oxygen content (Cao2) remained relatively stable throughout the anesthesia. Arterial carbon dioxide tension (Paco2) was significantly increased above baseline between 7 and 9 h after induction. Significant increases in body temperature as well as slight increases in arterial blood pressure was also noted. Mild metabolic acidosis existed at 4 h after induction and was related to tissue hypoperfusion. Small increases in pHa during the course of anesthesia were accompanied by significant increases in HCO3- concentration and significant decreases in BD between 5 and 10 h after induction. Three dogs suffered muscle and tissue swelling post surgically, but all dogs recovered completely.
Questions:
1. Name several parameters that can be measured to assess adequacy of anesthetic depth in the dog.
2. Name several parameters that can be measured during anesthesia to ensure adequate organ perfusion.
3. Name several parameters that can be measured during anesthesia to ensure adequate O2 supply and CO2 elimination.
Answers:(Not necessarily inclusive of every possible answer)
1. End Tidal Halothane, heart rate, arterial blood pressure, respiratory rate, several reflex tests (ie palpebral reflex)
2. Arterial blood pressure, urine output, i.v. infusion rate and acid-base data.
3. Inspiratory O2 concentration, tidal volume and minute volume.

The Guinea Pig Estrous Cycle:  Correlation of Vaginal Impedance Measurements with Vaginal Cytologic Findings. Laboratory Animal Science 47 (6): 632.
 The study reported here documents vaginal impedance as an improved means of determining accurately precise stages of the estrous cycle of guinea pigs. Impedance changes were correlated with cytologic changes observed in vaginal smears taken from the animals.  The start of the impedance peak corresponded with proestrus, the rising side of the peak with estrus, and the apex of the peak with metestrus; diestrus was seen approximately 3 days after the peak apex. These results contrast with those of previous studies.
   Mucosal vaccine strategies are being devloped for diseases such as Chlamydia trachomatis and HIV that enter via the mucosa.  Immunologic responses elicited after vaginal immunization of laboratory mammals are affected by the stage of the animal's estrous cycle at which antigen is delivered. The guinea pig is the most common model of human Chlamydia infection.
   Various dosage regimens of estradiol (1 to 1,000 micrograms/animal over 1 to 6 days) were used in guinea pigs in an attempt to invoke an extended (> 6 h) estrogen-induced mucosa. Parenteral administration of 1,000 micrograms of estradiol to guinea pigs daily for 6 days induced a 2- to 3-day estrus stage in these animals.
Questions:
q1.  What is the length of the guinea pig estrous cycle?
q2.  what is the usual method used to determine stage of the estrous cycle?
q3. The apex of the imepdance peak corresponded with what stage?
Answers
a1. 15-17 days
a2. vaginal cytology
a3 metestrus.

Genetic Characterization of Novel Strains of Rats Derived from Crosses Between Wistar-Kyoto and Spontaneously Hypertensive Rats, and Comparisons with their Parental Strains. Laboratory Animal Science 47 (6): 638.
The authors of this article describes two novel strains of rats that were generated from hybrid crosses of sponteously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.  The strains that were derived from these breeding pairs were the WKHT and the WKHA.  They differ in that the WKHT are hypertensive, but not hyperactive and the WKHA are hyperactive without being hypertensive.  They have been refined by a strict  brother to sister inbreeding program for more than 25 generations.    Upon further characterization it was found that the two novel strains were more genetically similar to the parent strains that they were to each other.  It was also found though immunogenetic analyes  that the WKY and the WKHT rats belonged to the RT1 l haplotype, and the SHR and WKHA rats belonged to the k haplotype.
Questions:
1. T or F The WKHA rat is hypertensive and hyperactive?
2.T or F  The WKHT rat is hypertensive , but not hyperactive?
3.The _____ and _____ rats are the parent strains of the WKHT and WKHA rats.
Answers:
1.F.
2.T
3. SHR and WKY

Diagnostic Exercis:  Illness, Cutaneous Hemorrhage, and Death in Two Squirrel Monkeys (Saimiri sciureus). Laboratory Animal Science 47 (6): 647.
Two female squirrel monkeys were presented for widespread cutaneous petechial hemorrhages.  Necropsy identified:  bloody fluid and clots in the peritoneal cavity; hemorrhage in the lungs, adrenal glands, and GI tract; petechiation of the epicardium; hemorrhage in the meninges; a pale liver with enhanced lobular patter; enlarged spleen; and enlarged and reddened cervial lymph nodes.  Histopathology:  necrosis of the lymph nodes, liver (adjacent to portal triads), and lung.  Hemorrhage noted in all other tissues.
 Hematology findings included:  decreased RBCs, Hb, PCV, MCHC, and WBCs.  Chemistry panels:  increased AST, direct bilirubin, creatinine; decreased Ca, TP and Alb.
 The animals had been housed outside.
 Franciscella tularensis.  This is a small, GN coccobacillus.  It is transmitted by fly or tick bites, but can gain entry via skin abrasion, animal bite, conjunctivae, ingestion or inhalation as well.  Presentation depends on route of infection.  These two cases suggested the oropharyngeal form of tularemia.  Diagnosis requires serolgy +/ bacterial isolation and identification.
No questions

Specific-Pathogen-Free Conditions Enhance Inflammatory Bowel Disease in T-Cell Receptor Knockout, but not C3H/HeJBir Mice. Laboratory Animal Science 47 (6): 650.
The authors describe that their experience has shown that Jackson Lab's C3H/HeJBir mice do not spontaneously develop IBD (at least under the conditions present at the U of Illinois).  They suggest that B6,129Tcra(tm1Mom) mice may be the better model for IBD in humans due to the environmental interactions with genetic and immunologic factors in this strain of mouse.
QUESTIONS:
1)  Signs of IBD in mice include:
    (a)  anal swelling
    (b)  occular discharge
    (c)  rectal prolapse
    (d)  diarrhea
    (e)  a, c, and d
ANSWERS:
1) E

Effects of Infusion Rates in Rats Receiving Repeated Large Volumes of Saline Solution Intravenously. Laboratory Animal Science 47 (6): 656.
The study was performed to evaluate iv saline infusion of high volumes.  Weight gain and loss were evaluated in control, restrained and untreated, and rats restrained and treated.  Some pulmonary infiltrates of eosinophils were seen in most rats with an increase in rats with more saline given.  80 ml\kg at 1 ml per min.  Weight loss was seen in all restrained animals whether they were catheterized or not.  Pulmonary granulomas were observed secondarily to catheter placement(skin and hair fragments were identified in the granulomas).
Glomerular filtration rate( 8.7 -11.5 ml\min ) will determine rats ability to clear excess water from the body.  The study concluded that large volumes of fluids 8% of blood volume can be given safely to healthy rats.
Question
1.  What is the approximate glomerular filtration rate in the rat?
2.  What is the maximum volume of saline that can be administered to healthy rats?
Answer
1.  8.7-11.5 ml\min
2.  8% of blood volume