Weight loss and diarrhea in a research dog. Laboratory Animal Science 49(6), 585.
Abstract: A 3-year old female Basenji/Greyhound cross presented for anorexia, diarrhea and weight loss. She was being maintained as a breeder for a model of airway hyper-responsiveness. The dog was afebrile and had lost 36.5+ACU- of her body weight in the last 3 months. Abnormal PE findings included cachexia, calculus, enlarged left stifle with associated muscular atrophy and irregular heart rhythm. Fecal exam, CBC, serum chemistry, thoracic radiographs and electrocardiogram were performed. Abnormal findings included a borderline lymphopenia, hypocalcemia and elevated alkaline phosphatase. Ekg detected a profound sinus arrythmia with sinus arrest. Supportive care was given and the dog responded well to just a change in diet to canned food from dry food. The dog relapsed after 11 days. Diagnostics were repeated. A leukocytosis with a mature neutrophilia was noted and the alkaline phosphatase remained elevated. Metronidazole and kaolin/pectin suspension therapy was initiated. Fecal cultures were negative, as were fecal occult blood and serum TLI. A presumptive diagnosis of enteritis of undetermined origin was given.
Serum protein electrophoresis revealed a polyclonal gammopathy consistent with chronic inflammatory disease. Treatment regimens involve immunosuppressive agents which would be contraindicated in this animal model. Therefore, the decision was made to euthanize the dog. Necropsy findings included a diffusely thickened bowel wall with edematous mucosa. Based on histopathology, the morphologic diagnosis was multifocal plasmacytic enteritis with mild villous atrophy. A condition has been described in Basenjis that parallels this case. Immunoproliferative enteropathy of Basenjis is characterized by anorexia, vomiting, diarrhea and weight loss.
Questions: Questions:
1. Differential diagnoses for this case should include:
a. exocrine pancreatic insufficiency
b. small intestine bacterial overgrowth
c. giardiasis
d. food allergy
e. neoplasia
f. mycotic and granulomatous enteridities
g. all of the above
2. What is the serum TLI test for ?
3. Alkaline phosphatase is present in high concentrations in which tissues?
Answers: Answers:
1. g. all of the above
2. TLI (trypsin-like immunoreactivity) tests for exocrine pancreatic insufficiency. The assay detects circulating proteins produced by a normally functioning exocrine pancreas. Decreased levels (+ADw-2.5 micrograms/liter) are diagnostic for EPI.
3. Alk Phos is present in liver, kidney, placenta, bone and intestine.

Experimental models of peripheral neuropathies. Laboratory Animal Science 49(6), 588.
Abstract: The term neuropathy is used to indicate damage of the peripheral nerve attributable to any cause, and can be mediated by neruonal and/or glial problems. The first clinical features of many peripheral neuropathies tend to involve sensory disturbances such as tingling, prickling or burning in the balls of the feet or the tips of the toes. Sensory and motor disturbances proceed in a centripetal symmetric manner, with muscular atrophy , pansensory loss, areflexia, and motor weakness. Because peripheral nerves, unlike CNS neurons, retain the capacity to regenerate, in some instances, such as chemical-induced peripheral neuropathies, there can be completed recovery of the patient after withdrawal of the causative agent. This paper presents experimental animal models for heritable demyelinating neuropathies such as Charcot-Marie Tooth disease (CMT) is also known as hereditary motor and sensory neuropathy type I (HMSN-I) there is distal muscular weakness, wasting, and variable degreees of sensory impairment, histologically there is axonal atrophy, segmental demyelination, onion bulb formations and Schwann cell overproliferation ; the cells enlarge so CMT is also known as hypertrophic neuropathy, hereditary neuropathy with liability to pressure palsies (HNPP) ?tomoculous neuropathy?, and Dejerine-Sottas syndrome (DSS).

Inherited demyelinating Neuropathies:
In dysmyelinating neuropathies, myelin does not form normally during development, whereas in demyelinating diseases, myelin is made but break down with age owing to glial and/or axonal defects.
1 Myelin protein zero (MPZ) -component of the myelin membrane with a role in membrane wrapping and maintenance of the compacted myelin-MPZ deficient mice are a model of CMT1B which is a severe form of CMT (mapped to chromosome 1 in humans), DSS and congenital hypomyelinating (CH) neuropathies.
2 Peripheral myelin protein 22 (PMP22) -component of the myelin membrane-PMP22 overexpressor mice and rats are models of CMT1A. Most CMT1A patients carry 3 copies of PMP22. Rats have a more severe phenotype than mice. The PMP22 deficient mice are models of HNPP this is a dominantly inherited neuropathy with recurrent episodes of severe, focal neuropathy at vulnerable sites of nerve compression. See photos
3 Connexin 32 (Cx32GJB1) -component of the myelin membrane-the connexin 32 deficient mouse is a model of CMTX which is an X-linked form of CMT and is associated with mutations in the gap junction protein, Cx32.
4 Zinc finger transcription factor Krox20 (EGR2, early growth response 2 gene)-a DNA binding protein that regulates myelin gene expression during Schwann development-the Krox20-deficient mouse is a model of CH neuropathy and CMT1.
The Trembler mouse (Tr) is a spontaneous mutant of the C57BL/6J strain is a model of CMT, this is a true dominant. Affected animals get quadriparesis. These mice get onion bulb formation and Schwann cell overproliferation. The Trembler?J (TrJ) mouse is an allelic variant of the trembler mouse and it has tomaculi which is classic in HNPP, this is a semi-dominant. Homozygous (TrJ) have a shorter lifespan than homozygous(Tr). See photos Tomaculi is focal sausage-shaped thickenings of the myelin membrane.

Inflammatory Neuropathies:
Guillian-Barre Syndrome (GBS) is an acute self-limiting , immune mediated demyelinating peripheral neuropathy and is triggered, in most instances by a preceding viral or bacterial infection. An example would be gastroenteritis due to Campylobacter jejuni inducing an immune response that cross reacts with neuronal tissues.
Chronic inflammatory polyradiculoneuropathy (CIPD) is a progressive or relapsing disease that leads to demyelination and axonal degeneration.
Experimental allergic neuritis (EAN) can be induced by inoculation with myelin proteins P0, P1, P2, and myelin-associated glycoprotein. The Lewis rat is the most sensitive and most commonly used model of GBS. The EAN rabbit develops a state of spontaneously recurring episodes of inflammation and remyelination similar to CIPD.

Diabetic Neuropathy:
Peripheral neuropathy of motor and sensory nerves is a common complication of long standing hyperglycemia of diabetes mellitus in humans. Hyperglycemia results in physiologic alterations in nerve conduction velocities.
Experimental animals with diabetes mellitus are models for neuropathic changes. It can be induced by the cytotoxic effects of alloxan and streptozotocin on pancreatic beta cells. Spontaneous genetic rodent models such as the C57BL/Ks db/db mouse develops insulin dependent diabetes mellitus and the Bio-Breeding (BB) Wistar rat develops non-insulin dependent diabetes mellitus.
Studies have indicated that sorbitol accumulation leads to nerve dysfunction and preventing accumulation of sorbitol in nerves by aldose reductase inhibitors improves nerve conduction velocities. Also neurotrophins may be useful in treating diabeteic neuropathies. Neurotrophin growth factor (NGF) is protective and accelerates regeneration of axons.

Chemical Neuropathy:
Chemotherapeutic agents such as cisplatin (affects large caliber myelinated sensory axons which leads to impairment of perception and propioception), taxol (impair neuronal microtubule formation involves small caliber sensory axons, and vincristine (impair neuronal microtubule formation involves small and large caliber axons) can induce dose dependent damage of the peripheral nerves.
Experimentally induced sensory neuropathy by use of cisplatin and taxol in mice can be prevented by co-administration of NGF (neurotrophin 3 (NT-3)) which reverses the slowing of large-caliber sensory axon conduction velocity in the rat cisplatin model.
Questions: No questions.

Experimental models of peripheral neuropathies. Laboratory Animal Science 49(6), 588.
Abstract: Peripheral neuropathies, disorders of peripheral nerves, result from genetic alterations or from metabolic, inflammatory, infectious or chemical insults. Experimental animals models, spontaneous or induced, exist for many of the common human peripheral neuropathies. This review provides an overview of available animal models for peripheral neuropathies, including heritable demyelinating, inflammatory, diabetic and chemical-induced neuropathies. Experimental animal models for heritable demyelinating neuropathies, such as Charcot-Marie-Tooth disease (CMT), hereditary neuropathy with liability to pressure palsies (HNPP) and Dejerine-Sottlas syndrome are emphasized.
Inherited Demyelinating Neuropathies
Myelin: a lipid-rich, multi-layered membrane deposited by glial cells in segments along the axons. Its function is to increase the conduction velocity of neuronal impulses. In dysmyelinating neuropathies, myelin does not form normally during development, whereas in demyelinating diseases, myelin is made but breaks down with age owing to glial and/or axonal defects.
Four genes where misexpression is know to cause heritable peripheral neuropathies have been identified. These include the myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), connexin 32 (Cx32GJB1) and the zinc finger transcription factor Krox20 (EGR2, early growth response 2 gene).
Most dominant heritable demyelinating peripheral neuropathies are classified as a form of CMT disease (aka hereditary motor and sensory neuropathy type I (HMSN-1) of Dyck and Lambert). Clinically there is progressive distal muscular weakness, wasting and variable degrees of sensory impairment. Pathologic findings include axonal atrophy, segmental demyelination, onion bulb formation and Schawann cell overproliferation. CMT nerves enlarge, thus it is also called hypertrophic neuropathies.
The Trembler mouse
All neuropathologic findings of CMT are present in the trembler mouse, a spontaneous mutant with neurologic alterations. Trembler (Tr) and its allelic variant, Trembler-J (TrJ), independently arose in the C57BL/6J strain at the Jackson Laboratory and have been used as models of hypertrophic demyelination neuropathies. Affected animals develop tremors that continue to worsen with age, leading to quadriparesis. After the cloning of PMP22 and its linkage to inherited peripheral neuropathies, single point mutations in PMP22 pf Tr and TrJ mice were quickly identified and the same amino acid substitutions have been identified in affected CMT1A patients. Also, the MPZ-deficient mice generated to elucidate the function of the protein in peripheral nerve and were subsequently used as models for CMT1B.
Krox20-deficient mice
Another molecule that was recently linked to CMT1 is the transcription factor Krox20. Homozygous Krox20-deficient mice had signs of peripheral neuropathy by postnatal day 10 and had severely dysmyelinated peripheral nerves.
Connexin 32-deficient mice, a model for CMTX
An X-linked form of CMT, termed CMTX, is associated with mutations in the gap junction protein Cx32.
PMP22-deficient mice (HNPP).
The HNPP, a dominantly inherited demyelinating neuropathy, is also associated with alteration in PMP22 gene expression. Clinically, HNPP, or "tomoculous neuropathy' is characterized by recurrent episodes of severe, focal neuropathy at vulnerable sites of nerve compression. The hallmarks of HNPP are tomoculi, sausage-shaped thickening of the myelin sheath.
Dejerine-Sottas Syndrome
This syndrome is also considered a CH neuropathy on the basis of its early childhood onset. The clinical and pathologic findings of DSS are more severe and tend to resemble those of CMT1B.
Inflammatory Neuropathies
Guillain-Barre Syndrome (GBS) and chronic inflammatory polyradiculoneuropathy (CIPD) are the most common human inflammatory demyelinating neuropathies. GBS is an acute and self-limiting neuropathy which is triggered in most instances to viral or bacterial infections such as gastroenteritis caused by Campylobacter jenuni which induce an immune response that cross reacts with neuronal tissues. CIPD condition has a progressive or relapsing course, leading to demyelination and axonal degeneration. Experimental allergic neuritis (EAN) can be induced by inoculation of animals with peripheral nerve myelin proteins to produce models for demyelinating diseases, such as GBS and CIPD.
Diabetic Neuropathy
Alloxan and steptozotocin, when administered systemically, induce a diabetic condition similar to that of insulin-dependent diabetes mellitus (DM) due to their cytotoxic effects on pancreatic beta cells. Also, spontaneous genetic rodent models, such as the C57BL/Ks dB/dB mouse and the Bio-Breeding (BB) Wisteria rat, develop diabetes mellitus similar to insulin-dependent and non-insulin-dependent DM, respectively. All these models develop nerve conduction deficits and morphologic alterations in the peripheral nerves resembling those of diabetic patients, including axonal atrophy and paranodal swelling. Neurotrophin nerve growth factor (NGF) may be a potential treatment in preventing sings of diabetic neuropathies.
Chemical Neuropathy
Agents such as ciplantin, taxol and vincristine can induce dose-dependent damage of peripheral nerves, resulting in peripheral neuropathies in human patients. Cisplatin affects the large-caliber, myelinated sensory axons, leading to impairment of perception and propioception. Taxol and vincristine impair neuronal microtubule formation, with taxol affecting the small-caliber sensory axons and vincristine leading to development of a mixed sensorimotor neuropathy involving small and large-caliber axons.
Questions: Questions
1) Which of the following genetically determined demyelinating neuropathies is also termed "tomoculous neuropathy"
a- DSS
b- CMT1A AND CMT1B
c- CMTX
d- HNPP
e- a and d
2) Guillain-Barre Syndrome (GBS) can occur as acute, self-limiting neuropathies triggered by gastroenteritis caused by pathogens such as
a- Helicobacter sp.
b- Campylobacter jejuni
c- Salmonella typhimurium
d- E. coli
e- none of the above
3) Which of the following chemotherapeutic agents does not cause peripheral neuropathies in human cancer patients
a- Tamoxaphen
b- Taxol
c- Cisplatin
d- Vincristine
e- b and d
Answers: Answers:
1) d
2) b
3) a

Pathogenesis of guinea pig adenovirus infection. Laboratory Animal Science 49(6), 600.
Abstract: A Guinea Pig adenovirus (dubbed GPAdV) has been implicated in fatal outbreaks of respiratory tract disease in guinea pigs since the 1980's. The disease is characterized by low morbidity / high mortality with intra nuclear inclusion bodies consistent with adenovirus inclusion bodies found in lung tissue of clinically ill animals.. Electron microscopy if tissue has identified viral particles with ultra structure typical of adenovirus. Recently unique sequences have been identified for GPAdV by PCR analysis, and thus provides a unique tool for further investigation of the virus. The purpose of this study was two fold. 1) To exam virus replication and distribution at various times following experimental inoculation via a natural route of infection and 2) to investigate the transmission and persistence of GPAdV in a group of animals. Guinea pigs were inoculated intra nasally with an innoculate homogenate that originated from three different natural outbreaks. The presence of GPAdV was confirmed by PCR analysis in all samples used. All isolates appeared to belong to the same strain supporting the assumption that GPAdV is a distinct adenovirus. Blood samples, nasal swabs and fecal samples were collected at timed intervals. Tissues were collected from animals at termination, and tested via PCR analysis and examined histologically using an H&E stain. None of the animals infected developed clinical disease, although inclusion bodies and virus could be detected in nasal mucosa from day 6-11 post inoculation. Transmission occurred from a single inoculated animal to only 2 of 5 cagemates. Results indicate that GPAdV induces a transient, subclinical infection of the respiratory tract of healthy guinea pigs. Apparently additional factors are necessary for disease outbreak to develop. The virus is shed by nasal secretion and is presumably transmitted for a period of 10 days after a 6 day incubation period. Transmission appears to be inefficient. Diagnosis of GPAdV can be achieved by 1) histologic identification of ad epithelium of clinically affected animals 2) serologic detection using murine reagents (mouse adenovirus type 1 and 2), and 3) PCR analysis for specific detection of the viral genome. PCR is the recommended method for diagnosis in subclinically infected animals, however it is only effective during the 10 day window when animals are actually infected. For screening of colonies, serologic testing is still the best method, even though a GPAdV specific antigen is not yet available.
Questions: QUESTIONS:
1) What is the best screening method for GPAdV?
2) What is the best diagnostic method for subclinically infected animals?
3) When are the animals infective?
4) What antigens are used for serologic testing for GPAdV?
5) T or F - GPAdV is significant cause of clinical respiratory disease in laboratory guinea pigs.
Answers: ANSWERS:
1) Serology
2) PCR analysis
3) 10 days after a 6 day incubation period
4) Mouse adenovirus Type 1 and type 2
5) False.

Herpesvirus papio 2: alternative antigen for use in monkey B virus diagnostic assays. Laboratory Animal Science 49(6), 605.
Abstract: Serologic testing for antibody to monkey B virus (BV, Cercopithicine herpesvirus 1) can be hazardous because BV is a BSL 4 so this group used Herpesvirus papio 2 (HVP2) which is a BSL 2 instead. HVP2 is closely related to BV more so than Herpes simplex 1. ELISA's were done on rhesus, cyno?s, Japanese, pigtail, and other macaque species and BV was detected.
BV, herpes simplex virus 1 and 2, and herpesvirus papio 2 are all alphaherpesviruses. BV after primary infection of mucous membranes, establishes latent infections in sensory ganglia.
Questions: Q1 Where does Cercopithicine hepersvirus 1 establish latent infections?
Q2Why did the authors search for an alternative antigen for the ELISA assay?
Answers: A1 Sensory ganglia
A2 Because BV is a BSL4 biohazardous agent.and HVP2 is closely related to BV

Effect of weaning time and associated management practices on postweaning chronic diarrhea in captive rhesus monkeys (Macaca mulatta). Laboratory Animal Science 49(6), 617.
Abstract: Post weaning diarrhea in primates can lead to metabolic problems, weight loss and death, as well as result in major negative economic impacts. Object of this study was to determine what extent postweaning diarrhea at the California Regional primate research center was associated with early weaning while adjusting for other management factors.

Materials and methods
227 monkeys artificially weaned between 1992 and 1995 (79 after 180 days and 148 before 180 days). Some were breast fed until weaning and others were separated from their mother and fed milk formula. At various times postweaning small groups were combined and moved to an outdoor corn crib unit until assigned as research animals or breeding stock. Data collected included sex of infants, duration of breast feeding, dam weight, weaning age, weaning weight, weaning year, and season when moved outdoors and inclusion in an SPF colony.
Definitions for this study
Weaning- infant removed from liquid feeding (breast or formula feeding) and introduced to solid food.
Early weaning- considered by young age (<6 months) or weight (<1.2kg) Diarrhea-semi-solid or liquid feces for at least 7 consecutive days. Episodes were considered distinct if separated by 10 days of normal feces
Diarrhea classifications
No diarrhea -no episodes within one year post weaning
Acute Diarrhea - one or more episodes each lasting 7 or more days but fewer than 30 days with 2 months of normal feces between episodes.
Persistent diarrhea- one episode lasting 30 days or more.
Recurrent diarrhea ? 2 or more episodes, each less than 12 month with less than 2 months of normal feces.
Chronic diarhea a monkey with persistent or recurrent diarhea.

Results
45.8 % of monkeys had at last one episode of diarrhea, of those 37.5% had acute diarrhea, 28.85% had recurrent diarrhea, 33.65% had persistent diarrhea. First episodes of chronic diarrhea developed as early as 8 days and as late as 351 days post weaning. For persistent episodes the mean duration was 43 days. Chronic diarrhea animals (65)- 2 were found dead, and 17 euthanized due to unfavorable prognosis. Case fatality for chronic diarrhea was 29.23% 13 (20%) of the monkeys that experienced chronic diarrhea and 9 (7.3%) of the monkeys that had no diarrhea or had acute diarrhea within 1 year of weaning had a diarrhea related death in the following years. A negative association between weaning weight and development of postweaning diarrhea was significant (P= 0.07) in a Cox proportional hazard regression model, but weaning age was not (p=0.024). Development of diarrhea before weaning was associated with an increased risk of postweaning chronic diarrhea (P=0.08).

Bottom line results:
Body weight at weaning , not age at weaning, was significantly associated with postweaning chronic diarrhea. Infants of lower weight were more likely to develop chronic diarrhea than heavier infants. Episode of preweaning diarrhea was a predictor for diarrhea after weaning.
Questions: No questions

Distribution of Helicobacter pylori in a Mongolian gerbil gastic ulcer model. Laboratory Animal Science 49(6), 622.
Abstract: Purpose: The acetic acid-induced gastric ulcer (AAU) model was used in the Mongolian gerbils for the evaluation of anti-ulcer drugs within a short experimental period. This model is established by injecting 20 ul of a 10% acetic acid under the serosal layer of the fundoantral border. Both treated and non-treated groups received 1.8x108 of colony forming units (cfu) of H. pylori.
Method and Materials: One-hundred twenty Mongolian gerbils were used, 60 as the AAU model and 60 as the non-AAU model. The animals were evaluated at 1,3,7,14,28 and 56 days. Tissues were stained with hemotoxylin and eosin or with an immunohistochemistry procedure.
Results:The surface mucous gel layer (SMGL) in the stomach of the AAU model had a disheveled striped pattern that extended into the lumen; however, the non-AAU model had a close laminated pattern. In the AAU model the gastric mucosa was acutely inflamed early and mononuclear cells were observed in the mucosa and submucosa. Inflammation spread to the mucosa of the fundic glands and finally into the gastric pits. In the later stages of the study at 28 and 56 days, lymph follicles formed at the pyloris. In the non-AAU model, inflammation was not observed until 14 days, and H. pylori organisms distributed at 28 days in the pyloric gland. The SMGL layer of the pyloric glands was stained with AB/PAS. UEA-I mucin reacted strongly in the pyloric gland which suggests that L-fucose is related to the H. pylori adhesive factor which is abundant in the pyloric gland region.
Discussion and Conclusion: The stomach of the AAU model animals indicated early inflammation and mononuclear cell infiltration compared to the non-AAU model animals which were observed near the end of the study at 56 days. Therfore, the findings for this ulcer model of H. pylori make it useful for the study of onset of infection and screening of anti-ulcer agents.
Questions: Questions:
1. What is the name of the model used in this study?
2. What was the name of the compound responsible for H. pyloris to have a greater affinity to the pyloric gland?
3. What were the two specific responses in the treated group?
Answers: Answers:
1. Acetic acid -induced gastric ulcer model
2. L-fucose
3. a. Immediate marked H. pyloric inflammation and infection of the gastric mucosa.
b. Rapid mononuclear infiltration in the early stages of exposure to H. pylori in ulcerated stomach tissue.

Open-thorax guinea pig model for defibrillation. Laboratory Animal Science 49(6), 628.
Abstract: Guinea pigs are often used in studies of ventricular tachyarrhythmias (VT) (including ventricular fibrillation and defibrillation) however, VTs in guinea pigs are usually transient. Therefore, it is difficult to determine if the cessation of VTs is a result of experimental treatment or simply due to their transient nature. This paper detailed a developed open-thorax guinea pig model of sustained ventricular fibrillation (VF).
Background:
Primates, dogs, sheep, swine, and rabbits are the primary animal models used to study human VF. The cost and facility requirements associated with use of these animals in research may preclude some scientists from conducting research in VTs. Development of a rodent model may result in increased research efforts. Previously, rodent tachyarrhythmias have been found to be difficult to induce and have been shown to reverse spontaneously in <5 secs. Guinea pigs are the only rodents known whose cardiac action potential and ventricular arrhythmias are similar to those of the human heart. This group has reported an acceptable closed-thorax guinea pig model and now reports an open-thorax guinea pig model for study of VF and defibrillation. An open-thorax model would allow activation mapping which is relevant to initiation and termination of VF.
Methods and Materials:
Eight guinea pigs (865 to 1,464 g)were anesthetized with IP sodium pentobarbital. Lead-I ECG, rectal temperature, and systemic blood pressure were monitored. Continuous positive pressure ventilation was performed. A circular thoracotomy was performed lateral to the xyphoid process by transection of the costochondral cartilage up to the level of the subclavian arteries. Two stainless steel sutures were placed in the epicardium. Bipolar pacing was performed. Once induced, VF duration was measured and ventricular defibrillation was attempted. All animal were euthanized at the conclusion of the study (prior to anesthetic recovery).
Results:
Animal survival was high prior to euthanasia. Seven of eight guinea pigs survived 30 attempts at VF induction and defibrillation. Six of seven guinea pigs sustained VFs for 2.5-10 minutes. All guinea pigs with sustained VF for > 10 minutes had a heart weight of >2.5 g.
Body size and therefore heart weight were shown to highly correlate with the ability of a guinea pig model to undergo and maintain VF. For guinea pigs with heart weight >2.5g, VF was sustained 100% of the time for > 25 secs. Selection of acceptable test subjects (which can be induced to maintain a sustained VF) may be achieved through noninvasive evaluation of heart mass such as with use of body weight, ultrasound, and/or MRI.
Questions: Question:
What are two possible limitations for the use of a guinea pig model for the study of human VTs?
Answers: Answer:
a. Guinea pig hearts may not respond to ischemia or infarction in a similar manner seen in larger animals. Guinea pig hearts have a marked resistance to infarction
b. Since this is a nonrecovery animal model evaluation of some VF therapies will not be possible.

Evaluation of cynomolgus (Macaca fascicularis) and rhesus (Macaca mulatta) monkeys as experimental models of acute Q fever after aerosol exposure to phase I Coxiella burnetii. Laboratory Animal Science 49(6), 634.
Abstract: Background: Q fever
Etiological agent - Coxiella burnetii, an obligate intracellular phagolysosomal bacterium of eukaryotic cells.
Transmission - usually inhalation but can be acquired by ingesting infected milk or parenterally by the by of an infected tick
Incubation period - usually 10-40 days (varies inversely according to infective dose)
Diagnosis - difficult due to the lack of unique clinical signs - usually made on basis of serological testing (In this report, monkeys were diagnosed by injecting blood from an infected monkey into the abdomen of CD1 mice and testing mouse sera 21 days later by ELISA for C. burnetii specific IgG antibodies)
Common clinical manifestations -
ever, headache and chills
atypical pneumonia
acute hepatitis with elevated ALT, AST
Purpose of study
Evaluate the suitability of cynomolgus and fascicularis monkeys as models of acute Q fever and select a species for vaccine efficacy testing.
Conclusions
Both the cynomolgus and rhesus monkeys were found to be good models of Q fever due to the many clinical similarities manifested in the these species of macaques to human disease such as:
Severity and duration of fever - 1.8 degrees above normal for approx. 1 week
Radiographic changes indicative of atypical pneumonia (more pronounced in cynomolgus)
Increase in liver transaminases
Normal WBC count
Thrombocytopenia and anemia
Questions: Questions
1. What clinical sign is pathognomonic for Q fever?
a. fever
b. headache
c. hepatitis
d. pneumonia
e. none
2. How is Q fever diagnosed?
a. culture of organisms
b. clinical signs
c. chest radiographs
d. serological testing
e. none of the above
Extra credit questions.
What does the Q in Q fever stand for?
What common domestic animal has recently been identified as a source of infection for people?
Answers: Answer: e. none
Answer: d. serological testing
Query
parturient cats

Insulin replacement therapy for the rat model of streptozotocin induced diabetes. Laboratory Animal Science 49(6), 639.
Abstract: The purpose of this study was to compare various insulin replacement protocols for the streptozotocin-induced diabetic rat model. SPF male Sprague-Dawley rats were randomly allocated into one of the following groups: control, streptozotocin-induced untreated diabetics, and three insulin treatment groups. Insulin treatment began 24 h after diabetic induction. Blood samples were taken twice daily, prior to each insulin injection, for blood glucose determinations. Near-normal glucose values were defined as 90 to 150 mg/dl, hyperglycemia as >150 mg/dl, moderate hypoglycemia as <70 mg/dl, and severe hypoglycemia as <50 mg/dl. Body weight was measured daily.
Three series of experiments were done. In the first study, PZI (protamine zinc insulin) and Ultralente (Humulin U) insulin given once daily and PZI given twice daily were compared. In the second study, twice daily administration of PZI, NPH (neutral protamine Hagedorn) insulin, and 70/30 (Humulin 70/30) insulin were compared. In the final study, daily PZI was compared with twice daily PZI and NPH insulin. All studies were conducted for 10 days. Only data from the last 5 days of each experiment were used for statistical analyses, as the first 5 days allowed acclimatization of rats to insulin treatment.
All insulin treated groups experienced weight gains comparable to that of control rats and significantly greater than that of untreated diabetic animals. Once daily treatment with insulin did not induce near-normal glucose values. In contrast, twice daily insulin provided more balanced control of glucose concentration. Insulin replacement dosage was adjusted in each experimental group so as to achieve near-normal glucose concentrations. The dosage required was roughly comparable among the various insulins, except for Ultralente insulin which required much higher dosages. In all experimental groups, the attempted normalization for glucose values was limited by hypoglycemia. To assess glycemic benefit, which takes into account the side effects of hypoglycemia, the "glucose control index" or GCI was determined. The GCI did not differ significantly among the various insulins (PZI, NPH, 70/30) given twice daily, but was significantly higher for insulins (PZI, Ultralente) given once daily.
This study therefore indicates that different metabolic objectives can be obtained by administration of insulin once or twice daily to rats with streptozotocin-induced diabetes mellitus. Normal weight gain can be achieved by treatment with PZI once daily. However, attainment of near-normal glucose values with somewhat less risk of hypoglycemia requires twice daily administration of PZI, NPH, or 70/30 insulin. Ultralente insulin appears to have reduced potency in this animal model of diabetes mellitus.
Questions: QUESTIONS:
1. List three examples of rodent animal models of spontaneous or naturally acquired diabetes.
2. List three ways in which diabetes can be experimentally induced.
3. What is the mechanism of action of Streptozotocin which leads to experimentally acquired diabetes?
4. Define "glucose control index" (GCI).
5. Which of the following statements are TRUE with respect to insulin replacement therapy in the streptozotocin-induced diabetic rat model?
a. Normal weight gain can be achieved when PZI is given once daily.
b. Ideally, both components of the GCI should be high.
c. Administration of PZI, NPH insulin, 70/30 insulin, and Ultralente insulin twice daily can induce near-normal glucose values.
d. Ultralente insulin does not have reduced bioeffectiveness in this animal model.
e. Better glycemic control is obtained with once daily insulin
administration.
Answers: ANSWERS:
1. Chinese hamster (Critcetulus griseus), Bio Breeding Wistar rat, Non-obese diabetic mouse
2. Pancreatectomy, Viral infection, Use of chemical agents like alloxan or streptozotocin
3. Streptozotocin depletes NAD+ in pancreatic B-cells, causing cell degranulation leading to necrosis.
4. Glucose control index (GCI) is defined as the product of (average daily glucose value) x (frequency of glucose concentration <50 mg/dl).
5.
a. True
b. False. Ideally, both components of GCI should be low.
c. False. Administration of PZI, NPH insulin, or 70/30 insulin twice daily can induce near-normal glucose values.
d. False. Ultralente insulin may have reduce bioeffectiveness in this animal model.
e. False. Better glycemic control is obtained with twice daily insulin administration.

Peripheral blood progenitor cell mobilization and leukapheresis in pigs. Laboratory Animal Science 49(6), 645.
Abstract: The authors study organ transplantation in a pig-to-baboon model . One method of inducing tolerance to the donor organ is to create a hematopoietic chimeric state in the recipient by giving it (the recipient) a bone marrow transplant from the donor. A difficulty with this is the low number of marrow cells obtained even if all the long bones and vertebrae are used. This paper describes a technique developed to obtain more cells. Miniature swine (19-35 kg.) were implanted with chronic catheters in the internal and external jugular veins and the carotid artery. The pigs received daily SQ injections of recombinant porcine interleukin 3 and porcine stem cell factor. On day 10 additional daily injections of recombinant human granulocyte colony-stimulating factor were begun. The cytokine treatment was intended to promote the mobilization, growth, and differentiation of bone marrow cells. Leukapheresis was begun on day 6 and continued daily through day 17, skipping the weekend days 11 and 12. Three blood volumes were processed during each leukapheresis procedure, requiring 4 to 5 hours. Granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units, which were the primary target of this procedure, were not detectable in the peripheral blood before cytokine treatment but formed 0.138% of the leukapheresis product during the first week. In their conclusion the authors refer to another of their papers that indicates that the cells produced by this procedure may be effective in producing hematopoietic chimerism and immunologic tolerance in the pig to baboon model.
This article was written in the style of a research paper but was simply a description of an established technique. This leaves me with some questions such as: If the hG-CSF is so effective at increasing the cell count, why wait until day 10 to begin using it? What do they do to ( or with) the animals after day 17? There are also conflicting statements indicating in the Methods section that sedation of the animals is required for leukapheresis and in the Discussion section that swine tolerated the procedure without sedation.
Questions: No questions

Comparison of two systems for tibial external fixation in rabbits. Laboratory Animal Science 49(6), 650.
Abstract: The tibias were removed from euthanised rabbits and two different external fixator systems were tested for four point bending stiffness in two planes, and torsional stiffness and the strength of the bone-fixator complexs were evaluated. A significant difference in structural properties between the two systems was found. Thus, selection of the fixator system is an important consideration in designing experiments using the rabbit long bone model.
Questions: Questions:
See photos of distration devices.
Hoffmann and Orthofix.

Comparison of three treatments for control of ear mites in ferrets. Laboratory Animal Science 49(6), 655.
Abstract: Ear Mites (Otodectes cynotis) can be a frequent and difficult problem to treat in ferrets (Mustela putorius furo). The mites are transmitted by direct contact with other affected animals and often infestation remains subclinical. Diagnosis is made with otoscopic examination and microscopic evaluation of aural debris.
Three treatment regimens were compared: subcutaneous injection of ivermectin, topical application of ivermectin to the ear canals, and topical administration of thiabendazole. Twenty seven mite infested ferrets were randomly assigned to one of three treatment groups.
1) Group A received 2 drops of thiabendazole in each ear canal SID x 7 days, followed by 7 days without treatment and finally reinstitute treatment for an additional 7 days.
2) Group B received topical 1% ivermectin, diluted 1:10 in propylene glycol, at a dosage of 400 ug/kg and divided equally between the two ear canals. Group B animals were treated on the first day of the study and again two weeks later.
3) Group C received subcutaneous injections of 1% ivermectin at a dosage of 400 ug/kg at the same two treatment times as described for Group B ferrets.
During the eight weeks of study, treatment response was evaluated by weekly microscopic examination of ear swab specimens. Topical treatments to the ear canal (Group A and B) were found to be considerably more efficacious in eliminating ear mites than was use of injectable ivermectin. Clinically, topical thiabendazole and ivermectin were equally effective. In contrast to fourteen days of total treatment with thiabendazole, two topical applications made ivermectin the most practical option. Since high dosages of ivermectin have been reported to cause birth defects in ferrets, ivermectin treatment should be avoided in pregnant jills during early gestation.
Questions: QUESTIONS:
1) T or F - Otodectes cynotis infestation in ferrets is often subclinical.
2) Which treatment option was most effective AND practical?
3) T or F - Treatment of pregnant jills in early gestation with high dosages of ivermectin is safe
Answers: ANSWERS:
1) T
2) topical ivermectin in the ear canal on day 1 and day 14
3) F

Effects of histamine, carbachol, and methacholilne on maximal expiratory lung mechanics in goats. Laboratory Animal Science 49(6), 658.
Abstract: The study was designed to determine the pulmonary response of goats to aerosol challenge with histamine, carbachol, and methacholine (all commonly-used non-antigenic bronchoconstrictors), using the negative-pressure, forced-expiratory flow method. This information was available in sheep, but not goats. Measurements were made with animals under ketamine/xylaxine anesthesia (in sternal recumbency) using low deadspace pheumotachomoters connected to an endotracheal tube and a differential pressure transducer, all coupled to a computer data acquisition system. Parameters measured (or calculated) included: dynamic compliance of the lung (CLdyn), resistance of the lung (RL), maximal expiratory flow volume (MEFV), inspiratory capacity (IC), forced vital capacity (FVC), expiratory reserve volume (ERV), residual volume (RV), functional residual capacity (FRC), and forced expiratory flow (FEF). Of 8 goats challenged with the 3 compounds, only 6 responded by increasing RL by 150% or decreasing CLdyn to 65% of control values. Histamine had a predominantly peripheral airway effect, while carbachol and methacholine had peripheral and central airway effects. Order of sensitivity to peripheral airway effects was histamine > carbachol > methacholine, while the order of sensitivity to central airway effects was methacholine > carbachol > histamine. These results are similar to those found in sheep, which is the most widely-used large animal model of acute pulmonary injury.
Questions: Questions:
1. In bronchoconstriction, which of the above parameters would you expect to be decreased?
2. Which would be increased?
(answering these questions was a very rocky trip down Memory Lane for me <g>)
3. In very loose terms, how are dynamic lung compliance and lung resistance related?
Questions
1. Carbachol and methacholine have what affect on the airways in goats and sheep?
a. affect only the peripheral airways
b. affect central and peripheral airways
c. have a greater affect on the peripheral airways than histamine
d. only affect the central airways
2. True or False. Goats respond similarly to sheep to the non-antigenic bronchoconstrictors histamine, carbachol and methacholine.
Answers: Answers:
1. Bronchoconstriction will cause a decrease in forced vital capacity, expiratory reserve volume, dynamic lung compliance. Inspiratory capacity may or may not be affected (usually not)
2. Bronchoconstriction will cause an increase in lung resistance, and reserve volume.
3. As lung resistance increases, lung compliance decreases (this is the problem for emphysema and asthma patients.)
Ans.
1. b
2. T

Depressive effects of anesthesia or sedation on exocrine pancreatic function in pigs. Laboratory Animal Science 49(6), 662.
Abstract: The purpose of this study was to determine the influence of anesthesia or sedation on the exocrine pancreatic secretion of pigs.
Pigs had catheters placed in the pancreatic duct for collection of pancreatic secretions and in the duodenum to reintroduce the pancreatic secretion.
Pigs were anesthetized with halothane or metomidate, or sedated with amperozide. Pancreatic secretions were collected for 2 one-hour periods during anesthesia or sedation. Control collections were done on different days in the same conscious pigs.
All three drugs reduced pancreatic secretion (halothane (largest reduction)>amperozide>metomidate). Halothane reduces visceral blood flow and abolished pancreatic secretion altogether after 30 minutes; amperozide affects dopaminergic nervous system; metomidate is a potent smooth muscle relaxant that may reduce blood flow to the GI tract and hence decrease pancreatic secretion.
Conclusions:
1. Halothane should not be used for functional gastrointestinal tract studies.
2. Experiments on conscious, long-term catheterized animals are preferred.
3. The effects of anesthesia are similar for long-term catheterized animals and for acute studies; therefore the effects in acute experiment are due to anesthesia and not surgical manipulation.
Questions: Questions:
1. Metomidate is
a) an opiod
b) a dissociative anesthetic
c) a steroid anesthetic
d) a barbiturate
e) a short acting hypnotic
f) neuroleptic
2. Amperozide (Hogpax)
a) an opiod
b) a dissociative anesthetic
c) a steroid anesthetic
d) a barbiturate
e) a short acting hypnotic
f) neuroleptic
Answers: Answers
1. d - with minimal effected on the cardiovascular system. It has little analgesic action when used alone; useful for providing unconsciousness. "Hynodil"
2. f - neuroleptic and sedative

Pathologic changes associated with use of Tribromoethanol (avertin) in the Sprague Dawley rat. Laboratory Animal Science 49(6), 665.
Abstract: This paper looked at the effects of IP administered tribromoethanol (TBE) anesthesia (low dose, therapeutic dose, and high dose). Clinical signs in the therapeutic and high dose included dehydration, hunched posture, coat disheveled, porphyrin staining of the eyes and nose (3/5 therapeutic dose, 4/5 high dose). All of the TBE treated animals had focal hepatic capsular fibrosis. Fibrous adhesions and peritonitis were also seen in 4/5 therapeutic dose and 4/5 high dose animals. The authors conclude that TBE anesthesia should not be used in rats for long term studies.
Questions: Questions:
1. What clinical signs were associated with tribromoethanol administration?
2. What histopathology findings were seen with tribromoethanol administration?
3. Under what conditions should tribromoethanol be stored to prevent decomposition to toxic components?
Answers: Answers:
1. dehydration, hunched posture, coat disheveled, porphyrin staining of the eyes and nose
2. hepatic capsular fibrosis, adhesions, peritonitis
3. 4oC in a dark, light proof container

Major histocompatibility haplotype does not impact the course of experimentally induced murine vaginal candidiasis. Laboratory Animal Science 49(6), 668.
Abstract: The purpose of the study is to characterize the genetic basis for vaginal candidiasis susceptibility using genetically identical mice of different strains ( quantification of infection and yeast clearance) Candida albicans is implicated in the most cases of recurrent vulvovaginal candidiasis (RVVC) in women. The rodent model of vaginal candidiasis was adapted for chronical vaginal candidiasis ( mice must be in estrus to be infected with Candida albicans, but as long as the hormone estradiol is present at high concentrations, the mice will carry an infection beyond 8 weeks)
Specific pathgen free 6 week old animals were used: C3H/Hej@Ars (H-2k), SJL/J@Arc(H-2s), BALB/cJ@(H-2d), DBA/2J@Arc (H-2d), and C57Bl/10ScSn@Arc (H-2b)
Estrus was induced in mice and three days later mice were infected intravaginally with viable Candida Albicans For analysis of fungal burden and for quantification of infection, the vaginas were washed weekly with PBS and absolute colony units (CFU) were compared overtime. The H-2b animals did not have significant differences in fungal titer . The H-2d animals likewise had similar fungal burdens overtime,and H2k animals has fungal buerdens equivalent to those of the H-2d and H-2b haplotypes. Yeast clearance ( inability to recover yeast from the vaginal washing) was not available on the genetic predisposition of the host toward vaginal candidiasis and the number of infected animals gradually decreased in all groups. The DBA/2Jstrain had the lowest average recoverable yeast, indicating that it has normal resistance to vaginal infection. This difference in resistance to vaginal infection was statistically significant only when compared with that of the SJL/J. The DBA strain has the H-2d allele, as does the BALB/c mouse, which has intermediate resistance. This indicates that the classII major histocompatibility (MHC) allotype alone is not responsible for resistance. The authors 's conclusion was that although clear correlation with the class-II haplotype was not observed in the most of the mouse strains, its role cannot be ruled out, especially in the case of the H-2s haplotype of the SJL@Arc mouse
Questions: QUESTIONS
1.- Strains with a normal resistance and intermediate resistance to vaginal infection
2.- Define yeast clearance
Answers: ANSWERS
1.- Normal resistance (DBA/2J) and intermediate resistance (BALB/c)
2.- Yeast clearance: The inability to recover yeast from the vaginal washings