Comparative Medicine
Volume 55, Issue 2 (April 2005)
Rodent Models of Rheumatoid Arthritis (pages 114-122)
There are many rodent models of arthritis, each with clear difference in etiology, however they all
result in inflammation and destruction of one or more joints. The most widely used are the K/BxN and
collagen-induced arthritis (CIA) mouse models.
Arthritis has 3 stages: inflammation, thickening of the synovium (pannus) and degradation of
cartilage and bone. Rheumatoid arthritis (RA) exhibits a strong association with MHC II antigens
HLA-Dr1 and HLA-DR4. There is a theory for cofactor influence, suggesting roles for
cytomegalovirus, Epstein-Barr virus and enteric bacteria. Because the exact etiology of RA is not
known, there are many models. This includes induced and spontaneous rodent models. Induced
models induction with albumin, type II collagen, human cartilage proteoglycan, cell-wall
peptidoglycans from Streptococcus and complete Freund's adjuvant(CFA). Spontaneous models
may more accurately reflect the human condition. Each model is slightly different and offers unique
avenues for studying this complex disease state.
The models are:
Collagen-induced arthritis (CIA): Collagen is emulsified in IFA for rats or CFA for mice and is
injected intradermally in the tail. DBA/1LacJ are most commonly used mouse strain with onset of
disease between days 14-21. Most often affects wrist or ankle and may take 8 weeks to run its
course. Inflammation will gradually subside often accompanied by ankylosis of the affected joints.
K/BxN arthritis model: Hybrid between KRN and nonobese diabetic mice resulted in a model
with developed severe destructive arthritis in all distal joints. This model is used widely today to study
inflammation, immune regulation and autoimmunity.
Antigen-induced arthritis (AIA): rodents are immunized with a model antigen (i.e. BSA)
followed by an intra-articular challenge with the same antigen. Arthritis it limited to the antigeninjected joint. Maximum swelling is achieve 4 days after challenge. Technique most easily performed
in rats and rabbits.
Adjuvant arthritis (AA): One of the first animal models. Certain strains of rats develop
arthritis after a single intracutaneous injection with CFA. It primarily affects the peripheral joints, but
there is spinal involvement and other manifestations such as uveitis, gastritis and weight loss. This
model is used to study efficacy of anti-inflammatory drugs.
Oil-induced arthritis (OIA): Arthritis can be induced by the intra-articular injection of IFA,
mineral oil, Arlacel A (mannide monooleate) and pristane (2,6,10,14-tetramethylpentadecane).
Pristane can also induce arthritis in mice following intraperitoneal injections. In the rat model,
intradermal injections of pristane are required.
Proteoglycan-induced arthritis (PGIA): Link protein (90), proteoglycans and gp-39 can
induce arthritis in rodents. Polyarthritis ensues in which peripheral joints and ankylosing spondylitis
peak at 7-9 weeks. Spinal involvement is evident. BALB/c mice are used which allows for each
acquisition of this model. SKG mice (ZAP-70 mutation): A point mutation in a BALB/c resulted in a
model which develops spontaneous arthritis. Mice also develop pneumonitis and dermatitis and have
high titers of rheumatoid factor. This is an excellent model for natural mechanisms leading to
autoimmune injury.
TNF-alpha and IL-1ra-/- transgenic mice: Mice expressing the transgene for TNF-alpha
develop a progressive, chronic polyarthritis in all joints. BALB/c mice which are deficient in the IL1Beta antagonist receptor develop a polyarthropathy as early as 5 weeks of age. This is being used
to investigate the role of IL-1Beta in rheumatic disease.
General considerations: Minimal group sizes of approximately 10 animals are necessary to
detect even slight alterations in incidence or severity. Repeat studies are typically needed also.
Animal welfare concerns are significant and require selection of humane endpoints. Analgesics are
problematic as they can influence inflammatory pathways. The use of soft bedding and frequent
assessment of clinical status is necessary.
NOTE: See chart on page 119 for comparisons of models.
Questions:
1. Which are the most frequently used mouse models?
2. What are the 3 necessary stages of arthritis?
3. What mouse model mimics autoimmune injury?
4. Pristane can be injected IP to create what arthritis model?
5. Name the first animal model of arthritis. What other clinical signs are noted?
Answers:
1. The most widely used are the K/BxN and collagen-induced arthritis (CIA) mouse models.
2. Arthritis has 3 stages: inflammation, thickening of the synovium (pannus) and degradation of
cartilage and bone.
3. SKG mice (ZAP-70 mutation)
4. Oil-induced arthritis (OIA)
5. Adjuvant arthritis (AA); uveitis, gastritis and weight loss
Low-dose infectivity of Staphylococcus aureus (SMH strain) in traumatized rat tibiae provides
a model for studying early events in contaminated bone injuries (pages 123-128)
This article describes an animal model of post-traumatic acute osteomyelitis (OM) by contaminating
mechanically traumatized rat tibia with various doses of S. aureus (SMH strain ? known to cause
human OM). Bacteria were introduced into the exposed medullary cavity of tibia. Curettage and
lavage were then performed, and at different time points, rat tibia were harvested for assessment of
bacterial load and determination of minimal infective doses for 50% (ID 50) and 95% (ID95). The doseresponse curve of inoculum showed a steep slope, indicating the model was responsive to low levels
of inocula. Logistic regression analysis determined the ID50 to be 1.8x103 CFU, and ID95 to be
9.2x103 CFU. Inocula above the ID95 did not increase bacterial load in tibia at 24 hours after
contamination. Intra-operative curette and lavage removed many bacteria from bone, but did not
prevent subsequent infection or disease. At 15 days after contamination, most (14 of 17) tibia were
infected, with macroscopic and radiological signs of established OM, despite minimal clinical signs
associated with the injury. Authors conclude that this rat model mimics human long-bone infection,
allowing scientists to study early pathology in contaminated bone injuries as well as evaluate clinical
interventions that may reduce infection and prevent disease.
Questions:
1.
What does ?ID50? and ?ID95? stand for?
2.
What cellular component does SMH strain of Staph. aureus binds to?
Answers:
1.
Minimal infective doses for 50% (ID50) and 95% (ID95) of subjects.
2.
Collagen.
Birth of rhesus macaque (Macaca mulatta) infants after in vitro fertilization and gestation in
female rhesus or pigtailed (Macaca nemestrina) macaques (pages 129-135)
SUMMARY: In rhesus macaques, previous studies have demonstrated successful in vitro fertilization
as well as the viability of early-stage embryos after cryopreservation. Heterospecific embryo transfers
have been successful in multiple species (cynomolgus monkey embryo in female rhesus, Indian
desert kitten to domestic cat, Przewalski horse and Grant’s zebra to domestic horses, goats to
Spanish ibex kids, and ewes to mouflon lambs. This study explored the use of in vitro fertilization and
gestation of rhesus macaques in female rhesus or pigtailed macaques. If successful, it would be
useful to have pigtails act as a surrogate for rhesus embryos/infants since rhesus (unlike pigtails) are
seasonal breeders. Therefore, it would be possible to create a more consistent supply of rhesus
infants for study. Also, the technique may be useful in the conservation of endangered primate
species.
Female rhesus were superovulated with a combination of recombinant follicle stimulating
hormone (rFSH) and recombinant HCG. Semen was collected by penile electrostimulation. Oocytes
were stripped of cumulus cells and then incubated with the semen. Selected embryos were frozen
and then thawed prior to embryo transfer. Embryos were implanted in the infundibulum or oviduct 3
days after the recipient females’ estradiol level peaked. Two embryo were implanted in each female.
After transfer, ultrasound examination was performed every 30 days. Infants were born by elective
cesarean section. Placental tissues were collected and examined at this time.
RESULTS;
Cycle length and estradiol levels: Menstrual cycle lengths didn’t differ between rhesus and pigtails or
between different seasons. Estradiol levels peaked earlier and at a higher level in pigtails.
Embryo transfers: 15 embryos were implanted in rhesus; 12 into pigtails. The efficiency of
generating pregnancies from heterospecific embryo transfers was significantly lower than with rhesus
recipients. 8 rhesus and 1 pigtail became pregnant. 8 rhesus infants were born (by c-section) to
rhesus surrogates. 3 infants were aborted. 1 infant was born to the pigtail surrogate and
subsequently grew and matured normally.
Placenta analysis: All macaques have hemochorial placentation and in all animal species
placental tissues are of fetal origins. “The placenta of the rhesus-pigtailed infant was bidiscoidal with
extremely rounded, thickened discs. The disks were “ball shaped” when compared with normal
flattened macaque placental disks.” The umbilical cord of the rhesus-pigtailed placenta was
unusually long and of small circumference. Histologically, there was hypertrophy of the chorionic
layer, evidence of maternal floor infarction, and thrombosis of the placental vascular tree. Although
the cause of the placental abnormalities is unknown, it was suggested that they may be the result of
incompatibility between rhesus conceptus and its pigtailed surrogate manifested through partial
rejection and malformation.
The conclusion of this study was that related macaques can be used for heterospecific
embryo transfers. Future studies will examine ways of improving the efficacy of the process.
No questions submitted
Use of frozen-thawed oocytes for efficient production of normal offspring from cryopreserved
mouse spermatozoa showing low fertility (pages 136-139)
Summary: In vitro fertilization is becoming a frequently-used tool for assisted reproduction in mice.
In many cases, spermatozoa and oocytes are frozen prior to the fertilization process. This allows for
transport or sharing of resources. However, spermatozoa have difficulty in penetrating oocytes
because of hardening of the zona pellucida during the freezing process. The paper compared fresh
and frozen gamete fertilization using intracytoplasmic sperm injection (ICSI). Unfertilized oocytes
were collected following superovulation of the mice with 5 IU pregnant mare serum gonadotropin IP
followed by injection of 5 IU of human chorionic gonadotropin 48 hours later. Sperm were collected
from the cauda epididymides of male mice. Gametes were frozen and thawed according to standard
protocols. ICSI was accomplished using piezo pulses with a piezo-micromanipulator.
Compared with fresh unfertilized oocytes, frozen-thawed unfertilized oocytes were highly tolerant to
damage by injection. Frozen-thawed oocytes that survived after sperm injection developed normally
and gave rise to offspring. These offspring also had reproductive ability; female mice became
pregnant and gave birth to normal pups. This technique was performed in C57Bl as well as
transgenic mice with the same success rate. These results indicate that ICSI is an efficient technique
for offspring production with frozen gametes.
Questions:
1. What is the technique for superovulation in mice?
2. What structure is collected for sperm harvesting in mice?
3. What is ICSI?
Answers:
1. 5 IU of pregnant mare serum gonadotropin IP followed by 5 IU of human chorionic gonadotropin
48 hours later.
2. cauda epididymides
3. intracytoplasmic sperm injection
Relationship Between Storage Temperature and Fertilizing Ability of Freeze-Dried Mouse
Spermatozoa (pages 140-144)
Summary: The authors describe the fertilizing ability of freeze-dried mouse spermatozoa that has
been stored at 4 different temperatures for 1 week, 1, 3, and 5 months. They compared the
temperature and times with fertility and normalcy of offspring produced. Sperm stored at -70, -20, and
+4 degrees centigrade for 5 months produced normal offspring. Sperm stored at +24 degrees
centigrade were maintain well for 1 month but degraded thereafter. The conclusion was that
spermatozoa can be stored at +4 degrees for at least 5 months without harming the genetic material.
They authors also suggest that sperm can be shipped at +24 degrees without harming the sperm.
Questions:
1.What are the advantages of freeze drying sperm rather than cryopreservation?
2.What are the disadvantages of freeze drying sperm rather than cryopreservation?
Answers:
1 Spermatozoa can be preserved without cyroprotectants and do not require a supply of liquid
nitrogen. They do not required dry ice to ship.
2. Spermatozoa lose their motility after rehydration and intracytoplasmic sperm injection is required
for fertilization of oocytes.
Survey of Captive Cynomologus Macaque Colonies for SRV/D Infection Using Polymerase
Chain Reaction Assays (pages 145-149)
The eradication of exogenous of SRV/D from breeding colonies of Asian Macaques is an essential
goal. Not all animals carrying the virus present with detectable antibodies for serological testing and
virus isolation can be cost prohibited and labor intensive. PCR is a rapid effective testing method for
a multitude of SRV/D serotypes. The authors designed an SRV/D-T specific PCR primer set based on
sequences of the aligned gag regions of SRV/D-1,-2, and -3 and SRV/D-T. A SRV/D-T specific
nested primer set was designed to increase the sensitivity of the PCR. Cynomologus monkeys in a
conventional and SPF colonies were tested using a direct PCR method with EDTA (ethlylenediamine
tetraacetic acid) treated whole blood comparing SRV/D-T specific primer set with established primer
sets that detect SRV/D. Utilization of established primers for SRV/D-1,-2 and-3 yielded no signals in
either colony. Use of primer sets for SRV/D that simultaneously detect multiple SRV/D subtypes failed
to identify SRV/D. SRV/D-T specific primers failed to amplify any products in the SPF animals tested.
Testing of the conventional colony using SRV/D-T specific primers amplified products from blood
DNA from 11 of 49 monkeys. The 381-bp products were sequenced to confirm that SRV/D-T was
most likely the predominant subtype present.
Questions
1). What does EDTA stand for?
2). SRV/D-T specific primers were designed based on the nucleic acid sequences in the pol region of
SRV/D-1,-2,-3 and SRV/D-T true or false
3) By treating whole blood with EDTA yields genomic DNA to be used as a template for nested PCR
allowing the detection of SRV/D-T from whole blood eliminating the need to purify PBMCs? True or
False
4) For the colony surveyed the established SRV/D primers failed to detect SRV/D-T from positive
animals? True or False
Answers
1). Ethlylenediamine tetraacetic acid.
2). False gag region
3). True
4). True
Title: Ovine Model to evaluate Ovarian Vascularization by Using Contrast-Enhanced
Sonography (pages 150-155)
Summary: This study evaluated a sheep model for use of a transvaginal ultrasound contrast agent to
visualize the microcirculation of normal ovaries. Purpose for this study is, in humans, detection of
ovarian tumors is hampered by their small size. Current techniques to detect ovarian tumors use
ultrasound with contrast agents. The earlier (smaller) that tumors can be detected, the better chance
of successfully treating. Sheep were chosen for their size similarity to humans and also their ovaries
behave similarly to humans histochemically and hormonally. Sheep do not normally get ovarian
tumors, but the authors currently are trying to develop a sheep ovarian tumor model. Ultrasound
contrast agents consist of microbubbles that are around 3 microns in size. These bubbles stay in the
vasculature for a short period of time, then are expired in the exhaled air within 15 minutes after
injection.
This study used a bolus injection of Sonovue, which is a second-generation agent in a
suspension of stabilized sulphur hexafloride. The first phase of the study compared enhancement in
the ovary at three different doses (2.5, 5.0, and 7.5 ml) of agent. It was determined that once a
plateau of enhancement is seen, higher doses make little difference. The dose of 5 ml per bolus was
optimal. The second phase of the study compared enhancement of signal, time to peak
enhancement, and enhancement ratio. The study compared ovaries at different stages of
development, from inactive to estrus to luteal. Overall, they found an enhancement of 248% with use
of a contrast agent. Time to enhancement was 10.8 sec and the peak enhancement was seen at
24.7 sec. The ovary on the side of ovulation and subsequent corpus luteum had a stronger
enhancement than the non-cycling ovary (358% vs 175%).
The authors summarized by stating the sheep is an excellent model for transvaginal ultrasound
examination of ovaries and with use of contrast agents, the microvasculature density can be
assessed. An increase in microvasculature density may be caused by an ovarian tumor, but the
authors warn that stage of the ovarian cycle can influence this.
Questions:
1. Sheep were chosen because of their similar size to humans, their ovaries behave similarly to
humans histochemically and hormonally, and they get spontaneous ovarian tumors, T or F
2. Ultrasound contrast agents work by _____________ the ultrasound signal.
a. Enhancing
b. Blocking
c. Obliterating
3. Ultrasound contrast agents generally leave the body within _______ minutes via the __________.
Answers:
1: False
2: A
3: 15 minutes, lungs
Reference Cardiopulmonary Values in Normal Dogs (pages 156-161)
Cardiopulmonary values on 97 instrumented, unsedated, normovolemic dogs. Body weight; arterial
and mixed-venous pH and blood gases; mean arterial, pulmonary arterial, pulmonary artery
occlusion, and central venous blood pressures; cardiac output; heart rate; hemoglobin; and core
temperature were measured. Body surface area; bicarbonate concentration; base deficit; cardiac
index; stroke volume index, systemic and pulmonary vascular resistance indices; left and right cardiac
work indices; alveolar partial pressure of oxygen (pO2) ; alveolar-arterial pO2 gradient (A-apO2);
arterial, mixed-venous, and pulmonary capillary oxygen content; oxygen delivery; oxygen
consumption; oxygen extraction; venous admixture; arterial and mixed-venous blood CO2 contents;
and CO2 production were calculated. In the 97 normal, resting dogs, mean arterial and mixed-venous
pH were 7.38 and 7.36, respectively; partial pressure of carbon dioxide (pCO2), 40.2 and 44.1 mm
Hg, respectively; base-deficit, -2.1 and -1.9 mEq/liter, respectively; pO2, 99.5 and 49.3 mm Hg,
respectively; oxygen content, 17.8 and 14.2 ml/dl, respectively; A-a pO2 was 6.3 mm Hg; and venous
admixture was 3.6%. The mean arterial blood pressure (ABPm), mean pulmonary arterial blood
pressure (PAPm), pulmonary artery occlusion pressure (PAOP) were 103, 14, and 5.5 mm Hg,
respectively; heart rate was 87 beats/min; cardiac index (CI) was 4.42 liters/min/m2; systemic and
pulmonary vascular resistances were 1931 and 194 dynes.sec.cm-5, respectively; oxygen delivery,
consumption and extraction were 790 and 164 ml/min/m2 and 20.5%, respectively. This study
represents a collation of cardiopulmonary values obtained from a large number of dogs (97) from a
single laboratory using the same measurement techniques.
Questions:
1. What is the significance of the venous admixture measurement? Is it usually increased or
decreased with pulmonary parenchymal disease?
2. True or false: Except for heart rate and mean blood pressure, most of the cardiopulmonary
values in this paper fall within the range of normal human values.
3. What is the significance of D02 (oxygen delivery, a calculated value)?
Answers:
1. It is a calculated value used to assess lung oxygenated efficiency. The value is usually increased
with pulmonary parenchymal disease.
2. True
3. Oxygen delivery, as the name implies, represents an overview of cardiopulmonary performance.
Any disease process that decreases blood oxygenation, hemoglobin concentration or cardiac output
tends to diminish D02.
Cardiomyopathy in Captive Owl Monkeys (Aotus nancymae) (pages 162-168)
Authors characterized incidence of cardiac disease in owl monkeys via use of
echocardiography. A survey of a colony of owl monkeys over the past 15 years revealed a significant
amount of cardiac disease. Although no animals showed clinical signs of cardiac disease at the time
of these exams, some monkeys died prior to completion of this study (e.g. 2nd exam, 14 months
following initial exam). A pathology exam (gross and histopath.) were conducted of the deceased
animals, and the data obtained from the echocardiography measurements supported the pathological
evidence of dilated cardiomyopathy in this colony.
Authors noted that animals found with a questionable diagnosis of cardiomyopathy during the
first exam ultimately showed progression of the disease over time. M-mode and 2D echocardiograms
were taken, using right parasternal short-axis views. Since the colony had a high prevelance of
disease, authors were reluctant to establish reference intervals for echocardiography for this species.
Hopefully, preliminary information can be utilized from this study to pursue further echocardiographic
guidelines in this species.
Questions:
1. Which other primate species has cardiomyopathy been identified?
a. vervet
d. baboons
b. squirrel monkeys
e. owl monkeys
c. all of the above
f. b, d, and e
2. Which view for conducting the echocardiogram exams provided the most repeatable,
consistent view?
a. dorsal view
c. parasternal short-axis view
b. parasternal long-axis view
d. ventral recumbency view
3. List some other Differentials for cardiac hypertrophy.
Answers:
1. f
2. c
3. chronic systemic hypertension; trypanosomiasis; taurine deficiency
Age-Related Diffuse Chronic Telogen Effluvium-Type Alopecia in female Squirrel Monkeys
(Saimiri boliviensis boliviensis) (pages 169-174)
Summary: The purpose of this study was to examine the pathology associated with chronic alopecia
observed in females from a colony of squirrel monkeys. Materials and Methods: All monkeys
were fed a high protein monkey chow supplemented with fresh fruit and vegetables. They were
housed in indoor-outdoor pens. One hundred (100) adult females and ten (10) adult males were
randomly selected for inclusion in this study. Evaluation included physical examination, evaluation of
haircoat, and serum biochemistry profile. To evaluate condition of hair, trichograms and skin biopsies
were performed and hair density was calculated. Finally, behavior was evaluated in 2 groups
consisting of 50 monkeys each. Results: No hair abnormalities were observed in the 10 male
monkeys. Of the 100 females, 65 had alopecia and 35 had no evidence of alopecia. Statistically
significant differences were observed for age and parity, but no differences were observed for body
weight and serum chemistry results. Hair densities were greater in the control group. The trichogram
demonstrated twice as many club hairs (telogen hairs) in the alopecia group versus the control
group. Analysis of behavior did not find enough activity to account for the hairloss observed in the
alopecia. Dominant males were responsible for most of the aggressive behavior directed against
females in the colony. Conclusion: After discussion of pathophysiology of several conditions in which
alopecia is a symptom, the authors stated that the hairloss pattern observed was consistent with
chronic telogen effluvium.
Questions:
1. Give the genus species of the squirrel monkeys in this study.
2. In a trichogram, how are telogen hairs identified?
3. What are the 3 differential diagnoses for diffuse scalp hair loss in human females?
4. Define telogen effluvium.
5. The lifespan of a hair is determined by the duration of anagen phase. T or F
6. The alopecia observed in the squirrel monkeys in this study was statistically associated with:
a) hormone levels
b) age
c) parity
d) position of dominance within group
e) age and parity
Answers:
1. Saimiri boliviensis boliviensis
2. Telogen hairs have a thinner shaft and bulbous ends ("club" hairs).
3. a) androgenetic alopecia, b) chronic telogen effluvium, and c) alopecia arreta.
4. Telogen effluvium is the disruption in the hair cycle resulting in increased shedding of telogen
hairs. Can be acute or chronic disease.
5. True.
6. The correct response is : e) age and parity
Susceptibility of rats to corneal lesions after injectable anesthesia (pages 175-182)
Corneal injury is a common side effect after general anesthesia in rats. This study examined several
different anesthesia methods to determine if the incidence of corneal opacities or ulcers was different
among the various methods. This study also examined strain variation in the development of corneal
ulcers. It was determined that animals anesthetized with ketamine-xylazine were at greater risk of
developing corneal ulcers compared to animals anesthetized with inhalational agents (isoflurane or
enflurane). It was also noted that Wistar, Long-Evans (LE), and Fischer 344 (F344) rats were more
likely to develop lesions than Sprague-Dawley (SD) and Lewis rats.
Materials and Methods: Results for this article were taken from three separate groups: a
retrospective study of animal records and tissues used in other studies, female Wistar rats assigned
to 5 experimental anesthetic groups, and male rats of 5 different strains anesthetized with ketaminexylazine. Retrospective study- Histopathology was performed on eyes from 402 male and female
Wistar rats used in other studies. Several anesthetic methods were used in this portion of the study:
enflurane, isoflurane, ketamine-xylazine, Hypnorm-midazolam. Anesthetic influence- The five
experimental groups were O2 control without jackets, O2 control with jackets, ketamine-xylazine,
pentobarbital, Hypnorm-midazolam, and isoflurane. Strain influence- The five strains compared were
Wistar, F344, SD, LE, and Lewis.
Results: Retrospective study- Animals anesthetized with ketamine-xylazine demonstrated the
greatest incidence of corneal lesions and ulcers- 71% of animals had lesions of a score of 2 or
greater. Animals anesthetized with inhalational methods had only a 2% rate of corneal changes (one
animal). There were no sex-associated differences. Anesthetic influence- Ketamine-xylazine
anesthesia was associated with the greatest incidence of corneal changes- 66%. In comparison, only
11% of animals anesthetized with isoflurane developed corneal changes. Strain influence- F344 rats
were most sensitive, developing the greatest number and most severe lesions. Wistar and LE rats
also developed corneal lesions after anesthesia. SD and Lewis rats were more resistant to changes.
Discussion: Results of this study indicate that despite precautions taken to prevent corneal damage
(ophthalmic ointment applied at anesthetic induction), corneal lesions are common in rats. Severe
lesions are associated with ketamine-xylazine anesthesia and with certain strains of rats. Lesion
development is thought to be associated with the vasoconstrictive effects of xylazine, and suppress
the parasympathetic tone to the iris. This may lead to local and systemic hypoxia resulting in corneal
injury. Repeated administration of eye lubricant may not have a beneficial effect, as studies in both
humans and rats show that repeated application of eye lubricant after traumatic injury may
exacerbate corneal damage.
Questions:
Which anesthetic method is associated with the greatest risk of corneal damage?
T or F- Male rats develop corneal lesions at a greater rate than do female rats.
T or F- Use of ophthalmic ointment can eliminate the risk of developing corneal lesions in
anesthetized animals.
Answers:
ketamine-xylazine
False- there is no sex-associated difference
False- All animals in this study received ophthalmic ointment at anesthetic induction, yet many
developed corneal lesions.
A National Survey of Laboratory Animal Workers Concerning Occupational Risks for Zoonotic
Diseases (pages 183-191)
The investigators conducted a cross sectional epidemiological study to estimate the
frequency of all episodes associated with laboratory animals regardless of their medical significance,
severity, consequences, or other aspects that will affect OSHA standards. A self administered survey
questionnaire, including return-reply postage, was mailed to all persons in the survey. Of 4802 survey
questionnaire supplied, 30% responded back, out of which 94% had worked with lab animal for past
five years and 84.5% worked with fresh tissues, blood or body fluids. Of these respondents there was
an estimate of 6202 person-years of zoonotic disease exposure. 70.1% of the respondents had
bachelor's degree and 26.6% had doctoral degree.
The overall estimated annualized incidence rate of occupationally acquired infection with
zoonotic agents from laboratory animals from this study was 45 cases per 10,000 worker-years.
Statistical analysis showed that persons working at AAALAC accredited institutions that had received
educational information about zoonotic diseases and had more years of experience were less likely to
have been medically evaluated for exposure to a laboratory animal zoonotic agent at work. Although
the data from this study confirmed that the zoonotic diseases of laboratory animals continue to be
important, although rare in the present environment. The data presented in the study may be biased,
especially by recall bias.
Questions.
True or False
1.
The incidence of occupational acquired infection from lab animal are high for the lab workers.
2.
The incidence of illness acquired from lab animal increases with education.
3.
Most of the institutions do not have a safety office/officer to evaluate zoonotic diseases from
lab animals.
Answers.
1.
False
2.
False
3.
False
Successful Cyclosporine Treatment for Atopic Dermatitis (AD) in a Rhesus Macaque (Macaca
mulatta) (pages 192-196)
A juvenile (1 year old ) female rhesus macaque (Macaca mulatta) developed a chronic active
skin condition characterized by pruritus, erythema, alopecia, scaling, exfoliation, and lichenification.
Lesions were limited to the ventrum, specifically rostral mandible and neck, axilla and inguinal
regions, distal extremities, and interdigital regions. Differential diagnoses included infection, dietary
deficiency, metabolic abnormality, endocrinopathy, and immunological injury. Diagnostic tests
included complete hemogram, serum chemistry, skin scrapes for ectoparasite detection, hair plucks
for dermatophyte culture, and a serum-based hypersensitivity panel. All results were within normal
limits. Dermal biopsies revealed lesions consistent with active allergic dermatitis, and a diagnosis of
atopic dermatitis was made. Oral cyclosporine (5 mg/kg daily) rapidly eliminated clinical evidence of
dermatitis. Histologically, lesions resolved after 12 months of treatment. Atopic dermatitis is an
inflammatory skin condition for which there are neither pathognomonic clinical or diagnostic features
nor a single successful therapy. Basic criteria such as pruritus, lichenification, a chronic course, and
history of allergies strongly support the diagnosis. One successful therapeutic agent is a macrolide
calcineurin inhibitor, cyclosporine. It represents a safer class of immunomodulatory drugs than
corticosteroids and provides targeted alteration of lymphocyte function.
Questions:
1)
Diagnostic tests to confirm AD are unreliable, suffering from inadequate specificity and
sensitivity. (T/F)
2)
Oral cyclosporine (5 mg/kg daily) rapidly eliminated clinical evidence of Atopic dermatitis.(T/F)
3)
Mode of action of cyclosporine might be due to preferential inhibition of T lymphocytes (T/F)
Answers:
1)
2)
3)
T
T
T