Food and water restriction protocols: physiological and behavioral considerations. Contemporary Topics 39(6), 09.
Abstract: Food and water restriction protocols stimulate considerable discussion and controversy at the IACUC level. Issues to be considered are:
1. Determination of the need for and degree of restriction
2. Potential for adverse consequences to the animal
3. Balancing animal welfare with attainment of research goals
Rational decision on these issues are facilitated by information regarding the impact of food and water restriction on animal physiology and behavior.
Definitions:
Deprivation: Total denial of food or water; refers to interval in which food or water is withheld from the animal.
Restriction: Limitation on ad libitum intake; either the amount of, or the access time to, food or water can be limited
Water Restriction:
Two physiological stimuli elicit thirst: cellular dehydration and hypovolemia. Dehydration due to decreased water intake or increased loss
(renal or evaporative) results in increased osmolality of extracellular fluids. This creates an osmotic gradient which pulls fluids out of the
cells and into the extracellular compartment, this creating cellular dehydration. A similar situation develops if excessive solutes such as
NaCl are ingested. Cellular dehydration can be assessed by measuring plasma osmolality and plasma sodium concentration.
In the case of hypovolemia, thirst develops following the loss of fluid from the circulation, which can be a result of simple dehydration or
hemorrhage. Hypovolemia can be assessed by measuring hematocrit and plasma protein levels.
During water deprivation, both cellular dehydration and hypovolemia occur. These stimulate thirst (cellular dehydration to a greater extent than hypovolemia) and also initiate renal mechanisms for fluid conservation. Fluid conservation mechanisms can allow an animal to maintain homeostasis even if fluids are restricted for up to 24 hours.
Conclusion: Water restriction will induce thirst but the animal can compensate through renal mechanisms. The animal will not suffer
physiologic impairment if it is adapted to the restriction schedule and receives enough water to replace daily losses.
Food Restriction:
The physiologic stimuli that elicit hunger are not clearly defined. The size of the previous meal is an important determinant, implying that satiety rather than hunger determines food intake. Food intake is greatly influenced by non-metabolic factors such as palatability and ease of acquiring food. Studies show that when animals are required to work for their food, food intake decreases as the work requirement
increases. Numerous studies have shown that calorie-restricited animals live longer and develop fewer spontaneous neoplasms.
If not harmful, is food restriction stressful? Glucocorticoid levels go up in rats fasted for 24 hours, but the magnitude of increase is less
than with other stressors. The increased levels of glucocorticoids could be considered an adaptive homeostatic response to food restriction through stimulation of gluconeogenesis and reduction of glucose utilization by peripheral tissues. However, levels of glucocorticoids increase markedly after 48 hours of food deprivation, suggesting an increase in metabolic and possibly psychological stress. Severe food restriction or deprivation is associated with gastric ulcer formation in rats.
How food is presented in feed restricted studies is criticial. Adequate time for eating is crucial in fixed-duration studies. Circadian
rhythms must be considered as rodents consume most of their food during the dark cycle. Mice and guinea pigs in particular require adaptation to food restriction schedules.
Conclusion: Animals learn to modify their food intake patterns to accommodate restricted access to food. Restriction resulting in a decrease to 80-85% of baseline body weight is adequate for behavioral training and proloings the lifespan of the animal.
Food or Water Restriction as a Motivational Tool:
There are 2 basic designs for studies that require the use of restriction schedules:
1. Animals are permitted to work for reinforcement until they become satiated or stop spontaneously
2. Animals are allowed to work for a limited period of time each day.
The degree of food or water restriction required to generate consistent results depends upon the difficulty of the task to be performed, the
experience of the animal being tested, and individual coping styles. The critical aspect is training the animal that food or water is limited in
availability. In all studies utilizing food or water restriction, careful monitoring of the animal is crucial to ensure that adequate intake
of food and water occurs to maintain homeostasis.
Questions: Questions:
1. What are the physiologic stimuli which elicit thirst? What clinical tests can be used to assess these?
2. Severe food restriction for >48 hours can cause what pathological lesion in rats?
3. Why is consideration of circadian rhythm important in food restriction studies?
4. What is the most important aspect of any food or water restriction protocol?
Answers: Answers:
1. Cellular dehydration and hypovolemia. Plasma osmolality and plasma sodium concentration (dehydration); hematrocrit and plasma protein level (hypovolemia).
2. Gastric ulcers
3. With fixed duration studies, it is important that the access time to food correspond to when animals normally eat. In the case, of rodents, that would be during the dark cycle.
4. Careful monitoring of the animal to ensure that food and water intake meets homeostatic requirements.
An evaluation of analgesic regimens for abominal surgery in mice. Contemporary Topics 39(6), 18.
Abstract: This article describes efficacy of several analgesic regimens for abdominal surgery in mice. A radiofrequency transmitter is implanted
intraperitoneally into mice via a midline laparotomy. This device telemetrically transmits signals related to core body temperature and locomotor activity that can be recorded. Three different analgesic regimens (acetaminophen, ibuprofen and acetaminophen + buprenorphine) were used in drinking water beginning on the day before surgery to seven days after surgery. In addition, one injectable
analgesic regemen (bubrenorphine, ip) was also evaluated. Effects of these analgesic regimens were seen on food and water intake, locomotor activity, and core body temperature. These experimental parameters were selected because it has been indicated that decreased food and water intake, decreased locomotor activity and changes in core body temperature may be associated with pain in
many species. Many of the variables remained unchanged as compared to those animals that did not receive analgesic medication. Ibuprofen analgesic treatment showed significantly increased locomotor activity and more rapid return to stable postsurgical levels of activity and water intake. Buprenorphine injections showed hyperactivity, hyperthermia, and reduced food and water intake. Results indicate that postsurgical changes in physiologic and behavioral variables can be used to asses the efficacy of analgesic treatments.
Questions: Questions:
1. True or False: Decreased food and water intake, decreased locomotor activity and change in body temperature may be signs of pain in many species.
2. What analgesics are popularly used by laboratory animal veterinarians?
Answers: Answers:
1. True
2. Opioid analgesics; buprenorphine and butorphanol.
A method of video-assisted thoracoscopic surgery for the collection of thymic biopsies in rhesus monkeys (Macaca mulatta). Contemporary Topics 39(6), 24.
Abstract: This study describes modification of a previously published procedure for endoscopic thymectomy in dogs for use in obtaining serial thymic biopsies in Rhesus Macaques using rigid endoscopy equipment. Video assisted rigid endoscopic surgery is now routine in human medicine and is much less invasive and painful than open procedures. Using such techniques in animals refines the technique and reduces the number of animals needed as the same animal can be serially sampled instead of requiring separate animals for each time point of a study. Of 15 animals used for the study, 8 underwent two biopsy procedures and the others one; minor adhesions from the first procedure were noted at the time of second procedures, but no clinical signs were seen. Also, this procedure took approx. 15 minutes --
much shorter than a full thoracotomy procedure.
Animals were anesthetized in a standard manner, maintained on isoflurane, and ventilated at 15 breaths/min. at 10-20 cm H2O pressure. Animal was placed in dorsal recumbency. The chest and sides were prepared for aseptic surgery. A 5 mm 0-degree angled rigid endoscope, electric insufflator, Babcock forceps, and Metzenbaum scissors were used. Three entry sites, 1 cm incisions, on the same side of the chest were used: 6th intercostal space at level of costochondral junction - for telescope, 5th intercostal space midway between first site and epaxial muscles - for Babcock forceps, and 3rd intercostal space at level of costochondral junction - for Metzenbaum scissors. The first incision at 6th intercostal space was made, 5 mm cannula introduced to allow insufflation and camera placement; then the other incisions were made with inside of chest visible. Thymus was located easily in younger animals, and in older animals the anatomic location was used as a guide although the tissue visibly looked like mediastinal fat. For closure a 20 g Teflon catheter was inserted under visualization to a space cranial to the 6th intercostal space and a 3 way stopcock and 20 ml syringe attached. Each port site was closed in three layers and then the pneumothorax reduced using the catheter and syringe. Chest radiographs were taken, which showed good resolution of pneumothorax. Buprenorphine was used for analgesia for 3 days after the procedure. All biopsies were successful in obtaining thymic tissue.
The article notes that it is standard in human medicine to be prepared for the possible need to convert to an open approach if necessary, and this should be included in animal protocols. Electric insufflation maintained the necessary level well without using cannulas at all sites (saves space in chest). Insufflation was maintained at 6 mm Hg for the chest procedure, using CO2. The small incisions used allowed passage of the instruments, but minimized loss of insufflation gas from the chest. The authors conclude that video-assisted thoracoscopic surgery is a safe, reproducible, and rapid method for thymic biopsy in both juvenile and adult rhesus monkeys.
Questions: QUESTIONS:
1. Where is the thymus located in a Rhesus macaque?
2. Which of the following are not advantages of thoracoscopic surgery vs. open thoracotomy? (may be more than one answer)
a. Shorter duration of surgery
b. Less invasive
c. Better work space and visibility
d. Less post-op pain
e. Less expensive instrumentation
3. Would you consider thoracoscopic surgery a major surgery in evaluating a protocol for this procedure? Why or why not?
Answers: ANSWERS:
1. The thymus is located just cranial to the heart. Landmarks mentioned in the article were: left atrium caudally, phrenic nerve dorsally, and vena cava ventrally (animal in dorsal recumbency).
2. c,e
3. Major survival surgery is defined as a procedure which penetrates and exposes a body cavity or produces substantial impairment of physical or physiologic functions. Minor surgery is defined as a procedure which does not expose a body cavity and causes little or no physical impairment. Therefore thoracoscopic surgery is a major survival surgery and serial biopsy would be multiple survival surgery. (even so, this is a refinement which makes repetitive surgery much easier on the animal and more likely to be approved by IACUC's)
The thin blue line: a review and discusssion of aseptic technique and postprocedural infections in rodents. Contemporary Topics 39(6), 27.
Abstract: Summary: The authors discuss aseptic technique in rodents and whether adhering to strict asepsis is practical or even necessary. They discuss that aseptic technique during surgical procedures has been deemed necessary to decrease postprocedural infections. Thereby decreasing the pain and distress of the animals. They state that the procedures that are done typically in larger animals and humans are impractical and expensive to do in rodents. They also say that most of the techniques that are used have not been proven to cause a decrease in post-procedural infections in rodents. They systematical go through all the basic aseptic technique procedures citing examples that show that even if the procedure isn't done the animal (s) shows no signs of infection. In the discussion on disinfection of the skin, they examine the dogma that alcohol is not a high level disinfectant while it is considered the standard in Europe. They stress that 70-90% alcohol provides rapid killing of vegetative organisms that is comparable or greater than that of other disinfectants. Although they do mention that alcohol is not thought to prove sustained activity and is best used in combination with either povidone-iodine or chlorhexidine. They question whether traditional surgical garb (mask, sterile gloves, booties, andcap) is necessary. Citing that the use of laminar flow cabinets mitigates any benefits of surgical garb and that there are no studies showing the efficacy of wearing protective clothing. They point out that draping is problematic (e.g. gets wet, doesn't stay in place) with rodents saying that the adhesive plastic material can be used but is problematic for cranial or peripheral incision sites. In summary they say the basic problem remains that we know that aseptic technique works, but we don't know why. They suggest more research needs to be done to find out why and what procedures are truly effective and necessary. This information would minimize the bacterial contamination as well as any unnecessary procedures thereby cutting cost and inconvenience of the investigators.
Questions: Questions:
1. T/F 70% alcohol provides sustained activity during surgical procedure
2. What are the methods to sterilize instruments
3. T/F cold sterilants require prolonged contact times for effective killing of sprores
Answers: Answers
* False it doesn't provide sustained activity although it is thought to provide rapid killing of vegetative organisms
* Steam, dry heat , ethylene oxide, chemical sterilants and radiation
* True, they are rapidly bactericidal and fungicidal but require prolonged activity for the killing of spores.
Evaluation of epidural morphine for postoperative analgesia in ferrets (Mustela putorius furo). Contemporary Topics 39(6), 33.
Abstract: During ovariohysterectomy and bilateral sacculectomy, the authors compared 5 female ferrets given pre-surgical epidural morphine with 5 that were given saline epidurals. The study was double blinded. Pain was assessed (pain scoring) and pre and post- surgical behavior changes (ethogram) were compared. Fecal cortisol levels were compared between the groups. The authors felt that the animals that received the morphine epidural recovered more quickly after surgery and exhibited more activity and less severe pain. Fecal cortisol levels were higher in both groups post-surgery, but the morphine group was less elevated than the saline control. The procedure for the epidural is described in detail. No adverse signs due to the epidural were noted.
Questions: 1.What is the genus and species of the domestic ferret?
2.What are the purported advantages of pre-emptive analgesia?
3.What is an ethogram?
4.What are the difficulties in designing a study to interpret pain in any laboratory animal species?
Answers: 1 Mustela putorius furo
2 Preemptive analgesia is thought to prevent physiologic sensitization of pain pathways in the CNS thereby lessening hyperalgesia to noxious stimuli. Additionally preemptive analgesia reduces the overall dose required to induce and maintain surgical anesthesia and provides post-operative analgesia.
3 An ethogram is a list of the typical behaviors for an animal and would include any observed activity including sleep patterns, eating, drinking, exploration, reproduction, play, etc..
4 There is a lack of a clear definition of pain. Different animal types may respond differently to painful stimuli. Behavioral observation can be misleading due to variation in individual animals. Quantitative scales attempt to be less subjective. Independent observer ranking perceived signs of pain may be the least biased way of assessing degree of pain.
Isoflurane anesthesia in the African clawed frog (Xenopus laevis). Contemporary Topics 39(6), 39.
Abstract: Isoflurane anesthesia by the topical route is a useful alternative for MS222 or hypothermia for anesthetizing one-day fasted Xenopus. Unlike Rana spp. that are terrestrial and air breathers, Xenopus spp. are aquatic, air breathers and rely on transcutaneous respiration to remain underwater for long periods. A pad saturated by the isoflurane dose (0.03 to 0.06 ml/g) placed in contact with the skin provides a working anesthetic time averaging 6 minutes. Topical application of isoflurane provides a safe and effective method for anesthesia with a short induction time, adequate duration for procedures, and relatively short recovery time.
Questions: Q.
1- What is the recommended fasting period to anesthetize Xenopus spp. with isoflurane?
2- Which method provides the safest isoflurane aneshtesia in the African Clawed Frog?
a. bubbling with oxygen into water
b. use of an absorptive patch placed topically on the dorsum
c. intracoelomic injection
d. subcutaneous injection
e. intramuscular injection
Answers: A.
1- 24-hour
2- B
The effect of propofol administered intravenously on appetite stimulation in dogs. Contemporary Topics 39(6), 43.
Abstract: This article details the use of Propofol as an appetite stimulant when given IV to dogs.
The term anorexia is defined as a diminished appetite or an aversion to food. The causes can be systemic illness, pain, fever, stress,
learned aversion to food, decreased palatability, metabolic disorders and others. Appetite is regulated by hunger centers in the lateral hypothalamus and satiety centers located in the ventromedial hypothalamus as by other components of the limbic system. The chemical name for propofol is 2,6-diisopropylphenol.
Animals in the study group received .5 through 3.0mg/kg of Propofol IV . Controls received saline. Food cumsumtion was measured at
various times after administration of the drug. The results showed that food consumption was observed during the 0 to15 minute time interval; no significant increase in food consumption was observed at any other time points.
There is a dose responce effect until 3.0mg/kg; pass this point the animals were ataxic and sedated and food consumpution decreased. There was no carry over effect because animals did not eat more food in the 24 period after the treatment. Propofol is a sedative hypnotic agent that induces a dose-dependent depression of the central nervous system. The dosage for anesthesia is 6 to 8 mg/kg. Propafol should not be used in dogs with a known hypersensitivity to the agent or when sedation or genral anesthesia is contraindicated. propofol has been associated with pain on injection , anaphylasis, respiratory and cardiovascular depression, excitation and vomiting. Propofol is highly bound to serum proteins in a nonsaturable process. It is unlikely that there will be an exaggerated response in patients with renal and hepatic disease following the administration of a standard propofol dose. This agent should be
used with caution in hypoproteinemia patients.
The mechanism of appetite stimulation is not described.
Questions: QUESTIONS:
1: What is the pharmacutical classification of Propofol?
2: Which of the following is the reported mechanism of propofol appetite stimulation?
A) suppression of satiety centers
B) stimulation of the limbic system
C) unknown mechanism of action.
Answers: Answers:
1: a sedative hypnotic agent
2: C
Use of ultrafiltration probes in sheep to collect interstitial fluid for measurement of calcium and magnesium. Contemporary Topics 39(6), 47.
Abstract: Summary: Blood and urine are usually sampled when studying the concentrations of chemical constituents of living animals. However, the concentrations may not reflect tissue levels. This analysis was performed to evaluate the use of ultrafiltration probes for determining bone mineral distributions in the interstitial fluid of the subcutis and muscle and of bone marrow in five mixed breed sheep.
The probe consisted of semipermeable membranes that were attached to narrow-bore nonpermeable tubing (pg 48). The semipermeable membranes had a molecular weight cut-off of 40Kd so that large proteins (protein-bound calcium) could not pass through it. Porous cuffs were added to the outside of the probes to allow tissue ingrowth and provide additional stability. The bone probe was implanted in the marrow cavity of the femur by using a guide-wire placed through holes drilled in the shaft and greater trochanter. A 10 gauge introducer was used to place the subcutaneous and muscle probes. After placement, the introducer was removed. Probes were sutured in place. Vacutainer tubes were used to supply the vacuum needed to suck up the fluids. Blood samples were also taken
from the sheep. Ion concentractions were determined by colorimetric assays/spectrophotometer or ion-selective electrode readings.
Calcium gluconate (which also contained some magnesium) was infused into the sheep by IV. During infusion, blood protein-bound and protein-complexed calcium peaked within 120 minutes. However, ionized calcium, which is the physiologically active form, rose only slightly. Peak concentrations in bone, muscle, and subcutaneous tissues peaked at the same time (magnitude of muscle & subcu similar, bone lower). Bone magnesium concentrations rose higher than plasma but later fell below baseline levels.
Questions: Questions
1. The physiologically active form of calcium is:
A. Protein-bound
B. Complexed
C. Chelated
D. Ionized
E. Calcium Oxide
2. The best statistical analysis to perform on a study like this, where multiple tissues are being analyzed in several animals over several time points, would be:
A. t-test
B. paired t-test
C. analysis of variance (ANOVA)
D. analysis of co-variance (ANCOVA)
E. regression
3. Unrelated sheep question:
Which best describes Coxiella burnetii (Q fever):
A. Rickettsia, obligate intracellular organism, transmission dependent on arthropod
B. Rickettsia, obligate intracellular organism, transmission not dependent on arthropod
C. Bacteria, high concentrations in amniotic fluid and fetal membranes, transmitted by coitus
D. Bacteria, high concentrations in amniotic fluid and membranes, transmitted by aerosal-inhalation
E. Protozoan, obligate intracellular organism, transmitted in the urine
Answers: Answers:
1. D - ionized
2. D - ANCOVA, this paper used a paired T-test, which is not the best for analyzing more than two groups. ANOVA is the method of choice for analyzing three or more groups. Once a significant difference is found by ANOVA, there are multiple follow-up tests that can be used compare individual groups to one another. The ANCOVA is the best test here because you have multiple parameters that could be interacting and influencing results. By analyzing the covariates, you can determine interactions that might be occurring between time, individual sheep, tissues, and minerals. A regression analysis assumes that there is a linear relationship between two parameters and that one causes an effect in the other. This is commonly used if predictions need to be made.
3. B. C. burnetti is an obligate intracellular rickettsia but in contrast to other members of this genus, it completes its life cycle in the phagosomes of nucleated cells (a location that kills most organisms), induces no typhus-like rash, and is not dependent on arthropod transmission.
Improving the environment of mice using synthetic gauze pads. Contemporary Topics 39(6), 51.
Abstract: 2 inch X 2 inch rayon/polyester fabric pads were evaluated as envionmental enrichment devices in mice that were housed in wire
bottom cages for toxicology studies. The pads were placed with the mice at 5-7 weeks of age and the study lasted 1 year. Clinical
observations, body weights and food consumption were measured during the study. The pad was changed once/week and use of the
pad was determined by estimating the amout of mesh structure remaining in the pad after 1 week. Mild use = greater than 90% of
the mesh structure intact. Heavy use = greater than 90% of the mesh structure destroyed. Moderate use = intermediate mesh
destruction between heavy and mild.
Undisturbed mice were observed always sitting on the pad. In addition, mice were observed manipulating the pad in the cage.
Mice with pads showed a significant reduction in food consumption, but their body weights and weight gains did not differ from control animals. The authors concluded that because nest formation and nesting behavior have an effect on energy conservation, the reduction in
food consumption was related to a reduction in the energy expenditure in mice housed with the pads.
Questions: Questions
1. Synthetic guaze pads used instead of cotton guaze because:
a. The exact components of synthetic guaze were known and therefore if chewed an ingested would not interfere with the data for this toxicology study.
b. The threads of the cotton gauze, if ingested, would act as a linear foreign body necessitating surgery or euthanasia; whereas, the synthetic gauze would be broken down by the stomach acid and not act as a linear foreing body.
c. Cotton gauze threads may entangle the digits and produce serious infections of, and trauma to, the feet.
d. Synthetic gauze was used because it is more durable and so would not have to be replaced in the cage as frequently as the cotton gauze.
Answers: Answers
1. c
Postnatal growth in a mouse genetic model of classical phenylkentonuria. Contemporary Topics 39(6), 54.
Abstract: Reduced growth rate as measured by stature has been reported in untreated boys with PKU. The effect was not seen in girls. However, there are conflicting findings and the study populations were small. Studies in suckling rats showed decreased growth after treatment with phenylalanine hydroxylase, the enzyme responsible for Phe metabolism.
The BTBR-Pah(superscript: enu2) mutant mouse model accurately represents the classical PKU syndrome while maintaining a manageable fertility. The mutants were identified by hypopigmentation (evident by 3 weeks of age) and phenylalanine (Phe) levels which were 10-fold higher than controls. Phe was measured after the study so as not to stress the animals.
This article compares growth in homozygous mutant mice (BTBR-Pah(superscript:enu2) ) and heterozygous littermate (BTBR) controls both fed a standard rodent diet. The mice were weighed every 2-3 days from 1 week of age until about 40 days of age. While both males and females were included, the only litters with sufficient numbers of both genotypes were male.
The body weights of male mutants were consistently reduced compared with controls. The percent difference ranged from 10-30%. The difference was a result of lower starting weights for mutants. The growth rate of homo and heterozygotes did not differ significantly. The author says that this model will be helpful in exploring the relationship between degree of treatment and growth rate.
Questions: 1. What aspect of growth did NOTdiffer between homo and heterozygotes?
2. What is classical PKU?
3. What are the symptoms of PKU in humans?
Answers: 1. Growth rate
2. In 'classic PKU', the enzyme that breaks down phenylalanine phenylalanine hydroxylase, is completely or nearly completely deficient.
3. Infants with PKU appear normal at birth. Many have blue eyes and fairer hair and skin than other family members.
About 50% of untreated infants have vomiting, rash, and a mousy odor to the urine. Some may also have nervous system function problems and later, mental retardation and seizures. Other commonly noted features in untreated children include: microcephaly (small head), prominent cheek and upper jaw bones with widely spaced teeth, poor development of tooth enamel, and decreased body growth.
Cholesterol granulomas in mice deficient in apolipoprotein E. Contemporary Topics 39(6), 57.
Abstract: Three 12-16 month old female B6,129 apolipoprotein E deficient mice maintained on a normal rodent diet spontaneously developed
bilateral, firm, subcutaneous masses and varying degrees of alopecia in the gluteal regions.In two of the animals, central 5 mm
ulcerated areas surrounded by alopecia covered the masses.
At necropsy visceral lesions included 1-2 mm white foci in the heart, lungs, kidneys and small intestine. Microscopically, the
masses were non expansile, encapsulated and extended from the superficial dermis to the underlying muscle layer and consisted
primarily of multinucleated giant cells surrounded by abundant cholesterol clefts and a loose network of spindle shaped cells. The
masses were diagnosed as subcutaneous cholesterol granulomas. Similar masses were also found on the nasal skin, choroid plexus,
spleen, kidneys, mesenteric lymph nodes, skeletal muscle, perivaginal fat and vulva. Other lesions included severe atherosclerosis of the aorta, aortic valves, renal and pulmonary arteries.
By 3 months of age, apo E deficient homozygous mice develop subendothelial deposits composed predominantly of foam cells in
the proximal aorta which can cause severe coronary arterial occlusions by 8 months of age.
This is the first report of apo E deficient mice fed a normal rodent diet that developed visceral, skeletal muscle and lymph node
cholesterol granulomas.
Questions: Questions:
1. What other clinical condition is commonly associated with xanthomatosis ?
2. What is the role of apolipoprotein E ?
Answers: Answers:
1. Canine diabetes mellitus
2. Apo E plays a pivotal role in lipoprotein metabolism in plasma and peripheral tissues, with deficiencies leading to increased serum lipids, atherosclerosis, xanthomatosis, cutaneous foam cell formation, memory deficits and cholinergic abnormalities.