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Metabolism of α‐Linolenic Acid from Flaxseed in Dogs

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Spontaneously hypertensive rats (SHR) and normotensive control, Wistar/Kyoto (WKY) rats through two generations were fed a semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha-linolenate). The cerebral lipid contents and phospholipid compositions did not differ between the two dietary groups of SHR rats. There were also no differences in the unsaturated/saturated ratios of individual phospholipids or the proportions of plasma-logens. However, the proportions of (n-3) and (n-6) fatty acids were significantly different. Decreases in the proportions of docosahexaenoate [22:6 (n-3)] in phosphatidylethanolamine and phosphatidylserine in the safflower oil group were compensated for with increases in the proportions of docosatetraenoic [22:4 (n-6)] and docosapentaenoic [22:5 (n-6)] acids as compared with the perilla oil group. These differences in phospholipid acyl chains were much smaller than the difference in the proportions of linoleate and alpha-linolenate of the diets. In a brightness-discrimination learning test, the total number of responses to the positive and negative stimuli were less in the groups fed perilla oil. However, the alpha-linolenate-deficient group took longer to decrease the frequency of R- responses and therefore longer to learn the discrimination. Consequently, the correct response ratios were higher in the perilla oil groups than in the safflower oil groups. Thus, the dietary alpha-linolenate/linoleate balance influenced the (n-3)/(n-6) balance of polyenoic fatty acids differently among brain phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)
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The objective was to determine the influence of consuming 50 g flaxseed/d for 4 wk on several indexes of nutrition in young healthy adults. During flaxseed consumption, alpha-linolenate was increased significantly in adipose tissue, and n-3 polyunsaturates were increased in plasma lipids. Plasma LDL cholesterol was also reduced by up to 8%, and total urinary lignan excretion was increased more than fivefold (P < 0.05). Muffins containing 25 g flaxseed did not differ significantly from control muffins in their content of thiobarbituric acid-reactive substances, and alpha-linolenate in the muffins was not significantly reduced by baking. Antioxidant vitamins and lipid hydroperoxides in plasma were not significantly affected by flaxseed consumption. Bowel movements per week increased by 30% while flaxseed was consumed (P < 0.05). We conclude that traditional flaxseed has modest beneficial effects on several indexes of nutritional status without compromising antioxidant status.
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Docosahexaenoic acid (DHA, 22:6n-3) is the major fatty acid of photoreceptor membranes that is necessary for optimal retinal function. Miniature poodle dogs with progressive rod-cone degeneration have lower plasma levels of DHA than normal dogs and higher 22:5n-3/22:6n-3 ratios. The purpose of this study was to test the hypothesis that the metabolic defect in dogs affected with progressive rod-cone degeneration was a reduced capacity for ocular synthesis of DHA from its precursor 22:5n-3. The in vivo retinal conversion of [14C]22:5n-3 to [14C]22:6n-3 was investigated by injecting normal dogs and dogs affected with progressive rod-cone degeneration intravitreally with [14C]22:5n-3. After 72 hours, rod outer segments, remaining retina, and retinal pigment epithelium/choroid were analyzed for metabolic products. Using high-performance liquid chromatography, six radioactive peaks were detected in both normal and affected dogs: [14C]20:5n-3, [14C]22:6n-3, [14C]22:5n-3, [14C]24:6n-3, [14C]24:5n-3, and [14C]18:0. The majority of the label in each tissue was in 22:6n-3 and there was no difference in the dpm% of [14C]22:6n-3 in normal and affected animals in any of the three tissues. Voss et al (J Biol Chem 1991;266:19995-20000) proposed a new pathway for the synthesis of DHA that involves elongation of 22:5n-3 to 24:5n-3, desaturation to 24:6n-3, and beta-oxidation to 22:6n-3. Identification of the products [14C]24:5n-3 and [14C]24:6n-3 verified that these putative intermediates are present in the dog retina. The finding of large amounts of label in DHA shows that the normal and progressive rod-cone-degenerated retina and retinal pigment epithelium are capable of DHA synthesis from 22:5n-3. The presence of radioactivity in 24:5n-3 and 24:6n-3 suggests that the synthesis of DHA in the retina is similar to that described in the liver.
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Rats were fed various levels of either ethyl linoleate, ethyl arachidonate, or ethyl linolenate. Weight gain, fat-deficiency status, and fatty acid composition of the liver lipids were determined. Dietary linoleate, fed in excess of 1% of calories, maintained good growth and cured fat deficiency. Increasing amounts of dietary linoleate were stored in the liver lipids and converted into fatty acids of the linoleate family—20:4 and 22:4. The concentration of 20:3 was decreased. Dietary arachidonate cured fat deficiency three times more effectively than linoleate. Increasing amounts of dietary arachidonate were stored in liver lipids and converted to 22:5ω6. The level of 20:3 was lowered three times more effectively than when linoleate was fed. No fatty acids of the linolenate family were synthesized from linoleate or arachidonate. Dietary linolenate did not support weight gain as efficiently as did linoleate or arachidonate. Fat-deficiency symptoms could not be cured completely. Increasing amounts of dietary linolenate increased the levels of fatty acids of the linolenate family; linolenic acid was stored, and 20:5, 22:5ω3, and 22:6 were synthesized from linolenate. The level of 20:3 was lowered in the same fashion as when linoleate or arachidonate was fed. Thr level of 20:4 was decreased with increasing amounts of dietary linolenate.
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About 1900, modern food selection and processing caused widespread of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a ypovitaminosis B, i.e., a mixture of beriberi and pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for . Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.
Article
Female rats were fed semi-purified diets containing 10% safflower oil or 10% soybean oil for six weeks prior to mating and through-out pregnancy and lactation. The progeny were weaned to the diet of the dam. Physical, neuromotor and reflex development was monitored in the progeny prior to weaning and learning ability of the mature progeny was assessed in a simple Y-maze test. Brain lipid analyses were conducted in the progeny at birth, 21 and 210 days of age. Inclusion of soybean oil in the diet resulted in higher levels of 22:6omega3 and lower levels of 22:5omega6 in the brain ethanolamine glycerophosphatides. The nature of the dietary fat exerted no effect on the physical development, onset of reflexologic responses or onset of neuromotor co-ordination in the pups. The soybean oil-fed animals spent more time in certain neuromotor activities possibly associated with explorative drive than did their safflower oil-fed counterparts. The performance of the mature soybean oil-fed progeny in the discrimination-learning test was superior to that of progeny fed safflower oil. The association of superior learning capacity with dietary soybean oil-induced incorporation of omega3 fatty acids into the brain glycerophosphatides is offered as support for an essential role for dietary linolenic acid for the young rat.
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The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune function, but prospective trials have not demonstrated their effects on clinical outcome. Patients (n = 85) who underwent operation for upper gastrointestinal malignancies were randomized to receive the supplemental diet or a standard enteral diet after surgery. Clinical patient characteristics were similar between the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs -6.6 gm/day) measured in the first 20 patients were significantly greater in the supplemented group than in the standard group (p = 0.05). In vitro lymphocyte mitogenesis was measured in the first 31 patients and was decreased on postoperative day 1 in both groups, but normal levels were regained only in the supplemented group. In the cohort of 77 eligible patients, infectious and wound complications occurred significantly less often (11% vs 37%) in the supplemented group than in the standard group (p = 0.02). Linear logistic models for infectious/wound complications with control for the amount of nitrogen suggested (p = 0.10) dietary treatment as the major factor. Mean length of stay in the hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/- 5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids instead of a standard enteral diet significantly improved immunologic, metabolic, and clinical outcomes in patients with upper gastrointestinal malignancies who were undergoing major elective surgery.
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The effects of dietary fatty acids on serum and cutaneous fatty acids of healthy dogs were evaluated under controlled conditions. Beagle puppies (n = 12) were fed a standard diet supplemented with sunflower oil (group A), olive oil (group B) or no supplementation (group C) for 12 weeks. There were no significant differences in food intake or growth rates between the three groups. Dogs in group A had significant increases (P < 0.05) in serum 18:2n6 (linoleic acid) and 20:3n6 (dihomo-gamma-linolenic acid), and cutaneous 18:2n6 with significant decreases in serum 20:4n6 (arachidonic acid) and cutaneous 18:1n9 (oleic acid) and 18:3n3 (alpha-linolenic acid). Dogs in group B had significant increases in serum 18:1n9, 20:3n6 and cutaneous 18:1n9 with decreases in serum 20:4n6, 22:4n6, 22:5n3 and 22:5n6, and cutaneous 18:2n6, 18:3n3 and 20:4n6. There were no significant changes in serum or cutaneous fatty acids for the dogs in group C. This study demonstrates that fatty acid supplements can be used to alter the serum and cutaneous fatty acid compositions of dogs.
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The importance of dietary fatty acids to the health of the skin was recognized more than 60 years ago. Fatty acids are important in providing membrane fluidity and maintaining the cutaneous water permeability barrier. Fatty acids function as precursors of eicosanoids. Eicosanoids, which include prostaglandins and leukotrienes, influence cellular interactions, cellular proliferation, and inflammation. Certain diseases, such as atopy and hypothyroidism, are characterized by abnormalities in fatty acid metabolism. Dietary manipulations may be useful in the treatment of diseases mediated by eicosanoids.
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The implication that essential fatty acids (EFA) can affect immune response was based on the observation that EFA deficiency can accentuate or improve symptoms of certain autoimmune diseases in animals, and that supplementation of linoleic acid to animals reversed such effects. Furthermore, treatment of animals with cyclooxygenase inhibitors abrogated the effect of linoleic acid. Administration of cyclooxygenase inhibitors to animals enhanced both cell-mediated and humoral immune responses. In vitro studies have shown that prostaglandin E (PGE) group inhibits both T and B lymphocyte functions; it is suggested that effects of EFA on immune response are, in part, mediated through eicosanoids. Growing evidence now suggests that the PGE group of prostaglandins can serve as a negative feedback modulator of immune response. However, in vitro effects of other cyclooxygenase-derived products, such as PGI2 and thromboxane A2 (TXA2) have not been well established, perhaps because of their instability in aqueous media. Unlike the PGE group, some of lipoxygenase-derived products of arachidonic acid have shown immunostimulatory effects, as assessed by lymphokine production in vitro. Whether such effects can be seen in vivo remains to be determined. Some lipoxygenase-derived products with strong chemotactic action may indirectly influence immune response by modulating the population of antigen-presenting macrophages in tissues. Thus, the net effect of eicosanoids synthesized in macrophages on modulating immune response may depend on relative amounts of cyclooxygenase-derived products as compared with lipoxygenase-derived products. Macrophages are the major source of eicosanoids among immunocompetent cells. The profile of eicosanoids, produced in vitro by macrophages, varies with type of stimuli and anatomical sites. It can also be affected by the fatty acid composition of tissue lipids, which in turn can be modified by the composition of dietary EFA. Whether manipulating dietary EFA can modulate immune response in normal humans and animals needs to be determined.
Article
Rats were fed a purified diet containing either 1.5% sunflower oil [940 mg linoleic acid [18:2(n-6)]/100 g diet; 6 mg alpha-linolenic acid [18:3(n-3)]/300 g diet] or 1.9% soybean oil [940 mg 18:2(n-6)/100 g diet; 130 mg 18:3(n-3)/100 g diet]. In all cases and tissues examined 22:6(n-3) was lower and 22:5(n-6) was higher in rats fed sunflower oil than in rats fed soybean oil. Levels of 22:4(n-6) and 20:4(n-6) were largely unaffected. Expressed as a percentage of that in soybean oil-fed rats, 22:6(n-3) in sunflower oil-fed rats was as follows: neurons, 49; astrocytes, 47; oligodendrocytes, 10; lung, 27; testes, 32; retina, 36; liver, 35 and kidneys, 45. Ten wk after the change in diet of 60-d-old rats from one containing sunflower oil to one containing soybean oil, the fatty acid composition of the brain cells had not reached control values, e.g., that obtained in animals continuously fed soybean oil; 22:6(n-3) was 77, 65 and 80% of control levels for astrocytes, oligodendrocytes and neurons, respectively. In contrast, the recovery measured by the decay of 22:5(n-6) was complete within 10 wk. For 22:6(n-3), it took approximately 2 wk for liver and kidney to recover to the control value, 3 wk for lung, 6 wk for retina and 10 wk for testes. The decrease of 22:5(n-6) was rapid: the control values were reached within 2 wk for kidney, liver and lung and within 6 wk for retina.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Aside from food hypersensitivities, nutritional skin diseases in pets fed commercial foods appear to be very uncommon. Nutritional deficiencies all cause seborrheic skin signs and most of the clinical presentations are not pathognomonic for a specific nutrient deficiency. Careful consideration of the history and the results of skin biopsies usually suggest which nutrient is deficient. Because nutritional supplements can unbalance an animal's diet, they should not be used indiscriminately but only when indicated. Balanced nutrition should minimize the need for supplements.
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Since the discovery in 1929 that certain polyunsaturated fatty acids (PUFA) are essential for life and health, intense investigation has revealed the multiplicity of members in each of several families of PUFA, no two of which are equivalent. The quantified nutrient requirements for the essential dietary precursors of the two dominant families of PUFA have been estimated, and the general functions of these families are slowly becoming known. The PUFA are essential components of structural membrane lipids. The functions of the individual members are not yet differentiated, except as they act as precursors of synthesis of unique octadecanoid, eicosanoid, and docosanoid products of oxidation that have potent biological properties. The PUFA occur in animals and higher plants as ubiquitous and essential components of structural lipid that are in a dynamic equilibrium with the pool of dietary acyl groups. Many human diseases have been found to involve unique essential fatty acid (EFA) deficiencies or distortions of the normal equilibrium pattern. The equilibrium is influenced by the level of dietary intake or precursors, by the presence of competing essential and nonessential acyl groups, by nonoptimum intake of other essential nutrients, by hormonal effects, by drug therapy, and by other effects upon physiological condition. With the many variables already known to modulate or control the equilibrium, it should be possible with more precise understanding of each variable to shift abnormal equilibria in the direction of normalcy. This perhaps will be the next area of intensive investigation in this field of nutrition and metabolism.
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Birthweights in the Faroe Islands are among the highest in the world. Compared with Denmark, the average birthweight of liveborn singleton infants of primiparous mothers is 194 g higher, and a substantial part of this difference seems to be attributable to longer gestation. Prostaglandins play an important part in the timing of parturition in human beings. Dietary (n-3)-polyunsaturated fatty acids (PUFA) in high amounts influence endogenous prostaglandin metabolism. Owing to the large consumption of marine fat, the average intake of (n-3)-PUFA in the Faroes by far exceeds that in Denmark. The hypothesis proposed is that dietary (n-3)-PUFA in high amounts prolong gestation in human beings by interfering with uterine production of prostaglandins, possibly by inhibiting the production of dienoic prostaglandins, primarily PGF2 alpha and PGE2, which are mediators of uterine contractions and cervical ripening.
Article
The effects of a dietary alpha-linolenic acid (18 : 3 n-3) deficiency on reproduction and postnatal growth in rats were studied during 3 successive gestations and 4 successive generations. Female rats received respectively a semi-synthetic diet in which the lipids were incorporated either as sunflower oil at 1.5% (deficient diet) or as soya oil at 1.87% (control diet). Both diets supplied the same amount of linoleic acid (18 : 2 n-6) (940 mg/100 g of diet), but the sunflower oil supplied 22 times less alpha-linolenic acid than the soya diet (6 mg vs 130 mg/100 g of diet). The results showed that, in our experimental conditions, the alpha-linolenic acid deficiency had no effect on fecundity (% of pregnant females), fertility (number of pups/litter), pup birth weight, food intake and weight of pregnant or lactating females, or pup growth during suckling. However, this deficiency did cause abnormally high rates of perinatal mortality from birth to postpartum day 3, namely on the average, for successive gestations: 18.5% in deficient pups vs 5.2% in the controls, and for successive generations: 16.6% in deficient pups vs 5.3% in the controls. Rat n-3 PUFA requirement during reproduction has been discussed; it appears to be more than 100 mg/100 g of feed. But this need should also be estimated in relation to n-6 PUFA supply; for female rats during reproduction, the ratio n-6: n-3 should be less than 10.
Article
The average birth weight of 10 132 liveborn infants delivered in the Faroes during the period 1969-81 was 3610 grams, which is the highest average weight reported by 33 countries from which we were able to obtain information. Comparison of live births only between the Faroes and Denmark shows a displacement between their birth weight curves of 225 grams. A less active elective delivery in the Faroes could not explain this considerable difference. When standardisation is made with respect to discrepancies in maternal age and marital status in the two populations, the difference between their average birth weights is increased by 5% and 9% respectively. A matching for maternal parity yields a difference between the averages which is 23% below the one between the total populations. Other factors must be responsible. Both environmental and genetic factors plus the possibility of the Faroes being closer to having an optimal birth weight than other countries are discussed.
Article
The brain is 60% structural lipid, which universally uses arachidonic acid (AA; 20:4n6) and docosahexaenoic acid (DHA; 22:6n-3) for growth, function, and integrity. Both acids are consistent components of human milk. Experimental evidence in animals has demonstrated that the effect of essential fatty acid deficiency during early brain development is deleterious and permanent. The risk of neurodevelopmental disorder is highest in the very-low-birth-weight babies. Babies born of low birth weight or prematurely are most likely to have been born to mothers who were inadequately nourished, and the babies tend to be born with AA and DHA deficits. Because disorders of brain development can be permanent, proper provision should be made to protect the AA and DHA status of both term and preterm infants to ensure optimum conditions for the development of membrane-rich systems such as the brain, nervous, and vascular systems.
Article
The metabolism and clinical potential for dietary polyunsaturated fatty acids (PUFAs) modifications using oil supplements containing n-3 and n-6 fatty acids are reviewed. Their use in such disorders as renal disease, inflammatory and immune-related disorders, and dermatological conditions in dogs and cats is discussed. The influence of n-3 fatty acid-rich rations on the endotoxin response in horses is described. Progress has been made toward understanding the clinical potential for PUFAs in these species. However, they have not yet been shown to be efficacious in any of the conditions investigated.
Article
It has previously been shown that miniature poodles with progressive rod-cone degeneration (PRCD) have lower plasma levels of docosahexaenoic acid (22:6n-3) than normal poodles and it has been suggested that affected animals have a defect in the metabolism of 22:6n-3. To test this hypothesis in vivo, PRCD-affected and normal miniature poodles were given daily oral supplements of linseed oil (enriched in 18:3n-3). Blood was drawn from food-deprived animals at predetermined times before, during and after supplementation, and plasma lipid fatty acids were analysed. There were no differences in the levels of 18:3n-3, 20:5n-3, and 22:5n-3 between affected and normal dogs. Therefore, there appears to be no abnormality in the elongation and desaturation system that takes 18:3n-3 to 22:5n-3. Surprisingly, the plasma level of 22:6n-3 was reduced in both groups following supplementation, but to a significantly greater extent in affected dogs. This resulted in a significantly higher 22:5n-3/22:6n-3 ratio in affected animals. These results support the earlier suggestion of an abnormality in 22:6n-3 metabolism in PRCD-affected miniature poodles. To determine the effect of n-3 supplementation on polyunsaturated fatty acid metabolism in dogs (not as a function of disease), results from both groups of dogs were pooled and compared at times before and near the end of supplementation. Dietary 18:3n-3 led to predictable increases in 18:3n-3, 20:5n-3, and 22:5n-3, but to a decrease in 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Atherosclerosis is the leading cause of coronary heart disease among older persons. With an increasing elderly population, cardiovascular disease has become an urgent public health concern. Diet plays an important role in atherogenesis with known beneficial effects on major risk factors among the younger population--cholesterol, hypertension, and diabetes. Intervention studies are needed to establish the benefits of diet therapy in the elderly segment of the population. Efforts are also needed to educate the elderly and health professionals about the benefits of a healthy Step I diet.
Article
Although linoleic and linolenic acids have been known to be necessary for normal growth and dermal function since 1930, the omega 3 essential fatty acids (EFA) have not received much attention until recently. The two families of acids are metabolized by the same enzymes, making them competitive. Gross deficiencies of omega 6 plus omega 3 EFA have been observed in humans, induced by attempts at total parenteral nutrition (TPN) with preparations devoid of lipids. Deficiency of omega 3 acids has been induced by TPN containing high omega 6 and low omega 3 fatty acids. In natural human populations, a wide range of omega 3 and omega 6 proportions have been found, ranging from high omega 3 and low omega 6 content to low omega 3 and high omega 6 content, showing inverse correlation between sigma omega 6 and sigma omega 3. In humans with neuropathy or impairment of the immune system, significant deficits of omega 3 EFA have been measured.
Article
Weanling rats were fed a fat-free diet supplemented with various ratios of corn and linseed oils to furnish a constant dietary level of linolenate at 1% of calories and levels of linoleate from 0.3 to 17.3% of calories. The fatty acid composition of the total liver lipids was analyzed by gas chromatography. Increasing amounts of dietary linoleate suppressed the levels of the 20:5, 22:5 and 22:6 metabolites of linolenic acid in the liver lipids. The level of dietary vitamin E had no effect upon this phenomenon. When the level of dietary linoleate was increased, the level of 22:4 in the liver lipids, as well as the other metabolites of linoleate, was shown to increase.
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The Hormel Institute, The University of Minnesota
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Douglas M. Bibus, PhD, The Hormel Institute, The University of Minnesota, 801, 16th Avenue, NE, Austin, MN 55912 (USA) Tel. 001 (507) 433 8804, Fax 001 (507) 437 9606, E-Mail bibus002@maroon.tc.umn.edu 198 Bibus/Stitt Downloaded by: UCSF Library & CKM 169.230.243.252 -2/20/2015 8:24:35 AM