Bcl-2 family proteins are essential for platelet survival.

Platelets are relatively short-lived, anucleated cells that are essential for proper hemostasis. The regulation of platelet survival in the circulation remains poorly understood. The process of platelet activation and senescence in vivo is associated with processes similar to those observed during apoptosis in nucleated cells, including loss of mitochondrial membrane potential, caspase activation, phosphatidylserine (PS) externalization, and cell shrinkage. ABT-737, a potent antagonist of Bcl-2, Bcl-X(L), and Bcl-w, induces apoptosis in nucleated cells dependent on these proteins for survival. In vivo, ABT-737 induces a reduction of circulating platelets that is maintained during drug therapy, followed by recovery to normal levels within several days after treatment cessation. Whole body scintography utilizing ([111])Indium-labeled platelets in dogs shows that ABT-737-induced platelet clearance is primarily mediated by the liver. In vitro, ABT-737 treatment leads to activation of key apoptotic processes including cytochrome c release, caspase-3 activation, and PS externalization in isolated platelets. Despite these changes, ABT-737 is ineffective in promoting platelet activation as measured by granule release markers and platelet aggregation. Taken together, these data suggest that ABT-737 induces an apoptosis-like response in platelets that is distinct from platelet activation and results in enhanced clearance in vivo by the reticuloendothelial system.

Effect of bradykinin metabolism inhibitors on evoked hypotension in rats: rank efficacy of enzymes associated with bradykinin-mediated angioedema.

BACKGROUND AND PURPOSE: Inhibition of bradykinin metabolizing enzymes (BMEs) can cause acute angioedema, as demonstrated in a recent clinical trial in patients administered the antihypertensive, omapatrilat. However, the relative contribution of specific BMEs to this effect is unclear and confounded by the lack of a predictive pre-clinical model of angioedema. EXPERIMENTAL APPROACH: Rats were instrumented to record blood pressure and heart rate; inhibitors were infused for 35 min and bradykinin was infused during the last 5 min to elicit hypotension, as a functional marker of circulating bradykinin and relative angioedema risk. KEY RESULTS: In the presence of omapatrilat bradykinin produced dose-dependent hypotension, an effect abolished by B(2) blockade. In the presence of lisinopril (ACE inhibitor), but not candoxatril (NEP inhibitor) or apstatin (APP inhibitor), bradykinin also elicited hypotension. Lisinopril-mediated hypotension was unchanged with concomitant blockade of NEP or NEP/DPPIV (candoxatril+A-899301). However, hypotension was enhanced upon concomitant blockade of APP and further intensified in the presence of NEP inhibition to values not different from omapatrilat alone. CONCLUSIONS AND IMPLICATIONS: We demonstrated that bradykinin is degraded in vivo with an enzyme rank-efficacy of ACE>APP>>NEP or DPPIV. These results suggest the effects of omapatrilat are mediated by inhibition of three BMEs, ACE/APP/NEP. However, dual inhibition of ACE/NEP or ACE/NEP/DPPIV elicits no increased risk of angioedema compared to ACE inhibition alone. Thus, novel BME inhibitors must display no activity against APP to avoid angioedema risk due to high prevalence of ACE inhibitor therapy in patients with diabetes and cardiovascular disease.

Hypertension induced by chronic renal adrenergic stimulation is angiotensin dependent.

We designed these studies to assess the role of the renin-angiotensin system in mediating the hypertensive and renal functional effects of chronic renal adrenergic stimulation. Norepinephrine was infused at 0.1 microgram/kg per minute for 7 days directly into the renal artery of uninephrectomized dogs under control conditions (n = 5) or after plasma angiotensin II (Ang II) concentration was fixed at control levels (n = 5) by chronic intravenous infusion of captopril (14 micrograms/kg per minute) and Ang II (0.58 +/- 0.04 ng/kg per minute). During the first 60 minutes of norepinephrine infusion in control dogs, mean arterial pressure increased 9 +/- 4 mm Hg in association with a twofold to threefold rise in plasma renin activity. Additionally, glomerular filtration rate, renal plasma flow, sodium excretion, and fractional sodium excretion decreased to 70 +/- 5%, 64 +/- 5%, 31 +/- 4%, and 38 +/- 6% of control, respectively, while filtration fraction increased 15 +/- 2%. In contrast to the pronounced short-term effects of norepinephrine on renal function, during chronic norepinephrine infusion, all indexes of renal function returned to control levels. However, elevations in both plasma renin activity and mean arterial pressure were sustained and on day 7 were 2.3 +/- 0.6 ng angiotensin I/mL per hour (control, 0.5 +/- 0.1) and 110 +/- 7 mm Hg (control, 90 +/- 3). In dogs with fixed plasma levels of Ang II, acute and chronic changes in renal function induced by norepinephrine were similar to those in control dogs except that acute reductions in glomerular filtration rate tended to be more severe, and changes in filtration fraction and fractional sodium excretion were either attenuated or abolished. Moreover, in the absence of a rise in plasma Ang II concentration, mean arterial pressure did not change either acutely or chronically during norepinephrine infusion. These findings suggest a critical role for Ang II in mediating the hypertension associated with elevated levels of renal adrenergic stimulation that have little or no long-term effect on renal blood flow.

Role of renal nerves in mediating the hypertensive effects of nitric oxide synthesis inhibition.

Recent studies suggest that enhanced renal sympathetic nervous activity plays an important role in mediating the renal hemodynamic and electrolyte excretion changes associated with acute inhibition of NO synthesis. The purpose of this study was to determine the importance of renal nerves in mediating the long-term hypertensive and renal actions of NO synthesis blockade. To achieve this goal, we infused N(G)-nitro-L-arginine methyl ester (L-NAME) at a rate of 25 microg/kg per minute for 2 weeks in control dogs and in bilaterally renal-denervated dogs. NO synthesis blockade in control dogs increased arterial pressure by 18%, from 94 +/- 3 to 111 +/- 4 mm Hg, and decreased heart rate from 74 +/- 4 to 57 +/- 4 beats per minute (bpm). L-NAME also decreased renal plasma flow from 195 +/- 18 to 166 +/- 18 mL/min while having no effect on glomerular filtration rate (67 +/- 7 versus 63 +/- 6 mL/min). In the renal-denervated dogs, inhibition of NO synthesis increased arterial pressure by 14%, from 92 +/- 4 to 105 +/- 5 mm Hg, and decreased heart rate from 80 +/- 4 to 65 +/- 5 bpm. Renal plasma flow in this group decreased from 195 +/- 20 to 165 +/- 20 mL/min, whereas glomerular filtration rate remained unchanged (66+/- 6 versus 64 +/- 6 mL/min). In addition, renal excretion of sodium and water in response to L-NAME was similar in each group. The results of this study indicate that the long-term hypertensive and renal effects of NO synthesis inhibition in the dog are not dependent on activation of the renal sympathetic nervous system.

Temporal influence of the renal nerves on renal excretory function during chronic inhibition of nitric oxide synthesis.

To determine whether the sympathetic nervous system contributes to the hypertension induced by long-term suppression of nitric oxide synthesis, we determined the neurally induced changes in renal excretory function during chronic administration of NG-nitro-L-arginine methyl ester (L-NAME). Studies were carried out in six conscious chronically instrumented dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into two hemibladders to allow separate 24-hour urine collection from denervated and innervated kidneys. Animals were studied during acute (100 minutes) and chronic (5 days) intravenous infusion of L-NAME at 37.1 nmol/kg per minute (10 micrograms/kg per minute). During the first 100 minutes of L-NAME, there were no significant changes in mean arterial pressure (control: 96 +/- 3 mm Hg), but heart rate fell from 66 +/- 6 to 55 +/- 7 beats per minute. Changes in glomerular filtration rate were not significant, but renal plasma flow and urinary sodium excretion decreased to approximately 75% and 50% of control values, respectively; however, these changes were comparable in both kidneys. In association with these responses, plasma concentrations of norepinephrine (control: 887 +/- 130 pmol/L or 150 +/- 22 pg/mL) and epinephrine (control: 691 +/- 192 pmol/L or 108 +/- 30 pg/mL) tended to decrease. In contrast to the acute responses, mean arterial pressure increased from 92 +/- 3 to 106 +/- 3 mm Hg and heart rate decreased from 72 +/- 4 to 57 +/- 5 beats per minute by day 5 of L-NAME infusion, while renal plasma flow and glomerular filtration rate were not significantly different from control values. Most importantly, there were no significant differences in urinary sodium excretion between innervated (control: 31 +/- 2 mmol/d) and denervated (control 33 +/- 2 mmol/d) kidneys during chronic L-NAME infusion or during the recovery period. These results indicate that the renal sympathetic nerves do not play an important role in promoting sodium retention during either acute or chronic inhibition of nitric oxide synthesis in conscious dogs. Thus, increased renal sympathetic nerve activity does not contribute significantly to L-NAME-induced hypertension.

Blunted natriuretic response to a high-sodium meal in obese dogs. Role of renal nerves.

Although the relation between body weight and arterial pressure is well established, the mechanisms involved in the pathogenesis of obesity-related hypertension are unclear. However, recent studies suggest that abnormalities in renal function may be involved. The purpose of this study was to test the hypothesis that obese animals have a reduced ability to excrete a sodium load as a result of abnormal renal nerve function. To quantify the role of renal nerves, we examined changes in renal hemodynamics and sodium excretion in response to a high-sodium meal (200 mmol Na) in separate innervated and denervated kidneys simultaneously within the same conscious dog. Two surgically designed hemibladders with indwelling catheters were used to collect urine from innervated and denervated kidneys of the same dog. Body weight averaged 19.9 +/- 1.0 kg in the control lean dogs and 25.1 +/- 1.1 kg in the obese dogs. Arterial pressure averaged 101 +/- 4 mm Hg in the obese dogs and 90 +/- 4 mm Hg in the lean dogs. In response to the high-sodium meal in lean dogs, urinary sodium excretion increased from 20.8 +/- 4.2 to 189.7 +/- 21.2 mumol/min in the innervated kidneys and from 25.3 +/- 5.9 to 194.8 +/- 26.9 mumol/min in the denervated kidneys. In contrast, urinary sodium excretion in obese dogs increased from 9.6 +/- 1.4 to 129.9 +/- 34.3 mumol/min in the innervated kidneys and from 18.4 +/- 3.7 to 125.2 +/- 30.5 mumol/min in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and renal responses to chronic hyperinsulinemia in obese, insulin-resistant dogs.

We previously reported that chronic hyperinsulinemia does not cause hypertension in normal insulin-sensitive dogs. However, resistance to the metabolic and vasodilator effects of insulin may be a prerequisite for hyperinsulinemia to elevate blood pressure. The present study tested this hypothesis by comparing the control of systemic hemodynamics and renal function during chronic hyperinsulinemia in instrumented normal conscious dogs (n = 6) and in dogs made obese and insulin resistant by feeding them a high-fat diet for 6 weeks (n = 6). After 6 weeks of the high-fat diet, body weight increased from 24.0 +/- 1.2 to 40.9 +/- 1.2 kg, arterial pressure rose from 83 +/- 5 to 106 +/- 4 mm Hg, and cardiac output rose from 2.98 +/- 0.29 to 5.27 +/- 0.54 L/min. Insulin sensitivity, assessed by fasting hyperinsulinemia and by the hyperinsulinemic euglycemic clamp technique, was markedly reduced in obese dogs. Insulin infusion (1.0 mU/kg per minute for 7 days) in obese dogs elevated plasma insulin from 42 +/- 12 microU/mL to 95 to 219 microU/mL but failed to increase arterial pressure, which averaged 106 +/- 4 mm Hg during control and 102 +/- 4 mm Hg during 7 days of insulin infusion. Hyperinsulinemia for 7 days in obese dogs elevated heart rate from 116 +/- 8 to 135 +/- 7 beats per minute but caused no significant changes in cardiac output, in contrast to normal dogs (n = 6), in which marked increases in cardiac output (31 +/- 5% after 7 days) and decreases in total peripheral resistance occurred during chronic insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced cardiac contractile responsiveness to isoproterenol in obese rabbits.

Although obesity is characterized by increased sympathetic nervous system activity, there is often a paradoxical reduction in cardiovascular end-organ response to sympathetic stimulation. Mechanisms involved in reduced sympathetic responsiveness in obesity have not been well characterized. Therefore, we determined cardiac contractile responsiveness to beta-stimulation in the obese rabbit model using both isolated heart (IH) and isolated papillary muscle (IPM) preparations. Female New Zealand White rabbits were fed control (IH: n=9; IPM: n=6) or 10% fat diets (IH: n=9; IPM: n=7) for 12 weeks. Contractile responsiveness in the IH was determined using a modified Langendorff preparation to evaluate the dose-response relationship between isoproterenol and 1) peak developed pressure/g of left ventricular wet weight and 2) maximal rate of pressure development (+dP/dt/P). Contractile responsiveness in the IPM was determined using right ventricular papillary muscles to evaluate the dose-response relationship between isoproterenol and (1) peak developed tension (T)/mm2 cross-sectional area (CSA) and (2) maximal rate of tension development (dT/dt/CSA). In the IH, baseline and maximum developed pressure/g were reduced in obese rabbits by 37% and 31%, respectively (P< or =.05). In the IPM, baseline and maximum T/CSA responses were reduced in obese rabbits by 59% and 33%, respectively (P< or =.05). Potency of isoproterenol as reflected by the EC50 did not differ between lean and obese animals in either preparation. These results demonstrate that left ventricular contractility in obesity is reduced at baseline and in response to stimulation with isoproterenol and suggest that decreased responsiveness to beta-stimulation may be a factor in the obesity-related systolic dysfunction.

Vitamin E and exertional rhabdomyolysis during endurance sled dog racing.

Exertional rhabdomyolysis (ER) is common in sled dogs, animals with high energy expenditures that consume high fat (60% of ingested calories) diets. Associations between pre-race plasma [vitamin E] and total antioxidant status (TAS) and risk of developing ER were examined in dogs competing in the 1998 Iditarod race. Pre-race blood samples were collected from 750 dogs and a second sample was collected from 158 dogs withdrawn from the race at various times. Plasma creatine kinase activity was used to identify withdrawn dogs with ER. There was no association between pre-race plasma [vitamin E] and risk of development of ER. Dogs that developed ER started the race with higher TAS, but when withdrawn, had lower TAS than unaffected dogs and had similar pre-race [vitamin E] but higher [vitamin E] at time of withdrawal. Hence, the risk of ER in sled dogs is not affected by plasma [vitamin E] before the race.

Exercise-associated hyponatremia in Alaskan sled dogs: urinary and hormonal responses.

Exercise-associated hyponatremia occurs in horses and humans, both species that sweat, and in sled dogs, which do not sweat. To investigate the mechanism of exercise-associated hyponatremia in sled dogs, we measured water turnover, serum electrolyte concentrations and osmolality, plasma renal hormone concentrations, and urine composition of 12 fit Alaskan sled dogs before, during, and after a 490-km sled dog race (Ex group). Water turnover and serum electrolyte concentrations were measured in six similarly fit dogs that did not run (Sed group). Water turnover was significantly larger (P < 0.001) in Ex [190 +/- 19 (SD) ml . kg-1 . day-1] than in Sed dogs (51 +/- 13 ml . kg-1 . day-1). There were significant (P < 0.001) decreases in serum sodium concentration (from 148.6 +/- 2.8 to 139.7 +/- 1.9 mmol/l) and osmolality (from 306 +/- 9 to 296 +/- 5 mosmol/kgH2O) of Ex, but not Sed, dogs during the race. Plasma concentrations of arginine vasopressin decreased, whereas aldosterone and plasma renin activity increased significantly (P < 0. 01) during the race. Urine osmolality was unchanged, whereas urine sodium, potassium, and chloride concentrations decreased significantly (P < 0.05) and urine urea concentration increased (P = 0.06). These results demonstrate increased water turnover associated with hyponatremia and renal sodium conservation with maintained high urine osmolality in exercising Alaskan sled dogs.

Isolation, characterization, and developmental expression of pig intestinal fatty acid-binding proteins.

The goal of this study was to characterize and quantify intestinal fatty acid-binding proteins of the pig. Small intestinal mucosa from 13-19 kg pigs was homogenized and centrifuged to obtain cytosol. Isolation of fatty acid-binding proteins from delipidated cytosol was achieved using molecular sieve, oleic acid affinity, and ion exchange chromatography. Fatty acid-binding protein isolation was monitored using a fatty-acid binding assay in conjunction with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Antisera to rat liver-fatty acid-binding protein cross reacted with an isolated intestinal fatty acid-binding protein of Mr = 13,000, whereas antisera to rat intestine-fatty acid-binding protein was not cross reactive with isolated pig intestinal proteins. These experiments identify a pig intestinal fatty acid-binding protein that exhibits strong immunochemical similarity to rat liver-fatty acid-binding protein. Cytosol prepared from intestinal mucosa of pigs at -4, 2, 4, 7, 15, 22, 28, and 35 d of age was assayed for fatty acid-binding protein activity. Preweaning fatty acid-binding protein activity in cytosol was maximal at 7 days of age when expressed as total jejunal fatty acid binding per kilogram bodyweight, intestinal or mucosal weight or milligram total protein. After weaning (21 d), fatty acid-binding protein activities declined to 28 days, but increased again by 35 days. Total soluble fatty acid-binding protein activity in pig intestine is regulated during postnatal development and this may account in part for the altered intestinal absorption of lipids observed in young pigs at weaning.

Association between vitamin E and enhanced athletic performance in sled dogs.

PURPOSE: To determine the association between prerace plasma vitamin E concentration and performance in sled dogs competing in the 1998 Iditarod Race. METHODS: Prerace blood samples were collected from 670 dogs. Samples were analyzed for plasma vitamin E concentration while controlling for selected hematological and biochemical variables and signalment. Starting in teams of 16, exercise consisted of running up to 1159 miles pulling a laden sled and musher via checkpoints. The records of dogs that were withdrawn from the race for health reasons, fatigue, or strategic or technical reasons, and those of dogs that finished the race were analyzed. Multiple logistic regression and Cox proportional hazards analysis were used to determine factors associated with endurance. Multiple linear regression analysis was used to determine factors associated with team speed. RESULTS: A total of 323 dogs (48%) were withdrawn from racing at various distances from the start. Median time to finish for 39 teams was 11.5 d and the winning time was 9.2 d. Dogs with prerace plasma vitamin E concentrations > 40.7 microg.mL-1 were 1.9 times more likely to finish (P = 0.0006) and had 1.8 times less of a risk of being withdrawn for every mile ran (P = 0.03) than were dogs with plasma vitamin E concentrations between 16.3 and 40.7 microg.mL-1. Neither a team's mean prerace vitamin E concentration, nor the proportion of dogs within a team with high (> 40.7 microg.mL-1) vitamin E concentration was associated with team speed. CONCLUSIONS: Dogs with higher plasma vitamin E concentrations have enhanced endurance compared with dogs with lower plasma vitamin E concentrations, but the plasma vitamin E status of a team is not associated with team speed.

A standardized gating technique for the generation of flow cytometry data for normal canine and normal feline blood lymphocytes.

Flow cytometry is becoming a commonly used technique to characterize a variety of cells. It provides a powerful application to rapidly determine the relative percentages of T-lymphocyte subsets and B-lymphocytes. The effectiveness of its application, however, is dependent on standardization, especially in a clinical setting. Application of flow cytometry to veterinary diagnostics has been limited by the unavailability of reagents and by the unstandardized characterization of normal values using antibodies not commercially available, but typically provided through the generosity of other researchers. This paper presents a standardized gating protocol, and average values and ranges observed for normal canine and feline blood lymphocytes using commercially available antibodies to cell surface markers for CD5, CD3, CD4, CD8, MHC II, and B lymphocytes. The averages for these markers on gated lymphocytes were as follows: Canine CD5 83.3%, Canine CD4 45.0%, Canine CD8 28.8%, Canine MHC II 98.0%, Canine B Cell 12.9%, Canine CD4/CD8 ratio 1.87, Feline T lymphocytes 77.3%, Feline CD4 44.5%, Feline CD8 25.7%, Feline B Cell 24.1%, Feline CD4/CD8 Ratio 1.75. Normal values were also established for a mixed breed group of dogs, and old versus young dogs. This information will provide researchers and clinicians with a standardized protocol for gating, which establishes a basis for comparison between techniques, and a measure of phenotypic percentages for flow cytometry in normal dogs and cats based on this standardization and commercially available antibodies.

Dietary lutein stimulates immune response in the canine.

The possible immuno-modulatory action of dietary lutein in dogs is not known. Female Beagle dogs (17-18-month old; 11.4+/-0.4kg body weight) were supplemented daily with 0, 5, 10 or 20mg lutein for 12 weeks. Delayed-type hypersensitivity (DTH) response to saline, phytohemagglutinin (PHA) and a polyvalent vaccine was assessed on Weeks 0, 6 and 12. Blood was sampled on Weeks 0, 2, 4, 8 and 12 to assess (1) lymphocyte proliferative response to PHA, concanavalin A (Con A), and pokeweed mitogen (PWM), (2) changes in peripheral blood mononuclear cell (PBMC) populations, (3) interleukin-2 (IL-2) production and (4) IgG and IgM production. After the completion of 12-week study, we continued to collect the blood weekly up to 17 weeks to evaluate the changes in immunoglobulin production upon first and second antigenic challenges on Weeks 13 and 15. Plasma lutein+zeaxanthin was undetectable in unsupplemented dogs but concentrations increased (P<0.05) rapidly on Week 2 in lutein-supplemented dogs. Thereafter, concentrations generally continued to increase in dose-dependent manner, albeit at a much slower rate. Dogs fed lutein had heightened DTH response to PHA and vaccine by Week 6. Dietary lutein increased (P<0.05) lymphocyte proliferative response to all three mitogens and increased the percentages of cells expressing CD5, CD4, CD8 and major histocompatibility complex class II (MHC II) molecules. The production of IgG increased (P<0.05) in lutein-fed dogs after the second antigenic challenge. Lutein did not influence the expression of CD21 lymphocyte marker, plasma IgM or IL-2 production. Therefore, dietary lutein stimulated both cell-mediated and humoral immune responses in the domestic canine.

Modulation of humoral and cell-mediated immune responses by dietary lutein in cats.

The immuno-modulatory role of dietary lutein in domestic cats is unknown. Female Tabby cats (10-month old; n=56) were supplemented daily for 12 weeks with 0, 1, 5 or 10mg lutein. Blood was collected on Weeks 0, 2, 4, 8 and 12 to assess the following: (1) mitogen-induced peripheral blood mononuclear cells (PBMCs) proliferation, (2) changes in PBMC subpopulations, (3) interleukin-2 (IL-2) production and (4) plasma immunoglobulin (Ig)G production. In addition, delayed-type hypersensitivity (DTH) response to concanavalin A (Con A) or a polyvalent vaccine was performed on Weeks 0, 6 and 12. Dietary lutein increased plasma lutein concentrations in a dose-dependent manner (p<0.001) and concentrations had not reached steady state after 12 weeks of feeding in cats given 5 or 10mg lutein. Concentrations of plasma retinol and alpha-tocopherol were not influenced by diet. The DTH response to vaccine but not to Con A increased (p<0.05) in a dose-dependent manner on Week 6. Compared to control, cats fed lutein also showed enhanced Con A- and pokeweed mitogen-stimulated PBMCs proliferation. Dietary lutein also increased the percentages of CD4+ and CD21+ lymphocytes on Week 12 but had no significant effect on pan T, CD8 and MHC class II markers. Plasma IgG was higher (p<0.05) in cats fed 10mg lutein on Weeks 8 and 12. These results support the immuno-modulatory action of lutein in domestic cats.

Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs.

The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6):(n-3) ratio of 25:1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6):(n-3) ratio of 5:1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-alpha production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence alpha-tocopherol status although older dogs had significantly lower serum alpha-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6):(n-3) fatty acid ratio of 5:1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs.

Evaluation of various extracted vegetable oils, roasted soybeans, medium-chain triglyceride and an animal-vegetable fat blend for postweaning swine.

A total of 280 crossbred pigs weaned at 21 d of age and weighing approximately 6 kg were utilized in five replicates to evaluate pig growth responses when fed a basal diet or one of several dietary lipid sources during a 4-wk postweaning period. A basal corn-soybean meal-corn starch-dried whey diet was compared with diets supplemented at a 7.75% level with one of the following lipid sources: corn oil, coconut oil, soybean oil, medium-chain triglyceride (MCT) or an animal-vegetable blend. A sixth treatment evaluated a roasted soybean diet formulated to an energy:lysine level equivalent to that of the fat-supplemented diets. In Exp. II, 36 crossbred weanling barrows were used to determine apparent fat and N digestibilities when soybean oil, roasted soybean, coconut oil or the MCT-supplemented diets were fed. Although pigs fed coconut oil grew somewhat faster, fat inclusion generally did not increase pig growth rate or result in lowered feed intake during the initial weeks postweaning; during the latter portion of the starter phase the addition of dietary fat resulted in a higher growth rate but feed intake was unaffected, resulting in an overall improvement in feed-to-gain ratio (P less than .05) for all but the roasted soybean diet. Pigs fed coconut oil had higher serum triglyceride and lower serum urea concentrations than did pigs fed diets containing most other lipid sources. Pigs fed MCT and coconut oil diets had a higher (P less than .01) apparent fat digestibility during the initial 2 wk postweaning than pigs fed soybean oil or roasted soybean diets. Pigs fed MCT and roasted soybeans had poorest growth rates; apparent fat and N digestibilities were lowest (P less than .05) for the roasted soybean diet.

Effect of weaning, week postweaning and diet composition on pancreatic and small intestinal luminal lipase response in young swine.

The effects of weaning, week postweaning and diet composition on concentration of lipase in the pancreas and small intestinal lumen were investigated in weanling swine. In Exp. 1, lipase levels were evaluated in suckling pigs from 2 to 35 d of age and in pigs weaned at 21 or 35 d of age. Pigs weaned at 21 d of age were fed a corn-soybean meal diet with lipase levels measured from 3 to 28 d postweaning. Pancreas weights increased during the suckling period; they were lowered at 3 d postweaning and were lower at 7 d postweaning than in suckling pigs but increased linearly from 3 to 28 d postweaning. Lipase level per unit wet tissue and total pancreatic levels increased from 2 to 35 d of age in suckling pigs (P less than .01). Weaning at 21 d of age resulted in a decline (P less than .05) in lipase levels in the pancreas at 3 and 7 d postweaning, but the levels subsequently tended to increase between 7 and 28 d postweaning. Whereas relative lipase levels in the intestinal lumen increased from 2 to 35 d of age in suckling pigs, total luminal enzyme did not decline upon weaning when pigs were weaned at either 21 or 35 d of age. Total luminal lipase per unit empty body increased linearly (P less than .01) each week postweaning. In Exp. 2, a 2 X 2 factorial arrangement of corn oil (0 or 6%) and dried whey (0 or 25%) was used to evaluate digestive lipase levels in pigs weaned at 21 d of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of group size and feeding regimen on nutrient digestibility studies with weanling pigs.

An experiment was conducted to determine the effects of feeding regimen and group size on nutrient (N, Lipid, Ca, P) balance measurements with weanling swine. Treatments imposed were 1) one pig pair-fed to 90% of treatment 3, 2) three pigs pair-fed to 90% of treatment 3 and 3) three pigs with ad libitum access to their diet. A total of 28 barrows weaned at 21 d of age (initial BW 5.9 kg) were allotted by weight and litter in a randomized complete block design with repeated measurements over time to the three treatments in four replicates. The pigs were placed in .6-m x 1.13-m stainless steel metabolism crates and fed the same experimental diet for an initial 4-d adjustment period. This was followed by a 5-d collection of urine and feces with a 2-d interval between collection periods each week of a 4-wk postweaning period. When feed was restricted, N intake, urine N, fecal N and retained N were similar whether pigs were fed as singles or in groups of three. Individually fed pigs had a higher urinary Ca but lower urinary P compared with those fed in groups of three. Lipid and P retention values were similar for individual and group-penned, restricted-fed animals. Pigs provided ad libitum access to feed had greater weight gains and nutrient intakes, excretions (urine, fecal) and retentions (P less than .01) than pigs that were limit-fed. Similar responses among treatments occurred each week of the 4-wk trial. These results suggest that effective weekly balance data can be collected each week sequentially with 21-d weanling pigs penned in groups and allowed to consume feed ad libitum, a situation more similar to natural nursery conditions.

Weekly digestibilities of diets supplemented with corn oil, lard or tallow by weanling swine.

Two experiments were conducted to evaluate supplementation of diets with 8% corn oil, lard or tallow. In Exp. 1, 36 barrows weaned at 21 d of age were used to evaluate the effects of these three diets on digestibilities of fat and dry matter and subsequent N retentions from wk 1 to 4 postweaning. In Exp. 2, 147 weanling pigs in six replicates were used to evaluate weekly growth and feed performance measurements when fed these same diets for a 4-wk postweaning period. A large quantity of fat was absorbed (P less than .01) during wk 1 postweaning by pigs fed the corn oil diet, with the quantity absorbed similar for the three sources of fat from wk 2 to 4. Diets with corn oil had a higher apparent fat digestibility than diets supplemented with lard or tallow during each week postweaning (P less than .05). Apparent digestibility of fat increased (P less than .01) for each fat source each week postweaning but appeared to reach a plateau by wk 3 postweaning. Differences in apparent digestibility of fat between fat sources narrowed from wk 1 to wk 4, with digestibility of corn oil increasing from 79 to 89% and of animal fat sources increasing from 67 to 84%. Apparent digestibility of dry matter tended (P less than .10) to be highest when corn oil was provided during the initial 2-wk postweaning period. Although N retention was highest during wk 1 postweaning when the corn oil was fed, this response was attributed to the higher feed intakes of pigs fed this diet.(ABSTRACT TRUNCATED AT 250 WORDS)