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Biomedical subjects

T H Elsasser

Publications and source records attributed to T H Elsasser.

At least 55 records · Page 3Linked to original sources

Endocrine modulation of physiological responses to catabolic disease.

Disease or endotoxemia alters the plasma concentrations of anabolic hormones, particularly growth hormone (GH) and insulin-like growth-factor I (IGF-I). In general, these hormones are inhibited during the catabolic disease state. A hypothesis has evolved that anabolic hormones might be useful in patients' recovery under these and other catabolic circumstances. The treatment of cattle with GH has provided significant improvement in the physiological response of the animals to the subsequent injection of bacterial lypopolysaccharide (LPS), perhaps via inhibition of tumor necrisis factor (TNF) release. However, this improved response to disease was not observed with animals treated with GH and infected with one of two parasitic organisms, Sarcocystis cruzi or Eimeria bovis. Recent attempts with other anabolic hormones, estradiol and progesterone, have proven remarkably effective in improving the adaptive physiological responses of calves to either E. bovis infection or to the injection of LPS. All animals displayed signs of infection, but the intensity and duration of symptoms were reduced. Although a mechanism is not yet known, there were no effects on TNF; cortisol; the percentages of lymphocytes expressing CD2, 4, or 8 antigens; or the production of antibodies.

Animals↗

Estradiol/progesterone implants increase food intake, reduce hyperglycemia and increase insulin resistance in endotoxic steers.

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.

Animals↗

Effects of Synovex-S and recombinant bovine growth hormone (Somavubove) on growth responses of steers: III. Muscle growth and protein responses.

We conducted this study to determine whether the growth responses of specific skeletal muscles in crossbred beef steers were differentially affected by treatment with recombinant bovine growth hormone (Somavubove, SbV, .1 mg/kg BW, i.m., daily), Synovex-S (200 mg progesterone + 20 mg 17-beta estradiol benzoate, SYN, ear implant), or a combination of the two. Starting body weights of steers averaged 182+/-1.8 kg. Five steers were used at this average BW to obtain data on weight and composition of individual muscles at d 0, and 20 other steers were assigned in equal numbers to control (C, no implant and placebo daily injection), SYN, SbV, and SYN + SbV treatment groups. After 56 d of treatment with placebo or growth promoters, complete rectus femoris (RF), triceps brachii (TB), supraspinatus (SS), psoas major (PM), and semitendinosus (ST) muscles were dissected, weighed, and then ground for determination of moisture, total protein, and fat. To calculate the average daily muscle wet weight, protein, and fat gains, the initial weight, protein content, and fat content of a muscle were subtracted from those obtained at slaughter and the difference divided by 56. Muscle weight was increased over C in TB and SS by SYN (P < .1); in TB by SbV (P < .09); and in RF (P < .05), TB (P < .03), and SS (P < .03) by SYN + SbV. Overall average daily wet tissue gain was increased over C by SbV + SYN (P < .05) in RF, TB, and SS. Average daily protein gain in RF and TB was increased by SYN (P < .1), SbV (P < .06), and SYN + SbV (P < .01) over that calculated for C. For RF, TB, and SS, average daily protein gain was greater (P < . 1) in SbV + SYN than that obtained with SbV or SYN alone. These data suggest that administration of growth promoters, such as somatotropin and Synovex, to cattle differentially affects growth characteristics in certain muscles and can have additive effects on protein gain when used together.

Adipose Tissue↗

Tumor necrosis factor-alpha in pregnant cattle after intravenous or subcutaneous vaccination with Brucella abortus strain RB51.

OBJECTIVE: To determine the influence of brucellosis vaccination on tumor necrosis factor-alpha (TNF-alpha) concentrations in pregnant cattle and the possible role of the bovine placenta in TNF-alpha production. ANIMALS: Polled Hereford heifers obtained from a nonvaccinated, brucellosis-free herd and bred at 16 to 27 months at age. All cattle were seronegative for Brucella abortus by results of the standard tube agglutination test. PROCEDURE: At 6 months' gestation, cattle were vaccinated i.v. with B abortus strain RB51 (n = 10), s.c. with B abortus strain RB51 (n = 5), or s.c. with B abortus strain 19 (n = 5); controls received pyrogen-free saline solution s.c. (n = 2). Blood samples were collected periodically for TNF-alpha assays. At necropsy, 8 to 12 weeks after vaccination, placental fluids and fetal blood were collected for TNF-alpha analysis and placental tissues were collected for immunohistochemical detection of TNF-alpha. RESULTS: Radioimmunoassays indicated no increase in TNF-alpha concentration in blood from i.v. or s.c. vaccinated cattle, compared with controls. Similarly, TNF-alpha concentrations in amniotic and allantoic fluids from s.c. vaccinated cattle were not different from values for controls. Although only i.v. vaccinated cattle developed placentitis, immunohistochemical analysis for TNF-alpha revealed increased immunoreactivity within placental trophoblastic epithelial cells of s.c. and i.v. vaccinated cattle. CONCLUSIONS: s.c. vaccination for prevention of brucellosis, using recommended adult dosages, does not result in increase of TNF-alpha concentration in plasma, serum, or placental fluids; however, vaccination of pregnant cattle stimulates trophoblastic epithelial cells to express TNF-alpha, although the physiologic and quantitative importance of this expression remains unknown.

Animals↗

Nutritional modulation of somatotropic axis-cytokine relationships in cattle: a brief review.

The objective of this review is to summarize data on the interrelationships that exist between nutrition, the endocrine system and their modulation of plasma tumor necrosis factor-alpha responses to endotoxin in cattle. During stress, intake of nutrients often is compromised and a percentage of available nutrients are diverted away from growth processes to stabilize other physiological processes of a higher survival priority. Management practices that minimize the magnitude and duration of disease stress will aid in speeding the return to homeostatic equilibrium. However, the shift away from growth during stress is almost inevitable as a mechanism to survive. Some degree of control and management of the metabolic cost of disease stress involves understanding the integration of nutritional, endocrine and immune signals by cells and working with the natural homeostatic processes. Endocrine hormones and immune system cytokine signals participate in redirecting nutrient use during disease stress. In an intricate interplay, hormones and cytokines regulate, modify and modulate each other's production and tissue interactions to alter metabolic priorities. Levels of dietary protein and energy intake affect patterns of hormones and cytokines in the blood after endotoxin challenge and further modulate the biological actions of many of these regulatory effectors. In vivo, administration of growth hormone to young calves has significant effects to decrease the many specific physiological responses to endotoxemia. Many aspects of nutrition can attenuate or facilitate this effect.

Animal Nutritional Physiological Phenomena↗

Dietary fatty acids modulate hormone responses in lactating cows: mechanistic role for 5'-deiodinase activity in tissue.

Supplemental dietary fat provides excess fatty acids (FA), which can alter circulating concentrations of several hormones. To test the effects of fatty acid isomer type and possible sites of regulation, we abomasally infused fat mixtures high in cis-C18:1 FA (iCIS), high in trans-C18:1 FA (iTRS) or no infusion (NI) and performed intravenous arginine (ARG) and intramuscular thyrotropin-releasing hormone (TRH) challenges. The experimental design was a replicated 3 x 3 Latin square. Challenges were conducted on Days 10 (ARG) and 12 (TRH) after initiation of fat infusion on each of three 4-wk experimental periods. Plasma concentrations of IGF-I were lower (P < 0.01) when cows received iCIS or iTRS compared with NI. Plasma insulin concentrations increased with ARG but responses were not affected by FA. Plasma growth hormone (GH) was unchanged after ARG. Peak plasma GH and thyroid-stimulating hormone (TSH) responses to TRH were blunted (P < 0.05 and P < 0.1, respectively), whereas thyroxine (T4) and triiodothyronine (T3) responses were augmented post-TRH (P < 0.01) when cows received either FA isomer. Prolactin responses to TRH were not different between infusion treatments, although basal plasma concentrations before TRH were higher in cows infused with iTRS (P < 0.05). To focus on fat regulation of the thyroid axis, we tested directly in vitro the ability of fatty acids dissolved with sodium taurocholate to affect Type-I 5'-deiodinase (5'D) activity in bovine liver homogenates. Homogenate 5'D was not affected by C2:0-C10:0 fatty acids, but decreased linearly (P < 0.01) with increasing concentrations of C12:0-C16:0 and C18:1 isomers. Cis C18:1 decreased 5'D more than the trans-isomer (P < 0.01), but the difference was only apparent at concentrations greater than 0.25 mM. The data suggest that various aspects of pituitary hormone regulation are differentially affected by FA composition. Fatty acid infusion may accentuate end organ responses in the thyroid axis and decrease IGF-I in the somatotropic axis. The data also suggest that FA isomer may alter patterns of extrathyroidal generation of thyroid hormones via direct influences on 5'D.

Animals↗

Roasted soybeans and an estrogenic growth promoter affect the thyroid status of beef steers.

We investigated the interactive effects of a roasted soybean (RSB)-supplemented diet and an estrogen ear implant [Synovex-S (SYN), 20 mg estradiol benzoate + 200 mg progesterone] in young beef steers on measures of thyroid status before and after challenge injections of thyrotropin-releasing hormone (TRH) + growth hormone-releasing hormone (GHRH). Twenty steers (body weight 255 +/- 5 kg) were assigned to the following treatments: 1) no SYN and a soybean meal-supplemented diet, 2) no SYN and a RSB-supplemented diet, 3) plus SYN and soybean meal, and 4) plus SYN and RSB. Steers were individually fed 1.13 MJ metabolizable energy/kg metabolic body wt daily of an 18% protein diet. After a 5-wk growth period, all steers were challenged (intravenous injection) over a 3-wk period with three dose levels of a combination of TRH + GHRH (0.1 + 0.01, 1.0 + 0.1 and 2.5 + 0.25 microg/kg body wt). There were no dose by SYN or RSB interactions. Across dose levels, values for baseline plasma thyroid-stimulating hormone (TSH) were 0.37, 0.35, 0.61 and 0.33 microg/L for treatments 1, 2, 3 and 4, respectively (SYN, P < 0.07; RSB, P < 0.01; SYN x RSB, P < 0.03; SEM 0.06). Net areas under the response curve for TSH were 66.4, 51.3, 91.4 and 64.4 (microg/L) x min, respectively (RSB, P < 0.08; SEM 12.0). Similar treatment effects and/or numerical differences after challenge were noted for thyroxine (T4) but not triiodothyronine (T3). Baseline (2.22 vs. 2.00 microg/L, P < 0.02) and peak (3.07 vs. 2.03 microg/L, P < 0.03) T3 concentrations were less for steers fed RSB than for steers fed soybean meal. This study indicates that in young growing beef steers, SYN increases TSH release from the adenohypophysis and that the primary effect of RSB is reduced plasma T3, possibly through an effect on peripheral T4 deiodination.

Animal Feed↗

TNF-alpha in smoke inhalation lung injury.

Adult respiratory distress syndrome is a major cause of morbidity in fire victims. Tumor necrosis factor-alpha(TNF-alpha) is edematogenic and has been associated with the etiology of other forms of adult respiratory distress syndrome. In the sheep lymph fistula model, we measured TNF-alpha after 48 (n = 7) or 128 (n = 3) breaths of cotton smoke and compared this with sham controls (n = 5) or controls in which left atrial pressure was elevated to 20 mmHg (n = 5) to increase lymph flow in the absence of inflammation. Smoke induced a rise in lymph flow and pulmonary arterial pressure with either no fall in lymph-to-plasma protein ratio (128 breaths) or a modest fall in lymph-to-plasma protein ratio (48 breaths), consistent with a change in microvascular permeability as well as a rise in microvascular pressure. Lymph concentration of TNF-alpha fell in both groups, although lymph flux (concentration x flow) transiently rose in both. In neither case did TNF-alpha flux exceed that induced by left atrial pressure elevation. TNF-alpha was detectable in only one out of five sheep in alveolar lavage. Thus, by utilizing a sensitive and specific radioimmunoassay, we were unable to demonstrate a role for TNF-alpha in smoke-induced microvascular lung injury in sheep.

Animals↗

Expression of adrenomedullin and its receptor in normal and malignant human skin: a potential pluripotent role in the integument.

Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including growth regulation and antimicrobial activity. We have determined by immunohistochemistry and in situ hybridization that AM and its receptor are present in all the epithelial cells of the normal skin, including keratinocytes of the epidermis and hair follicles, as well as cells of the glands and secretory ducts. We also have detected AM in the sweat, by RIA. In addition, AM and its receptor were found in skin tumors of different histologies. The presence of AM and its receptor in normal and neoplastic skin was confirmed by RT-PCR and Western blot analysis performed on cell extracts from human skin cell lines. Radiolabeled AM bound to specific sites in cultured cells with a Kd of 9 nM. This binding was blocked by the addition of cold AM but not by related peptides such as AM 22-52, pro-AM 20 N-terminal peptide, calcitonin gene-related peptide, calcitonin gene-related peptide 8-37, or amylin. Finally, exposure to synthetic AM resulted in an increase of thymidine intake by skin cells. These results implicate AM as a potential player in skin defense against infectious microorganisms and as a possible autocrine growth factor in normal skin physiology and tumor development.

Adrenomedullin↗

Supplemental dietary chromium does not influence ACTH, cortisol, or immune responses in young calves inoculated with bovine herpesvirus-1.

Twelve Holstein bull calves (6 to 8 wk of age) were used to determine the influence of supplemental dietary Cr on ACTH, cortisol, and immune responses of calves experimentally inoculated with bovine herpesvirus-1 (BHV-1). Calves supplemented with Cr received 3 mg Cr/d (Chromium, n = 6) of a high-Cr-yeast product. Following 53 d of treatment, all calves were fitted with jugular catheters, and blood samples were collected every 4 h into tubes containing ETDA. Twenty-four hours later, all calves were inoculated intranasally with BHV-1 (1 x 10(7) plaque-forming units in each naris). Serial blood collection continued at 4-h intervals for 6 d. Plasma was harvested, immediately frozen in liquid nitrogen, and stored at -20 degrees C. Individual rectal temperatures and urine samples were collected at the same time each day. Rectal temperatures were elevated (P < .05) on d 2, 3, 4, and 5 but were not affected by Cr treatment. Treatment with Cr did not affect secretion of ACTH, cortisol, or plasma tumor necrosis factor-alpha, although clear circadian variation in ACTH and cortisol occurred. No differences were detected in the concentrations of trace minerals excreted daily in the urine, lymphocyte proliferative response to mitogen stimulation, and neutrophil bactericidal function. The acute phase proteins, ceruloplasmin and fibrinogen, also were not affected by treatment or viral challenge. These data suggest the Cr supplementation using high-Cr yeast (3 mg/d) did not alter stress responses of calves experimentally inoculated with BHV-1.

Adrenocorticotropic Hormone↗

Effects of a long daily photoperiod on milk yield and circulating concentrations of insulin-like growth factor-1.

Relative to a short daily (24-h) photoperiod, exposure to a long daily photoperiod increases the milk yield of dairy cows. However, the endocrine basis for this phenomenon is unknown. The present study was designed to test the hypothesis that a long daily photoperiod is associated with increased circulating insulin-like growth factor (IGF)-I, a hormone that is galactopoietic in ruminants. Forty lactating cows were exposed to either a natural photoperiod (< or = 13 h of light/d) or to a long daily photoperiod (18 h of light and 6 h of darkness) between January and April 1995. Cows were fed for ad libitum intake a total mixed diet formulated to meet the nutritional demands of lactation. Milk yield and dry matter intake were quantitated each day, and blood samples were collected by coccygeal venipuncture every 14 d. Plasma was harvested and assayed for IGF-I. The long photoperiod increased milk yield relative to the natural photoperiod (36.1 +/ 0.6 vs. 33.9 +/ 0.6 kg/d); the increase became significant after 28 d of treatment and was maintained for the duration of the study. In addition, cows exposed to a long photoperiod had greater circulating concentrations of IGF-I than did cows exposed to the ambient natural photoperiod (60.1 +/ 2.0 vs. 52.6 +/ 2.0 ng/ml). Concentrations of IGF binding protein -2 and -3 in plasma did not differ between treatments. These results support the hypothesis that a long daily photoperiod increases circulating concentrations of IGF-I in lactating cows and reveal a possible endocrine mechanism for the galactopoietic response to a long daily photoperiod.

Animal Nutritional Physiological Phenomena↗

Nutritional regulation of plasma tumor necrosis factor-alpha and plasma and urinary nitrite/nitrate responses to endotoxin in cattle.

Effects of dietary protein level with and without L-arginine (Arg) infusion on plasma tumor necrosis factor-alpha (TNF-alpha) response to endotoxin (lipopolysaccharide [LPS]) as well as plasma concentration and urine output of nitrite and nitrate (NOx), the stable end products of nitric oxide radical (NO), were studied in beef heifers (275-310 kg body wt). The animals were fed low- (LP; 7.96%) or high- (HP; 13.94%) protein diets for 10 days before LPS administration (Escherichia coli; 0.2 microgram/kg, iv). L-Arginine in saline (0.5 g/kg body wt) or saline was infused for 8 hr with one-third of total Arg infused before LPS administration. Plasma TNF-alpha concentrations increased in all heifers after LPS injection (peak at 1 hr and return to baseline at 4 hr); however, concentrations were lower in HP- than in LP-fed heifers at 1, 2, and 3 hr. Infusion of Arg did not affect plasma TNF-alpha response to LPS. Plasma NOx concentrations increased in all heifers after LPS challenge; compared with saline, Arg infusion increased the total response (integrated area under concentration curve) in LP- but not in HP-fed heifers. Relative to pretreatment period, the rate of NOx output in urine collected 2-6 hr after LPS administration increased in all heifers regardless of dietary protein level and was further amplified by Arg infusion. The rate of NOx output in urine collected 6-24 hr after LPS challenge was even higher in LP-fed heifers infused with Arg but returned to the basal values in other groups. Activity of hepatic inducible NO synthase was not affected by LPS, Arg, or dietary protein level at the time points studied. The data suggest that dietary protein levels can modulate both TNF-alpha and NO responses to LPS in cattle; high dietary protein intake decreases TNF-alpha response and attenuates the conversion of supplemental Arg to NO.

Animals↗

Hormonal modulation of the physiologic responses of calves infected with Eimeria bovis.

OBJECTIVE: To determine whether an estradiol-progesterone (EP) growth implant would have an effect on febrile responses and on the catabolic component of Eimeria bovis infection. ANIMALS: 27 Holstein bull calves. PROCEDURE: Calves were assigned to treatment groups as: control (n = 5), EP implant (EP, n = 5), E bovis-inoculated (coccidia: C, n = 7), pair fed (n = 4), or EP plus E bovis-inoculated coccidia (EP/C, n = 6) groups. Calves were provided subcutaneous EP implants at 8 weeks of age, and were inoculated with 2 x 10(5) oocysts of E bovis at 11 weeks of age. Body weight was measured on postinoculation day (PID) 0, 14, and 28. Rectal temperature and food intake were determined and fecal samples were collected daily from PID 15 to 28. Blood samples were collected on PID 24 for analysis of CD2+, CD4+, and CD8+ antigens and plasma insulin-like growth factor I concentration. Blood samples were collected at 15-minute intervals for measurement of pulsatile growth hormone release. RESULTS: Group-EP/C calves had fever for 2 days versus 5 days for group-C calves (P < 0.05). These calves had diarrhea for fewer days than did their group-C counterparts (P < 0.05). Fibrinogen and glucose values were high in group-C (P < 0.05) but not group-EP/C calves. The latter had positive weight gain from PID 14 to 28, whereas group-C calves had weight loss (P < 0.05). Plasma insulin-like growth factor I concentration was reduced by infection (P < 0.05). EP-treated noninfected calves had increased numbers of CD2+, CD4+, and CD8+ blood mononuclear cells (P < 0.05). CONCLUSIONS: EP has a protective effect in calves infected with E bovis. This may relate to changes in immune function induced by EP. CLINICAL RELEVANCE: Treatment of calves with EP could offer some protection against the often severe wasting and debilitation associated with E bovis infection.

Animals↗

Physiological responses to repeated endotoxin challenge are selectively affected by recombinant bovine somatotropin administration to calves.

The study determined 1) whether the pretreatment of calves with recombinant bovine somatotropin (bST, sometribove) would alter the change in packed cell volume (PCV), rectal temperature (RT), and the plasma concentrations of Ca2+, Fe2+, glucose (G), urea N (PUN), nonesterified free fatty acids (NEFA), albumin (ALB), and blood cell populations after endotoxin challenge (EC) and 2) whether the natural development of physiologic tolerance to repeated EC was affected by bST. Twelve steer beef calves were assigned to either control (-bST) or +bST treatment in equal numbers. Calves were injected intramuscularly with either HCO3(-)-buffered saline or bST (0.1 mg/kg) daily for 5 d. On Day 6, the first EC was administered (Escherichia coli, 055:B5, 0.2 microgram/kg, intravenous bolus in pyrogen-free saline). Saline or bST injections were continued from Day 7 up to the repeat of EC on Day 11. RT and PCV were measured hourly through 12 and 6 hr, respectively. Jugular blood was obtained at 0, +1, 2, 3, 4, 6, 8, 12, and 24 hr relative to each EC. bST had no effect on the increase in RT, the hyperglycemic phase of the G response, the biphasic change in Fe2+, or increases in NEFA and PUN. PCV increased after each EC only in -bST. The mean decrease in G during the hypoglycemic phase was less in +bST. Hypocalcemic responses were significantly less in +bST. ALB concentrations decreased after each challenge; the response was unaffected by bST. CD2+, CD4+, and CD8+ T-lymphocyte populations were unaffected by bST and EC. Overall, the magnitude of change in all plasma variables was less after the second EC compared with the first, either in terms of magnitude or duration. The data suggest that the treatment of calves with bST diminishes the magnitude of hypoglycemic, hypocalcemic, and PCV changes after EC and does not compromise fever response, changes in blood cell populations, or tolerance to repeated EC.

Animals↗

Hormonal and nutritional modulation of hepatic arginase activity in growing cattle.

The hormonal and nutritional modulation of hepatic arginase activity (HARG) was characterized in growing cattle in two studies. In the first study, 20 steers (initial weight, 182 +/- 2 kg) were assigned in equal numbers to either Synovex-S (SYN) (ear implant), recombinant bovine somatotropin (Somavubove; SbV; 0.1 mg/kg intramuscularly daily), SYN + SbV, or nothing (control). Steers were individually fed, for 56 d, a concentrate (80% diet dry matter [DM]) and silage (20% diet DM) diet providing 20 g of crude protein (CP) and 252 kcal metabolizable energy (ME) per kg body weight0.75. On Day 57, samples of liver were obtained at slaughter and subsequently assayed for HARG by the incubation of a tissue homogenate for 2 hr with 250 mM arginine, with and without Mn2+ and heat activation, and the measurement of the resulting urea. HARG was uniformly increased by divalent cation (Mn2+) and heating. SYN had no effect on HARG, whereas SbV treatment resulted in an overall 34% decrease in HARG. Plasma urea nitrogen (PUN) was decreased by SbV but not consistently affected by SYN. In the second study, 16 steers (avg. initial weight, 284 +/- 5 kg) were initially fed a concentrate basal diet consisting of 11% CP and 1.96 Mcal ME for 21 d. Steers were then assigned to one of four dietary treatments (6.4 kg DM/hr per day) in a factorial arrangement of high and low CP (8 and 14%) and two levels of energy (1.96 and 2.67 Mcal ME/kg of diet DM) for 210 d and slaughtered. HARG and PUN were higher in steers fed 14% CP but were lower at each level of CP fed at the higher level of ME. The data suggest that hormonal repartitioning compounds and diet composition may modulate nitrogen metabolism by affecting the activity of arginase in the liver as well as by affecting the total content of arginase in association with changes in organ size.

Animal Nutritional Physiological Phenomena↗

Roasted soybeans and an estrogenic growth promoter affect growth hormone status and performance of beef steers.

This study investigated the effects of a roasted soybean (RSB)-supplemented diet and an estrogen implant (SYN; Synovex-S ear implant, 20 mg estradiol benzoate plus 200 mg progesterone) in young crossbred beef steers on their performance and plasma growth hormone (GH) response to challenge injections of thyrotropin-releasing hormone (TRH) + GH-releasing hormone (GHRH). Twenty individually fed steers (body weight 255 +/- 5 kg) were assigned to the following treatments: 1) no SYN and fed a soybean meal-supplemented diet, 2) no SYN and fed the RSB-supplemented diet, 3) plus SYN and soybean meal, and 4) plus SYN and RSB. Steers were fed 1.13 MJ metabolizable energy/kg metabolic body weight daily of an 18% protein diet. After a 5-wk growth period, all steers were challenged (intravenous injection) over a 3-wk period with three levels of a combination of TRH + GHRH (0.1 + 0.01, 1.0 + 0.1, 2.5 + 0.25 microg/kg body weight, respectively). After an additional 3 wk, steers were reimplanted and a second 5-wk growth period was followed by a single challenge of the 1.0 + 0.1 TRH + GHRH dose level. Plasma nonesterified fatty acid concentration was greater when steers were fed the RSB compared with soybean meal (265 vs. 205 micromol/L; P < 0.01; SEM = 9.5). Body weight gains for treatments 1, 2, 3 and 4 were 1.35, 1.21, 1.47 and 1.38 kg/d, respectively (RSB, P < 0.10; SYN, P < 0.07; SEM = 0.06). Gain/dry matter intake (g/kg) means were 184, 167, 197 and 184 (RSB, P< 0.04; SYN, P < 0.07; SEM = 7.5). Feeding roasted soybeans results in depressed area under the GH response curve [907, 555, 827 and 989 microg/(L*min) (SYN x RSB, P < 0.03; SEM = 117)] and depressed peak response (37.2, 26.6, 33.5 and 41.1 microg/L [SYN x RSB, P < 0.05; SEM = 4.5]), an effect alleviated by estrogen for young growing steers (Period 1) but not for heavier steers (Period 2).

Animals↗

TNF-alpha and the pathophysiology of endotoxin-induced acute respiratory failure in sheep.

We studied changes in cardiovascular and pulmonary function during prolonged endotoxemia in conscious sheep. Sheep with chronic lung lymph fistulas received a 12-h infusion of Escherichia coli endotoxin (10 ng x kg-1 x min-1) and allowed to recover for 12 h. Supportive therapies were withheld. Prolonged endotoxemia without volume support caused systemic hypotension associated with reduced cardiac output and increased systemic vascular resistance, pulmonary hypertension, and acute lung injury with progressive respiratory failure. Plasma tumor necrosis factor-alpha (TNF-alpha) concentrations increased transiently. Sustained pulmonary hypertension and increased pulmonary and systemic vascular resistances contributed to a poor outcome in 9 of 34 sheep (26%). Plasma TNF-alpha concentrations were significantly greater in survivors with sustained pulmonary hypertension and in nonsurviving sheep than in surviving sheep without pulmonary hypertension. Endotoxin (1 ng/ml) increased neutrophil expression of TNF-alpha in vitro. Addition of interleukin-6 prevented this response. Synthesis and release of TNF-alpha may be an important proximal event influencing the development of sustained pulmonary hypertension and progressive respiratory failure with endotoxemia. Interleukin-6 may contribute to the phasic nature of the TNF-alpha response.

Acute Disease↗

Regulation of insulin secretion and blood glucose metabolism by adrenomedullin.

Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species, as demonstrated by immunocytochemistry. Electron microscopic studies with double immunogold showed colocalization of AM and pancreatic polypeptide. A homogeneous expression of AM receptor was found throughout the islet using in situ hybridization. Six different insulin- producing cell lines have been analyzed by reverse transcription-PCR and showed expression of both AM and its receptor. Two experimental models have been used to study the effects of AM in pancreatic physiology. 1) Analysis of isolated rat islets shows that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was able to increase insulin release 5-fold; this effect was reversed by the addition of synthetic AM. 2) Oral glucose tolerance tests showed that iv injection of AM reduces the levels of insulin in the bloodstream with a concomitant increase in circulating glucose. These studies implicate AM as a newly defined factor of the insulin regulatory system that could be involved in disorders such as diabetes and obesity.

Adrenomedullin↗