Supplemental methionine and time of supplementation effects on ruminal fermentation, digesta kinetics, and in situ dry matter and neutral detergent fiber disappearance in cattle

Two experiments were conducted to study the effects of methionine supplementation on ruminal fermentation and digesta kinetics. In Exp. 1, nine ruminally cannulated beef heifers (average initial BW = 527 kg) in a crossover design were fed low-quality grass hay and cottonseed meal with or without 11.4 g of supplemental methionine (polysaccharide-coated). Particulate and fluid kinetics, rate of DM and NDF disappearance, ruminal VFA and NH3 N concentrations, and pH were not altered (P > .10) by supplemental methionine; however, ruminal purine concentration was greater (P < .05) in methionine-supplemented heifers than in unsupplemented heifers. In Exp. 2, 12 ruminally cannulated Holstein steers (average initial BW = 622 kg) grazing a fescue pasture were allotted to one of three groups: no supplemental methionine (CON) or 11.4 g of supplemental methionine fed at 0700 (AM) or at 1200 (PM). Forage intake, particulate kinetics, ruminal fluid kinetics, pH, VFA, and NH3 N concentrations were not altered (P > .10) by supplemental methionine or supplementation time. In situ rate of DM and NDF disappearance was greater (P < .05) in supplemented steers than in CON steers; AM steers exhibited faster (P < .05) rates than PM steers. Overall, methionine supplementation of low-quality forage increased ruminal purine concentration but did not alter in situ fermentation or digesta passage, whereas supplementation at 0700, but not at 1200, of steers grazing fescue forage increased rate of NDF fermentation.     

Effects of prenatal androgenization and postnatal steroid treatment on growth hormone, insulin-like growth factor I and II, insulin, thyroxine, and triidothyronine concentrations in beef heifers

A 2 x 3 factorial arrangement of treatments was used to elucidate the mechanism(s) by which prenatal androgenization improves postnatal rate and efficiency of growth and composition of gain in beef heifers. Fifteen control (C) and 15 prenatally androgenized (PA) Angus x Simmental heifers (prenatal treatment, Pretrt) received no (N), estrogen (E), or estrogen and testosterone (ET) implants postnatally (postnatal treatment, Posttrt) to evaluate whether the postpubertal growth response after prenatal androgenization could be induced in prepubertal heifers. Blood was collected from the heifers at 6 +/- 1, 9 +/- 1, and 12 +/- 1 mo of age and analyzed from serum concentrations of growth hormone (GH), IGF-I, IGF-II, insulin, thyroxine (T4), and triiodothyronine (T3). Season of the year had a greater effect on hormone concentrations than either Pretrt or Posttrt, and there were no Pretrt x Posttrt interactions. Prenatal treatment, PA, had no effect on GH; however, Posttrt E and ET increased (P < .001) GH concentrations. Prenatal treatment, PA, increased (P < .05) IGF-I concentrations, and there was a nonsignificant increase (P = .11) in IGF-I concentrations with Posttrt E and ET. Concentrations of IGF-II were unaffected by Pretrt PA; however, they were lower (P < .01) in the Posttrt E and ET groups. Insulin, T4, T3, BW, and ADG were not affected by Pretrt and Posttrt. Concentrations of GH and IGF-I were increased in heifers that received Pretrt PA and(or) Posttrt E and ET in a manner to support improved growth performance; however, BW and ADG were similar. In prepubertal beef heifers, factors in addition to increased GH and IGF-I seem to be necessary for improved growth performance.     

Vaccination against ergot alkaloids and the effect of endophyte-infected fescue seed-based diets on rabbits

Three sequential experiments were conducted with rabbits to 1) determine the effect of endophyte-infected (E+) tall fescue seed on rabbit performance and examine the effect of anti-ergot alkaloid immunization on rabbit performance and protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total ergot alkaloids) had reduced (P < .05) intake and weight gain compared with endophyte-free (E-) controls, whereas apparent diet digestibility was not different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac) with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05) intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2, rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid hapten, H100-different protein carrier, B conjugate), or combinations of both with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab) titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n = 4/treatment) were immunized with the immunogen H100-B in conjunction with six adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and intake were reduced by feeding E+ fescue seed diets, immunization against ergot alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune response. We believe that rabbits may serve as a model animal for fescue toxicosis research.     

Response of pigs to space allocation and diets varying in nutrient density

Three experiments were conducted to determine the main and interacting effects on growth performance of floor space allowance and dietary lysine and energy concentrations for growing-finishing pigs. In each experiment, space allocations of .56 or .78 m2/pig were achieved with 14 or 10 pigs per pen, respectively. In Exp. 1, diets investigated were National Research Council (NRC) recommended nutrient densities, NRC plus 5% added fat (F), NRC plus .15% added L-lysine. HCl (L), and NRC plus fat plus lysine (FL) in a 4 x 2 x 2 factorial arrangement of diets with space and season (winter vs summer). In Exp. 2 and 3, a 2 x 3 factorial treatment arrangement was used to investigate space and diet effects. Diets investigated contained 0, 2.5, or 5% added fat (choice white grease [Exp. 2]; tallow [Exp. 3]) with L-lysine.HCl added to maintain a constant lysine:ME ratio. In Exp.1, pigs given .56 m2/pig vs .78 m2/pig ate less feed (P < .001) and grew slower (P < .001) with no difference in gain:feed ratio or carcass lean percentage. Feed intake was decreased (P < .005) and gain:feed ratio increased (P < .001) for the FL vs L diet. In Exp. 2, pigs given .56 m2/pig vs .78 m2/pig grew slower (P < .001) with a poorer gain:feed ratio (P < .05) and a slower rate of lean gain (P < .05). In Exp. 3, pigs given .56 m2/pig vs .78 m2/pig grew slower (P < .05) with no difference in gain:feed ratio and a slower rate of lean gain (P < .005). There was a linear improvement in ADG (P < .01, Exp. 2; P = .011, Exp. 3) and gain:feed ratio (P < .001, Exp. 2 and 3) with increasing amounts of fat in the diet. The lack of space x diet interactions in these experiments suggests that the reduction in ADG associated with the reduction in ADFI for pigs given less space is independent of dietary lysine and energy concentrations.     

Effect of food on the bioavailability of stavudine in subjects with human immunodeficiency virus infection

A randomized, three-way crossover study was carried out to determine the effects of food ingestion on the pharmacokinetics of stavudine (d4T). Fifteen subjects with human immunodeficiency virus (HIV) infection and CD4(+) cell counts of >/=200/microliter received 70 mg of d4T in a fasting state or 1 h before or 5 min after a standardized high-fat breakfast. A 7- to 15-day washout period was included between treatments. Blood and urine were collected before and for 10 h after dosing, and plasma and urine d4T concentrations were determined with a validated radioimmunoassay. Plasma drug concentration-time data were analyzed with a noncompartmental model. The mean maximum plasma drug concentration (Cmax) and the time to Cmax (Tmax) for administration of d4T after a meal were significantly lower and longer (P = 0.0001 for both measures) than those observed in the fasting state, although the area under the concentration-time curve from time zero to infinity (AUC0-infinity) was not significantly different. Neither of these parameters was significantly altered when d4T was taken 1 h before a meal. The bioavailability of d4T taken after a meal was 95% of that observed in the fasting state, and it was 97% when d4T was administered before a meal (P > 0.05 for both comparisons with the fasting state). The results of this study indicate that (i) ingestion of food does not affect the bioavailability of d4T and that patients with HIV infection can take it without regard to meals, and (ii) absorption is essentially complete within 1 h when d4T is administered in the fasted state.     

Treatment with growth hormone suppresses cortisol production in man

The effect of biosynthetic human growth hormone (GH) on the cortisol production rate was determined in healthy men (N=8) using the stable isotope dilution technique and mass spectrometry. 1alpha,2alpha-D-Cortisol was infused at a dose of 110+/-9 microg/h for 10 hours (8 AM to 6 PM). Blood samples obtained at 20-minute intervals from 2 PM to 6 PM were pooled during two 2-hour periods. Subsequently, each subject received a daily dose of biosynthetic human GH (4 IU/d subcutaneously [SC]) for 7 days. This resulted in an increase of plasma somatomedin C from a basal level of 0.65+/-0.13 U/mL to 1.18+/-1.2 U/mL on day 7 (P < .0001). Plasma concentrations of corticotropin (ACTH) and cortisol-binding globulin (CBG) were similar before and after administration of GH. Determination of the cortisol production rate was repeated on day 7 of treatment with GH. Due to its physiological diurnal rhythmicity, endogenous production of cortisol during basal conditions was higher (P < .05) between 2 and 4 PM (0.70+/-0.30 mg/h) versus 4 to 6 PM (0.55+/-0.28 mg/h). Following treatment with GH, the values were 0.40+/-0.11 mg/h (2 to 4 PM, P < .01 v day 1) and 0.31+/-0.11 mg/h (4 to 6 PM, P < .01 v day 1). Thus, in healthy men, treatment with SC, GH induces a decrease in endogenous cortisol production rates.     

Neuropeptide Y in cortisol-induced hypertension in male volunteers

1. Cortisol-induced blood pressure rises in men are not accompanied by increases in plasma catecholamines. The present study examines the effects of cortisol on the sympathetic co-transmitter, neuropeptide Y (NPY). 2. Eight normal men were given cortisol 200 mg/day over 5 days and haemodynamic, metabolic and hormonal measures were taken. Plasma NPY-like immunoreactivity (NPY-LI) concentrations were measured by direct radio-immunoassay. 3. Cortisol significantly increased systolic, diastolic and mean arterial pressure, bodyweight, plasma glucose and total white cell concentration and decreased plasma potassium and total eosinophil count, as in previous studies. Plasma NPY concentrations were not altered significantly during cortisol treatment, but increased following cessation of cortisol treatment (P = 0.006). 4. The essentially unchanged pattern for NPY concentration with cortisol treatment resembles that previously reported for adrenaline and noradrenaline, but the increase in NPY on cortisol withdrawal was not seen for adrenaline or noradrenaline. These data do not support a role for sympathetic activation in the genesis of cortisol-induced hypertension.     

Systematic reviews and making decisions

OBJECTIVE: To compare cortisol responses to three corticotrophic preparations in normal dogs. ANIMALS: Eight clinically normal dogs (four intact males, four intact females) of medium size. PROCEDURES: Each dog received four treatments on four separate occasions in a duplicated Latin square pattern. Treatments were two adrenocorticotrophin (ACTH) preparations given intramuscularly at 2.2 U/kg, one of the ACTH preparations given intramuscularly at 1 U/kg and a synthetic polypeptide with ACTH-like activity (tetracosactrin, cosyntropin) given intravenously at 5 micrograms/kg. Plasma samples were taken for cortisol assay before and at 0.5, 1, 2 and 4 h after treatment. RESULTS: Plasma cortisol concentrations were similar with the two ACTH preparations and at both dose rates. Tetracosactrin produced smaller mean peak cortisol concentrations, which tended to occur earlier than with ACTH, and smaller values for the area under the curve of plasma cortisol concentration from zero time to 4 h. CONCLUSION: The findings suggest that canine adrenal function can be tested adequately by giving ACTH intramuscularly at 1 U/kg and measuring plasma cortisol in samples taken at 0 and 2 h, or by giving tetracosactrin intravenously at 5 micrograms/kg and determining cortisol concentration at 0 and 1 h.     

Acute effects of short-term feed deprivation and refeeding on circulating concentrations of metabolites, insulin-like growth factor I, insulin-like growth factor binding proteins, somatotropin, and thyroid hormones in adult geldings

Two studies were performed with Standardbred geldings 7 to 21 yr of age to determine the sequence of changes in blood plasma concentrations of some hormones and metabolites during feed deprivation for 48 h and for 12 h after refeeding. Plasma hormone and metabolite concentrations were determined with methods validated for horse plasma. Insulin-like growth factor binding proteins (IGFBP) were determined with radioligand analysis following SDS-PAGE electrophoresis. In both experiments, plasma concentrations of triiodothyronine and thyroxine decreased (P < .01) during feed deprivation and increased (P < .01) during refeeding. Plasma glucose and IGF-I either decreased or were not altered during feed deprivation. In contrast, plasma concentrations of NEFA and urea nitrogen increased (P < .01) during feed deprivation and decreased (P < .01) during the refeeding period. Plasma somatotropin (ST) increased (P < .01) approximately 80% at 24 to 36 h of feed deprivation, declined (P < .01) to control values at 48 h of feed deprivation, increased (P < .01) nearly three fold at 3 h after refeeding, and returned to control values by 6 h after refeeding. We identified five IGFBP, and their plasma concentrations were not significantly altered during feed deprivation or following refeeding. We conclude that metabolite availability during feed deprivation and following refeeding alters the secretion of thyroid hormones, ST, and possibly IGF-I, thereby maintaining homeostasis in horses.     

The nitric oxide system and cortisol-induced hypertension in humans

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol-induced hypertension in humans. 2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day cortisol and in subjects on an unrestricted nitrate diet who were treated with cortisol (80 mg/day, n = 6, or 200 mg/day, n = 10) for 5 days. 3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of cortisol treatment (to 11 +/- 1, 10 +/- 1, 11 +/- 1 pmol/L, respectively) compared with pretreatment (16 +/- 1 pmol/L; P < 0.01). There were no significant changes in plasma arginine, ADMA or SDMA concentrations. 4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol-induced hypertension in humans.     

Hyperinsulinemia is not a cause of cortisol-induced hypertension

There is much interest in the relationship of hypertension to hyperinsulinemia. Six male volunteers received cortisol, 50 mg orally four times daily, for 5 days. Plasma insulin concentration increased from 11.8 +/- 3.0 mU/L to 16.1 +/- 4.0 mU/L (P = .034). Fasting glucose increased from 4.7 +/- 0.3 to 5.8 +/- 0.1 mmol/L (P = .001). The insulin-to-glucose ratio was unchanged. Octreotide has been reported to lower blood pressure in obese, hyperinsulinemic, hypertensive patients. The hypothesis that cortisol-induced hypertension might be secondary to steroid-induced hyperinsulinemia was examined by determining whether reversal of hyperinsulinemia by octreotide would reverse cortisol-induced hypertension. Five healthy men were given two subcutaneous injections of 0.05 mg of octreotide before and on the fifth day of cortisol administration. Cortisol increased blood pressure, weight, plasma glucose concentration, and white cell count, with decreases in plasma potassium concentration and packed cell volume. Plasma cortisol concentrations were unchanged following octreotide in the control period but decreased after cortisol treatment. Insulin concentrations were reduced profoundly after octreotide, both in the control period (12.5 +/- 3.7 mU/L, falling to 1.1 +/- 0.3 mU/L at 30 min) and on cortisol (22.3 +/- 4.5 to 2.3 +/- 0.5 mU/L at 30 min). Octreotide did not lower pressure before or after cortisol treatment. Thus, octreotide was effective in lowering plasma insulin concentrations but di not lower blood pressure in normal subjects with cortisol-induced hypertension. These data do not support the notion that steroid-induced hyperinsulinemia is responsible for steroid-induced hypertension.     

Pretreatment of young pigs with vitamin E attenuates the elevation in plasma interleukin-6 and cortisol caused by a challenge dose of lipopolysaccharide

The effect of a short-term, high-dose intramuscular injection of d-alpha-tocopherol was studied in pigs given a challenge dose of lipopolysaccharide (LPS). Twenty-four pigs surgically fitted with jugular catheters were used in a 2 x 2 factorial design. Pigs received either 0 or 600 mg d-alpha-tocopherol by intramuscular injection for 3 d before receiving an intraperitoneal injection of saline containing either 0 or 5 microgram/kg body weight Escherichia coli LPS. Blood was collected from indwelling jugular catheters at 0, 1, 2, 4, 6, 8, 12 and 24 h after injection of LPS. Plasma alpha-tocopherol levels were 13-fold greater (P < 0.01) at time 0 in pigs pretreated with 600 mg d-alpha-tocopherol (9.9 +/- 1.3 mg/L) than in those not treated with d-alpha-tocopherol (0.74 +/- 0.09 mg/L). Injection of LPS increased (P < 0.05) plasma levels of interleukin-6 (IL-6) and cortisol at 2-h postinjection, regardless of vitamin E treatment. However, pigs that received alpha-tocopherol before the LPS challenge had substantially lower (P < 0.05) peak levels of IL-6 and cortisol than pigs not receiving alpha-tocopherol. These results suggest that supplementation with a surfeit level of vitamin E reduces the response of pigs to endotoxin.     

Bromocriptine given orally to periparturient of lactating sows inhibits milk production

Gilts were assigned as controls (CTL, n = 6) or received orally 10 mg of bromocriptine thrice daily from d 110 of gestation until farrowing, (BRPP, n = 7), from d 1 to 6 postpartum (PP) (BRL1, n = 6), from d 7 to 13 PP (BRL2, n = 7), from d 14 to 20 PP (BRL3, n = 6), or from d 21 to 27 PP (BRL4, n = 6). Weights of pigs were recorded at birth, 24 h later, and on d 7, 14, 21, 28, 31 (weaning), 42, and 56 PP. Jugular blood samples were collected from sows on d 109 of gestation and every other day until farrowing, as well as on d 1, 6, 13, 20, and 27 PP. Behavioral observations of sows and litters were taken every 3 min for a 24-h period beginning 48 h after the onset of the treatments. In experimental sows, bromocriptine induced marked reductions in prolactin levels during treatment (P < .001). Compared to CTL sows, concentrations of IGF-I were higher at d 21 (P = .01) and 28 (P = .003) PP in BRL3 and BRL4 sows, respectively. In bromocriptine-treated sows, weight gain of litters was either drastically reduced or abolished (P < .001) during the week of treatment. Treatments also altered significantly the suckling behavior of pigs at all stages studied. Therefore, the present results strongly suggest that prolactin is essential for the initiation and the maintenance of milk production in sows. Results also indicate that prolactin does not seem to be involved in the maintenance of lactational anestrus during a 4-wk lactation.     

Evaluation of copper sulfate and a copper lysine complex as growth promoters for weanling swine

Two 5-wk trials using 176 weanling pigs (average initial weight of 8.3 kg and age of 31 d) were conducted to examine the effect of feeding varying levels of dietary Cu from copper sulfate (CuSO4) or a copper lysine complex (CuLys) on performance, mineral stores, serum copper, and serum mitogenic activity. Dietary treatments were 0 (15 mg/kg of Cu in basal diet), 100, 150, or 200 mg/kg of supplemental Cu from CuSO4 or CuLys. Average daily gain and ADFI increased linearly (P < .01) with increasing dietary levels of Cu during wk 1 to 2, 3 to 5, and 1 to 5, with no difference (P > .10) between the Cu sources. Overall gain:feed ratios were not consistently affected by Cu source. Dietary Cu linearly increased liver, kidney (P < .001), and brain (P < .05) concentrations of Cu. In the liver, the linear response to supplemental Cu differed between Cu sources (P < .001); pigs fed 200 mg/kg of Cu from CuLys had the highest concentration of Cu. Serum Cu concentrations increased linearly during wk 1 to 2 (P < .01), 3 to 5, and 1 to 5 (P < .001), with no difference (P > .10) between sources. Serum mitogenic activity increased linearly during wk 1 to 2 and 1 to 5 (P < .05). Growth performance was linearly improved as the dietary level of Cu increased from 15 to 200 mg/kg, with similar responses for both Cu sources. Serum and tissue concentrations of Cu were generally equally affected by the two Cu sources, except liver Cu concentration, which was onefold higher for pigs fed 200 mg/kg of Cu as CuLys.     

Different effects of nifedipine and amlodipine on circulating catecholamine levels in essential hypertensive patients

OBJECTIVE: To compare the acute and chronic effects of nifedipine retard (NPA), nifedipine gastrointestinal therapeutic system (NGITS) and amlodipine at trough and peak plasma concentrations of drug on blood pressure and heart rate, and on plasma norepinephrine and epinephrine levels in patients with mild-to-moderate hypertension (diastolic blood pressure 95-115 mmHg). DESIGN AND METHODS: After 3-4 weeks' placebo treatment, patients of both sexes were randomly allocated to be administered 10 or 20 mg NPA twice a day, 30 or 60 mg NGITS once a day, and 5 or 10 mg amlodipine once a day for 6 weeks. Initially, for the first 2 weeks, the lowest dose of each drug was used, but higher doses were administered after 2 weeks if sitting diastolic blood pressure was > 90 mmHg. Patients were evaluated after administration of the first dose and after 6 weeks' therapy in a hospital setting. Blood samples were taken for high-performance liquid chromatography measurement of catecholamine and drug levels at various intervals for a period covering trough to peak drug level ranges. RESULTS: Administration of all three drugs reduced clinic blood pressure to the same level after 6 weeks' therapy, but heart rate was increased slightly only with amlodipine (P < 0.05). Administration of NPA reduced blood pressure more abruptly whereas administrations of NGITS and amlodipine induced smoother falls after acute and chronic treatments: a significant increase in heart rate was observed with amlodipine after chronic treatment. Both acute and chronic treatments with NPA (n = 19) increased norepinephrine levels (P < 0.01) transiently (2-4 h). In contrast, administration of NGITS (n = 22) did not increase norepinephrine levels and even induced a slight but significant decrease in norepinephrine levels 5-6 h after chronic treatments. Although administration of amlodipine (n = 22) did not increase norepinephrine levels transiently either after acute or after chronic administration, it did induce a sustained rise in basal norepinephrine levels by more than 50% after chronic therapy (P < 0.01). Plasma epinephrine levels were not increased by any of the treatments and even a slight decrease was observed 4 h after administration of a dose following chronic treatments with NGITS and amlodipine (P < 0.05). CONCLUSIONS: The transient increase in norepinephrine levels observed with NPA and the sustained increases in norepinephrine levels observed after chronic treatment with amlodipine suggest that sympathetic activation occurs with those two drugs. The lack of increase in norepinephrine levels after administration of NGITS suggests that this formulation does not activate the sympathetic system. The lowering of epinephrine levels after administrations of NGITS and amlodipine suggests that inhibition of release of epinephrine by the adrenal medulla occurs with longer-acting dihydropyridine formulations.     

Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide

The emerging view is that reduced feed intake, lean muscle accretion, and growth in immunologically challenged pigs is the result of increased cytokine activity, but this has not been directly tested. To begin addressing this issue, 72 crossbred barrows and gilts (11.55 +/- .19 kg BW) were not fed for 12 h and then injected i.p. with 0, .5, or 5 micrograms/kg of Escherichia coli lipopolysaccharide (LPS). Blood was collected by jugular puncture at 0, 2, 4, 8, 12, and 24 h after injection. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cortisol, plasma urea nitrogen (PUN), NEFA, and triglycerides were determined. Immunological stress was induced by LPS as indicated by increased secretion of TNF-alpha, IL-6, and cortisol. In pigs receiving 5 micrograms/kg of LPS, plasma TNF-alpha was increased 10-fold at 2 h after injection and was still elevated (P < .01) at 4 h. In these same pigs, plasma concentration of IL-6 was increased at 2 h and peaked at 4 h with levels exceeding baseline values by 200-fold (P < .01). Cortisol was elevated at 2, 4, and 8 h after injection (P < .01). The increased secretion of cytokines and cortisol in pigs injected with 5 micrograms/kg of LPS was followed by an increase in protein degradation, as evidenced by PUN values that were increased two- and threefold at 8 and 12 h after injection, respectively. However, unlike previous reports in laboratory animal species, plasma glucose, NEFA, and triglycerides were not altered by LPS. Nonetheless, as the period of feed deprivation progressed from 12 to 36 h, plasma NEFA and triglycerides increased (P < .05) and plasma glucose tended to decrease. We believe that immunological challenge induces cytokine synthesis and secretion in swine which, in turn, may induce protein catabolism.     

Suppressibility of plasma adrenocorticotropin by hydrocortisone: potential usefulness in the diagnosis of Cushing's disease

Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with Cushing's disease led to the present study of the prevalence of this phenomenon in 58 patients with otherwise incontrovertible evidence of Cushing's disease. Because as many as 23% of these patients manifested this phenomenon, we investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients and 16 controls. The data showed invariable suppression of plasma ACTH to < or = 10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same times in 14/14 patients with active Cushing's disease, including 3 patients whose cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7 patients with intermittent hypercortisolism. Occasional variations in plasma cortisol elevations after the oral dose require that plasma cortisol concentration be monitored at 60 min after the oral hydrocortisone dose, because the present evidence supports the validity of the conclusion that a plasma ACTH concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of ACTH suppressibility by cortisol would be worthwhile, to confirm its potential value in facilitating positive diagnosis of Cushing's disease when dexamethasone suppressibility seems misleading.     

Influence of Neotyphodium coenophialum on copper concentration in tall fescue

Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity.     

Endocrine and reproductive function in ewes exposed to the organochlorine pesticides lindane or pentachlorophenol

The effects of lindane (LIN, gamma-hexachlorocyclohexane) and pentachlorophenol (PCP) on reproduction and general endocrine function were examined in breeding ewes as a model for wild and domestic ungulates, which may be exposed to low levels of pesticides that are potential endocrine-disrupting chemicals. Ewes (n = 13/group) were fed either a control untreated diet (CON), or a diet treated with LIN (1 mg/kg/d) or PCP (1 mg/kg/d) during the 5 wk prior to mating and throughout pregnancy and lactation. Mating response, ovulation rate, follicle and corpus luteum size, gestation length, pregnancy rate, lambing rate, and lamb birth weight were recorded. After weaning, 6 ewes from each group were bled at 15-min intervals for 8 h during the day and night and for 1 h before and 5 h after i.v. administration of gonadotropin-releasing hormone, thyroid-stimulating hormone (TSH), and adrenocorticotropin, to measure serum concentrations of luteinizing hormone, follicle-stimulating hormone, thyroxine (T4), and cortisol. Ewes were then killed and endocrine tissues examined histologically. Pregnancy rate as a result of matings taking place at the synchronized estrus was significantly decreased by the lindane treatment However, PCP and lindane did not markedly affect any other aspect of reproductive function studied. In PCP-treated ewes, serum concentrations of T4 were significantly reduced compared to control ewes during the day and night; however, the T4 response to TSH was not altered by PCP treatment. No other measured endocrine parameters were consistently affected by lindane or PCP. Thyroid follicle size was significantly increased in the LIN and PCP ewes compared to the control ewes. Low serum concentrations of T4 in the PCP ewes may have resulted in increased TSH secretion and increased thyroid follicle size. In conclusion, although pesticide treatments had no serious adverse effects on reproductive function in breeding ewes, PCP reduced T4 concentration, which in the long term could influence reproductive and general performance.     

Functional diversity and clonal frequencies of reactivity in the available antibody repertoire

Our objective was to determine the effect of level and chemical form of dietary selenium on productivity of beef cows, concentrations of triiodothyronine (T3), and thyroxine (T4) in plasma, and immunoglobulins (IgG and IgM) in plasma and colostrum of cows. Pregnant cows (n = 60) were randomly allocated among four dietary treatments of 20, 60, or 120 ppm Se as selenite and 60 ppm as selenomethionine from selenized yeast (SeY) in salts offered free-choice. Treatments began 90 d prepartum and continued through the second parturition. Treatments did not affect the final body weights of cows or birth weights or weaning weights of calves. At parturition, cows given salt with 20 ppm Se as selenite had lower (P < . 05) concentrations of Se in blood than cows with access to higher-Se salts. Treatments affected (P < .01) the concentration of T3 and the ratio of T3:T4 in plasma of cows. The concentration of T3 in plasma of cows with access to salt with 20 ppm Se was 14% lower than that in cows supplemented with 60 ppm Se as selenite or SeY. Plasma IgG in cows and calves, colostrum, and Se concentrations in colostrum, casein, and whey were lowest (P < .01) for cows given salt with only 20 ppm Se. Thus, salts with concentrations of 60 and 120 ppm Se improved measures of Se status in cows and calves. Consideration should be given to the concentrations of T3 and IgG when determining the nutritional requirements for Se in cattle.