Effects of prenatal stress on suckling calves

Pregnant Brahman cows (n = 42), bred to either Brahman or Tuli bulls, were randomly assigned to one of three treatments: 1) transported in a stock trailer for 24.2 km, unloaded at a second farm and penned for 1 h, and then returned to the original farm (TRANS); 2) i.v. injection of ACTH, 1 IU/kg BW (ACTH); or 3) walked through the handling facilities (SHAM). Treatments were initiated on d 60 and repeated at 80, 100, 120, and 140 d of gestation. The calves from these cows were subjected to tests to measure their capacity to react to stress. In Test 1, Tuli-sired calves were restrained at 10 and 150 d of age for 3.5 h. In Test 2, Brahman-sired calves were restrained for 3.5 h and given an injection of ACTH (.125 IU ACTH/kg of BW). In Test 3, Test-2 calves were restrained at 180 d of age and hot-iron branded. In Test 4, Test-1 calves were restrained at 180 d of age and given an injection of cortisol (6.7 ng/kg BW) to estimate cortisol clearance rate. During all tests, calves were restrained for 3.5 h, and heart rates were recorded and blood samples were taken at -15, 0, 15, 30, 45, 60, 90, 120, and 180 min. The 10- and 150-d-old TRANS calves maintained greater plasma cortisol in Test 1 (restraint) than the ACTH and SHAM calves (P < .01). The ACTH challenge (Test 2) increased plasma cortisol and ACTH, but cow treatment did not alter the response (P > .4). In response to branding (Test 3), the TRANS, ACTH, and SHAM calves' overall mean plasma cortisol was not affected by treatment (52, 51, and 43 +/- 3 ng/mL, respectively; P > .1), nor was the calves' overall heart rate (91, 94, and 86 +/- 3 beats/min, respectively; P > . 1). In Test 4, TRANS calves cleared plasma of cortisol at a slower rate than did the SHAM calves (P < .01), but not the ACTH calves (261, 374, and 473 +/- 50 mL/min, respectively; P > .1). The TRANS calves had an overall greater heart rate than did the ACTH or the SHAM calves (91, 79, and 77 +/- 2 beats/min, respectively; P < .001). Exposing cows to repeated transportation stress during gestation altered their calf's physiological response to stress, and these alterations could have a profound influence on the calfs ability to adapt to stress, thereby influencing its welfare. Further research should examine the growth, immune function, and reproductive function of prenatally stressed calves to determine whether these changes in plasma cortisol are beneficial or deleterious.     

Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five awake dogs. Four hours after endotoxin or saline challenge human corticotrophin-releasing hormone (hCRH; 1.0 microgram/kg) was administered. Plasma ACTH and cortisol levels increased considerably in response to endotoxin, from 13 +/- 1 ng/l to 360 +/- 85 ng/l (p < 0.01) and from 60 +/- 20 nmol/l to 710 +/- 80 nmol/l (p < 0.01). Despite a considerable difference in ACTH and cortisol levels prior to CRH administration between both studies (p < 0.01), the absolute increase in ACTH levels induced by hCRH was not different (231 +/ 43 ng/l vs 238 +/- 45 ng/l, control vs endotoxin). Plasma cortisol levels increased significantly in the control study (from 40 +/- 10 nmol/l to 330 +/- 40 nmol/l, p < 0.01), whereas they did not change in the endotoxin study after hCRH administration (from 710 +/- 80 nmol/l to 730 +/- 70 nmol/l, ns). We conclude that the HPA-axis reacts initially to endotoxin in such a way that cortisol, but not ACTH, secretion is maximized. Therefore, a blunted cortisol response to CRH testing is part of the initial response to infection.     

Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects

Recent animal and human studies have suggested that leptin secretion is closely linked to the functions of the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, both of which are crucial in influencing the course and outcome of critical illness. Therefore, we measured basal plasma leptin levels and examined the circadian secretion of leptin, in parallel with the hormones of the HPA axis and a key cytokine, interleukin-6, in critically ill patients with acute sepsis. Sixteen critically ill patients from the University of Leipzig Intensive Care Unit were recruited for this study. All of these patients fulfilled the standard diagnostic criteria for sepsis. Plasma leptin levels were measured in all patients and controls at 09:00. In addition, in a subgroup of eight critically ill patients and all of the nine controls plasma leptin, cortisol, ACTH and interleukin-6 concentrations were measured every 4 hours for 24 hours. Mean plasma leptin levels were three-fold higher (18.9 +/- 4.5 ng/ml) in critically ill patients than controls (3.8 +/- 1.0 ng/ml, p < 0.05). Similarly, ACTH levels were lower (7.8 +/- 3.4 pmol/l) in patients than in controls (17.1 +/- 1.5 pmol/l, p < .001), while plasma cortisol levels were increased (947.6 +/- 144 nmol/l) in patients compared to controls (361.1 +/- 29, p < 0.001). Morning plasma interleukin-6 levels were markedly elevated in all patients with sepsis (1238.0 +/- 543.1 pg/ml) versus controls (6.4 +/- 1.7, p < 0.001). The controls exhibited a nyctohemeral fluctuation in plasma leptin levels with peak levels at 23:00; in contrast, septic patients, had no nocturnal rise of leptin. In healthy controls, plasma leptin and cortisol had reciprocal circadian rhythms with high nocturnal leptin levels and low nocturnal cortisol concentrations; in critically ill patients, this relation was abolished. Mean leptin levels were three-fold higher in patients who survived the septic episode (25.5 +/- 6.2, n = 10) than in non-survivors (8.0 +/- 3.7, n = 6, p < 0.01). We conclude that in addition to its function as an anti-obesity factor, leptin may play a role in a severe stress state such as acute sepsis.     

Coordinate activation of the corticotropic axis by insulin-induced hypoglycemia: simultaneous estimates of beta-endorphin, adrenocorticotropin and cortisol secretion and disappearance in normal men

In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), beta-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77 +/- 15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma beta-endorphin concentration, the maximal value of which was 96 +/- 11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734 +/- 14 nmol/l. Maximal plasma ACTH and beta-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5 +/- 2.7 and 10.6 +/- 2.0 pmol.l-1.min-1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114 +/- 20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 micrograms (50% of daily production and 0.5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4 +/- 0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088 +/- 137 nmol/l and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, beta-endorphin and cortisol were 17 +/- 0.6, 22 +/- 1.7 and 65 +/- 5.3 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of bosentan, pinacidil and nitroprusside on human pulmonary arteries: comparison with rat pulmonary arteries

OBJECTIVE: The general objective of the Etude du Viellissement Arterial (EVA) program is to follow vascular aging and the decline in cognitive functions at the cerebrovascular level longitudinally over a 4-year period. One of the specific objectives of this EVA study is to examine epidemiologically the relationship between the markers of oxidative stress (lipid peroxidation), the antioxidant micronutrient status (particularly of selenium, vitamin E, and the carotenoids) and the prevalence of chronic disorders occurring during the pre-aging period. METHODS: 1389 subjects aged from 59 to 71 years were studied. RESULTS: The concentration of plasma lipid peroxides was higher than in young adults (2.91 +/- 0.38, men; 2.97 +/- 0.40, women (mumol/l). On the other hand, plasma Se (1.09 +/- 0.21, men; 1.10 +/- 0.19, women (mumol/l)), erythrocyte vitamin E (5.32 +/- 1.29, men; 5.52 +/- 1.28, women (mumol/l)), and total plasma carotenoids (2.19 +/- 0.98, men; 3.07 +/- 1.33, women (mumol/l)) were comparable to values in young adults. In our cohort, 40% of subjects had unremarkable medical histories. The disorders most often encountered were lipemia (29.8% of men, 36.1% of women), and hypertension (28.9% of men, 30.4% of women). CONCLUSION: Se and vitamin E levels were raised in cases of lipemia, especially in those treated with fibrates. The mechanism of the increase is unknown. In hypertensives and diabetics, there was a decrease in total carotenoids associated with increased peroxidative risk.     

Changes in oxytocin and cortisol levels in primiparous cows after changing from 21 days of suckling calves to machine milking

Four first-calvers of the Black-Pied breed with calves sucking their milk until day 21 of lactation were included in a trial. One suckler cow had four calves. The trial took place within five days which included days 20 and 21 in the first-calvers, that means the last two days with sucking calves (designated as day 1 and day 2 of trial-first and second calf sucking) and days 22 and 24, that means the first and third day after the cows were moved to a cowshed (designated as the third and fifth day of trial-first and third evening machine milking). The first-calvers were separated from the calves and moved to a cowshed at 8 o'clock a.m. on day 3 of trial (Tab. I). The responses to calf sucking were investigated after four-hour prevention of calves to approach the cows (12.00-16.00 p.m.). Blood was sampled with a catheter which was introduced into the vena jugularis a day before the trial outset. Blood samples for cortisol determination were taken in two-hour intervals (when the cows were moved to the cowshed twice in half-an-hour interval and once in an hour interval). Blood samplings were effectuated by day, before, during and after milking, or sucking. Machine milking was finished within 7 to 8 minutes. Two to four calves were intensively sucking a cow within the first 15 minutes, then sucking was irregular. Plasma samples were deep-frozen and stored at -20 degrees C until determinations were performed. Oxytocin and cortisol in the blood plasma were determined by radioassays. In the first evening machine milking (day 3) the second cow yielded 8.23 kg milk while on day 5 in the third milking it was 7.98 kg. The other first-calvers gave by 30-45% less milk on day 3 in comparison with evening milking on day 5 (Tab. II). A trend of the higher average values of oxytocin was observed in machine milking on day 5 of trial if compared with the values recorded during calf sucking, or the first milking (day 3), Fig. 1a, Tab. III. The mean oxytocin concentration during 7-minute milking (12.39 +/- 5.81 pg/ml) was significantly lower in the first-calvers on day 3 in comparison with the mean values recorded on day 5 (28.01 +/- 18.56 pg/ml; P < 0.001), or during sucking (18.32 +/- 7.15 pg/ml; P < 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

Activity of some serum enzymes in calves suffering from white muscle disease

The paper described the findings of the activity of aspartate amino transferase (GOT) and alanine amino transferase (GPT), lactate dehydrogenase (LDH), alkaline phosphatase (AP), and aldolase in the blood serum of calves examined for white-muscle disease (WMD). Relapsing mass accurrence of the disease was reported from various agricultural enterprises where calves were fed a milk replacer without vitamin E. In comparison with clinically healthy calves fed a feed mixture with vitamin E, calves suffering from the clinical form of WMD showed an alkaline phosphatase level decrease from 32.3 +/- 7.6 u. K. A. to 15.1 +/- 8.2 u. K. A. On the other hand, the activites of ALD, GOT, GPT, and LDH showed a statistically significant increase. The acute and sub-acute course of the disease increased enzyme activities as follows: ALD from 4.2 +/- 1.1 mumol (= 70.0 +/- 17.0 i.u.) to 9.7 +/- 2.1 mumol (= 163.0 +/- 33.2 i. u.), GOT from 0.9 +/-0.5 mumol (= 68.0 +/- 5.8 i.u.) to 16.7 +/- 11.7 mumol (= 567.0 +/-40.0 i. u.) GPT from 0.2 +/- 0.8 mumol (= 5.0 +/- 12.4 i. u.) to 9.8 +/- 2.8 mumol (= 330.0 +/- 40.4 i.u.), LDH from 46.1 +/- 5.4 mumol (= 765.0 +/- 40.0 i.u.) to 72.7 +/- 24.3 mumol (= 1,207.0 +/- 403.0 i.u.). In WMD-affected herds, similar enzyme activity fluctuations were observed even in calves showing no clinical signs of the disease. It follows from the study that the examination of serum enzymes provides a method to demonstrate the clinical and pre-clinical forms of white-muscle disease and that it can be included in the set of tests for the diagnosis of diseases in calves. The significant differences in all calves in the affected herds show that the disease is a danger to all animals in the herd fed a deficient mixture.     

Effect of duodenal glucose infusion on blood glucose concentration in endotoxin-treated calves

The effect of endotoxemia on the intestinal absorption of glucose was evaluated in nine experiments performed on seven 3- to 5-week-old calves fitted with a duodenal cannula. An intraduodenal glucose load trial (infusion of 2 g glucose/kg b.w. as a 10% aqueous solution through the cannula over 60 min) was conducted in a group of 5 calves three times during the 4-day period: 48 h before and at 2 and 24 h after i.v. injection of E. coli 0111:B4 endotoxin (LPS) at a dose of 0.1 microgram/kg b.w. Control calves were treated similarly but instead of glucose they were infused intraduodenally with deionised water at a volume of 20 ml/kg b.w. In trial with glucose load performed 48 h before LPS administration, blood glucose concentration increased during the absorptive phase from 4.32 +/- 0.32 mmol/l to 11.45 +/- 0.87 mmol/l at 60 min and then decreased to a minimum value of 3.16 +/- 0.51 mmol/l at 240 min. During the initial phase of endotoxemia, blood glucose concentration did not change from baseline values in both groups of calves. Glucose concentration in control calves started to decrease at 165 min reaching a minimum value of 1.39 +/- 0.17 mmol/l at 210 min and then increased to 2.44 +/- 0.11 mmol/l at 480 min after LPS administration. The intraduodenal infusion of glucose at 2 h after LPS administration resulted in an increase in blood glucose concentration during the absorptive phase only in one calf. Blood glucose concentration in this calf increased between 30 and 90 min reaching a maximum value of 7.19 mmol/l at 60 min, and then decreased to a minimal value of 0.94 mmol/l at 180 min after glucose load. In the remaining four calves in this group, blood glucose concentration ranged from 3.89 +/- 0.37 mmol/l to 4.48 +/- 0.45 mmol/l up to 120 min, and then steadily decreased to a minimal value of 2.41 +/- 0.41 mmol/l at 300 min. In trial with glucose load performed 24 h after LPS administration, the rate of entry of glucose into the circulation during the absorptive phase was similar to that observed in the trial performed 48 h before LPS administration. In conclusion, these results indicate that endotoxemia impairs the intestinal absorption of glucose in calves. The magnitude of the absorption disturbance may vary in individual calves, and the inhibitory effect of LPS on the intestinal glucose absorption lasts less than 24 h.     

Acidosis and hyperlactatemia in acute sodium valproate poisoning

OBJECTIVES: We searched for signs of metabolic acidosis and associated hyperlactatemia in case of sodium valproate overdose. PATIENTS AND METHODS: A retrospective study was conducted in the toxicology intensive care unit at the Fernand Widal hospital from 1990 to 1995. Patients retained for study had sodium valproate levels above the therapeutic range (> 600 mumol/l). Data collected included past history, intubation for mechanical ventilation, administration of catecholamines and infusion of bicarbonate or sodium lactate, and blood pressure. Laboratory tests included serum sodium valproate, pH, PCO2, bicarbonate, anion balance and lactate. RESULTS: The study included 22 consecutive patients. None had a history of liver disease. Thirteen patients were intubated before admission to intensive care. Two received catecholamines. None of the patients received bicarbonate or sodium lactate. Mean blood pressure was 118 +/- 16 mmHg, mean serum sodium valproate was 2668 +/- 2437 mumol/l, mean pH was 7.41 +/- 0.08, mean PO2 35.6 +/- 8.0, mean anion imbalance 23.2 +/- 6.0 mmol/l and mean lactate 5.0 +/- 2.1 mmol/l. There was a significant correlation between lactase and pH (p < 0.003). CONCLUSION: We found metabolic acidosis with major anion imbalance and high lactate levels in patients with acute sodium valproate intoxication. Hyperlactatemia could be due to the direct effect of sodium valproate or to an unknown mechanism.     

Hormone action and chromatin remodelling

In this study, we analyzed the influence of vitamin E succinate (5-80 microM), supplemented in the culture medium, on the survival of cultured retinal cells. The release of lactate dehydrogenase (LDH) was decreased in the presence of low concentrations (10-20 microM) of vitamin E succinate, whereas high concentrations (80 microM) induced a significant increase (about 2-fold) in the release of LDH, indicating a reduction of plasma membrane integrity. Supplementing with vitamin E succinate (80 microM) greatly enhanced its cellular content, as compared to vitamin E acetate (80 microM), and the membrane order of the retinal cells, as evaluated by the fluorescence anisotropy (r) of TMA-DPH (1-(4-(trimethylammonium)-phenyl)-6-phenylhexa-1,3,5-triene), was not altered. Furthermore, vitamin E succinate was more potent than vitamin E acetate in reducing thiobarbituric acid reactive substances (TBARS) formation upon ascorbate-Fe2+-induced oxidative stress (TBARS formation after cell oxidation decreased by about 15-fold or 1.6 fold, respectively, in the presence of 20 microM vitamin E succinate or 20 microM vitamin E acetate). A decrease in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction induced by supplementing with vitamin E succinate (80 microM), to 35.99 +/- 1.96% as compared to the control, but not by vitamin E acetate (80 microM), suggests that vitamin E succinate may affect the mitochondrial activity. Vitamin E succinate also reduced significantly the ATP:ADP ratio in a dose-dependent manner, indicating that vitamin E succinate-mediated cytotoxic effects involve a decrement of mitochondrial function.     

Circulating leptin levels during acute experimental endotoxemia and antiinflammatory therapy in humans

Leptin, a newly discovered adipose tissue-derived weight-reducing hormone, is increased in acute inflammation and may be involved in the anorexia and wasting syndrome associated with infection. To determine whether this hormone responds to an acute inflammatory stimulus, plasma leptin concentrations were measured in 12 healthy subjects after intravenous administration of endotoxin. These subjects were randomized to receive concurrently ibuprofen or placebo normal saline (6 in each group). Endotoxin administration resulted in fever, leukocytosis, and an increase in plasma levels of the stress hormones adrenocorticotropic hormone (3.2 +/- 0.3 to 132.6 +/- 75.5 pmol/L, P = .001) and cortisol (431.6 +/- 44 to 796.9 +/- 99 mmol/L, P = .001). Plasma leptin levels, however, did not change significantly from baseline values after administration of endotoxin (0 h: 6.9 +/- 3.1 ng/mL; 6 h: 6.0 +/- 2.2; 24 h: 6.5 +/- 2.8). While ibuprofen suppressed fever and symptoms associated with endotoxemia, it had no effect on the plasma levels of leptin. In conclusion, acute experimental human endotoxinemia is not associated with acute changes in circulating leptin levels.     

Oxidative stress and advancing age: results in healthy centenarians

OBJECTIVE: Our study aims at investigating the degree of oxidative stress in centenarians DESIGN: Indices of oxidative stress (reaction products of malondialdehyde with thiobarbituric acid (TBARS) and lipid hydroperoxides (LPO)), and plasma concentrations of antioxidant defenses (plasma vitamin E and C concentrations and reduced/oxidized glutathione ratio (GSH/GSSG)) were determined. SUBJECTS: Eighty-two subjects volunteered for the study. They were divided into three groups: (1) adults (<50 years of age, n=30); (2) aged subjects (70-99 years, n=30); (3) centenarians (age > or=100 years, n=22). MEASUREMENTS: TBARS and LPO, plasma vitamin E and C concentrations, and plasma GSH/GSSG ratio were determined. Insulin action was assessed by euglycemic hyperinsulinemic glucose clamp. MAIN RESULTS: TBARS (0.44+/-0.07 vs 0.31+/-.05 nmol malondialdehyde/mL plasma, P=.020) and LPO (0.36+/-0.05 vs 0.31+/-.04 micromol/L, P=.050) were lower in centenarians than in aged subjects. In contrast, plasma GSH/GSSG ratio (0.82+/-0.09 vs 1.17+/-.06, P=.010), vitamin C (72.3+/-4.6 vs 59.4+/-3.8 micromol/L P=.010), and vitamin E (29.1+/-2.2 vs 24.4+/-2.3 micromol/L P=.050) concentrations were more elevated in centenarians than in aged subjects. Differences in daily vegetable intake, in fasting plasma glucose and free fatty acid (FFA) concentrations, and in insulin action are significant determinants of degree of oxidative stress. A specific genetic background in centenarians might also provide a possible explanation. CONCLUSIONS: The degree of oxidative stress is lower in healthy centenarians than in aged subjects.     

A method for simultaneous determination of plasma and erythrocyte antioxidant status. Evaluation of the antioxidant activity of vitamin E in healthy volunteers

1. Since oxygen free radicals are directly involved in a variety of pathologies such as atherosclerosis, diabetes mellitus, inflammation and/or when a deficit of defences of the organism against radicals occurs, we developed a suitable and simple method to determine both the erythrocyte sensitivity to an oxidative stress and plasma antioxidant protective capacity. 2. This test is based on the introduction at 37 degrees C of a radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), within an erythrocyte suspension leading to a membrane alteration and ultimately to haemolysis. The latter can be quantified by determining the lacticodeshydrogenase activity released in the medium. The erythrocyte sensitivity to haemolysis and the volume of plasma inhibiting 50% of the haemolysis were determined. 3. Intra-assay CVs were 1.9% for erythrocyte sensitivity to oxidative stress and 3.4% for inhibitory 50% plasma volume. Inter-assay CVs for both erythrocyte sensitivity and inhibitory 50% plasma volume were 4%. 4. The reliability of this method was assessed and applied to test the protective effect of vitamin E, a well known antioxidant agent, in six healthy volunteers. Two weeks after daily administration of 500 mg of vitamin E, the mean plasma vitamin E concentration increased by 41% from 10.7 +/- 2.0 mg l-1 before treatment (P < 0.05). As the vitamin E concentration increased, the mean inhibitory 50% plasma volume and the percentage of haemolysed erythrocytes decreased respectively by 29% from 3.35 +/- 0.5 microliter (P < 0.05) and 18% from 71.5 +/- 3.8% (P < 0.05). No significative variation of these parameters was observed in six adult men without vitamin E supplementation. 5. Thus, this global and simple test permits an antioxidant status evaluation of a patient. It can be applied to various pathologies and allows the potency of new antioxidant molecules to be evaluated.     

Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events

We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.     

Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer

Antioxidants are crucial components of fruit/vegetable rich diets preventing cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; randomized intervention with synchronous rectification of vitamins A + C + E + B + minerals reduces CVD and counteracts precancerous lesions; high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: > or = 30 mumol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); > or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio > 1.3-1.5; > or = 0.4 mumol/l beta- (> or = 0.5 mumol/l alpha+ beta-) carotene. CONCLUSIONS: In CVD vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients.     

A biomechanical evaluation of cyclic and static stretch in human skeletal muscle

Hexarelin (HEX) is a synthetic GHRP which acts on specific receptors at both the pituitary and the hypothalamic level to stimulate GH release both in animals and in humans. Like other GHRPs, HEX possesses also acute ACTH and cortisol-releasing activity similar to that of hCRH. The mechanisms underlying the stimulatory effect of GHRPs on hypothalamo-pituitary-adrenal (HPA) axis are still unclear, although a CNS-mediated action has been demonstrated. In 6 normal healthy young women (26-34 years) we studied the effects on ACTH and cortisol secretion of HEX (2.0 microg/kg i.v. at 0 min) alone and preceded by dexamethasone (DEXA, 1 mg p.o. at 23.00 h on the previous night) or alprazolam (ALP, 0.02 mg/kg p.o. at -90 min), a benzodiazepine which binds to GABA receptors and possesses CRH-mediated inhibitory activity on HPA axis. ACTH and cortisol secretion after saline administration as well as the GH response to HEX alone and preceded by DEXA or ALP were also studied. HEX administration elicited an increase in ACTH (peak vs. baseline, mean +/- SEM: 28.0 +/- 6.7 vs. 11.7 +/- 2.2 pg/ml, p < 0.05) and cortisol secretion (162.6 +/- 15.0 vs. 137.7 +/- 12.6 microg/l, p < 0.05). DEXA pretreatment strongly inhibited basal ACTH (3.2 +/- 0.7 pg/ml, p < 0.01) and cortisol levels (11.3 +/- 2.5 microg/l, p < 0.001) and abolished the ACTH and cortisol responses to HEX (3.6 +/- 0.9 pg/ml, p < 0.01 and 10.7 +/- 2.0 microg/l, p < 0.001), respectively. On the other hand, ALP pretreatment did not significantly modify basal ACTH (7.9 +/- 2.0 pg/ml) and cortisol levels (127.6 +/- 14.5 microg/l) but abolished the HEX-induced ACTH and cortisol secretions (8.6 +/- 2.4 pg/ml, p < 0.05 and 111.0 +/- 6.0 microg/l, p < 0.05), respectively. ACTH and cortisol levels after HEX when preceded by ALP overlapped with those recorded during saline. HEX induced a clear GH response (peak at 15 min vs. baseline: 65.5 +/- 20.5 vs. 2.2 +/- 0.7 microg/l, p < 0.03) which was blunted by ALP (peak at 15 min: 21.5 +/- 5.5 microg/l, p < 0.05) while it was not modified by DEXA pretreatment (78.7 +/- 7.6 microg/l). In conclusion, our present data demonstrate that the ACTH- and cortisol-releasing effect of HEX is abolished by either dexamethasone or alprazolam, a benzodiazepine, which is even able to blunt the GH-releasing activity of the hexapeptide. These findings suggest that, in physiological conditions, the stimulatory effect of GHRPs on HPA axis is sensitive to the negative glucocorticoid feedback and could be mediated by GABAergic mechanisms; the latter seem also involved in the GH-releasing activity of GHRPs.     

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.     

Lipid metabolism in horses with hyperadrenocorticism

Lipid metabolism was studied in 21 horses with hyperadrenocorticism. To be included in the study, horses had to have histologic evidence of a pars intermedia adenoma found at necropsy (n = 9), a baseline ACTH concentration greater than 400 pg/ml (n = 6), or a plasma cortisol concentration 2 hours after i.v. administration of 25 IU of ACTH greater than 413 nmol/L (n = 16). Mean +/- SD baseline plasma cortisol concentration was 338 +/- 261 nmol/L (n = 20), mean +/- SD plasma insulin concentration was 97 +/- 54 microU/ml (n = 15), mean +/- SD plasma beta-hydroxybutyrate concentration was 1.8 +/- 1.2 mg/dl (n = 21), and mean +/- SD plasma nonesterified fatty acids concentration was 6.2 +/- 6.4 mg/dl (n = 21). None of the horses had hyperlipemia. Compared with clinically normal horses, horses with hyperadrenocorticism had increased lipolysis and increased ketogenesis. It was concluded that cortisol cannot be the sole factor contributing to insulin resistance in horses with hyperadrenocorticism.     

Bone mineral assessments in the calcaneus after anterior cruciate ligament injury. An investigation of 92 male patients before and two years after reconstruction or revision surgery

Dairy calves under 14 days of age with naturally occurring, uncomplicated diarrhea were treated for 3 days with a hypertonic oral electrolyte solution with (n = 15) or without (n = 12) psyllium. Clinical response and clinical pathology data were compared between the 2 groups. Glucose absorption was evaluated on days 1 and 3 by measurement of plasma glucose and lactate and serum insulin concentrations for 4 hours after formula administration. On day 1, glucose, lactate, and insulin concentrations were lower in psyllium-fed calves than in control calves, with significant differences noted in glucose and lactate concentrations at several time points (P < 0.05). Plasma lactate concentrations were higher at several times in both treatment groups on day 3 than on day 1 (P < 0.05). Fecal consistency was markedly different in psyllium-fed calves as compared with control calves within 24 hours of psyllium supplementation. Fecal percent dry matter content was lower in psyllium-fed calves than in control calves at least once a day during supplementation and on day 3 compared with day 0 in the psyllium-fed calves (P < 0.05). There were no significant differences in clinical performance scores, hydration status, arterial blood gas, serum anion gap, electrolyte, or total CO2 concentrations. Addition of psyllium to an oral electrolyte solution resulted in immediate alterations in glucose absorption without impairing rehydration in diarrheic calves, but differences were transient and did not affect clinical outcome.     

The absence of a procoagulant effect after TNK-t-PA: a comparison with streptokinase and rt-PA

A limitation of current fibrinolytic drugs is the procoagulant activity induced by their administration. TNK is a mutant of tissue plasminogen activator (t-PA) with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and slow plasma clearance, which is administered in a single intravenous bolus. In this study we investigated the procoagulant effect of TNK-t-PA compared to streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40 mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with contraindications to thrombolysis (control group). All patients received a similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn before the start of treatment (time 0) and after 2 hours. Thrombin formation was assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The four patient groups did not differ significantly in age, sex, time to treatment, infarct location, and TAT values at time 0 (mean value +/- standard error of the mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK and controls). In conclusion, our data suggest that, in patients with acute myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions, is devoid of procoagulant effects, evaluated 2 hours after its administration.