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Selected AbstractsAdenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig modelACTA PHYSIOLOGICA, Issue 2 2001S. G. Friberg There is a growing body of evidence supporting the idea that nerve growth factor (NGF) may be involved in the development of asthma-associated symptoms, such as airway hyper-responsiveness. Increased levels of NGF have recently been described in serum and in the airways of asthmatics. We have examined whether exhaled nitric oxide (NO) levels might be altered during the increased airway responses upon NGF treatment in guinea-pigs in vivo. Intravenous (i.v.) administration of histamine normally elicits a rapid peak in insufflation pressure (IP) and in exhaled NO, followed by a period of decreased concentrations of exhaled NO. Anaesthetized guinea-pigs were pre-treated intravenously with either saline, 4 or 80 ng kg,1 NGF 30 min before i.v. challenge with 16 ,g kg,1 histamine. At 80 ng kg,1 NGF significantly enhanced the airway obstruction caused by histamine, whereas the peak acute increase in exhaled NO was not enhanced. Following the increase, came a rapid drop, an effect enforced in the NGF treated animals. Subsequently, the time to return to 90% of resting exhaled NO was increased, from 12 min in saline-treated animals to 48 min in NGF-treated animals. Our data confirm that NGF can enhance airway responses to histamine. Moreover, our study shows a decrease in exhaled NO following a histamine challenge, an effect enhanced by NGF. A reduced ability to release exhaled NO may be a mechanism for increased airway responses during elevated NGF levels. The interaction between NGF and airway NO formation, and its relation to airway responses, merit further investigation. [source] Modelflow estimates of cardiac output compared with Doppler ultrasound during acute changes in vascular resistance in womenEXPERIMENTAL PHYSIOLOGY, Issue 4 2010Kenneth S. Dyson We compared Modelflow (MF) estimates of cardiac stroke volume (SV) from the finger pressure-pulse waveform (Finometer®) with pulsed Doppler ultrasound (DU) of the ascending aorta during acute changes in total peripheral resistance (TPR) in the supine and head-up-tilt (HUT) postures. Twenty-four women were tested during intravenous infusion of 0.005 or 0.01 ,g kg,1 min,1 isoprenaline, 10 or 50 ng kg,1 min,1 noradrenaline and 0.3 mg sublingual nitroglycerine. Responses to static hand-grip exercise (SHG), graded lower body negative pressure (LBNP, from ,20 to ,45 mmHg) and 45 deg HUT were evaluated on separate days. Bland,Altman analysis indicated that SVMF yielded lower estimates than SVDU during infusion of 0.01 ,g kg,1 min,1 isoprenaline (SVMF 92.7 ± 15.5 versus SVDU 104.3 ± 22.9 ml, P= 0.03) and SHG (SVMF 78.8 ± 12.0 versus SVDU 106.1 ± 28.5 ml, P < 0.01), while larger estimates were recorded with SVMF during ,45 mmHg LBNP (SVMF 52.6 ± 10.7 versus SVDU 46.2 ± 14.5 ml, P= 0.04) and HUT (SVMF 59.3 ± 13.6 versus SVDU 45.2 ± 11.3 ml, P < 0.01). Linear regression analysis revealed a relationship (r2= 0.41, P < 0.01) between the change in TPR from baseline and the between-methods discrepancy in SV measurements. This relationship held up under all of the experimental protocols (regression for fixed effects, P= 0.46). These results revealed a discrepancy in MF estimates of SV, in comparison with those measured by DU, during acute changes in TPR. [source] Angiotensin II-based hypertension and the sympathetic nervous system: the role of dose and increased dietary salt in rabbitsEXPERIMENTAL PHYSIOLOGY, Issue 5 2007Fiona D. McBryde There is accumulating evidence that angiotensin II may exert its hypertensive effect through increasing sympathetic drive. However, this action may be dependent on the dose of angiotensin II as well as salt intake. We determined the effect of different doses of angiotensin II and different levels of salt intake on neurogenic pressor activity. We also examined the effect of renal denervation. New Zealand White rabbits were instrumented to continuously measure arterial pressure. The depressor response to the ganglionic blocker pentolinium tartrate (5 mg kg,1) was used to assess pressor sympathetic drive on days 0, 7 and 21 of a 20 or 50 ng kg,1 min,1 continuous i.v. angiotensin II infusion. A 50 ng kg,1 min,1 infusion caused an immediate increase in pressure (23 ± 5 mmHg), whereas a 20 ng kg,1 min,1 infusion caused a slow increase in pressure, peaking by day 12 (17 ± 4 mmHg). The ganglionic blockade profiles indicated sympathoinhibition in the 50 ng kg,1 min,1 group by day 7 and sympathoinhibition in the 20 ng kg,1 min,1 group at day 21, corresponding to the development of hypertension. Animals receiving increased dietary salt (0.9% NaCl in drinking water), however, showed a similar slow increase in pressure with 20 ng kg,1 min,1 angiotensin II (16 ± 5 mmHg) but no sympathoinhibition at day 21. Bilateral renal denervation delayed the onset but not the extent of hypertension in this group. We conclude that different doses of angiotensin II produce distinct profiles of hypertension and associated changes in pressor sympathetic drive and that increased dietary salt intake disrupts the normal sympathoinhibitory response to angiotensin II-based hypertension. [source] Aflatoxin contamination of consumer milk caused by contaminated rice by-products in compound cattle feedJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 2 2009Erik Nordkvist Abstract BACKGROUND: Elevated levels of aflatoxin M1 were observed in routine checks of consumer milk in southern Sweden in early 2006. A trace-back study revealed contaminated milk from several farms, and a total of 68 farms were banned from delivering milk to dairies for shorter or longer periods. The maximum level of aflatoxin M1 in a single sample from an individual farm was 257 ng kg,1 fresh milk. RESULTS: Aflatoxin analyses of commercial compound feed revealed that the contamination originated from the ingredient rice feed meal, a by-product from the preparation of Basmati rice for human consumption. Up to 56 µg kg,1 of aflatoxin B1 was found in rice feed meal at one feed mill. CONCLUSION: The present example shows that an aflatoxin-contaminated minor feed ingredient included at less than 10% (w/w) of compound cattle feed can significantly contaminate the milk produced. This emphasises the need for effective monitoring of the feed chain of food-producing animals in order to prevent food contamination. Copyright © 2008 Society of Chemical Industry [source] Time-Course and Mechanisms of Restored Vascular Relaxation by Reduced Salt Intake and Angiotensin II Infusion in Rats Fed a High-Salt DietMICROCIRCULATION, Issue 3 2009SCOTT T. MCEWEN ABSTRACT Objective: This study determined the mechanisms and time-course of recovery of vascular relaxation in middle cerebral arteries (MCAs) of salt-fed Sprague-Dawley rats returned to a low-salt (LS) diet (0.4% NaCl) or infused with low-dose angiotensin II (ANG II). Methods: Rats were fed a high-salt (HS) diet (4% NaCl) for 3 days or 4 weeks before returning to an LS diet for various periods. Other rats fed a HS diet (HS+ANG II) received a chronic (3 days) intravenous (i.v.) infusion of a low dose of ANG II (5 ng kg,1 min,1) to prevent salt-induced ANG II suppression. Results: The HS diet eliminated the increase in cerebral blood flow in response to acetylcholine (ACh) infusion and the relaxation of MCA in response to ACh, iloprost, cholera toxin, and reduced PO2. Recovery of vascular relaxation was slow, requiring at least 2 weeks of the LS diet, regardless of the duration of exposure to a HS diet. Hypoxic dilation was mediated by cyclo-oxygenase metabolites and ACh-induced dilation was mediated via nitric oxide in LS rats and in HS rats returned to the LS diet or receiving ANG II infusion. Conclusions: Returning to a LS diet for 2 weeks or chronic 3-day ANG II infusion restores the mechanisms that normally mediate cerebral vascular relaxation. [source] Cholecystokinin octapeptide increases rectal sensitivity to pain in healthy subjectsNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2002J-M. Sabaté Abstract, Hypersensitivity during rectal distension has been demonstrated in irritable bowel syndrome (IBS). Studies performed in animals and indirect data in humans suggest that cholecystokinin (CCK) could modulate visceral sensations. The aim of this study was to assess the effects of i.v. infused sulphated cholecystokinin octapeptide (CCK-OP) on rectal sensitivity in response to distension. In eight healthy subjects, rectal sensitivity and compliance were determined during a randomized double-blind study, with four sessions each separated by 7 days. Sensory thresholds and rectal compliance were assessed during slow-ramp (40 mL min,1) and rapid-phasic distensions (40 mL s,1, 5 mmHg stepwise, 1-min duration), and were compared before and during continuous infusion of either saline or CCK-OP at 5, or 20 or 40 ng kg,1 h,1. During rapid phasic distension but not during slow ramp distension, CCK-OP at 40 ng kg,1 h,1 produced a significant decrease in sensory thresholds compared with the basal period. Rectal compliance was not modified by any infusion. At pharmacological doses, CCK-OP decreases sensory thresholds during rapid phasic distension that may preferentially stimulate serosal mechanoreceptors, but has no effect on mucosal mechanoreceptors stimulated during slow ramp distensions. Modulation of rectal sensitivity by CCK could be implicated in the pathogenesis of the rectal hypersensitivity observed in IBS. [source] Secretin induces variable inhibition of motility in different parts of the Australian possum sphincter of OddiNEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2001B. O. Al-Jiffry The sphincter of Oddi (SO) may not function as a single structure. We aimed to determine the response of the proximal and distal segments of the bile duct (BD-SO) and pancreatic duct (PD-SO) components of the SO to secretin, with and without neural blockade with tetrodotoxin (TTX). In anaesthetized Australian possums, separate manometry catheters were placed in the proximal and distal BD-SO or PD-SO segments to record motility. Secretin, 50,1000 ng kg,1, was administered, followed by TTX, and re-administration of secretin, 500 and 1000 ng kg,1. Changes in the motility index (MI, frequency × mean amplitude) were determined. Statistical analysis utilized repeated-measures ANOVA. Secretin produced a dose-dependent decrease in MI from the proximal and distal BD-SO and PD-SO (all P < 0.001). The maximum inhibition, at 1000 ng kg,1, was 21 ± 4%, 33 ± 6% and 42 ± 5% of control (mean ± SEM), for proximal and distal BD-SO, and distal PD-SO, respectively. The proximal PD-SO MI, however, was inhibited to 62 ± 6% of control, at 1000 ng kg,1. TTX enhanced the secretin-induced response to the same level at the four sites (P < 0.02). We conclude that secretin inhibits the motility of the possum SO in a nonuniform manner and is modulated by neural activity. [source] Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurementsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2000P.-O. Grände Background: The endogenous substance prostacyclin is a substance with the potential to improve microcirculation and oxygenation around contusions in the brain following a head trauma by its vasodilatory, antiaggregatory and antiadhesive effects. Microdialysis measurements of local concentrations of selected interstitial substances in the brain, and measurements of venous jugular bulb oxygenation reflecting overall brain oxygenation, might be useful to evaluate possible therapeutic effects of a specific therapy, such as treatment with prostacyclin. Methods: This case report study on six patients, of whom five were given prostacyclin, includes cerebral microdialysis measurements of interstitial lactate (n=5), pyruvate (n=3), glycerol (n=5) and glucose (n=4), and is combined with measurements of venous jugular bulb oxygenation in three of the patients. One microdialysis catheter was placed adjacent to a contusion, and in four of the patients another catheter was also placed in the contralateral less injured side for comparison. Low-dose prostacyclin infusion (0.5,1.0 ng kg,1 min,1) was started when lactate concentrations in the more injured side was raised at a constant level for more than 10 h. The study also includes one patient used as control to whom no prostacyclin was given. Results: Lactate was markedly lower in the less injured than in the more injured area of the brain. During the prostacyclin infusion elevated lactate and lactate/pyruvate ratio were reduced. Elevated glycerol decreased, a low glucose increased and jugular bulb blood oxygenation increased following start of prostacyclin. The control patient showed an increase in lactate and lactate/pyruvate ratio. Conclusion: The microdialysis data combined with the jugular bulb oxygenation data indicated that low-dose prostacyclin exerts effects compatible with improved oxygenation and reduced cell damage in the severely traumatised brain. [source] Assessment of estradiol and its metabolites in meatAPMIS, Issue 1 2001D. MAUME Most studies related to research on steroids in main edible tissues (muscle, liver or kidney) have focused on measurement of parent or major metabolite residues. In order to evaluate the estradiol content in bovine edible tissues, a multi-step extraction procedure was developed in conjunction with parallel metabolism studies of [14C],17,-estradiol in cattle (1,2). Various classes of free estradiol and conjugates were separated: estradiol ,17, and ,17,, estradiol-17-fatty acid esters, estradiol 17-glycoside, estradiol 3,glucuronide, estradiol,17-glycoside and 3- glucuronide (diconjugates) were separated. No sulphates conjugated forms have been found at the detection level of the method. The quantification was realized by calibration with deuterated 17, -estradiol -d3 standard and was validated at the ng kg,1 (ppt) level. Muscle, liver, kidney and fat samples from control or Revalor S® single (licensed implantation) or multi-implanted steers have been assayed. The results show a wide variation between animals, but both the highest value and the mean of total estradiol content in each group proportionally increase from untreated to multi-implanted animals. In accordance with international rules, a calculation of the daily food supply of estradiol by such edible tissues in comparison with the acceptable daily intake was performed. [source] Adrenaline hypothesis: effect of formoterol on noradrenaline releaseAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 5 2001E. Maignan Summary 1 Originally, the so-called `adrenaline hypothesis' related the release of noradrenaline (NA) to stimulation of presynaptic ,2 -receptors in nerve endings; now it confers a possible role to adrenaline taken up then released by nerves endings. It represents a potentially useful therapeutic pathway. The present study aims to investigate the effects of formoterol, a highly selective ,2 -adrenoceptor agonist. 2 It was carried out in freely moving rats, the isotope dilution technique being used to measure the NA spill over rate (NA-SOR) and metabolic clearance rate (MCR). 3 A series of three results are reported. (a) When compared with adrenaline on equimolar basis, formoterol (2.3 ,g kg,1 min,1) increased NA-SOR while mean arterial blood pressure was decreased and heart rate increased. Thus, it was difficult to separate a direct presynaptic effect from indirect baroreflex-dependent activation of the sympathetic system. (b) When formoterol was infused at 1 ng kg,1 min,1, a dose empirically defined to induce no haemodynamic effect, NA-SOR was significantly increased, while NA-MCR remained unchanged. (c) The NA-SOR response to formoterol was not amplified by the presynaptic ,2 -adrenoceptor blocker, yohimbine, in contrast to the NA-SOR response to adrenaline. 4 In conclusion, formoterol, a ,2 -adrenoceptor agonist, is shown to increase the release and plasma concentration of NA while its clearance was not changed. [source] Effects of sepsis on mast cells in rat dura mater: influence of L -NAME and VIPBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2001F Tore The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. Three different populations of mast cells were identified in control rats: connective tissue type mast cells (CTMC) which contain rat mast cell protease1 (RMCP1), histamine, serotonin and heparin, mucosal type mast cells (MMC) which contain RMCP2, histamine and serotonin, and intermediate type which contains both RMCP1 and RMCP2 and probably various proportions of amines and heparin. LPS (25 mg kg,1 i.p.) caused changes in the proportions of the various types of mast cells. The number of MMC and intermediate type mast cells significantly increased and the number of mast cells immunopositive for both heparin and serotonin significantly decreased. Biochemical analysis showed that the histamine concentration of dura increased while its serotonin concentration decreased. While vasoactive intestinal peptide (VIP) (25 ng kg,1 i.p.) appears to potentiate LPS effects on dura mater mast cells, non-selective inhibition of nitric oxide (NO) synthase by Ng -nitro- L -arginine methyl ester (L -NAME) (30 mg kg,1 i.p.) did not influence sepsis-induced mast cell changes. These findings suggest that mast cells of dura mater may play a role in brain protection during sepsis. British Journal of Pharmacology (2001) 134, 1367,1374; doi:10.1038/sj.bjp.0704412 [source] Antagonism of AT2 receptors augments Angiotensin II-induced abdominal aortic aneurysms and atherosclerosisBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Alan Daugherty We have recently demonstrated that chronic infusion of Angiotensin II into apoE,/, mice promotes the development of abdominal aortic aneurysms. To determine the involvement of specific Angiotensin II receptors in this response, we co-infused Angiotensin II (1000 ng kg,1 min,1 for 28 days) with losartan (30 mg kg,1 day,1) or PD123319 (3 mg kg,1 day,1) to antagonize AT1 and AT2 receptors, respectively. Infusion of Angiotensin II promoted the development of abdominal aortic aneurysms in 70% of mature female apoE,/, mice. The formation of aortic aneurysms was totally inhibited by co-infusion of Angiotensin II with losartan (30 mg kg,1 day,1; P=0.003). In contrast, the co-infusion of Angiotensin II with PD123319 resulted in a marked increase in the incidence and severity of aortic aneurysms. To determine whether AT2 antagonism also promoted Angiotensin II-induced atherosclerosis, Angiotensin II was infused into young female apoE,/, mice that had little spontaneous atherosclerosis. In these mice, co-infusion of PD123319 led to a dramatic increase in the extent of atherosclerosis. This increase was associated with no change in plasma lipid concentrations and only transient and modest increases in blood pressure during co-infusion with PD123319. While antagonism of AT1 receptors totally prevented the formation of aneurysms, antagonism of AT2 receptors promoted a large increase in the severity of Angiotensin II-induced vascular pathology. British Journal of Pharmacology (2001) 134, 865,870; doi:10.1038/sj.bjp.0704331 [source] | |||||||||||||