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P Nellgård

Publications and source records attributed to P Nellgård.

17 recordsLinked to original sources
PubMed2006

Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury.

OBJECTIVE: We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. METHODS: Patients with severe TBI (n = 39, Glasgow Coma Scale score 2,126 pg/mL on days 2 to 3 discriminated between dead and alive (sensitivity of 100% and a specificity of 81%). A vCSF total tau level of >702 pg/mL on days 2 to 3 discriminated between bad (GOSE 1 to 4) and good (GOSE 5 to 8) outcome (sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. CONCLUSION: The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury (TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.

Adolescent↗
PubMed2002

Effect of inositol-trisphosphate on fluid transport and protein extravasation in the obstructed small bowel.

BACKGROUND: Small-bowel obstruction is characterized by accumulation of fluid in the obstructed intestine. A pronounced inflammation in the obstructed gut wall has been shown to play an important role in the pathogenesis of the profuse fluid losses. alpha-Trinositol (D-myo-inositol-1,2,6-trisphosphate; PP56) has potent anti-inflammatory as well as antisecretory properties. The effects of alpha-Trinositol on inflammation and fluid losses in the obstructed small intestine are examined. METHODS: A total obstruction of the proximal part of the rat jejunum was induced during 18 h by thread ligation. A small segment of the obstructed intestine, with intact vascular and nervous supply, was placed in a chamber suspended from a force displacement transducer allowing for continuous registration of net fluid transport on a Grass polygraph. Three groups were included. One group (n = 12) received low-dose alpha-Trinositol (bolus: 2 mg kg(-1); IV infusion: 10 mg kg(-1) min(-1)), a second group (n = 10) received high-dose alpha-Trinositol (bolus: 12 mg kg(-1); IV infusion: 60 mg kg(-1) min(-1)), while a control group (n = 9) received corresponding volumes of isotonic saline (bolus: 0.5 ml; IV infusions 15 microl min(-1)). Quantitative measurement of extra-vasated Evans blue albumin in the obstructed jejunum was used as a marker of inflammation. RESULTS: High-dose alpha-Trinositol induced a significant (P < 0.001) inhibition of net fluid secretion, while low-dose alpha-Trinositol had no significant effect versus saline. In contrast, both doses of alpha-Trinositol induced significant inhibition of EB-albumin leakage (P < 0.05). CONCLUSION: High-dose alpha-Trinositol is a potent inhibitor of fluid secretion in obstructive ileus, most probably involving an anti-inflammatory mechanism.

Animals↗
PubMed1998

Topical local anaesthetics (EMLA) inhibit burn-induced plasma extravasation as measured by digital image colour analysis.

Amide local anaesthetics have previously been shown to reduce oedema and improve dermal perfusion following experimental burns. Previous studies have used invasive techniques for burn oedema quantification which do not allow continuous monitoring in the same animal. The present study used digital image colour analysis to investigate the effect of topical local anaesthetics on burn-induced extravasation of Evans blue albumin. A standardised full-thickness burn injury (1 x 1 cm) was induced in the abdominal skin of anaesthetised rats. The burn area was subsequently covered with 0.5 g of lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA, ASTRA, Sweden) or placebo cream during the first hour post-burn. One hour after the burn trauma, animals received Evans blue dye intravenously. Skin colour appearances were recorded by macrophotography before the burn and 5, 60. 65, 90, 120, 150, and 180 min post-burn. Colour slides were digitised and colour changes were analysed using the normalised red-green-blue (n-rgb) colour system. Results showed a significant inhibition of Evans blue extravasation between 60 and 180 min post-burn in EMLA-treated animals versus controls. Topical local anaesthetics are potent inhibitors of burn-induced plasma albumin extravasation, probably by direct action on vascular permeability and by inhibition of various steps of the pathophysiological response after burn injury.

Administration, Topical↗
PubMed1996

Effects of D-myo-Inositol-1,2,6-triphosphate on eicosanoid formation in burned skin.

D-myo-Inositol-1,2,6-triphosphate (IP3) has been shown to reduce edema and progressive ischemia following experimental skin burns. The mechanism(s) are not identified but could be related to antiinflammatory effects of the agent. In the present ex vivo study we compared the effects of IP3 with those of saline and indomethacin on eicosanoid formation by normal and burned rat skin. In burned skin IP 3 treatment reduced the release of thromboxane B2 (TXB2) (P < 0.01) and leukotriene B4 (LTB 4) (P < 0.05) but there was only a weak trend for less prostaglandin E (PGE) compared to burned control animals receiving saline. Indomethacin reduced the release of TXB2 (P < 0.01), and PGE (P < 0.001), but not LTB 4 from burned skin compared to skin from saline-treated burned animals. In non-burned skin IP 3 increased the release of PGE (P < 0.01) and LTB 4 (P < 0.01), but did not significantly influence TXB2 accumulation in the incubation fluid compared to the saline-treated group. Indomethacin reduced the release of TXB2 (P < 0.001) and PGE (P < 0.001), but increased LTB 4 (P < 0.001) in normal skin compared to the saline-treated group. In conclusion, IP 3 inhibited the release of TXB2 and LTB 4 from burned skin ex vivo, but increased PGE and LTB 4 release from normal skin. These results suggest that the mode of action of IP 3 differs from that of nonsteroidal antiinflammatory drugs. The effects of IP 3 on the arachidonic acid cascade also seem to differ in burned versus normal skin.

Animals↗
PubMed1996

Small-bowel obstruction and the effects of lidocaine, atropine and hexamethonium on inflammation and fluid losses.

BACKGROUND: The profuse fluid losses and morbidity of patients suffering from obstructive ileus are closely related to inflammatory changes in the obstructed bowel wall. Previous experimental studies have shown that use of steroids and NSAIDs can reduce fluid losses in obstructive ileus. In the present study, we investigated the effects of lidocaine on fluid losses since local anesthetics have been shown to possess wide and potent anti-inflammatory properties. Hexamethonium and atropine were used to study the importance of the autonomic nervous system in bowel obstruction. METHOD: Experiments were performed in rats in vivo. After 18 h of total obstruction of the jejunum by thread ligation, a segment of the obstructed jejunum was placed in a chamber with intact nervous and vascular supply and net fluid transport was continuously registered by a gravimetric technique. Extravasation of Evans blue albumin as marker of inflammation was quantified by spectrophotometry. RESULTS: Hexamethonium (10 mg.kg-1 i.v.) significantly inhibited net fluid secretion (P < .05), while atropine (0.25 mg.kg-1 i.v.) had no significant effect. Net fluid secretion was reversed into absorption following an intravenous bolus dose of lidocaine (2 mg.kg-1) (P < 0.01) and topical administration of lidocaine (20 mg) on the serosa of the obstructed gut (P < 0.01). Single topical administration of lidocaine (20 mg) immediately before ligation significantly reduced net fluid secretion (P < 0.05) and inflammation (P < 0.05) in the obstructed bowel 20 h post-ligation compared to obstructed controls. CONCLUSION: Lidocaine significantly inhibited or prevented fluid losses when administered intravenously or topically to the obstructed gut. Mechanisms of action could be inhibition of nerve reflexes involved in fluid secretion and by inhibition of inflammation in the bowel wall. The inhibition of fluid losses by hexamethonium further supports the importance of the autonomic nervous system in the pathophysiology of bowel obstruction.

Administration, Topical↗
PubMed1995

Importance of vasoactive intestinal peptide and somatostatin for fluid losses in small-bowel obstruction.

BACKGROUND: Previous observations have shown vasoactive intestinal peptide (VIP) to be an important secretagogue in the gut, whereas somatostatin has been reported to inhibit VIP release and fluid secretion. METHODS: The possible role of VIP as mediator of the inflammation and fluid losses in obstructive ileus was investigated in vivo and in a chronic rat model with thread ligation of the jejunum. Extravasated Evans blue (Eb)-stained albumin was quantified by spectrophotometry. Net fluid secretion was measured by a gravimetric technique. VIP antiserum was used to inhibit the effects of endogenous VIP. A somatostatin analogue, octreotide, was used to inhibit the release of VIP. RESULTS: Results showed a pronounced plasma Eb-albumin extravasation in the wall of the obstructed gut, which was significantly inhibited by VIP antiserum (p < 0.05) or octreotide (p < 0.01). Obstruction of the jejunum resulted in net fluid secretion that was significantly reduced by administration of octreotide (p < 0.01) or VIP antiserum (p < 0.05). Net fluid secretion in control animals remained constant. CONCLUSIONS: These findings suggest that VIP is an important mediator of the pathophysiology in mechanical intestinal obstruction and that somatostatin may be involved in the endogenous control of fluid losses.

Animals↗
PubMed1995

Influence of adrenoceptor agonists and antagonists on fluid secretion in small bowel obstruction.

OBJECTIVES: To investigate the importance of adrenoceptors on fluid losses in small bowel obstruction. DESIGN: Evaluation of the effects of adrenergic agonists and antagonists on in-vivo net fluid secretion in chronic small bowel obstruction in rats. METHODS: Net fluid transport in a jejunal segment was continuously registered in vivo after 18 h of mechanical obstruction of the small bowel in anaesthetized rats. The effect on net fluid transport of adrenoceptor agonists and antagonists and of isotonic saline was quantified. RESULTS: Clonidine, an alpha 2-agonist, had a significant (P < 0.05) anti-secretory effect, while yohimbine, an alpha 2-antagonist, significantly (P < 0.05) increased net fluid secretion. Phenylephrine, an alpha 1-agonist, and prazosin, an alpha 1-antagonist, lacked significant effects on net fluid transport. Similarly, prenalterol, a beta 1-agonist, and metoprolol, a beta 1-antagonist, had no significant effect on the net fluid transport. The beta 2-agonist salbutamol significantly (P < 0.001) decreased net fluid secretion, while the beta-antagonist propranolol significantly (P < 0.001) decreased net fluid secretion. CONCLUSION: Activation of alpha 2-adrenoceptors and blockade of beta 2-adrenoceptors significantly reduce net fluid secretion in small bowel obstruction. Results also demonstrate a continuous stimulatory effect on fluid secretion mediated by beta 2-receptors and a continuous inhibitory effect mediated by alpha 2-receptors.

Adrenergic Agonists↗
PubMed1994

Adrenergic, cholinergic and VIP-ergic influence on gastric phasic motility in the rat.

We investigated the effects of adrenergic, cholinergic and vasoactive intestinal polypeptide (VIP)-ergic agonists and antagonists on the amplitude of gastric phasic contractions in the anaesthetized rat using a volumetric model. The amplitude of the phasic contractions was reduced significantly by atropine, hexamethonium or bilateral cervical vagotomy indicating that cholinergic neural activity involving both muscarinic and nicotinic receptors and intact vagal nerve function are integral parts of the control of basal gastric phasic motility. In contrast, neither selective alpha 1-, alpha 2- or non-selective beta-blockers had any significant influence on the amplitude of the gastric contractions suggesting that adrenergic neurones are not tonically active in the maintenance of basal phasic motility in the stomach. The amplitude of the gastric phasic contractions was, however, significantly reduced by the alpha 1-agonist L-phenylephrine, the alpha 2-agonist clonidine and a close intraarterial injection of VIP (3 micrograms kg-1) but not be the selective beta 1-agonist, prenalterol, or the beta 2-agonist, salbutamol. These data suggest the presence of superimposed inhibitory control of phasic activity by VIP-ergic stimulation and by adrenergic neurones via alpha-receptor stimulation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1993

Involvement of vasoactive intestinal polypeptide in gastric reflex relaxation.

We have previously presented evidence for a non-adrenergic, vagally mediated colono-gastric inhibitory reflex induced by distension of the colon. We also found that pain stimulation by putting pressure on a testicle induced a pronounced gastric relaxation mediated by both adrenergic and vagal non-adrenergic fibres in anesthetized rats. Previous in vitro studies by other workers have strongly indicated that vasoactive intestinal polypeptide (VIP) is a neural mediator of gastric relaxation. The aim of the present in vivo study was to investigate, in anesthetized rats, whether VIP is involved in the gastric reflex relaxation induced by colonic distension and pain stimulation. A volumetric method was used to monitor changes in gastric volume. Gastric reflex relaxation following colonic distension was significantly and markedly inhibited by VIP antiserum as compared to the control relaxation before administration of the antiserum. Non-immunized control serum did not significantly influence gastric relaxation caused by colonic distension. Pain-induced gastric relaxation was moderately but significantly reduced after the administration of VIP antiserum but not after control serum. The selective beta 2-adrenoceptor agonist, salbutamol, induced a pronounced gastric relaxation of the same magnitude before and after the administration of VIP antiserum. VIP antiserum changed the pattern of gastric motility by inducing a specific type of gastric contraction appearing spontaneously or in response to colonic distension. A close intra-arterial injection of VIP induced gastric relaxation and inhibition of phasic gastric contractions. The present results in the rat suggest that VIP or a VIP-like peptide is involved in gastric reflex relaxation induced by colonic distension and pain stimulation.

Animals↗
PubMed1993

Inflammation as a major cause of fluid losses in small-bowel obstruction.

The importance of inflammation for fluid losses in obstructive ileus was investigated in vivo in the rat. Inflammation was quantified by spectrophotometry of extravasated Evans blue (Eb)-albumin. Net fluid secretion in the obstructed jejunum was measured by a continuous gravimetric technique. The inflammation in the obstructed gut wall was significantly more pronounced than that in the gut distal to the obstruction and the sham-obstructed gut. The inflammation was significantly more pronounced in the serosa and external muscle layer than in the mucosa-submucosa. Acid-base balance in obstructed animals showed a significant metabolic alkalosis, whereas serum albumin and electrolytes were normal. Lumen fluid in obstructed animals showed low levels of albumin and total calcium as compared with serum, whereas fluid from the peritoneal cavity of obstructed rats showed high contents of albumin. Indomethacin and hydrocortisone given intravenously to obstructed animals significantly reduced the degree of extravasated Eb-albumin in the obstructed gut wall. Sham-operated animals showed net fluid absorption, whereas obstructed rats showed net fluid secretion. Secretion in obstructed animals was in all cases reversed into net fluid absorption after intravenous administration of indomethacin and hydrocortisone. These findings suggest that a pronounced inflammation occurs in the wall of the obstructed small intestine and that this inflammation plays an important role in the pathogenesis of the profuse fluid losses of obstructive ileus.

Analysis of Variance↗
PubMed1992

Pain-induced inhibition of gastric motility is mediated by adrenergic and vagal non-adrenergic reflexes in the rat.

Painful stimuli have been shown to inhibit gastric motility in animal experiments and delay gastric emptying in humans. The aim of the present study was to investigate in detail mechanisms involved in pain-induced gastric inhibition. Pain stimulation by exerting pressure on a testicle induced a prompt gastric relaxation which lasted throughout the period of stimulation. Pain-induced gastric relaxation was significantly reduced by the selective alpha-1 blocker, prazosin, and by the non-selective beta-blocker, propranolol. Similarly pain-induced inhibition of gastric tone was significantly reduced by bilateral cervical vagotomy. In contrast, gastric relaxation following pain stimulation was significantly potentiated by the selective adrenergic alpha-2 blocker, yohimbine. Combined administration of prazosin and propranolol followed by bilateral cervical vagotomy abolished gastric relaxation in response to pain stimulation. In conclusion, gastric relaxation in response to painful stimulation was found to be reflex-mediated via sympathetic neurons acting on alpha-1 and beta receptors and possibly also via vagal non-adrenergic fibres. Pain-induced inhibition of gastric tone was significantly increased by yohimbine. It is suggested that yohimbine by blocking presynaptic inhibitory receptors on adrenergic neurons facilitates the release of noradrenaline in response to pain stimulation.

Anesthesia↗
PubMed1991

Effects of selective adrenergic agonists and antagonists on gastric tone in the rat.

The aim of the present in vivo study was to investigate in anaesthetized rats, the effects of selective adrenergic agonists and antagonists on basal gastric tone and phasic contractions by the use of a volumetric method. L-phenylephrine, an alpha-1 agonist, induced hypertension, bradycardia and a significant gastric relaxation. Clonidine, an alpha-2 agonist, caused hypotension, bradycardia and a significant gastric contraction and a reduction of the amplitude of phasic contractions. Salbutamol, a beta-2 agonist, induced a dose-dependent tachycardia and a significant inhibition of gastric tone whereas prenalterol, a beta-1 agonist, induced tachycardia without any significant influence on gastric basal tone. Yohimbine, an alpha-2 blocker, significantly decreased gastric basal tone and reversed the inhibition of phasic contractions induced by clonidine. Prazocine, a selective alpha-1 blocker, and propranolol, a non-selective beta-blocker, had no significant influence on gastric basal tone or phasic contractions. It is concluded that sympathetic inhibition of basal gastric tone in the rat is mediated by alpha-1 and beta-2 adrenergic receptors. Activation of alpha-2 adrenergic receptors significantly increased basal gastric tone and reduced the amplitude of phasic contractions. A blockade of alpha-2 receptors significantly decreased basal gastric tone and restored the amplitude of phasic contractions.

Adrenergic alpha-Agonists↗
PubMed1990

Amide local anesthetics reduce albumin extravasation in burn injuries.

Burn injury was induced in anesthetized rats by exposing the abdominal skin to a temperature of 55 degrees C by means of a hot aluminum rod. Temperature was registered on a Grass polygraph. Skin exposure was interrupted when hot rod temperature had decreased to 45 degrees C. A full-thickness burn trauma of the skin was induced as judged from histologic sections. The burned skin was dissected and extravasation of Evans blue (EB) bound plasma albumin was quantified by a spectrophotometric technique and visualized by fluorescence microscopy. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g; EMLA) for 1.5 h starting 15 min after inducing the burn injury. In one control group (n = 14) the thermal injury was treated with placebo cream. A second control group (n = 15) was topically treated with placebo cream without being exposed to thermal trauma. Results showed a significant inhibition of EB-albumin extravasation in the skin of burned rats treated with lidocaine-prilocaine cream compared with placebo-treated burned skin (P less than 0.001). EB-albumin contents in the skin of burned rats treated with lidocaine-prilocaine cream did not differ significantly from unburned skin (P greater than 0.05). In the second set of experiments continuous iv lidocaine infusions at a rate of 5 (n = 10), 10 (n = 12), 20 (n = 10), or 30 (n = 10) micrograms.kg-1.min-1 was given.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMedDate not supplied

Reduced albumin extravasation in experimental rat skin and muscle burn injury by D-myo-inositol-1,2,6-trisphosphate treatment.

This study investigated the effects of the anti-inflammatory agent D-myo-inositol-1,2,6-trisphosphate (IP3) on burn edema. Two sets of experiments were performed. In the first set, a full-thickness burn injury was induced in the abdominal skin of anesthetized rats. Postburn intravenous treatment was given with IP3, indomethacin or saline solution. Extravasation of Evans blue albumin in the burned tissue was quantified by a spectrophotometric technique. Results showed significant inhibition of albumin extravasation by IP3 in three of five different doses compared to saline-treated animals. In the second set of experiments, a deep full-thickness burn through the abdominal skin and rectus muscle was induced. The therapeutic window of IP3 could be more well-defined. Resulted showed a significant reduction of albumin extravasation in the skin at all four dose levels and in the abdominal muscle at three of four doses. Indomethacin had no significant effect on postburn edema formation. The mechanisms responsible for the inhibition of albumin leakage by IP3 could be secondary to reduced formation of edema-promoting inflammatory mediators by the agent, resulting in improved vascular patency.

Albumins↗
PubMedDate not supplied

Local anesthetics improve dermal perfusion after burn injury.

Deep partial-thickness burn injury was induced in the abdominal skin of anesthetized rats. Dermal perfusion was assessed by laser Doppler flowmetry. In the first set of experiments, one group of rats (n = 15) was topically treated with a lidocaine-prilocaine cream 5% (25 mg of each in 1 g) for 6 hours, starting 5 minutes after inducing the burn injury. In one control group (n = 14), the thermal injury was treated with placebo cream. Results showed a markedly reduced perfusion in the skin of the control animals within the first hour after burn injury, with further decrease during the following 5 hours of observation. In animals treated with the lidocaine-prilocaine cream, skin perfusion in the burned area was significantly increased during the first 30 minutes after the burn injury compared to before the burn (p < 0.01), followed by a decrease to a level below the preburn stage but significantly higher than that of control animals during the first hour after burn injury (p < 0.05). As opposed to burned control animals, skin perfusion gradually recovered toward preburn levels at the end of the experiment in local anesthetic-treated animals. In the second experimental set, four groups of animals were burned and subsequently treated with a bolus dose of lidocaine intravenously (2 mg/kg), followed by continuous intravenous lidocaine infusions at a rate of 50 (n = 10), 100 (n = 11), or 150 (n = 10) micrograms.kg-1.min-1. The infusions were started 5 minutes after the burn injury and lasted for 6 hours. Corresponding volumes of saline solution were given to burned control animals (n = 10). Results showed a significantly improved skin perfusion in the lidocaine-treated group in a dose-response fashion as compared to control animals. A maximum improvement of dermal perfusion in the burned area was induced by intravenous lidocaine at an infusion rate of 150 micrograms.kg-1.min-1 as compared to burned controls treated with isotonic saline solution infusions (p < 0.01). Results showed that topical or systemic administration of local anesthetics can prevent progressive dermal ischemia after thermal injury.

Administration, Topical↗