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Per Vaagenes

Publications and source records attributed to Per Vaagenes.

10 recordsLinked to original sources
PubMed2006

Seven days' around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes.

Both exhaustive physical exertion and starvation have been reported to induce depression of immune function. The aim of the present study was to investigate the inflammatory environment and state of activation and mediator-producing potential of circulating leukocytes during prolonged physical activity with concomitant energy and sleep deprivation. Eight well-trained males were studied during 7 days of semi-continuous physical activity. Sleep was restricted to about 1 h/24 h, energy intake to 1.5- 3.0 MJ/24 h. Blood was drawn at 07.00 A.M.: on days 0, 2, 4, and 7. Plasma levels of inflammation markers were measured. The response of circulating leukocytes to lipopolysaccharide (LPS; 1 microg mL(-1)), and the effect of added hydrocortisone (10 and 100 nmol L(-1)), were measured in the supernatant after 3 h of incubation in an ex vivo whole blood model. Activation of leukocytes steadily increased as measured by plasma matrix metalloproteinase-9, tumour necrosis factor-alpha, interleukin-1beta, and interleukin-6. Inhibitors of systemic inflammation were either unaltered (tissue inhibitor of matrix metalloproteinase-1) or elevated (plasma interleukin-1 receptor antagonist). Cortisol levels increased on days 2 and 4, but thereafter reverted to baseline values. The leukocytes responded to LPS activation with increasing release of inflammatory cytokines throughout the study period. The anti-inflammatory potency of hydrocortisone decreased. Prolonged multifactorial stress thus activated circulating immune cells and primed them for an increased response to a subsequent microbial challenge.

Adult↗
PubMed2005

[Brominated flame retardants may cause brain injuries in the fetus and the newborn].

BACKGROUND: Brominated flame retardants are incorporated into an ever-increasing number of ordinary consumer goods, which has lead to pollution of the environment, wildlife, food of animal origin, and human blood, adipose tissue, and mother's milk. This group of chemicals has a striking structural similarity with the thyroid hormones and may constitute a potential health risk by interfering with thyroid hormone homeostasis. MATERIAL AND METHODS: We focus on these features and discuss possible clinical consequences, on the basis of Medline searches and our own experience. RESULTS: The thyroid hormones are essential for normal brain development. Disruption of the hormonal balance may lead to serious and permanent defects of neurological functioning. Brominated flame retardants may interfere with thyroid synthesis, transport, receptor binding, and elimination. The clinical consequences have so far not been firmly established, but results from animal studies suggest that even subtle disturbances of thyroid homeostasis during pregnancy may have serious implications for the developing brain. INTERPRETATION: Numerous scientific reports confirm the neurotoxic potential of these chemicals. The foetus and newborn are especially vulnerable.

Animals↗
PubMed2005

N-Acetylcysteine administered as part of the immediate post-traumatic resuscitation regimen does not significantly influence initiation of inflammatory responses or subsequent endotoxin hyporesponsiveness.

Polytrauma and resuscitative efforts induce extensive alterations in the host's internal environment and cellular responses that may be a serious threat to these patients. Administration of exogenous thiols has been recommended to modulate the post-traumatic inflammatory responses. In this study, we have investigated the effect of N-acetylcysteine (NAC) on the early markers of leukocyte activation and subsequent endotoxin hyporesponsiveness. Twenty-eight pigs were exposed to a standardized gunshot injury. First aid treatment and initial life saving surgery was started without delay. One group (n = 14) was randomised to receive NAC 200 mg kg(-1) over 20 min, the remaining group was given the same volume of vehicle. Blood samples drawn at time points 0 and 75 min were also studied in vitro and stimulated with LPS or LPS plus NAC. Selected physiologic variables and degree of organ injury were equal in both groups. TNF-alpha, IL-1beta, and reactive oxygen species (ROS) tended to be lower in the NAC-group (NS). In vitro, NAC significantly reduced the release of the same cytokines after the LPS challenge in blood drawn before injury. NAC did not influence post-traumatic endotoxin tolerance. Adding NAC to the immediate resuscitation fluid did not influence the early post-traumatic organ injury, and initiation of inflammatory responses significantly, or endotoxin tolerance. In vitro, NAC significantly reduced proinflammatory cytokine release, but only in normal blood. The clinical value of this treatment regimen is probably restricted, both due to the unfavourable post-traumatic internal environment and imposed dosing limitations.

Acetylcysteine↗
PubMed2005

Chronic glycine treatment inhibits ligature-induced periodontal disease in Wistar rats.

OBJECTIVE: Dysregulation of immune and stress responses plays a significant role for the development and progression of inflammatory diseases, including periodontal disease. The non-essential amino acid glycine modulates immune and central nervous system (CNS) responses, and has been shown to beneficially affect tissue destructive inflammatory conditions. The purpose of this study was to test the ability of orally administered glycine to influence periodontal disease progression, as well as immune and hypothalamic-pituitary-adrenal (HPA) responses following lipopolysaccharide stimulation. METHODS: Glycine was supplied in the drinking water during the whole experiment to male Wistar rats, starting 3 days before the induction of experimental ligature-induced periodontal disease. Control rats were given tap water only. The periodontal breakdown was assessed after the ligatures had been in place for 34 days. Following intraperitonal lipopolysaccharide stimulation, concentrations of the proximal cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-10, as well as the HPA axis-derived hormone corticosterone, were measured in blood serum. RESULTS: Orally administered glycine significantly reduced periodontal bone loss as measured by digital X-rays (p = 0.007). Bone loss was negatively correlated with increased serum glycine, whereas no significant relationship was found with TNF-alpha, interleukin-10, or corticosterone. CONCLUSION: Chronic ingestion of glycine supplied in the drinking water significantly reduced periodontal bone loss. No effect of glycine on immune and HPA-axis responses was revealed. Further studies are needed to clarify the mechanisms of action.

Alveolar Bone Loss↗
PubMed2004

[Glycine].

BACKGROUND: Glycine is an essential component of important biological molecules, a key substance in many metabolic reactions, the major inhibitory neurotransmitter in the spinal cord and brain stem, and has anti-inflammatory, cytoprotective, and immunomodulatory qualities. MATERIAL AND METHODS: Based on available literature we discuss some important biological properties of glycine and give a short account of our own studies in this field. RESULTS: The main area of glycine research has traditionally been associated with its role as a neurotransmitter in the central nervous system. During the last few years there has been a mounting interest in effects on other organs and tissues as well. Glycine-gated chloride channels, originally demonstrated on neurons in the central nervous system, have been found on most leukocytes and a number of other cell types. This has provided a unifying mechanism of action that explains how glycine may influence such important and diverse biological processes as transmission of nerve signals and initiation of the immune response. INTERPRETATION: Glycine is a simple, easily available and inexpensive substance with few and innocuous side effects. Despite the recent unveiling of tantalizing aspects regarding its mechanism of action, biological activities and therapeutic potential, clinical use has remained scant.

Glycine↗
PubMed2003

Delaying defibrillation to give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial.

CONTEXT: Defibrillation as soon as possible is standard treatment for patients with ventricular fibrillation. A nonrandomized study indicates that after a few minutes of ventricular fibrillation, delaying defibrillation to give cardiopulmonary resuscitation (CPR) first might improve the outcome. OBJECTIVE: To determine the effects of CPR before defibrillation on outcome in patients with ventricular fibrillation and with response times either up to or longer than 5 minutes. DESIGN, SETTING, AND PATIENTS: Randomized trial of 200 patients with out-of-hospital ventricular fibrillation in Oslo, Norway, between June 1998 and May 2001. Patients received either standard care with immediate defibrillation (n = 96) or CPR first with 3 minutes of basic CPR by ambulance personnel prior to defibrillation (n = 104). If initial defibrillation was unsuccessful, the standard group received 1 minute of CPR before additional defibrillation attempts compared with 3 minutes in the CPR first group. MAIN OUTCOME MEASURE: Primary end point was survival to hospital discharge. Secondary end points were hospital admission with return of spontaneous circulation (ROSC), 1-year survival, and neurological outcome. A prespecified analysis examined subgroups with response times either up to or longer than 5 minutes. RESULTS: In the standard group, 14 (15%) of 96 patients survived to hospital discharge vs 23 (22%) of 104 in the CPR first group (P =.17). There were no differences in ROSC rates between the standard group (56% [58/104]) and the CPR first group (46% [44/96]; P =.16); or in 1-year survival (20% [21/104] and 15% [14/96], respectively; P =.30). In subgroup analysis for patients with ambulance response times of either up to 5 minutes or shorter, there were no differences in any outcome variables between the CPR first group (n = 40) and the standard group (n = 41). For patients with response intervals of longer than 5 minutes, more patients achieved ROSC in the CPR first group (58% [37/64]) compared with the standard group (38% [21/55]; odds ratio [OR], 2.22; 95% confidence interval [CI], 1.06-4.63; P =.04); survival to hospital discharge (22% [14/64] vs 4% [2/55]; OR, 7.42; 95% CI, 1.61-34.3; P =.006); and 1-year survival (20% [13/64] vs 4% [2/55]; OR, 6.76; 95% CI, 1.42-31.4; P =.01). Thirty-three (89%) of 37 patients who survived to hospital discharge had no or minor reductions in neurological status with no difference between the groups. CONCLUSIONS: Compared with standard care for ventricular fibrillation, CPR first prior to defibrillation offered no advantage in improving outcomes for this entire study population or for patients with ambulance response times shorter than 5 minutes. However, the patients with ventricular fibrillation and ambulance response intervals longer than 5 minutes had better outcomes with CPR first before defibrillation was attempted. These results require confirmation in additional randomized trials.

Adult↗
PubMed2003

Rapid rewarming after mild hypothermia accentuates the inflammatory response after acute volume controlled haemorrhage in spontaneously breathing rats.

Accidental hypothermia is a common companion of trauma/haemorrhage, and several clinical studies have identified reduced body temperature as an independent risk predisposing to increased morbidity and mortality. Accordingly, the majority of trauma care guidelines prescribe early and aggressive rewarming of hypothermic patients. Enzyme reactions are generally downregulated at temperatures below 37 degrees C, including most of those responsible for the inflammatory response. The rationale for adhering to these recommendations uncritically may therefore be questioned. In a rat model of mild hypothermia and haemorrhagic shock we wanted to compare the influence of rapid rewarming with persistently reduced temperature on the synthesis of early inflammatory mediators and organ function. Thirty-four male albino Sprague-Dawley rats were studied. Withdrawal of 2.5 ml blood/100 g body weight was performed over 10 min, with simultaneous reduction of body temperature to 32.5-33.5 degrees C. Seventy-five minutes after initiation of bleeding, two-thirds of the shed blood was retransfused. One group (n=17) was rewarmed to normothermia, the other (n=17) was kept hypothermic. The study was terminated after an observation period of 2 h. At the end of the study the rewarmed animals had a significantly lower mean arterial pressure, higher heart rate, higher synthesis of reactive oxygen species from peritoneal phagocytes, increased circulating levels of nitric oxide, and higher values of the organ markers aspartate aminotransferase and urea. The pro-inflammatory cytokines TNF-alpha and IL-6, the anti-inflammatory cytokine IL-10, the organ markers alanine aminotransferase, alpha-glutathione S-transferase and creatinine, as well as organ injury scores were equal in both groups. Three rewarmed rats died prematurely, versus one hypothermic animal. In conclusion, the results suggest that during the early stages after haemorrhagic shock, rapid rewarming from mild hypothermia may have unfavourable effects both on basic haemodynamic variables, and on the internal inflammatory environment of cells and tissues.

Animals↗
PubMed2003

Hydrocortisone and the mitogen-activated protein kinase inhibitor U0126 acutely suppress reactive oxygen species generation from circulating granulocytes after gunshot injuries in the pig.

OBJECTIVE: Several external stimuli, including trauma, increase the endogenous production of reactive oxygen species that spontaneously attack vital biological molecules. In addition to their direct toxic effects, several secondary messenger systems are induced. To forestall a subsequent organ dysfunction, a short-term posttraumatic down-regulation of granulocyte function has been advocated. Corticosteroids are potent and universal anti-inflammatory agents, but they have well-known side effects. Modulation of the mitogen-activated protein kinase cascade is an alternative approach. The purpose of this study was to investigate how the posttraumatic production of reactive oxygen species can be modulated by hydrocortisone or the extracellular signal-regulated kinase inhibitor U0126. DESIGN: Prospective randomized trial. SETTING: Field hospital and research laboratory. SUBJECTS: Seventeen male pigs. INTERVENTIONS: In general anesthesia, the pigs were exposed to a standardized insult: one gunshot hitting the right femur from a distance of 25 m, and one pistol shot to the left upper abdomen from close range. Following immediate first aid treatment, the animals were transported to a nearby field hospital. According to randomization, the animals received either hydrocortisone 250 mg intravenously (group 1, n = 9) or a similar amount of saline (group 2, n = 8). The injections were given 5 mins after the last shot. Blood samples were drawn before shooting, immediately before hydrocortisone was given, and 60 mins after shooting. Circulating neutrophils were isolated, and the production of reactive oxygen species was measured fluorometrically. Neutrophils from nine randomly chosen animals (five from group 1 and four from group 2) were treated in vitro with the extracellular signal-regulated kinase inhibitor U0126. MEASUREMENTS AND MAIN RESULTS: The injuries as evaluated by the abbreviated injury scale did not differ between the animals. All survived the first 60 mins. While the in vivo production of reactive oxygen species tended to increase in the controls, a significant reduction was measured in the hydrocortisone group. Subsequent treatment with U0126 further reduced the synthesis of reactive oxygen species by about two thirds in both groups, independently of time. CONCLUSIONS: Early injection of hydrocortisone after trauma inhibits the synthesis of reactive oxygen species from circulating neutrophils. Inhibition of the extracellular signal-regulated kinase branch of the mitogen-activated protein kinase signaling cascade is an alternative approach. The powerful in vitro capacity of selective extracellular signal-regulated kinase inhibitors to reduce the posttraumatic reactive oxygen species generation deserves further investigations, and compelling evidence of their in vivo usefulness is still lacking.

Animals↗