Down-regulation of GRK2 after oxygen and glucose deprivation in rat hippocampal slices: role of the PI3-kinase pathway.

G protein-coupled receptor kinase 2 (GRK2) modulates G protein-coupled receptor desensitization and signaling. We previously described down-regulation of GRK2 expression in vivo in rat neonatal brain following hypoxia-ischemia. In this study, we investigated the molecular mechanisms involved in GRK2 down-regulation, using organotypic cultures of neonatal rat hippocampal slices exposed to oxygen and glucose deprivation (OGD).

A role for G protein-coupled receptor kinase 2 in mechanical allodynia.

Inflammation and nerve injury can both induce mechanical allodynia via mechanisms involving the production of pro-inflammatory cytokines and increased neuronal activity. Many neurotransmitters involved in pain signal via G protein-coupled receptors (GPCRs). GPCR kinase (GRK)2 is a member of the GRK family that regulates agonist-induced desensitization and signalling of GPCRs.

Taxol normalizes the impaired agonist-induced beta2-adrenoceptor internalization in splenocytes from GRK2+/- mice.

G protein-coupled receptor kinase 2 (GRK2) is involved in the agonist-induced desensitization of beta2-adrenoceptors. In addition, GRK2 is capable of binding and phosphorylating tubulin. Interestingly, microtubule dynamics profoundly affect agonist-induced internalization of beta2-adrenoceptors.

Enhanced cortisol suppression in response to dexamethasone administration in traumatized veterans with and without posttraumatic stress disorder.

Background: While enhanced cortisol suppression in response to dexamethasone is one of the most consistent biological findings in posttraumatic stress disorder (PTSD), the relative contribution of trauma exposure to this finding remains unclear.

Methods: Assessment of diurnal salivary cortisol levels and 1600 h salivary cortisol before and after oral administration of 0.5mg dexamethasone in veterans with PTSD, veterans without PTSD (trauma controls) and healthy controls.

Cortisol and severe fatigue: a longitudinal study in adolescent girls.

Fatigue is a common complaint among adolescents, especially in girls, and is associated with high rates of school absenteeism. Severe fatigue is often accompanied by psychological and physical symptoms. In the chronic fatigue syndrome (CFS) functioning of the hypothalamic-pituitary-adrenal (HPA)-axis has previously been found to be altered.

Leukocyte glucocorticoid receptor expression and immunoregulation in veterans with and without post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is associated with a dysregulation of the hypothalamus-pituitary-adrenal axis (HPA axis). In addition, there is evidence for altered glucocorticoid receptor (GR) expression and function in peripheral blood mononuclear cells. The aim of the present study was to differentiate between the effect of trauma exposure and PTSD on leukocyte GR expression and glucocorticoid immune regulation.

G protein-coupled receptor kinase 6 controls chronicity and severity of dextran sodium sulphate-induced colitis in mice.

Background: Infiltration of inflammatory cells into the colon plays an important role in the onset and course of inflammatory bowel disease. G-protein-coupled receptor kinase 6 (GRK6) is an intracellular kinase that regulates the sensitivity of certain G-protein-coupled receptors, including those involved in the migration of inflammatory cells. Therefore, it is hypothesised that GRK6 plays a role in determining the course of inflammation.

Reduced life expectancy in rats after neonatal dexamethasone treatment.

The glucocorticoid dexamethasone (Dex) is widely used in preterm infants for the prevention of chronic lung disease. However, major concern has arisen about the long-term sequelae of this therapy. Here we report that neonatal treatment with dexamethasone significantly shortens the lifespan by 25% of male rats (28.

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

Objective: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases.

Methods: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15).

Immune and endocrine function in burnout syndrome.

Objective: Burnout is a stress-induced work-related syndrome. It is associated with a higher incidence of infections possibly pointing to a compromised immune system. In the present study, endocrine and ex vivo immune function of severe cases of burnout were investigated.

Differences in behavioral outcome and motor development at school age after neonatal treatment for chronic lung disease with dexamethasone versus hydrocortisone.

Neonatal dexamethasone (DEX) for chronic lung disease is associated with adverse outcome. We compared behavioral and motor development at school age of children who neonatally received DEX to children neonatally treated with hydrocortisone (HC) in a retrospective matched cohort study. DEX- and HC-treated groups matched for gestational age, birth weight and year, gender, and severity of respiratory distress syndrome were compared with a reference group (REF) and a group treated only antenatally with betamethasone (BMETH).

Acetylsalicylic acid as an adjuvant therapy for schizophrenia.

Background: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia.

Methods: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment.

Receptor regulation in neuroendocrine-immune communication: current knowledge and future perspectives.

Immune cells express receptors for every hormone or neurotransmitter we know so far. The neuroendocrine system signals to the immune system via the release of hormones and neurotransmitters that regulate cellular activity via these receptors. Much attention has been focused on the effect of glucocorticoids and catecholamines on the immune system.

Hydrogen peroxide impairs GRK2 translation via a calpain-dependent and cdk1-mediated pathway.

Oxidative mechanisms of injury are involved in many neurodegenerative diseases such as stroke, ischemia-reperfusion injury and multiple sclerosis. G protein-coupled receptor kinase 2 (GRK2) plays a key role in G protein-coupled receptor (GPCR) signaling modulation, and its expression levels are decreased after brain hypoxia/ischemia and reperfusion as well as in several inflammatory conditions. We report here that hydrogen peroxide downregulates GRK2 expression in C6 rat glioma cells.

Public speaking stress-induced neuroendocrine responses and circulating immune cell redistribution in irritable bowel syndrome.

Objectives: Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls.

Methods: Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls.

GRKs and arrestins: regulators of migration and inflammation.

In the immune system, signaling by G protein-coupled receptors (GPCRs) is crucial for the activity of multiple mediators, including chemokines, leukotrienes, and neurotransmitters. GPCR kinases (GRKs) and arrestins control GPCR signaling by mediating desensitization and thus, regulating further signal propagation through G proteins. Recent evidence suggests that the GRK-arrestin desensitization machinery fulfills a vital role in regulating inflammatory processes.

Exogenous surfactant restores lung function but not peripheral immunosuppression in ventilated surfactant-deficient rats.

The authors have previously shown that mechanical ventilation can result in increased pulmonary inflammation and suppressed peripheral leukocyte function. In the present study the effect of surfactant therapy on pulmonary inflammation and peripheral immune function in ventilated surfactant-deficient rats was assessed. Surfactant deficiency was induced by repeated lung lavage, treated rats with surfactant or left them untreated, and ventilated the rats during 2 hours.

Respiratory distress syndrome-associated inflammation is related to early but not late peri/intraventricular hemorrhage in preterm infants.

Objective: To investigate whether or not peri/intraventricular hemorrhages (PIVHs) occurring in the first 12 hours of life (early PIVHs) are related to respiratory distress syndrome (RDS)-associated inflammatory factors in contrast to PIVHs developing after 12 hours of life (late PIVHs).

Study Design: Blood samples obtained at 0 to 12 hours, 48 to 72 hours, and 168 hours of life were evaluated for determination of the proinflammatory cytokines interleukin (IL)-8 and IL-6, tumor necrosis factor (TNF)-alpha, and malondialdehyde (MDA) as measures of lipid peroxidation. Simultaneously, cranial ultrasonography was performed in 114 neonates under 32 weeks gestational age.

Severe fatigue in adolescents: a common phenomenon?

Objective: The purpose of this study was to determine the prevalence of severe fatigue in adolescent boys and girls, to explore the role of lifestyle factors in fatigue, and to investigate whether severe fatigue in a healthy population is associated with depression, anxiety, and comorbid factors also observed in chronic fatigue syndrome patients.

Methods: In a sample of 1718 boys and 1749 girls, fatigue severity and duration were measured using a multidimensional questionnaire (Checklist Individual Strength). In addition, self-reports of depressive symptoms, anxiety, chronic fatigue syndrome-related symptoms, and lifestyle characteristics were assessed by means of questionnaires.

Gender-specific neuroprotection by 2-iminobiotin after hypoxia-ischemia in the neonatal rat via a nitric oxide independent pathway.

We have shown earlier that 2-iminobiotin (2-IB) reduces hypoxia-ischemia (HI)-induced brain damage in neonatal rats, and presumed that inhibition of nitric oxide synthases (NOS) was the underlying mechanism. We now investigated the effect of 2-IB treatment in P7 rat pups to determine the role of gender and the neuroprotective mechanism. Pups were subjected to HI (occlusion of right carotid artery and 120 mins FiO(2) 0.

A longitudinal study on cortisol and complaint reduction in burnout.

Several studies have investigated the association between burnout and HPA-axis functioning, but the results are far from consistent. This does not preclude the possibility that within a group of burnout patients a recovery of symptoms in a longitudinal course corresponds to (changes in) cortisol parameters. The latter possibility is tested in the present study before and after treatment, and at follow-up.

Cortisol deviations in people with burnout before and after psychotherapy: a pilot study.

Burnout is characterized by exhaustion, cynicism, and feelings of reduced competence. These complaints may be reflected in disturbances in the main stress regulatory endocrine system: the hypothalamus pituitary adrenal (HPA) axis. In this study, the HPA-axis hormone cortisol was sampled after awakening and during the day in 22 participants with clinical burnout and in 21 healthy controls.

Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage.

Perinatal hypoxia ischemia (HI) is a frequent cause of neonatal brain injury. This study aimed at describing molecular changes during the first 48 h after exposure of the neonatal rat brain to HI. Twelve-day-old rats were subjected to unilateral carotid artery occlusion and 90 min of 8% O2, leading to neuronal damage in the ipsilateral hemisphere only.

Selective inhibition of nuclear factor-kappaB activation after hypoxia/ischemia in neonatal rats is not neuroprotective.

Activated nuclear factor-kappaB (NFkappaB) has been shown to increase transcription of several genes that could potentially contribute to neuronal damage, such as proinflammatory cytokines, chemokines, and inducible nitric oxide synthase. The aim of our study was to investigate whether inhibition of NFkappaB activation could prevent hypoxia/ischemia (HI)-induced cerebral damage in neonatal rats. We used a cell permeable peptide (NEMO binding domain [NBD] peptide) that is known to prevent the association of the regulatory protein NEMO with IKK, the kinase that activates NFkappaB.