Leptin and leptin receptor genes in Atlantic salmon: Cloning, phylogeny, tissue distribution and expression correlated to long-term feeding status

The present study reports the complete coding sequences for two paralogues for leptin (sLepA1 and sLepA2) and leptin receptor (sLepR) in Atlantic salmon. The deduced 171-amino acid (aa) sequence of sLepA1 and 175 aa sequence for sLepA2 shows 71.6% identity to each other and clusters phylogenetically with teleost Lep type A, with 22.4% and 24.1% identity to human Lep. Both sLep proteins are predicted to consist of four helixes showing strong conservation of tertiary structure with other vertebrates. The highest mRNA levels for sLepA1 in fed fish (satiation ration = 100%) were observed in the brain, white muscle, liver, and ovaries. In most tissues sLepA2 generally had a lower expression than sLepA1 except for the gastrointestinal tract (stomach and mid-gut) and kidney. Only one leptin receptor ortholog was identified and it shares 24.2% aa sequence similarity with human LepR, with stretches of highest sequence similarity corresponding to domains considered important for LepR signaling. The sLepR was abundantly expressed in the ovary, and was also high in the brain, pituitary, eye, gill, skin, visceral adipose tissue, belly flap, red muscle, kidney, and testis. Fish reared on a rationed feeding regime (60% of satiation) for 10 months grew less than control (100%) and tended to have a lower sLepA1 mRNA expression in the fat-depositing tissues visceral adipose tissue (p < 0.05) and white muscle (n.s.). sLepA2 mRNA levels was very low in these tissues and feeding regime tended to affect its expression in an opposite manner. Expression in liver differed from that of the other tissues with a higher sLepA2 mRNA in the feed-rationed group (p < 0.01). Plasma levels of sLep did not differ between fish fed restricted and full feeding regimes. No difference in brain sLepR mRNA levels was observed between fish fed reduced and full feeding regimes. This study in part supports that sLepA1 is involved in signaling the energy status in fat-depositing tissues in line with the mammalian model, whereas sLepA2 may possibly play important roles in the digestive tract and liver. At present, data on Lep in teleosts are too scarce to allow generalization about how the Lep system is influenced by tissue-specific energy status and, in turn, may regulate functions related to feed intake, growth, and adiposity in fish. In tetraploid species like Atlantic salmon, different Lep paralogues seems to serve different physiological roles.     

Transportation of critically ill patients on extracorporeal membrane oxygenation

Serious pulmonary and cardiac failure may be treated with extracorporeal membrane oxygenation (ECMO) when conventional treatment fails. In some severely ill patients, it may be necessary to initiate ECMO at the local hospital and, thereafter, transport the patient back to the ECMO center. The aim of this study was to evaluate our experiences with transportation of patients on ECMO. From Oct 1992 to Jan 2008 23, patients were transported on ECMO from local hospitals to Rikshospitalet. The study included seventeen patients with pulmonary failure and four patients with cardiac failure. All age groups were represented. Aircraft were used in 17 cases, ground vehicles in six. The times from decision until ECMO was established, the time from ECMO to departure from the local hospital and the transportation time were registered. All transportations were uneventful. After 10.3 +/-6.7 days, six patients died on ECMO and another patient died within 30 days. Mean ECMO time for those who died was 13.3 +/- 9.6 vs. 8.5 +/- 4.7 days for survivors, p=0.34. Seventeen patients were able to be successfully weaned from ECMO. Thirty day survival was 67%. The mean age for survivors was 15.3+/-18.3 (range 0-54.6) vs. 23.6 +/- 20.3 years (range 0-55.9) in fatal cases, p=0.41. The time from referral to initiating ECMO was a mean of 7.32 +/- 2.3 (3.0-12.0) hours for survivors vs. 7.88 +/- 3.0 (3.50-13.40) hours for non- survivors, p=0.76. The time from initiating ECMO to departure was 5.1 +/- 6.5 (0.58-23.75) hours in survivors vs. 9.1 +/- 6.8 (0.55-18.45) hours in non-survivors, p=0.18. Time from departure to arrival at Rikshospitalet was a mean of 3.2 (0.50-5.10) hours for survivors versus 2.5 (0.5-4.40) for non-survivors, p=0.41. This study shows that ECMO can be successfully established at local hospitals, using an experienced team, and that transportation of patients on ECMO can be performed safely and without technical difficulties. Survival for this group of patients did not differ from patients treated at the ECMO center.     

Estradiol and neurodegenerative oxidative stress

Estradiol is a potent preventative against neurodegenerative disease, in part, by activating antioxidant defense systems scavenging reactive oxygen species, limiting mitochondrial protein damage, improving electron transport chain activity and reducing mitochondrial DNA damage. Estradiol also increases the activity of complex IV of the electron transport chain, improving mitochondrial respiration and ATP production under normal and stressful conditions. However, the high oxidative cellular environment present during neurodegeneration makes estradiol a poor agent for treatment of existing disease. Oxidative stress stimulates the production of the hydroperoxide-dependent hydroxylation of estradiol to the catecholestrogen metabolites, which can undergo reactive oxygen species producing redox cycling, setting up a self-generating toxic cascade offsetting any antioxidant/antiapoptotic effects generated by the parent estradiol. Additional disease-induced factors can further perpetuate this cycle. For example dysregulation of the catecholamine system could alter catechol-O-methyltransferase-catalyzed methylation, preventing removal of redox cycling catecholestrogens from the system enhancing pro-oxidant effects of estradiol.     

Similarities in stress physiology among patients with chronic pain and headache disorders: evidence for a common pathophysiological mechanism?

One common feature of chronic musculoskeletal pain and headaches are that they are both influenced by stress. Among these, tension-type headache (TTH), fibromyalgia (FMS) and chronic shoulder/neck pain (SNP) appear to have several similarities, both with regard to pathophysiology, clinical features and demographics. The main hypothesis of the present study was that patients with chronic pain (TTH, FMS and SNP) had stress-induced features distinguishing them from migraine patients and healthy controls. We measured pain, blood pressure, heart rate (HR) and skin blood flow (BF) during (1 h) and after (30 min) controlled low-grade cognitive stressor in 22 migraine patients, 18 TTH patients, 23 FMS patients, 29 SNP patients and 44 healthy controls. FMS patients had a lower early HR response to stress than migraine patients, but no differences were found among FMS, TTH and SNP patients. Finger skin BF decreased more in FMS patients compared to migraine patients, both during and after the test. When comparing chronic pain patients (chronic TTH, FMS and SNP) with those with episodic pain (episodic TTH and migraine patients) or little or no pain (healthy controls), different adaptation profiles were found during the test for systolic and diastolic blood pressure, HR and skin BF in the chronic group. In conclusion, these results suggest that TTH, FMS and SNP patients may share common pathophysiological mechanisms regarding the physiological responses to and recovery from low-grade cognitive stress, differentiating them from episodic pain conditions such as migraine.     

Predictors and moderators of outcome in child and adolescent anxiety and depression: a systematic review of psychological treatment studies

The aim of this literature review was to examine pre-treatment child and adolescent characteristics as predictors and moderators of outcome in psychotherapy treatment trials of anxiety and depressive disorders. A literature search was conducted using several databases and resulted in 45 published studies (32 anxiety studies and 13 depression studies) meeting predefined methodological criteria. Ten client demographic (age, gender, ethnicity, IQ) and clinical factors (duration, type of diagnosis, pre-treatment severity, comorbidity) were examined across studies. The majority of findings showed non-significant associations between demographic factors (gender and age) with treatment outcome for both the anxiety and the depression treatment trials. Some important differences between the results of the anxiety and depression treatment trials were found. The majority of findings for the anxiety studies suggest that there are no demographic or clinical factors that predict or moderate treatment outcome. For the depression studies, however, the findings suggest that baseline symptom severity and comorbid anxiety may impact on treatment response. Overall, existing studies of pre-treatment patient variables as predictors and moderators of anxiety and depression treatment outcome provide little consistent knowledge concerning for what type of patients and under what conditions treatments work. Suggestions for future research are discussed.     

Topographic imaging of quantitative EEG in response to smoked cocaine self-administration in humans.

Quantitative electroencephalographic (qEEG) profiles were studied in cocaine-dependent patients in response to an acute, single-blind, self-administered dose of smoked cocaine base (50 mg) vs placebo. qEEG data were averaged using neurometric analytical methods and the spectral power of each primary bandwidth was computed and topographically imaged. Additional measures included cocaine-induced high, craving, and related subjective ratings, heart rate, blood pressure, and plasma cortisol and homovanillic acid levels. In all, 13 crack cocaine-dependent subjects were tested. Cocaine produced a rapid increase in subjective ratings of cocaine high and good drug effect, and a more persistent increase in cocaine craving and nervousness. Cocaine also produced a rapid rise in heart rate and a prolonged increase in plasma cortisol. Placebo, administered in the context of cocaine cues and dosing expectations, had no cocaine-like subjective or physiological effects. Cocaine produced a rapid increase in absolute theta, alpha, and beta power over the prefrontal cortex (FP1, FP2), lasting up to 25 min after dosing. The increase in theta power was correlated with good drug effect, and the increase in alpha power was correlated with nervousness. Cocaine also produced a similar increase in delta coherence over the prefrontal cortex, which was positively correlated with plasma cortisol, and negatively correlated with nervousness. Placebo resulted in an increase in alpha power over the prefrontal cortex. These data demonstrate the involvement of prefrontal cortex in the qEEG response to acute cocaine. Evidence indicates slow wave qEEG, delta and theta activity, involvement in the rewarding properties of cocaine.     

Validation of the Dental Fear Scale and the Dental Belief Survey in a Norwegian sample

Abstract –The aim of this study was to validate the Kleinknecht's Dental Fear Scale and the Getz's Dental Belief Survey in a Norwegian sample by 1) testing their ability to discriminate between fearful (n= 151) and regular (n= 160) patients, and 2) correlating them. Both instruments were highly reliable (Cronbach's alpha >0.90). Between 81% and 95% of the fearful and regular patients were correctly assigned to their appropriate groups with both instruments. It may thus be concluded that both instruments are valid. Also, the correlation between the instruments was 0.68, indicating that they to a large extent seem to measure the same concept. The most important predictor items for both instruments were related to avoidance of dental treatment.     

Single Dose Pharmacokinetics of Trazodone in Healthy Subjects

Abstract: Eight healthy subjects were administered trazodone-HCl orally (100 mg) with and without food and by infusion in a three way cross-over study. Unchanged trazodone was determined in serum and urine by high performance liquid chromatography after an alkaline extraction. Absorption of trazodone was irregular in fasting subjects and improved after food intake. Food intake significantly decreased the maximum serum concentrations of trazodone from 1.88 ± 0.42 to 1.47 ± 0.16 μg/ml, and increased the time for reaching maximum concentration from 1.3 ± 0.8 hr to 2.0 ± 1.5 hr. No differences were observed in the total amount of trazodone absorbed with or without food with bioavailability values of 65 ± 6 and 63 ± 4 per cent, respectively. The apparent volume of distribution and total body clearance for trazodone were estimated to 0.84 ± 0.16 1/kg and 5.3 ± 0.9 1/hr, respectively. The terminal elimination half-life of 7.3 ± 0.8 hr showed no significant differences between the different ways of administration. Urinary excretion of unchanged trazodone during 26 hr was less than 0.13 per cent of the administered dose, suggesting a high degree of trazodone metabolism. Earlier statements of enterohepatic circulation of trazodone and pharmacokinetic differences between males and females were not confirmed by the present study. Due to the irregular absorption in fasting subjects, trazodone should preferably be administered after food.     

Associations of prepregnancy cardiovascular risk factors with the offspring's birth weight

Low birth weight of offspring has been associated with increased risk of maternal cardiovascular mortality, and cardiovascular risk factors measured within pregnancy have been related to offspring birth weight. It is not clear whether cardiovascular risk factors assessed prior to pregnancy are associated with the offspring's birth weight. The authors combined baseline data from 3,461 women in the HUNT Study (1995-1997) and data on deliveries from the Medical Birth Registry of Norway up to 2005. They used linear regression to prospectively study associations between diastolic and systolic blood pressures, concentrations of triglycerides, serum total cholesterol, and high density lipoprotein cholesterol measured before conception and birth weight for gestational age of the offspring. Blood pressure measured before pregnancy was inversely associated with birth weight for gestational age, whereas unfavorable levels of serum total cholesterol, high density lipoprotein cholesterol, triglycerides, and glucose were positively associated with birth weight for gestational age. Thus, women with relatively high blood pressure tend to deliver small babies, whereas women with unfavorable lipid levels tend to give birth to large babies, suggesting reduced glucose tolerance. These findings suggest that low as well as high birth weight of the offspring may indicate increased cardiovascular risk for the mother.