Antidepressant-like effect of agmatine is not mediated by serotonin

The aim of this study was to characterize the behavioral effects of systemically administered agmatine in animal models predictive of antidepressant- and anxiolytic-like activity and clarify whether the effects of agmatine depend on the intact serotonergic system. Only the highest dose of agmatine tested (50 mg/kg) decreased immobility of mice in the forced swimming test. The magnitude of the effect was slightly smaller than that of the tricyclic antidepressant imipramine (15 mg/kg). Agmatine did not change the locomotion of mice in the open field. Pretreatment with the tryptophane hydroxylase inhibitor PCPA for 3 days resulted in more than 70% drop in the tissue levels of 5-HT and 5-HIIA but did not counteract the antidepressant-like effect of agmatine. The administration of agmatine did not modify behavior of animals in the light-dark compartment test of anxiety. We conclude that the antidepressant-like effect of agmatine seems not to be mediated by the serotonergic system. We failed to confirm the reported anxiolytic-like activity of agmatine.     

Sleep Duration and Regularity are Associated with Behavioral Problems in 8-year-old Children

Background  

Relatively little is known about the significance of normal variation in objectively assessed sleep duration and its regularity in children's psychological well-being.     

Use of estradiol-progestin therapy associates with increased risk for uterine sarcomas

Objective

Insufficient data exist on the effect of postmenopausal hormone therapy as the risk factor for uterine sarcomas. We therefore evaluated the association of estradiol-progestin therapy (EPT) with the risk of uterine sarcoma in nation-wide cohort study.

Methods

All Finnish women (> 50 years of age) who had used EPT during the years 1994-2008 for at least 6 months (n = 243,857) were identified from the national Medical Reimbursement Registry. Their incidence of uterine stromal and leiomyosarcoma among the EPT users was compared to that in the background population with the aid of the Finnish Cancer Registry.

Results

A total of 76 uterine sarcomas were encountered in the EPT cohort; 45 (59%) were leiomyosarcomas, 24 (32%) stromal sarcomas and 7 (9%) other sarcomas. The exposure to EPT for less than 5 years did not associate with significant rises in the sarcoma risk but longer exposure was accompanied with significant risk elevations for all uterine sarcomas: the standardized incidence ratio (SIR) for 5-10 years of use was 2.0, 95% confidence interval (CI) 1.4-2.9 and for ≥ 10 years of use 3.0 (1.3-5.9): the SIRs were highest for leiomyosarcoma. The sequential and continuous uses of progestin were associated with similar increased SIRs for uterine sarcoma.

Conclusions

The use of EPT for 5 years or more is associated with an increased risk for uterine sarcomas. This turns to an absolute excess risk of 2-3 extra uterine sarcoma cases per 10,000 long-time EPT users followed for 10 years.     

Tracking and determinants of LDL particle size in healthy children from 7 to 11 years of age: the STRIP Study

Serum low-density lipoprotein (LDL) particle composition varies according to lifestyle and age. To analyze its long-term tracking, we studied LDL particle size consecutively in 100 children at the ages of 7, 9 and 11 years using a high-resolution 3% polyacrylamide gel tube, electrophoresis method, searching also for long-term determinants of the particle size. The mean LDL particle sizes at 7 and 9 years, and at 7 and 11 years correlated directly (r = 0.72 and 0.39, respectively). The probability that children would remain in the same LDL particle size tertile between 7 and 11 years of age was 48% (p = 0.008). Longitudinally, total, high-density lipoprotein (HDL) and LDL cholesterol concentrations and body mass index (BMI) associated directly with mean LDL particle size, and triglyceride concentration and triglyceride/HDL cholesterol ratio correlated inversely. A shift from pre-puberty to puberty was associated with an increase in LDL particle size. Sex, serum insulin concentration, or energy nutrient intakes did not associate with LDL particle size. In conclusion, although mean LDL particle size tracks in 7- to 11-year-old healthy children, changes in serum triglycerides, HDL, LDL, and total cholesterol concentration, BMI, and pubertal status all modify LDL particle size.     

A randomized intervention since infancy to reduce intake of saturated fat: calorie (energy) and nutrient intakes up to the age of 10 years in the Special Turku Coronary Risk Factor Intervention Project

OBJECTIVE: To evaluate the longitudinal impact of dietary counseling on children's nutrient intake. DESIGN: A prospective, randomized, clinical trial. PARTICIPANTS: Children were recruited to the study between December 1, 1989, and May 30, 1992. At the age of 7 months, children were randomized to the intervention group (n = 540) or the control group (n = 522) and were followed up until the age of 10 years.Intervention Families in the intervention group have, since randomization, received regularly individualized counseling about how to modify the quality and quantity of fat in the child's diet, the goal being an unsaturated-saturated fat ratio of 2:1. MAIN OUTCOME MEASURES: Nutrient intakes between the ages of 4 and 10 years based on annual 4-day food records. RESULTS: The fat intake of the intervention children was constantly around 30% of the calorie (energy) intake, while that of the control children was 2 to 3 calorie percentage units higher (P<.001). The intervention children received 2 to 3 calorie percentage units less saturated fats and 0.5 to 1.0 calorie percentage unit more polyunsaturated fats than the control children (P<.001 for both). However, neither group reached the 2:1 goal set for the unsaturated-saturated fatty acid ratio. The vitamin and mineral intakes of the intervention and control children closely resembled each other despite the marked differences in fat intake. CONCLUSION: Individualized, biannually given, fat intake-focused dietary counseling that began at the child's age of 8 months continued to influence favorably the diet of 4- to 10-year-old intervention children without disadvantageous dietary effects, but the 2:1 goal for unsaturated-saturated fat ratio was not reached.     

Outcome of Left Atrial Isomerism at a Single Institution

Left atrial isomerism includes a complex spectrum of cardiac and extracardiac anomalies. The records of all patients with left isomerism born during the period of 1973–2010 and treated at the Children’s Hospital, Helsinki were reviewed. The short- and long-term outcomes were studied. The review included 38 patients (50% females). The overall survival with left atrial isomerism was 63% during a median follow-up time of 16 years (range, 4–30 years). Extracardiac anomalies were noted in 14 (37%) of 38 cases. Cardiac defects included dextrocardia in 26%, partially or totally anomalous pulmonary venous return in 29%, common atrium in 50%, atrioventriculoseptal defect in 73%, single ventricle in 40%, ventriculoseptal defect without atrioventricular defect in 11%, transposition in 21%, double outlet of the right ventricle in 26%, pulmonary stenosis or atresia in 61%, and left ventricular outflow obstruction in 24% of the cases. Cardiac arrhythmias were presented in 71% and pacemaker treatment in 29% of the cases. Of the 38 patients, 33 had cardiac surgery. Simple palliative methods were used in 11 cases, single-ventricle palliation in 12 cases, and operation with a biventricular track in 10 cases. In the groups that had surgery, 3 of 11 patients, 3 of 12 patients, and 3 of 10 patients died, respectively. In this review, 14 deaths occurred, associated with extracardiac anomalies in five cases and with cardiac arrhythmia in four cases. Five postoperative deaths occurred. At this writing, all three patients who had heart transplantation are alive. Complicated heart defects associated with severe arrhythmias and extracardiac anomalies contribute to a high mortality rate with left isomerism. Cardiac transplantation was considered a good option for selected patients.     

Insomnia symptoms and mortality: a register‐linked study among women and men from Finland,Norway and Lithuania

Evidence on the association between insomnia symptoms and mortality is limited and inconsistent. This study examined the association between insomnia symptoms and mortality in cohorts from three countries to show common and unique patterns. The Finnish cohort comprised 6605 employees of the City of Helsinki, aged 40–60 years at baseline in 2000–2002. The Norwegian cohort included 6236 participants from Western Norway, aged 40–45 years at baseline in 1997–1999. The Lithuanian cohort comprised 1602 participants from the City of Palanga, aged 35–74 years at baseline in 2003. Mortality data were derived from the Statistics Finland and Norwegian Cause of Death Registry until the end of 2012, and from the Lithuanian Regional Mortality Register until the end of 2013. Insomnia symptoms comprised difficulties initiating sleep, nocturnal awakenings, and waking up too early. Covariates were age, marital status, education, smoking, alcohol, physical inactivity, obesity, diabetes, cardiovascular diseases, depression, shift work, sleep duration, and self‐rated health. Cox regression analysis was used. Frequent difficulties initiating sleep were associated with all‐cause mortality among men after full adjustments in the Finnish (hazard ratio 2.51; 95% confidence interval 1.07–5.88) and Norwegian (hazard ratio 3.42; 95% confidence interval 1.03–11.35) cohorts. Among women and in Lithuania, insomnia symptoms were not statistically significantly associated with all‐cause mortality after adjustments. In conclusion, difficulties initiating sleep were associated with mortality among Norwegian and Finnish men. Variation and heterogeneity in the association between insomnia symptoms and mortality highlights that further research needs to distinguish between men and women, specific symptoms and national contexts, and focus on more chronic insomnia.