Ectonucleoside triphosphate diphosphohydrolase 1 and 5'-nucleotidase ecto gene polymorphisms and acute cellular rejection after liver transplantation.

The single nucleotide polymorphisms (SNPs) rs11188513, rs7071836, rs10748643, rs9450279, rs4458647, and rs6922 map in the genes of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) and 5'-nucleotidase ecto. We investigated whether these SNPs and haplotypes of these SNPs are associated with an acute cellular rejection after liver transplantation. A total of 69 recipients with an acute cellular rejection and 138 recipients without an acute cellular rejection were analyzed. Analyzed individually, no SNP demonstrates an association, but the haplotype rs11188513T-rs7071836G-rs10748643A of the ENTPD1 gene appeared more frequently in recipients without rejection and conversely, the haplotype rs11188513T-rs7071836G-rs10748643G of the ENTPD1 gene was more often represented in recipients with rejection. These two haplotypes seem to be important for the susceptibility of an acute cellular rejection after liver transplantation.

Myocardial metabolism in heart failure: Purinergic signalling and other metabolic concepts.

Despite significant therapeutic advances in heart failure (HF) therapy, the morbidity and mortality associated with this disease remains unacceptably high. The concept of metabolic dysfunction as an important underlying mechanism in HF is well established. Cardiac function is inextricably linked to metabolism, with dysregulation of cardiac metabolism pathways implicated in a range of cardiac complications, including HF. Modulation of cardiac metabolism has therefore become an attractive clinical target. Cardiac metabolism is based on the integration of adenosine triphosphate (ATP) production and utilization pathways. ATP itself impacts the heart not only by providing energy, but also represents a central element in the purinergic signaling pathway, which has received considerable attention in recent years. Furthermore, novel drugs that have received interest in HF include angiotensin receptor blocker-neprilysin inhibitor (ARNi) and sodium glucose cotransporter 2 (SGLT-2) inhibitors, whose favorable cardiovascular profile has been at least partly attributed to their effects on metabolism. This review, describes the major metabolic pathways and concepts of the healthy heart (including fatty acid oxidation, glycolysis, Krebs cycle, Randle cycle, and purinergic signaling) and their dysregulation in the progression to HF (including ketone and amino acid metabolism). The cardiac implications of HF comorbidities, including metabolic syndrome, diabetes mellitus and cachexia are also discussed. Finally, the impact of current HF and diabetes therapies on cardiac metabolism pathways and the relevance of this knowledge for current clinical practice is discussed. Targeting cardiac metabolism may have utility for the future treatment of patients with HF, complementing current approaches.

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany.

OBJECTIVES: This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany. METHODS: The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January-31 December 2016 (n = 1643) were identified and followed up for ≤12 months from first prescription. Patients with ≥1 heart failure (HF) diagnosis during the study period, ≥1 additional HF diagnosis in the full history of the database, and ≥1 prescription for an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and a ß-blocker during the study period, without a prescription for sac/val (n = 25,264), were included as a reference cohort. Changes in clinical parameters in the 12 months before and after sac/val initiation were investigated and compared with those from the PARADIGM-HF study. RESULTS: The characteristics of patients prescribed sac/val more closely resembled those of patients enrolled in PARADIGM-HF (e.g. younger age, higher proportion of men than women, lower systolic blood pressure) than patients in the reference cohort. Most patients were initiated on the lowest dose of sac/val irrespective of clinical setting. Significant decreases (p < 0.001) in NT-proBNP and glycated haemoglobin levels were observed following sac/val initiation. CONCLUSIONS: Patients prescribed sac/val had similar baseline demographics and clinical characteristics to those from PARADIGM-HF, and most patients were initiated on the lowest dose. Changes in clinical parameters before and after initiation mirrored findings from the PARADIGM-HF study.

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders.

Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study.

BACKGROUND: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data. METHODS: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment. RESULTS: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively. CONCLUSION: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.

Patient preference and tolerability of a DPP-4 inhibitor versus a GLP-1 analog in patients with type 2 diabetes mellitus inadequately controlled with metformin: a 24-week, randomized, multicenter, crossover study.

OBJECTIVE: The present study aimed to assess the patient preference and tolerability of oral dipeptidyl peptidase-4 inhibitor (vildagliptin) versus injectable glucagon-like peptide-1 analog (liraglutide) in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. METHODS: This 24-week, randomized, multicenter, crossover study, patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapy with hemoglobin A1c (HbA1c) ⩾6.5% and ⩽9.0% were randomized in a crossover manner to receive either vildagliptin/metformin single-pill combination (SPC) 50/1000 mg twice daily (n = 32) or 1.2 mg liraglutide as an add-on to metformin (0.6 mg [weeks 0-1] followed by 1.2 mg [weeks 2-12] once daily/1000 mg twice daily) (n = 30) for the first 12 weeks. RESULTS: Patient preference at week 24 was similar, with 51.7% (n = 31) patients preferring vildagliptin/metformin SPC compared with 48.3% (n = 29) preferring liraglutide as an add-on to metformin therapy (p = 0.449). Post hoc analyses showed that more elderly patients (⩾65 years) preferred vildagliptin (65%; n = 13) over liraglutide (35%; n = 7) therapy. Liraglutide was associated with better improvement in fasting plasma glucose (-21.5 mg/dl versus -3.4 mg/dl) and HbA1c (-0.5% versus -0.3%) levels. Fewer adverse events were reported with vildagliptin/metformin SPC (n = 16) compared with liraglutide as add-on to metformin treatment (n = 46). CONCLUSIONS: In this pilot study, although both vildagliptin and liraglutide therapies were preferred similarly by the patients and showed effective control of glycemia over 12 weeks, vildagliptin was associated with fewer adverse events and was preferred more by elderly patients.

Pill Burden in Patients With Type 2 Diabetes in Germany: Subanalysis From the Prospective, Noninterventional PROVIL Study.

IN BRIEF Type 2 diabetes and its associated comorbidities often require polypharmacotherapy, which may result in poor adherence to treatment. This study evaluated, using subjective patient and physician questionnaire surveys, the impact of pill burden and its associated consequences on patients treated with vildagliptin as add-on to metformin, a fixed-dose combination of vildagliptin/metformin, or another dual oral antidiabetic therapy. Patients' responses were also analyzed by age (<65 or ≥65 years). The surveys revealed that a high pill count in antidiabetic therapy constitutes a large burden for patients with type 2 diabetes. Treating physicians are aware of the problems that result from a high pill burden, and a majority of them prefer prescribing fixed-dose combinations that have better efficacy and tolerability to reduce pill burden.

Vildagliptin versus insulin in patients with type 2 diabetes mellitus inadequately controlled with sulfonylurea: results from a randomized, 24 week study.

OBJECTIVE: There is limited evidence to guide the selection of second-line anti-hyperglycemic agents in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with sulfonylurea monotherapy and are intolerant to metformin. We compared the efficacy and safety of vildagliptin 50 mg qd and Neutral Protamine Hagedorn (NPH) insulin qd in such patients. METHODS: This was a 24 week, multicenter, randomized, open-label study. The co-primary endpoints were (i) proportion of patients achieving HbA1c <7.0% without any confirmed hypoglycemic events (HEs) or weight gain ≥3% (composite endpoint); (ii) rate of confirmed HEs. Treatment satisfaction was assessed using the TSQM-9 questionnaire at study end. RESULTS: A total of 162 patients were randomly assigned to vildagliptin (n = 83) and NPH insulin (n = 79). Similar proportion of patients achieved the composite endpoint in vildagliptin versus NPH insulin group (35.4% versus 34.2%; OR 0.985; 95% CI 0.507, 1.915; p = 0.96). After 24 weeks, 48.8% of patients in the vildagliptin group and 60.8% in the NPH insulin group achieved HbA1c <7.0%; 13.4% in the vildagliptin group and 29.1% in the insulin group had at least one confirmed HE; while 11.0% in the vildagliptin group and 22.8% in the insulin group experienced weight gain. The rate of confirmed HEs was significantly lower in patients receiving vildagliptin versus NPH insulin (1.3 versus 5.1 events per year). The TSQM-9 score for 'convenience' at week 24 increased significantly more with vildagliptin than with NPH insulin. CONCLUSIONS: Addition of vildagliptin and NPH insulin resulted in a similar number of patients reaching HbA1c target without HEs or weight gain in T2DM patients inadequately controlled with sulfonylurea. The addition of vildagliptin to sulfonylurea could be considered as a treatment option prior to intensification with insulin, with the advantages of a lower HE rate and greater patient convenience. Study results are limited by a higher drop-out rate in the vildagliptin arm.

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

BACKGROUND: Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients. METHODS/DESIGN: Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault, chronic kidney disease epidemiology collaboration and Hoek formulae); the incidence of proteinuria; the incidence of adverse events and serious adverse events; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis. DISCUSSION: This study aims to demonstrate superior renal function, comparable efficacy, and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with standard tacrolimus. This study also evaluates the antiviral benefit by early initiation of everolimus. TRIAL REGISTRATION: NCT01551212 .

Higher Risk of Hypoglycemia with Glimepiride Versus Vildagliptin in Patients with Type 2 Diabetes is not Driven by High Doses of Glimepiride: Divergent Patient Susceptibilities?

INTRODUCTION: In a previously published study, vildagliptin showed a reduced risk of hypoglycemia versus glimepiride as add-on therapy to metformin at similar efficacy. Glimepiride was titrated from a starting dose of 2 mg/day to a maximum dose of 6 mg/day. It is usually assumed that the increased hypoglycemia with glimepiride was driven by the 6 mg/day dose; it was therefore of interest to assess whether the risk of hypoglycemia is also different between vildagliptin and a low (2 mg/day) dose of glimepiride. METHODS: Data (n = 3,059) were from the aforementioned randomized, double-blind study. Comparisons between vildagliptin (50 mg twice daily) and glimepiride (subgroups of patients on 2 mg/day, 6 mg/day, and 'other', and overall glimepiride group) were done by modeling hypoglycemia risk as a function of time and last-measured glycated hemoglobin (HbA1c) using discrete event time modeling, with treatment, age, gender as additional covariates. RESULTS: The hypoglycemia risk was significantly lower in patients receiving vildagliptin versus patients remaining on glimepiride 2 mg/day throughout the study, with similar results unadjusted or adjusted for last HbA1c [adjusted hazard ratio (HR) = 0.06 (95% CI 0.03, 0.11)]. The risk of hypoglycemia was very low with vildagliptin over the full HbA1c range, while the risk with glimepiride 2 mg/day increased with lower HbA1c. The increase for lower levels of HbA1c was more pronounced in the glimepiride 2 mg/day than 6 mg/day subgroup, with the 6 mg/day subgroup showing the lowest hypoglycemia risk among the glimepiride groups [adjusted HR vildagliptin vs. 6 mg/day glimepiride = 0.21 (95% CI 0.11, 0.40)]. CONCLUSION: The data show a substantially lower risk of confirmed hypoglycemia with vildagliptin compared to low-dose (2 mg/day) glimepiride. The analysis indicates that the previously reported results are not driven by high doses of glimepiride and points to interesting differences among patients regarding the susceptibility to hypoglycemia with sulfonylureas.

Real-life effectiveness and tolerability of vildagliptin and other oral glucose-lowering therapies in patients with type 2 diabetes in Germany.

INTRODUCTION: Metformin is an established first-line treatment for patients with type 2 diabetes mellitus (T2DM), but treatment intensification with other oral antidiabetes drugs (OADs) is usually required over time. Effectiveness of diabetes control with vildagliptin and vildagliptin/metformin was a 1-year, large observational study of 45,868 patients with T2DM across 27 countries which assessed effectiveness and safety of vildagliptin as add-on therapy to other OADs versus other comparator OAD combinations. Here, we present the data from Germany. METHODS: Patients inadequately controlled with monotherapy were eligible only after the add-on treatment was finalized. Patients were assigned to either vildagliptin or comparator OADs [sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors or metformin, excluding dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon-like peptide-1 mimetic/analogues]. The primary efficacy endpoint was the proportion of patients achieving a glycosylated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event or weight gain ≥5%. One secondary efficacy endpoint was the proportion of patients achieving HbA1c <7% without hypoglycemia and weight gain. Change in HbA1c from baseline to study endpoint and safety were assessed. RESULTS: Of 8,887 patients enrolled in Germany, 6,679 received vildagliptin and 1,695 received other OADs. The mean ± SD baseline age, HbA1c, and T2DM duration were 62.8 ± 11.0 years, 7.7 ± 1.2%, and 5.8 ± 4.9 years, respectively. The proportion of patients achieving the primary (34.5% vs. 30.5%, p < 0.01) and secondary (25.4% vs. 21.7%, p = 0.01) endpoints was higher with vildagliptin than comparator OADs. Vildagliptin showed a numerically greater reduction in HbA1c (0.7%) from baseline vs. comparator OADs (0.6%). The overall incidence of adverse events was similar. CONCLUSION: In real life, treatment with vildagliptin is associated with a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared with other OADs in Germany.

Vildagliptin in addition to metformin improves retinal blood flow and erythrocyte deformability in patients with type 2 diabetes mellitus - results from an exploratory study.

Numerous rheological and microvascular alterations characterize the vascular pathology in patients with type 2 diabetes mellitus (T2DM). This study investigated effects of vildagliptin in comparison to glimepiride on retinal microvascular blood flow and erythrocyte deformability in T2DM.Fourty-four patients with T2DM on metformin monotherapy were included in this randomized, exploratory study over 24 weeks. Patients were randomized to receive either vildagliptin (50 mg twice daily) or glimepiride individually titrated up to 4 mg in addition to ongoing metformin treatment. Retinal microvascular blood flow (RBF)and the arteriolar wall to lumen ratio (WLR) were assessed using a laser doppler scanner. In addition, the rythrocyte elongation index (EI) was measured at different shear stresses using laserdiffractoscopy.Both treatments improved glycaemic control (p < 0.05 vs. baseline; respectively). While only slight changes in RBF and the WLR could be observed during treatment with glimepiride, vildagliptin significantly increased retinal bloodflow and decreased the arterial WLR (p < 0.05 vs. baseline respectively). The EI increased during both treatments over a wide range of applied shear stresses (p < 0.05 vs. baseline). An inverse correlation could be observed between improved glycaemic control (HbA1c) and EI (r = -0.524; p < 0.0001) but not with the changes in retinal microvascular measurements.Our results suggest that vildagliptin might exert beneficial effects on retinal microvascular blood flow beyond glucose control. In contrast, the improvement in erythrocyte deformability observed in both treatment groups,seems to be a correlate of improved glycaemic control.

Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study.

AIM: To investigate efficacy and safety of vildagliptin compared to other oral antidiabetics in clinical practice in Germany. METHODS: In this prospective, open, observational study, patients with type 2 diabetes mellitus (T2DM) previously on oral monotherapy were selected by their treating physician to receive either vildagliptin add-on to metformin (cohort 1), vildagliptin + metformin single-pill combination (SPC) (cohort 2) or another dual combination therapy with oral antidiabetic drugs (OADs) (cohort 3). According to routine clinical practice, interim examinations occurred every 3 mo: at baseline, after approximately 3 mo and after approximately 6 mo. Parameters documented in the study included demographic and diagnostic data, history of T2DM, data on diabetes control, vital signs, relevant prior and concomitant medication and disease history. Efficacy was assessed by changes in HbA1c and fasting plasma glucose (FPG) 3 mo and 6 mo after initiation of dual combination therapy. Safety was assessed by adverse event reporting and measurement of specific laboratory values (serum creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatine kinase). RESULTS: Between October 2009 and January 2011, a total of 3881 patients were enrolled in this study. Since 47 patients were withdrawn due to protocol violations, 3834 patients were included in the statistical analysis. There were no relevant differences between the three cohorts concerning age, body weight and body mass index. Average diabetes duration was approximately 6 years and mean HbA1c was between 7.6% and 7.9% at baseline. Antidiabetic treatment was recorded in 3648 patients. Patients were treated with vildagliptin add-on to metformin (n = 603), vildagliptin + metformin (SPC) (n = 2198), and other oral OADs including combinations of metformin with sulfonylurea (n = 370), with glitazones (n = 123), other dipeptidyl peptidase-4 inhibitors (n = 99). After 6 mo of treatment, the absolute decrease in HbA1c (mean ± SE) was significantly more pronounced in patients receiving vildagliptin add-on to metformin (-0.9% ± 0.04%) and vildagliptin + metformin (SPC) (-0.9% ± 0.03%) than in patients receiving other OADs (-0.6% ± 0.04%; P < 0.0001). In addition, significant cohort differences were observed for the improvement in FPG after 6 mo treatment (vildagliptin add-on to metformin: -291 mg/L ± 18.3 mg/L; vildagliptin +metformin (SPC): -305 mg/L ± 9.6 mg/L; other antidiabetic drugs: -209 mg/L ± 14.0 mg/L for (P < 0.0001). Moderate decreases in body weight (absolute difference between last control and baseline: mean ± SE) were observed for patients in all cohorts (vildagliptin add-on to metformin: -1.4 kg ± 0.17 kg; vildagliptin + metformin (SPC): -1.7 kg ± 0.09 kg; other OADs: -0.8 kg ± 0.13 kg). No significant differences in adverse events (AEs) and other safety measures were observed between the cohorts. When performing an additional analysis by age (patients < 65 years vs patients ≥ 65 years), there was no relevant difference in the most common AEs between the two age groups and the AE profile was similar to that of the overall patient population. CONCLUSION: Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients.

Sleep and brain energy levels: ATP changes during sleep.

Sleep is one of the most pervasive biological phenomena, but one whose function remains elusive. Although many theories of function, indirect evidence, and even common sense suggest sleep is needed for an increase in brain energy, brain energy levels have not been directly measured with modern technology. We here report that ATP levels, the energy currency of brain cells, show a surge in the initial hours of spontaneous sleep in wake-active but not in sleep-active brain regions of rat. The surge is dependent on sleep but not time of day, since preventing sleep by gentle handling of rats for 3 or 6 h also prevents the surge in ATP. A significant positive correlation was observed between the surge in ATP and EEG non-rapid eye movement delta activity (0.5-4.5 Hz) during spontaneous sleep. Inducing sleep and delta activity by adenosine infusion into basal forebrain during the normally active dark period also increases ATP. Together, these observations suggest that the surge in ATP occurs when the neuronal activity is reduced, as occurs during sleep. The levels of phosphorylated AMP-activated protein kinase (P-AMPK), well known for its role in cellular energy sensing and regulation, and ATP show reciprocal changes. P-AMPK levels are lower during the sleep-induced ATP surge than during wake or sleep deprivation. Together, these results suggest that sleep-induced surge in ATP and the decrease in P-AMPK levels set the stage for increased anabolic processes during sleep and provide insight into the molecular events leading to the restorative biosynthetic processes occurring during sleep.

Increased slow wave sleep and reduced stage 2 sleep in children depending on exercise intensity.

BACKGROUND: There is controversy about the consequences of physical exercise on human sleeping behaviors. Evidence suggests that voluntary physical exercise affects brain structures and functions. However, there are inconsistent data regarding the effects of exercise on sleep architecture and sleep continuity, especially the amounts of slow wave sleep (SWS) and rapid eye movement (REM) sleep. OBJECTIVE: The aim of the present study was to investigate the effects of moderate and high intense physical exercise on vigilance state and sleep patterns in school-aged children. METHODS: Eleven healthy children (12.6+/-0.8 years old) were recruited for this polysomnographic study and underwent two exercise sessions. The two exercise sessions on a bicycle ergometer were performed 3-4h prior to bedtime, lasted 30min and varied in intensity. The moderate-intensity exercise was at 65-70% of maximal heart rate (HR(max)) while the high-intensity exercise was at 85-90% HR(max) to exhaustion. Polysomnographic and physiological measurements, including oximetry, were made on three nights in random order and separated by 1 week. Vigilance tests were carried out before and after the three sleep periods. RESULTS: Only high-intensity exercise resulted in a significantly elevated SWS proportion and less sleep in stage 2 as well as a higher sleep efficiency and shorter sleep onset latency. No significant effects on REM sleep were found. CONCLUSION: The results suggest that exercise intensity is responsible for the effects on stage 2 sleep and SWS in children and support the hypothesis of homeostatic sleep regulation.

Impact of singular excessive computer game and television exposure on sleep patterns and memory performance of school-aged children.

OBJECTIVE: Television and computer game consumption are a powerful influence in the lives of most children. Previous evidence has supported the notion that media exposure could impair a variety of behavioral characteristics. Excessive television viewing and computer game playing have been associated with many psychiatric symptoms, especially emotional and behavioral symptoms, somatic complaints, attention problems such as hyperactivity, and family interaction problems. Nevertheless, there is insufficient knowledge about the relationship between singular excessive media consumption on sleep patterns and linked implications on children. The aim of this study was to investigate the effects of singular excessive television and computer game consumption on sleep patterns and memory performance of children. METHODS: Eleven school-aged children were recruited for this polysomnographic study. Children were exposed to voluntary excessive television and computer game consumption. In the subsequent night, polysomnographic measurements were conducted to measure sleep-architecture and sleep-continuity parameters. In addition, a visual and verbal memory test was conducted before media stimulation and after the subsequent sleeping period to determine visuospatial and verbal memory performance. RESULTS: Only computer game playing resulted in significant reduced amounts of slow-wave sleep as well as significant declines in verbal memory performance. Prolonged sleep-onset latency and more stage 2 sleep were also detected after previous computer game consumption. No effects on rapid eye movement sleep were observed. Television viewing reduced sleep efficiency significantly but did not affect sleep patterns. CONCLUSIONS: The results suggest that television and computer game exposure affect children's sleep and deteriorate verbal cognitive performance, which supports the hypothesis of the negative influence of media consumption on children's sleep, learning, and memory.