Phosphocreatine interacts with phospholipids, affects membrane properties and exerts membrane-protective effects

A broad spectrum of beneficial effects has been ascribed to creatine (Cr), phosphocreatine (PCr) and their cyclic analogues cyclo-(cCr) and phospho-cyclocreatine (PcCr). Cr is widely used as nutritional supplement in sports and increasingly also as adjuvant treatment for pathologies such as myopathies and a plethora of neurodegenerative diseases. Additionally, Cr and its cyclic analogues have been proposed for anti-cancer treatment. The mechanisms involved in these pleiotropic effects are still controversial and far from being understood. The reversible conversion of Cr and ATP into PCr and ADP by creatine kinase, generating highly diffusible PCr energy reserves, is certainly an important element. However, some protective effects of Cr and analogues cannot be satisfactorily explained solely by effects on the cellular energy state. Here we used mainly liposome model systems to provide evidence for interaction of PCr and PcCr with different zwitterionic phospholipids by applying four independent, complementary biochemical and biophysical assays: (i) chemical binding assay, (ii) surface plasmon resonance spectroscopy (SPR), (iii) solid-state (31)P-NMR, and (iv) differential scanning calorimetry (DSC). SPR revealed low affinity PCr/phospholipid interaction that additionally induced changes in liposome shape as indicated by NMR and SPR. Additionally, DSC revealed evidence for membrane packing effects by PCr, as seen by altered lipid phase transition. Finally, PCr efficiently protected against membrane permeabilization in two different model systems: liposome-permeabilization by the membrane-active peptide melittin, and erythrocyte hemolysis by the oxidative drug doxorubicin, hypoosmotic stress or the mild detergent saponin. These findings suggest a new molecular basis for non-energy related functions of PCr and its cyclic analogue. PCr/phospholipid interaction and alteration of membrane structure may not only protect cellular membranes against various insults, but could have more general implications for many physiological membrane-related functions that are relevant for health and disease.

Short-term effects of hygiene education for preschool (kindergarten) children: a clinical study

AIM: To evaluate the outcomes of short (15 minutes) oral hygiene vs. hand hygiene education for preschool children 4 weeks after these interventions. MATERIALS AND METHODS: Sixty-one preschool children (age range 4-6 years) attending four kindergarten classes participated in a 15-minute health education programme on the importance of body cleanliness for general health. In addition, specific instructions on oral hygiene were provided for two randomly selected classes (30 children), while the remaining two classes (31 children) were given instruction of hand and nail cleaning. The oral hygiene status was assessed usingthe plaque control record (PCR). The cleanliness of the hands and fingernails was determined using a hand hygiene index (HHI) and a nail hygiene index (NHI). All three parameters were assessed before the intervention as well as 4 weeks thereafter. RESULTS: Four weeks after education, the PCR had improved for all children from 79.95% to 72.35% (p < 0.001). The NHI had improved from 74.91% to 61.71% (p < 0.001). In addition, the mean PCR of the children given oral hygiene instruction decreased from 83.67% to 72.40%, while the mean PCR of the children given hand and nail cleaning instruction decreased from 76.23% to 72.29% (interaction effect 'time x type of instruction': p = 0.044). Girls' PCR improved significantly more than boys' PCR (Girls, 80.98 vs. 69.71; boys, 78.33 vs. 75.31; p = 0.021). CONCLUSIONS: The results of the study show that even a short, school-based educational intervention at an early age may affect children's oral health promotion significantly. Teachers should, therefore, be encouraged to educate children from an early age about oral hygiene promotion.

Pineal calcification in Alzheimer's disease: an in vivo study using computed tomography

Melatonin has been postulated to have diverse properties, acting as an antioxidant, a neuroprotector, or a stabilizer within the circadian timing system, and is thus thought to be involved in the aging process and Alzheimer's disease (AD). We used computed tomography to determine the degree of pineal calcification (DOC), an intra-individual melatonin deficit marker, as well as the size of uncalcified pineal tissue, in 279 consecutive memory clinic outpatients (AD: 155; other dementia: 25; mild cognitive impairment: 33; depression: 66) and 37 age-matched controls. The size of uncalcified pineal tissue in patients with AD (mean 0.15 cm(2) [S.D. 0.24]) was significantly smaller than in patients with other types of dementia (0.26 [0.34]; P=0.038), with depression (0.28 [0.34]; P=0.005), or in controls (0.25 [0.31]; P=0.027). Additionally, the DOC in patients with AD (mean 76.2% [S.D. 26.6]) was significantly higher than in patients with other types of dementia (63.7 [34.7]; P=0.042), with depression (60.5 [33.8]; P=0.001), or in controls (64.5 [30.6]; P=0.021). These two findings may reflect two different aspects of melatonin in AD. On the one hand, the absolute amount of melatonin excretion capability, as indicated by uncalcified pineal volume, refers to the antioxidant properties of melatonin. On the other hand, the relative reduction in melatonin production capability in the individual, as indicated by DOC, refers to the circadian properties of melatonin.

Musculoskeletal spectroscopy

Magnetic resonance spectroscopy (MRS) of skeletal muscle has been successfully applied by physiologists over several decades, particularly for studies of high-energy phosphates (by (31)P-MRS) and glycogen (by (13)C-MRS). Unfortunately, the observation of these heteronuclei requires equipment that is typically not available on clinical MR scanners, such as broadband capability and a second channel for decoupling and nuclear Overhauser enhancement (NOE). On the other hand, (1)H-MR spectra of skeletal muscle can be acquired on many routine MR systems and also provide a wealth of physiological information. In particular, studies of intramyocellular lipids (IMCL) attract physiologists and endocrinologists because IMCL levels are related to insulin resistance and thus can lead to a better understanding of major health problems in industrial countries. The combination of (1)H-, (13)C-, and (31)P-MRS gives access to the major long- and short-term energy sources of skeletal muscle. This review summarizes the technical aspects and unique MR-methodological features of the different nuclei. It reviews clinical studies that employed MRS of one or more nuclei, or combinations of MRS with other MR modalities. It also illustrates that MR spectra contain additional physiological information that is not yet used in routine clinical applications.

Effects of a comprehensive rehabilitation program on quality of life in patients with chronic heart failure

This evaluation was performed to assess the effects of a new, comprehensive outpatient rehabilitation program on generic and disease-specific quality of life related to exercise tolerance in stable chronic heart failure patients. Fifty-one patients (aged 59+/-11 years; 84% men) were treated for 12 weeks. Patients underwent optimized drug treatment, exercise training, and counseling and education. At baseline and at the end of the program, functional status, exercise capacity, and quality of life were assessed using the Medical Outcomes Study 36-item Short-Form Health Survey and the Minnesota Living with Heart Failure Questionnaire. Left ventricular ejection fraction and New York Heart Association functional class, as well as measures of physical fitness and walking distance covered in 6 minutes, improved significantly (by 11%-20% and by 58% on average, respectively). Physical functioning (effect size, 0.38; p<0.0001), role functioning (effect size, 0.17; p<0.05), and mental component score (effect size, 0.47; p<0.0001) on the questionnaire improved significantly. Disease-specific quality of life improved in sum score (effect size, 0.24; p<0.0001) and physical component score (effect size, 0.35; p<0.0001). The latter was inversely correlated to improvement in peak power output (r= -0.31; p<0.05). In patients with stable chronic heart failure, significant improvements in both generic and disease-specific quality of life related to improved exercise tolerance can be achieved within 12 weeks of comprehensive rehabilitation.

Salt sensitivity of children with low birth weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.

Outcome indicators for vitrectomy in Terson syndrome

PURPOSE: There is no general agreement on the best indication and timing of vitrectomy in patients suffering from Terson syndrome. Therefore, we reviewed our cases in order to assess factors interfering with the functional outcome and complication rates after vitrectomy. METHODS: In this retrospective consecutive case series, the records from all patients undergoing vitrectomy for Terson syndrome between 1975 and 2005 were evaluated. RESULTS: Thirty-seven patients (45 eyes) were identified, 36 of whom (44 corresponding eyes) were eligible. The best-corrected visual acuity (BCVA) at first and last presentation was 0.07 +/- 0.12 and 0.72 +/- 0.31, respectively. Thirty-five eyes (79.5%) achieved a postoperative BCVA of > or = 0.5; 26 (59.1%) eyes achieved a postoperative BCVA of > or = 0.8. Patients operated on within 90 days of vitreous haemorrhage achieved a better final BCVA than those with a longer latency (BCVA of 0.87 +/- 0.27 compared to 0.66 +/- 0.31; P = 0.03). Patients younger than 45 years of age achieved a better final BCVA than older patients (0.85 +/- 0.24 compared to 0.60 +/- 0.33; P = 0.006). Retinal detachment developed in four patients between 6 and 27 months after surgery. Seven patients (16%) required epiretinal membrane peeling and seven cataract surgery. CONCLUSION: Ninety-eight per cent of our patients experienced a rapid and persisting visual recovery after removal of a vitreous haemorrhage caused by Terson syndrome. A shorter time between occurrence of vitreous haemorrhage and surgery as well as a younger patient age are predictive of a better outcome. Generally, the surgical risk is low, but complications (namely retinal detachment) may occur late after surgery.

The moderating effect of personal mastery and the relations between stress and Plasminogen Activator Inhibitor-1 (PAI-1) antigen

OBJECTIVE: This study tested whether feelings of personal control over one's life circumstances (i.e., personal mastery) would attenuate the relations between stress (i.e., negative life events and caregiving distress) and Plasminogen Activator Inhibitor (PAI)-1 antigen, an inhibitor of fibrinolysis implicated in the development of cardiovascular disease. DESIGN: Seventy-one spousal dementia caregivers were assessed for plasma levels of PAI-1 antigen, negative life events, caregiver distress, and feelings of personal mastery. Regression analysis was used to determine if personal mastery moderated the relations between stress (i.e., life stress and caregiving distress) and PAI-1 antigen levels. MAIN OUTCOME MEASURE: Plasminogen activator inhibitor (PAI)-1 antigen in plasma. RESULTS: After controlling for other factors associated with PAI-1 antigen levels, negative life events were positively associated with plasma PAI-1 antigen concentrations in participants low in personal mastery (beta = .31; p = .050) but not in individuals high in personal mastery (beta = .22; p = .184). The moderating effect of mastery on the relations between caregiving distress and PAI-1 antigen did not reach statistical significance (p = .091). CONCLUSIONS: These data suggest that mastery may protect individuals from some of the alterations in hemostatic factors that have been linked to cardiovascular risk.

Relationship between heart rate variability, interleukin-6, and soluble tissue factor in healthy subjects

Decreased heart rate variability (HRV) has been associated with an increased risk of atherosclerosis. We hypothesized that a decrease in frequency domains of resting HRV would be associated with elevated plasma levels of interleukin (IL)-6 and soluble tissue factor (sTF) both previously shown to prospectively predict atherothrombotic events in healthy subjects. Subjects were 102 healthy and unmedicated black and white middle-aged men and women. We determined IL-6 and sTF antigen in plasma and HRV measures from surface electrocardiogram data using spectral analysis. All statistical analyses controlled for age, gender, ethnicity, smoking status, blood pressure, and body mass index. Low amounts of low frequency (LF) power (beta=-0.31, p=0.007) and high frequency (HF) power (beta=-0.36, p=0.002) were associated with increased amounts of IL-6, explaining 7% and 9% of the variance, respectively. Interactions between LF power and IL-6 (p=0.002) and between HF power and IL-6 (p=0.012) explained 8% and 5%, respectively, of the variance in sTF. Post hoc analyses showed associations between IL-6 and sTF when LF power (beta=0.51, p<0.001) and HF power (beta=0.48, p<0.001) were low but not when LF power and high HF power were high. The findings suggest that systemic low-grade inflammatory activity is associated with a decrease in HRV. Furthermore, there was a positive relationship between plasma levels of IL-6 and sTF antigen when HRV was low. Inflammation and related hypercoagulability might particularly contribute to atherothrombotic events in a setting of decreased HRV.

One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial

BACKGROUND: Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. OBJECTIVES: To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. MATERIAL AND METHODS: Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. RESULTS: Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. CONCLUSIONS: Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

Context: Sarcopenia is thought to be associated with mitochondrial (M) loss. It is unclear whether the decrease in M content is consequent to aging per se or to decreased physical activity. Objectives: To examine the influence of fitness on M content and function, and to assess whether exercise could improve M function in older adults. Design and subjects: Three distinct studies were conducted: 1) a cross-sectional observation comparing M content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults (A) and sedentary (S) subjects matched for age and gender; 3) a 4-month exercise intervention in S. Setting: University-based clinical research center Outcomes: M volume density (Mv) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins (ETC) by western blotting, mRNAs for transcription factors involved in M biogenesis by qRT-PCR and in-vivo oxidative capacity (ATPmax) by (31)P-MR spectroscopy. Peak oxygen uptake (VO2peak) was measured by GXT. Results: VO2peak was strongly correlated with Mv in eighty 60-80 yo adults. Comparison of A vs. S revealed differences in Mv, ATPmax and some ETC complexes. Finally, exercise intervention confirmed that S are able to recover Mv, ATPmax and specific transcription factors. Conclusions: These data suggest that 1) aging per se is not the primary culprit leading to M dysfunction, 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle M content and may prevent aging muscle comorbidities and 3) the improvement of M function is all about content.

Changes in situational and dispositional factors as predictors of job satisfaction

Arguably, job satisfaction is one of the most important variables with regard to work. When explaining job satisfaction, research usually focuses on predictor variables in terms of levels but neglects growth rates. Therefore it remains unclear how potential predictors evolve over time and how their development affects job satisfaction. Using multivariate latent growth modeling in a study with 1145 young workers over five years, we analyzed how well job satisfaction is predicted a) by levels of situational (i.e., job control) and dispositional (i.e., Core Self-Evaluations (CSE)) factors and b) by growth per year of these predictors. Results showed both intercepts and slopes to be related to each other, suggesting a joint growth of job control and CSE during early careers. Job satisfaction after five years was best predicted by the slopes of job control (β = .31, p < .001) and CSE (β = .34, p < .01). These findings provide further longitudinal evidence for the role of situational as well as dispositional factors for predicting job satisfaction. In addition, growth rates per year were better predictors than initial levels. Furthermore, a lack of change in job control or CSE went along with a drop in job satisfaction, implying that young workers need to perceive things to be improving in order to increase, or at least maintain, their level of job satisfaction. In terms of theory, the relative importance of levels versus changes deserves more attention. In terms of practical implications, our results suggest a double emphasis on job design (i.e., granting sufficient, and increasing, control) and on personal development (e.g., through training) so that people experience a match between both. Finally, negative associations between initial levels and growth rates suggest that people are quite successful in achieving a reasonable fit between their job characteristics and their needs and goals.

Surgery for low-grade glioma infiltrating the central cerebral region: location as a predictive factor for neurological deficit, epileptological outcome, and quality of life

OBJECT A main concern with regard to surgery for low-grade glioma (LGG, WHO Grade II) is maintenance of the patient's functional integrity. This concern is particularly relevant for gliomas in the central region, where damage can have grave repercussions. The authors evaluated postsurgical outcomes with regard to neurological deficits, seizures, and quality of life. METHODS Outcomes were compared for 33 patients with central LGG (central cohort) and a control cohort of 31 patients with frontal LGG (frontal cohort), all of whom had had medically intractable seizures before undergoing surgery with mapping while awake. All surgeries were performed in the period from February 2007 through April 2010 at the same institution. RESULTS For the central cohort, the median extent of resection was 92% (range 80%-97%), and for the frontal cohort, the median extent of resection was 93% (range 83%-98%; p = 1.0). Although the rate of mild neurological deficits was similar for both groups, seizure freedom (Engel Class I) was achieved for only 4 (12.1%) of 33 patients in the central cohort compared with 26 (83.9%) of 31 patients in the frontal cohort (p < 0.0001). The rate of return to work was lower for patients in the central cohort (4 [12.1%] of 33) than for the patients in the frontal cohort (28 [90.3%] of 31; p < 0.0001). CONCLUSIONS Resection of central LGG is feasible and safe when appropriate intraoperative mapping is used. However, seizure control for these patients remains poor, a finding that contrasts markedly with seizure control for patients in the frontal cohort and with that reported in the literature. For patients with central LGG, poor seizure control ultimately determines quality of life because most will not be able to return to work.

An examination of the metabolic processes underpinning critical swimming in Atlantic cod (Gadus morhua L.) using in vivo 31P-NMR spectroscopy.

Traditionally, critical swimming speed has been defined as the speed when a fish can no longer propel itself forward, and is exhausted. To gain a better understanding of the metabolic processes at work during a U(crit) swim test, and that lead to fatigue, we developed a method using in vivo (31)P-NMR spectroscopy in combination with a Brett-type swim tunnel. Our data showed that a metabolic transition point is reached when the fish change from using steady state aerobic metabolism to non-steady state anaerobic metabolism, as indicated by a significant increase in inorganic phosphate levels from 0.3+/-0.3 to 9.5+/-3.4 mol g(-1), and a drop in intracellular pH from 7.48+/-0.03 to 6.81+/-0.05 in muscle. This coincides with the point when the fish change gait from subcarangiform swimming to kick-and-glide bursts. As the number of kicks increased, so too did the Pi concentration, and the pH(i) dropped. Both changes were maximal at U(crit). A significant drop in Gibbs free energy change of ATP hydrolysis from -55.6+/-1.4 to -49.8+/-0.7 kJ mol(-1) is argued to have been involved in fatigue. This confirms earlier findings that the traditional definition of U(crit), unlike other critical points that are typically marked by a transition from aerobic to anaerobic metabolism, is the point of complete exhaustion of both aerobic and anaerobic resources.