'Dynamic' Starling mechanism: effects of ageing and physical fitness on ventricular-arterial coupling

Cardiovascular diseases increase with advancing age, associated with left ventricular and arterial stiffening in humans. In contrast, daily exercise training prevents and/or improves both ventricular and arterial stiffening with ageing. We propose a new approach to quantify the dynamics of the Starling mechanism, namely the beat-to-beat modulation of stroke volume (SV) caused by beat-to-beat alterations in left ventricular filling, which we propose reflects the complex interaction between ventricular and arterial stiffness. We hypothesized that the dynamic Starling mechanism would be impaired with ageing, and that this impairment would be prevented and restored by daily exercise training. Two different approaches were employed: (1) a cross-sectional study to assess the effects of ageing and life-long exercise training; and (2) a longitudinal study to assess the effects of one-year endurance training in the elderly. Spectral transfer function gain between beat-to-beat changes in left ventricular end-diastolic pressure and SV was used as an index of the dynamic Starling mechanism. Gain was significantly lower in the sedentary elderly (70 ± 3 years) than in both young individuals (27 ± 6 years) and Masters athletes (68 ± 3 years), and it was significantly lower in Masters athletes than in young controls (elderly: 0.37 ± 0.11; Masters athletes: 0.96 ± 0.55; young: 1.52 ± 0.42 ml m⁻² mmHg⁻¹, mean ± s.d. ). Gain increased by 65% after one-year exercise training in the elderly, although the response was quite variable ( P = 0.108). These findings suggest that the dynamic Starling mechanism is impaired with human ageing possibly due to ventricular–arterial stiffening. Life-long daily exercise training may minimize this impairment, although the effect may be limited particularly when started later in life.     

Allostasis and the development of internalizing and externalizing problems: changing relations with physiological systems across adolescence

Allostasis, or the maintenance of stability through physiological change, refers to the process by which individuals adjust to the continually changing demands that are put upon somatic activity by salient events. Bauer and colleagues proposed that allostasis could be detected through patterns of the joint reactivity of the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis system under stressful conditions. We examined the associations between ANS and HPA reactivity and the development of externalizing and internalizing problems over 2 years in a sample of 215 adolescents. The interactions of ANS and HPA reactivity were contemporaneously associated with, and longitudinally predictive of, adolescents' emotional and behavioral problems. Adolescents with symmetrical high reactivity across systems had more internalizing and fewer externalizing problems initially. Over time, both symmetrical and asymmetrical reactivity predicted increasing internalizing problems in girls, depending on the measure of ANS activity that was examined, heart rate, or blood pressure reactivity. Implications for the understanding of allostasis and the dynamic nature of the relations between multiple physiological regulatory systems and adolescents' developing psychopathology are discussed.     

A monoclonal antibody raised against a synthetic peptide representative of part of the amino acid sequence of rat immunoglobulin E detects thermally induced changes in that region of the IgE molecule.

A mouse monoclonal antibody (mAb) has been produced by conventional cell fusion methods against a synthetic peptide, p123, representative of a portion of the CH4 domain of rat immunoglobulin E (IgE). This monoclonal antibody was reactive with both peptide and purified rat IgE (p.rat IgE) by indirect enzyme immunosorbent assay (ELISA), and its binding to p.rat IgE was found to be inhibitable by pre-incubation with rat ascitic fluid containing the immunocytoma 162 (IR162) IgE. Heating of the immunocytoma IgE in solution at 56 degrees for 1 hr resulted in its enhanced binding of the mAb. The effect of this treatment was investigated further using p.rat IgE heated at 56 degrees for various time intervals between 0 and 60 min. The mAb showed enhanced binding to IgE heated for as little as 10 min, a similar level of binding being shown by samples heated for 30 and 60 min. The degree of aggregation of the IgE molecules brought about by the heat treatments was measured by differential UV absorption. This revealed a decrease in the proportion of monomeric IgE with an accompanying increase in the percentage of dimer and larger aggregates with increased time of heating at 56 degrees. These absorption data, together with the ELISA inhibition data, suggest that, rather than inducing changes mediated by aggregation of the IgE molecules in solution, heating at 56 degrees causes subtle alterations in the conformation of individual IgE molecules at specific sites within their CH4 domains, one of which is detected by this mAb.     

Interactions between clock gene mutation, circadian phenotype and tumor growth in mice

The relation between circadian physiology (rest-activity and body temperature) and the growth of a grafted tumor (Glasgow osteosarcoma-GOS) was investigated in the mice with mutation of clock gene (ClockDelta19(-)) or gene controlled by the clock (Vpac(-/-)). Circadian rhythms in temperature and activity were stable, with an approximately 24-h period in all the mice synchronized by the alternation of 12 h of light and 12 h of darkness (LD 12:12). Following exposure to constant darkness (DD), both rhythms persisted in ClockDelta19(-), yet with a lengthening of the period by 4.5 h compared to wild type. In DD, the amplitude increased by 45.9% for the temperature rhythm (p<0.001) and by 17.4% for the activity one (p=0.08) as compared to LD 12:12 in ClockDelta19(-). The improvement of circadian coordination and/or the lengthening of the circadian period observed in ClockDelta19(-) kept in DD was associated with a moderate slowing down of tumor growth. Although the exposure to DD ablated the activity and temperature rhythms in Vpac(-/-), no modification in tumor growth was observed as compared to wide type or Vpac(-/-) in LD 12:12. Major alternations of circadian physiology can result from interactions between photoperiodic environment and mutation of clock gene or gene controlled by the clock. In these conditions, we have shown that the alternation of the circadian phenotype does not seem to constitute an essential determinant of the growth of a grafted tumor.     

Meditation with yoga, group therapy with hypnosis, and psychoeducation for long-term depressed mood: a randomized pilot trial

This randomized pilot study investigated the effects of meditation with yoga (and psychoeducation) versus group therapy with hypnosis (and psychoeducation) versus psychoeducation alone on diagnostic status and symptom levels among 46 individuals with long-term depressive disorders. Results indicate that significantly more meditation group participants experienced a remission than did controls at 9-month follow-up. Eight hypnosis group participants also experienced a remission, but the difference from controls was not statistically significant. Three control participants, but no meditation or hypnosis participants, developed a new depressive episode during the study, though this difference did not reach statistical significance in any case. Although all groups reported some reduction in symptom levels, they did not differ significantly in that outcome. Overall, these results suggest that these two interventions show promise for treating low- to moderate-level depression.     

Increased urinary nitric oxide oxidation products in children with active coeliac disease

BACKGROUND: Nitric oxide (NO) production catalyzed by iNOS (inducible NO synthase) is thought to take place mainly in macrophages after activation by inflammatory mediators. NO is subsequently oxidized to nitrite and nitrate, which are excreted in urine. The concentration of inflammatory mediators in small bowel biopsy specimens from patients with coeliac disease is increased. The latter could induce increased NO production by stimulation of intestinal macrophage iNOS, resulting in high levels of urinary NO oxidation products, nitrite and nitrate (NOx). AIM: In the present study we evaluated the urinary NOx/creatinine ratios in children with active coeliac disease (n = 22), coeliac disease patients on a gluten-free diet (n = 9), healthy (n = 11) and sick control children (n = 18). METHODS: The Griess reagent method was used for measuring urinary NOx. RESULTS: Median NOx/creatinine ratios of active coeliac disease patients, coeliac disease patients on a gluten-free diet, healthy and sick control patients were 1.21, 0.19, 0.10 and 0.13 mmol/mmol, respectively. All active coeliac disease patients showed increased NOx/ creatinine ratios. Urinary NOx/creatinine ratios of the active coeliac disease patients were significantly higher than those of healthy controls (p < 0.0001), sick controls (p < 0.0001) and coeliac disease patients on a gluten-free diet (p < 0.0001). CONCLUSION: The urinary NOx/creatinine ratio is increased in patients with active coeliac disease and reverts to normal on a gluten-free diet.     

Predominance of nocturnal hypertension in pediatric renal allograft recipients

Hypertension is common in children with end-stage renal disease who have undergone renal transplantation. We performed ambulatory blood pressure monitoring (ABPM) in renal allograft recipients who were on stable maintenance immunosuppressive medications and were more than six months post-transplant. Echocardiographic measurement of left ventricular mass index (LVMI) was obtained at the time of ABPM. Twenty-nine children with a mean age of 14.8 yr (8-18 yr) were evaluated 4.3 yr (0.6-12.8 yr) after deceased donor (n = 13) or living donor (n = 16) transplantation. BP levels were higher during sleep compared with when awake using the 95th percentile to standardize mean BP for each period: mean BP was expressed as a standard deviation score (SDS) for each time period, awake vs. sleep: systolic (s) BP SDS were 0.43 +/- 1.3 vs. 1.29 +/- 1.2 (p < 0.001) and diastolic (d) BP SDS were 0.04 +/- 1.3 vs. 1.34 +/- 1.2 (p < 0.001). Significant differences between awake and sleep BP were also confirmed using the mean BP for each period expressed as a BPI. Hypertension (HTN) during sleep was more common than awake HTN. Based upon BPI, 21% had sHTN when awake compared with 48% during sleep and 7% had dHTN when awake compared with 41% during sleep (p < 0.05). Based upon mean BP load, 38% had sHTN when awake compared with 55% during sleep and 21% demonstrated dHTN when awake compared with 52% during sleep (p < 0.05). Left ventricular mass (LVM) was abnormally increased in six of 17 children (35%); LVM was not correlated with BP. Children prescribed angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARB) had significantly lower systolic BP compared with those on calcium channel blocking agents (CCB). Mean sSDS was -0.11 +/- 1.1 in those children on ACEi/ARB compared with 1.6 +/- 1.2 in those on CCB (p = 0.02): sSDS during sleep was significantly lower in the ACEi/ARB group compared with CCB (0.70 +/- 1.1 vs. 2.0 +/- 1.1, p = 0.04). Isolated nocturnal HTN is more common than daytime HTN among clinically stable pediatric renal allograft recipients. Detection and treatment of nocturnal HTN in pediatric allograft recipients could potentially affect graft survival.