The short-term effects of fasting on the neuroendocrine system in patients with chronic pain syndromes

It is commonly reported that short term fasting leads to mood enhancement and emotional harmonisation. We investigated psychosocial well-being and the neuroendocrine response, assessed by nightly urinary excretion of cortisol and catecholamines, in 28 inpatients with chronic pain syndromes during and after a one-week modified fast. Twenty-two of the patients (51.4 +/- 2.7 years, BMI 26.8 +/- 1.0 kg/m2) participated in a 7-day fast with daily intake of 300 kcal/day, six control patients (47.5 +/- 4.0 years; BMI 22.9 +/- 1.1 kg/m2) received a vegetarian-based diet. With fasting significant increases of the urinary concentration of noradrenaline (17.8 +/- 3.0-27.8 +/- 3.8 microg/ml), adrenaline (1.5 +/- 0.2-3.4 +/- 0.7 microg/ml) and cortisol (26.1 +/- 3.7-40.7 +/- 6.1 microg/ml) were observed, whereas controls showed no significant endocrine changes. The neuroendocrine response to fasting was pronounced in younger subjects (age <50 years) and in the presence of a BMI >25 kg/m2, moreover the increase in cortisol excretion was significantly higher in subjects with lower baseline cortisol levels. Mood and well-being increased non-significantly in both groups. Fasting was well tolerated, and regarded as beneficial by most fasting patients. Our results show that short-term fasting leads to neuroendocrine activation and may suggest that the extent of this response is dependent on the individual metabolic and endocrine state at baseline.     

Evaluation of endomorphin-1 on the activity of Na(+),K(+)-ATPase using in vitro and in vivo studies

The goal of this study was to investigate the effects of endomorphin-1 on Na(+),K(+)-ATPase activity in mouse brain synaptosome in vitro, and its antinociceptive interaction with the Na(+),K(+)-ATPase inhibitor ouabain. Endomorphin-1 (0.1 nM-10 microM) produced a concentration-dependent (EC(50): 43.19 nM, CI: 23.38-65.71 nM, E(max): 25.86%, CI: 24.53-27.20%), naloxone-reversible increase of the synaptosomal Na(+),K(+)-ATPase activity. The intrathecally (i.t.) administered endomorphin-1 (2-20 microg) produced a dose-dependent short-lasting increase in the tail-flick latency. Ouabain itself (1-1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain significantly decreased the antinociceptive effect of 2 microg endomorphin-1, but none of the other combinations did significantly differ from the endomorhin-1-treated groups. These data indicate that endomorphin-1 increases the activity of Na(+),K(+)-ATPase in vitro but this effect may play a weak role in the antinociception induced by intrathecal endomorphin-1.     

Monitoring cardiovascular changes during hemodialysis in children

Hemodialysis (HD) causes rapid volume shifts and circulatory changes. In chronic renal failure (CRF) Na+/K+ATP-ase is depressed, whereas endogenous digoxin-like factor (EDLF) is elevated. Our aim was to characterize HD-induced cardiovascular adaptation and its possible links to Na+/K+ATP-ase and EDLF. Eleven children with CRF on HD (aged 14.7 +/- 3.7 years) and 11 healthy children were investigated for basic circulatory parameters. Thoracic impedance (Zo) and circulatory parameters were monitored by impedance cardiography (ICG) during HD. Erythrocyte Na+/K+ATP-ase and EDLF were measured before and after HD. Up to the loss of 6% of total body weight, Zo rose linearly with fluid removal, above this no further increase occurred. Heart rate and mean arterial pressure (MAP) were inversely related (r = -0.97); MAP rose in the first and decreased in the second part of HD. Systemic vascular resistance paralleled MAP, whereas stroke volume rapidly decreased, but stabilized in the second part of HD. The ratio of preejection period/ventricular ejection time (PEP/VET) correlated positively with HD duration (r = 0.92), suggesting diminished cardiac filling. Cardiac index (CI) remained stable. EDLF was high in uremia accompanied by depressed Na+/K+ATP-ase (P < 0.05 and P < 0.01, respectively). Following HD Na+/K+ATP-ase normalized. Correlation between Na+/K+ATP-ase activity and MAP was linear (r = 0.85). In conclusion, ICG during HD provides detailed information concerning circulatory adaptation resulting in stable CI, suggesting that the dialysis-induced hypovolemia is compensated by the centralization of the blood volume. Changes of Na+/K+ATP-ase indicate that dialyzable blood pressure-regulating substance(s) inhibit(s) the pump. However, lack of further correlation between Na+/K+ATP-ase, EDLF, and cardiovascular parameters indicates the complexity of the regulatory processes.     

Prolonged fasting in patients with chronic pain syndromes leads to late mood-enhancement not related to weight loss and fasting-induced leptin depletion

Abstract

Periods of fasting are practiced worldwide on a cultural/religious background, and related mood-enhancing effects are postulated. We aimed to assess the effect of fasting on mood and to explore the interaction with neuroendocrine activation and leptin depletion in a controlled explorative study on consecutive inpatients (BMI < 35 kg/m²) of a nutritional ward. 36 subjects (38.9 ± 7.0 years; 29 female, BMI 26.7 ± 4.1 kg/m²) participated in an 8-day modified fast (300 kcal/day), 19 patients (38.1 ± 5.9 years; 18 female, 23.5 ± 4.1 kg/m²) received a mild low calorie diet. Measurements included daily ratings of mood (VAS), weight and levels of leptin and cortisol at four time-points of the 2-week study period. Weight loss was 4.8 ± 1.2 and 1.6 ± 0.9 kg in fasters and controls, respectively. Fasters showed a more pronounced decrease of leptin (58% vs. 20%; P < 0.001) and a 17% increase of cortisol levels (P < 0.001). Mood ratings increased significantly in the late phase of fasting (P < 0.01) but were not related to weight-loss, leptin-depletion or cortisol increase. Our findings suggest that fasting induces specific mood-enhancement. The physiological mediator appears to be neither leptin nor cortisol, the role of other mechanisms has to be further studied.     

Comparative study of acetate and bicarbonate hemodialysis in children with chronic uremia

Comparative studies on 5 children suffering from chronic uremia were performed regarding the efficacy of acetate and bicarbonate hemodialysis. Clinical symptoms, acid-base and blood gas analysis, serum osmolality, blood pressure and EEG were examined. On authors experience the patients tolerated better the bicarbonate dialysis. Laboratory data and blood pressure were found to be closer to the normal values too. The abnormality of EEG made after bicarbonate dialysis were not so expressed than that of acetate dialysis. On the basis of this examinations the authors suggest the bicarbonate hemodialysis in uremic patients with severe cardiovascular and/or neurological complications.     

Emergence of a unique group of necrotizing mycobacterial diseases.

Although most diseases due to pathogenic mycobacteria are caused by Mycobacterium tuberculosis, several other mycobacterial diseases-caused by M. ulcerans (Buruli ulcer), M. marinum, and M. haemophilum-have begun to emerge. We review the emergence of diseases caused by these three pathogens in the United States and around the world in the last decade. We examine the pathophysiologic similarities of the diseases (all three cause necrotizing skin lesions) and common reservoirs of infection (stagnant or slow-flowing water). Examination of the histologic and pathogenic characteristics of these mycobacteria suggests differences in the modes of transmission and pathogenesis, though no singular mechanism for either characteristic has been definitively described for any of these mycobacteria.     

Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

Although depression is known to be an independent risk factor for cardiovascular disorders, the mechanisms behind this connection are not well understood. However, the reduction in the number of endothelial progenitor cells (EPCs) in patients with cardiovascular risk factors has led us to hypothesize that depression influences the number of EPCs. EPCs labeled with CD34, CD133 and vascular endothelial growth factor receptor-2 (VEGFR2) antibodies were counted by flow cytometry in the peripheral blood (PB) of 33 patients with a current episode of major depression and of 16 control subjects. Mature (CD34+/VEGFR2+) and immature (CD133+/VEGFR2+) EPC counts were decreased in patients (vs controls; P<0.01 for both comparisons), and there was a significant inverse relationship between EPC levels and the severity of depressive symptoms (P<0.01 for both EPC phenotypes). Additionally, we assayed the plasma levels of VEGF, C-reactive protein (CRP) and tumor necrosis factor (TNF)-alpha and observed significantly elevated TNF-alpha concentrations in patients (vs controls; P<0.05) and, moreover, a significant inverse correlation between TNF-alpha and EPC levels (P<0.05). Moreover, by means of a quantitative RT-PCR approach, we measured CD34, CD133 and VEGFR2 mRNA levels of PB samples and found a net trend toward a decrease in all the investigated EPC-specific mRNA levels in patients as compared with controls. However, statistical significance was reached only for VEGFR2 and CD133 levels (P<0.01 for both markers). This is the first paper that demonstrates evidence of decreased numbers of circulating EPCs in patients with a current episode of major depression.     

Psychophysiology of visceral pain in IBS and health

The psychophysiology of visceral pain as it relates to gastrointestinal motility, visceral sensitivity, and putative mechanisms of the processing of visceral stimuli by the central and peripheral nervous systems are discussed. Peripheral mechanisms may include low-grade mucosal inflammation, and it is likely that central nervous mechanisms such as neuronal plasticity at the level of the spinal cord and attentional bias at the cortical level are relevant for the chronification of visceral pain. From a psychophysiological perspective, visceral pain therefore remains a complex symptom because behavioral variables, such as the way an individual deals with stress, may be as important for the etiology of visceral pain as, for example, a history of inflammation.