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Reduce Sodium in Diet - Link
Excess correlated with 1,500 deaths per year

Restricting environmental stimulation influences levels and variability of plasma cortisol

J. W. Turner Jr and T. H. Fine
Department of Physiology and Biophysics, Medical College of Ohio, Toledo 43699-0008.

Restricting stimulation from the environment has been shown to alter psychological and physiological states. The present study of 27 healthy subjects examines the effects of restricted environmental stimulation technique (REST) on plasma levels of cortisol and variability in plasma cortisol levels across repeated REST sessions. The REST environment consisted of a 1.2 X 1.2 X 2.4-m ovoid chamber containing 25 cm of saturated MgSO4 solution (sp gr 1.28) maintained at 34.5 degrees F. The buoyant supinely floating subject experienced a minimum of light, sound, and temperature awareness and spatial orientation. The non-REST environment was a cushioned reclining chair in a quiet dimly lit room. The 5-wk protocol consisted of four visits for blood sampling during a 2-wk baseline followed by eight REST or non-REST sessions, 40 min each, with blood samples taken on four nonsession days between sessions 5 and 8. Variability in plasma cortisol was expressed in terms of standard deviation. REST was associated with across-session decreases of 21.6% in plasma cortisol and 50.5% in plasma cortisol variability, whereas no changes in these measures occurred in non-REST. It is concluded that REST influences both static and dynamic aspects of adrenocortical function, possibly altering the feedback monitoring of plasma cortisol.

Effects of flotation therapy on relaxation and mental state

Emotional state improved
It has been reported that flotation therapy can improve the subject's emotion state.［4,7,8,9］ The results of this study show flotation could improve mood state and reduce anxiety and depression level significantly. The mechanisms may be as follows: ① Some psychologists have proposed that along with cognitive activities and emotions, every individual has their own ideal level of stimulation and arousal. Researchers studying flotation therapy believe that the usual level of stimulation encountered in modern society is too much for some individuals to handle. An environment of overwhelming stimulation leads to too much stimulation and information flooding the cognitive system of the individual. The individual cannot deal with all this information and stimulation effectively. So maladaptive reactions to the situation occur. If the individual is taken out of that environment and put into a less demanding one, these reactions could be avoided, reduced or eliminated. The person's whole mood status could be improved as well. ② According to the cognitive theory of emotion, emotion is affected by three factors: environmental, physiological and cognitive.［10］ During flotation therapy, external stimuli are extremely reduced so the stimulating events are few. So the mood is improved. ③ Some preliminary studies have suggested that flotation therapy may facilitate the release of endogenous beta-endorphin in the brain: beta-endorphin is a peptide that can induce euphoria state in human beings.［6］ ④ Flotation can induce deep relaxation. An individual feels comfortable, amused and pleasing when he or she is relaxed. ⑤ The effect of improving mood state may come from the collaborative operation of all the mechanisms.

Considering the results of this study and other studies, it can be suggested that flotation therapy may be helpful in the treatment of many psychological disorders and psychosomatic diseases. In hypertensive patients we have obtained good results through flotation therapy, but in patients with other psychological disorders or psychosomatic diseases must be tested in further studies and clinic works.

A previous study has shown that gender has no influence on the effects of REST. The results of this study shows that gender may influence the mood improving effect of flotation therapy. The improvement for women is better than that for men. This show that the flotation therapy may be better suited for females, but it needs further study and clinical work.

Vasorelaxation in Space

Compared with the ground-based upright posture, our data show that cardiac output is increased and the vasculature dilated and relaxed from the very onset of weightlessness and until at least a week into spaceflight. Systemic vasodilatation is most probably accounted for by chronic stimulation of blood pressure reflexes to prevent blood pressure from increasing. That central blood volume is expanded in space is indicated by the chronic increase in cardiac output and is supported by previous echocardiographic indications that weightlessness distends the heart chambers.^6–8

Because functional residual capacity is increased in space compared with that of the ground-based supine position, the increase in cardiac output is not only accomplished by the lack of pull of gravity on the blood column but also by expansion of the lungs and thoracic cage. Expansion of the lungs and thoracic cage creates a negative pressure around the heart and central vessels, which increases venous return and thus cardiac output. That this is the case is indicated by previous results from our group that esophageal pressure, which reflects changes in interpleural pressure, decreases more by acute weightlessness than central venous pressure does when referring to the 1-G supine position.⁸ Thus, central transmural venous pressure increases. This is probably the reason that Buckey et al⁶ observed a decrease in central venous pressure shortly into spaceflight despite the fact that the heart chambers were expanded. Such a condition, in which cardiac output is elevated and the lungs and thoracic cage simultaneously expanded, cannot be simulated on the ground. Thus, the lung–heart interaction is unique in weightlessness and important for maintaining cardiac output increased during prolonged spaceflight.

Our observation that systemic vascular resistance decreased in space might at first glance seem contradictory to observations by Watenpaugh et al,⁹ who reported that calf vascular resistance doubled after 4 to 12 days of spaceflight. However, these investigators used the ground-based supine position as reference. Therefore, their observations are in accordance with ours that systemic vascular resistance tended to increase in space compared with when the subjects were ground-based supine (Figure 2). However, this increase was much less than the doubling in calf vascular resistance observed by Watenpaugh et al.⁹ Therefore, it is likely that there are regional differences in the human circulation during spaceflight concerning degree of vasodilatation or constriction.

That cardiac output is increased and the circulation chronically dilated throughout a week in space is in contrast to the previously observed high levels of sympathetic nervous activity and renin-angiotensin-aldosterone during spaceflight.^10–12 Such activations of vasoconstrictor hormones usually reflect that the vasculature is constricted and central blood volume reduced. This was clearly not the case in this study. Therefore, whether the vascular sensitivity to sympathetic nervous activity and renin-angiotensin is reduced by weightlessness should be investigated in the future.

By comparing the data in Figure 1 with those in Figure 2, it is clear that the cardiovascular changes were attenuated throughout a week in space compared with the immediate 20-s responses. This attenuation over time could have been caused by a reduction in blood volume and by a smaller cardiac muscle mass.^13,14 It is noteworthy that cardiac output and systemic vascular resistance after a week in weightlessness adapt to a level in between that of the ground-based seated and horizontal supine positions (Figure 2). This is similar as to how renal responses to saline and water loadings adapt to spaceflight.^10,11 This level of adaptation in between supine and upright might constitute the natural operating point for control of circulation and fluid volume because humans constantly change position throughout life between the 2.

Possible Limitations
By using the foreign gas rebreathing method, we measured the pulmonary capillary blood flow of oxygenated blood, which is similar to cardiac output, when there is no significant physiological shunting of the blood in the lungs. Therefore, if different degrees of physiological shunting of blood had been present during the ground-based and in-flight conditions, this could have impacted our determinations of cardiac output. However, we have, in a previous study, observed that only when the arterial oxygen saturation is <95% can it lead to significant underestimations of cardiac output.¹⁵ It is not likely that this was the case in our healthy astronauts.

Because of the peripheral location in the finger of our blood pressure measurements, it could be argued that local vasoconstriction could have led to erroneous estimations of mean arterial pressure. However, we evaluated the continuous arterial pressure curves carefully for such artifacts. Another argument for error is that location of the hydrostatic reference point at the fourth intercostal space for the arterial pressure measurements was not correct. Location of the hydrostatic reference point is crucial when comparing ground based measurements with those during weightlessness because in this latter condition, all hydrostatic pressure gradients are abolished. We chose the fourth intercostal space as the hydrostatic reference point during the upright 1-G conditions because it is near to mid-heart level, at which brachial blood pressure is usually measured by the standard clinical methods.

Our data also have implications for understanding how gravity stresses patients with heart failure. Heart failure is characterized by a high sensitivity to the pull of gravity because the pumping capacity of the heart is reduced. Therefore, the vasculature is constricted to prevent blood pressure from falling. To alleviate the stress of gravity in compensated heart failure, we previously immersed heart failure patients into thermoneutral water (34.5°C). Compared with the upright seated control position, water immersion increased stroke volume index and decreased vascular resistance.^20,21 Thus, the circulatory condition in the heart failure patients improved. Because our results presented here from parabolic flights and spaceflight are in compliance with those of water immersion,^20,21 it is fair to conclude that gravity is a constant burden for heart failure patients and that it aggravates their condition. Therefore, a future purpose should be to investigate how to alleviate gravitational stress in heart failure.

Cardiovascular and neuroendocrine responses to water immersion in compensated heart failure

Conclusions. The results of this study demonstrate that central blood volume expansion in compensated HF elicits a reduction in systemic vascular resistance similar to that of normal control subjects, despite blunted forearm vascular responses. Concomitantly, release of AVP, renin, and NE is suppressed in HF patients to the same extent as in healthy subjects. Thus the baroreflex-mediated decrease in systemic vascular resistance and in release of vasoactive hormones is dissociated from the reflex control of forearm vascular beds and heart rate in compensated HF during WI-induced central blood volume expansion.

Perspectives. The increase in central blood volume improved cardiac performance, decreased sympathetic nerve activity and systemic vascular resistance, and suppressed the release of vasoactive and sodium- and water-retaining hormones in compensated HF. In fact, WI tended to normalize the levels of these variables. Therefore, the effects of WI on renal sodium and water handling in HF should be addressed in future studies. Such investigations may provide further insight into the pathophysiology of extracellular fluid volume control and may have implications for the treatment of HF.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12439605&query_hl=7

Cancer Immunol Immunother. 2002 Dec;51(11-12):603-13. Epub 2002 Oct 18

Atanackovic D, Nierhaus A, Neumeier M, Hossfeld DK, Hegewisch-Becker S.

Department of Oncology and Hematology, University Clinic Eppendorf, Hamburg, Germany. atanackd@mskcc.org

Whole body hyperthermia (WBH) has been used as an adjunct to radio-/chemotherapy in patients with various malignant diseases. Although clear evidence is still missing, it has been hypothesized that an activation of the immune system might contribute to the therapeutic effect of WBH. To examine whether a treatment with 60-minute 41.8 degrees C WBH as an adjunct to chemotherapy (WBH-CT) induces an activation of T cells, blood samples were collected at numerous time points before and up to 48 h post-treatment. The aim of this study was to examine the effect of WBH-CT on the expression of a broad range of activation markers on peripheral blood lymphocytes (PBL), on serum cytokines and intracellular cytokine levels in T cells, and the capacity of these cells to proliferate. Immediately after 41.8 degrees C WBH-CT treatment, a drastic increase in peripheral natural killer (NK) cells ( P<0.05) and CD56+ cytotoxic T lymphocytes (CTL; P<0.01) in the patients' peripheral blood was observed. At 5 h post-treatment, the percentages of both effector cell types had returned to baseline levels. This transient phenomenon was accompanied by a short period of reduced T cell activity, indicated by diminished serum levels of soluble interleukin-2 receptors (sIL-2R) at 3 h post-WBH-CT ( P<0.05) and decreased lymphocytic proliferation at the same point in time. This first phase was followed by a marked but short-lived increase in the patients' serum levels of interleukin-6 (IL-6; P<0.01) during the first 5 h following treatment, with a subsequent decrease to baseline levels at 24 h and significantly increased serum levels of tumor necrosis factor-alpha (TNF-alpha) at 0 h ( P<0.01), 3 h ( P<0.05), 5 h ( P<0.05) and 24 h ( P<0.01) post-WBH-CT. The third phase of the immunological consequences of WBH-CT consisted of an increase in the percentage of peripheral cytotoxic T lymphocytes (CTL) expressing CD56, reaching a maximum at 48 h post-WBH ( P<0.01). Furthermore, the percentage of CD4+ T cells expressing the T cell activation marker CD69 increased nearly two-fold over time, reaching its maximum at 48 h ( P<0.05). As an additional marker for T cell activation, serum levels of sIL-2R increased markedly ( P<0.01), reaching maximum levels at the same point in time. Elevated intracellular concentrations of interferon-gamma (IFN-gamma) and/or TNF-alpha in CD8+ T cells were found in 4 out of 5 patients at 24 h post-WBH-CT. Since similar changes were not observed in patients receiving chemotherapy alone, this is the first study to provide evidence for prolonged WBH-CT-induced activation of human T cells.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3132509&query_hl=7

Downing JF, Martinez-Valdez H, Elizondo RS, Walker EB, Taylor MW.

Department of Biology, Indiana University, Bloomington 47405.

Induction of hyperthermia (39 degrees C) in human volunteers by immersion in warm water (41-45 degrees C) rapidly alters the cell populations in the peripheral blood. In addition to granulocytosis, there is an alteration of the normal ratios among T-lymphocyte subsets. Following in vitro mitogen stimulation, lymphocytes from hyperthermic individuals produce as much as 10-fold more interferon-gamma (IFN-gamma) than cells withdrawn at basal core temperatures from the same individuals. A temperature threshold of 39 degrees C for this response suggests potential relevance to fever. No change was noted in the activity of the macrophage population. The possible involvement of interleukin-2 (IL-2) in this enhanced production is discussed. No changes were noted in the circulating levels of IFN-gamma

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12796371&query_hl=6

Hegewisch-Becker S, Braun K, Otte M, Corovic A, Atanackovic D, Nierhaus A, Hossfeld DK, Pantel K.

Department of Oncology/Hematology, University Hospital Hamburg-Eppendorf, Hamburg D-20246, Germany. hegewisc@uke.uni-hamburg.de

PURPOSE: Combining heat with antineoplastic drugs has produced evidence of antitumor synergism. An increasing number of trials are investigating whole body hyperthermia (WBH) in combination with chemotherapy in patients with advanced malignancies. Here we investigated whether the hyperdynamic state of the circulation as a consequence of WBH may stimulate dissemination of malignant cells. EXPERIMENTAL DESIGN: WBH in combination with chemotherapy was administered by a radiant heat device to 20 consecutive patients with advanced epithelial malignancies. One WBH session lasted for approximately 4 h (90 min heating time, 60 min plateau at 41.8 degrees C, and 60-80 min cooling). Peripheral blood was drawn before WBH treatment (baseline), at the end of the plateau (1 h), and 24 h and 48 h thereafter. After removal of leukocytes using anti-CD45 magnetic beads, circulating tumor cells were detected immunocytochemically using the monoclonal antibody A45-B/B3, which binds to a common epitope present on various cytokeratins. RESULTS: The method used to detect tumor cells in the peripheral blood proved to be specific and very sensitive (detection limit 1 tumor cell per 1.7 x 10(5) peripheral blood mononuclear cell). Before WBH, 6 of 20 patients had cyto-keratin-positive cells in their blood. A treatment-induced increase in the number of circulating tumor cells became statistically significant at 24 h after WBH (P = 0.043) and was detected in a total of 9 patients, 5 of whom had no detectable malignant cells at baseline. There was no evidence of a correlation between an increase in the number of circulating tumor cells and increased metastasis frequency. CONCLUSIONS: Our findings suggest that WBH might induce a temporary release of tumor cells into the circulation, but this spread appears to be clinically not significant in patients with advanced malignancies.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8040029&query_hl=7

Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):821-6.

Shen RN, Lu L, Young P, Shidnia H, Hornback NB, Broxmeyer HE.

Department of Medicine (Hematology-Oncology), Indiana University School of Medicine, Walther Oncology Center, Indianapolis 46202-5121.

PURPOSE: To determine whether hyperthermia is to the benefit or detriment of host immune function, the effect of hyperthermia was evaluated on various functions of T-lymphocytes from human umbilical cord blood and compared to that of adult blood. METHODS AND MATERIALS: Nonadherent mononuclear cells from cord blood or adult blood were used as the effector cells. To generate lymphokine activated killer (LAK) cells, effector cells were kept in culture for 5 days in complete medium containing recombinant human interleukin-2. To activate effector cells to become cytotoxic, cells were kept in culture in complete medium containing Con A. Cytotoxicity was determined in a standard 4-h chromium release assay using K-562 human erythroleukemic cells (in the natural killer cell activity assay) or Daudi cells (in the LAK cell activity or Lectin dependent cytotoxicity assay) as targets. For heat effects, cells in complete medium were heated at the desired temperature in a water bath for 1 h. RESULTS: Lymphokine-activated killer cell activity, lectin-dependent cytotoxicity and T-cell proliferative capacity were not deficient in human cord blood. Cytotoxic activities of T-cells from adult blood as well as from cord blood can be enhanced at febrile range (< or = 40 degrees C), and were significantly decreased by exposure to 1 h at 42 degrees C. CONCLUSION: The febrile responses (< or = 40 degrees C) to infection, in the course of malignant disease and with biological response modifiers treatment, may all be related to host defense mechanisms. Based on these observations, whole body hyperthermia (< or = 40 degrees C), in combination with the appropriate cytokines, may have therapeutic potential in the treatment of neonatal infections and malignancies under certain circumstances. Hyperthermia in febrile range may, therefore, confer an important immunoregulatory advantage to the host. In contrast, tumor killing therapeutic temperature (> 42 degrees C) which inhibits host immunocompetence should probably be used only for local hyperthermia.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2286438&dopt=Citation

Singh M, Singhi S, Walia BN.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh.

In a prospective controlled evaluation of steam therapy, in severe acute lower respiratory tract infection (ALRI) requiring hospitalization, 16 cases of bronchiolitis and 20 cases of pneumonia were assigned alternately to receive steam therapy in a cloth tent (Study Group); others served as controls. Respiratory status was assessed at the time of admission and subsequently at 6 hourly interval for 48 hours. No advantage of steam therapy could be identified in children with pneumonia. Bronchiolitis patients on steam therapy, as compared to the controls, showed a significant decrease in respiratory distress within first 24 hours after hospitalization and took significantly shorter time for recovery from the distress. The study patients also showed a tendency for rapid improvement in hypoxemia. Further critically controlled studies with a larger sample size are warranted.

http://jap.physiology.org/cgi/content/abstract/14/5/768

Ten male subjects in apparently good health were submitted to artificial hyperpyrexia of 2°–3°C above their initial orally determined body temperature for 2-hour periods. The pulse rate was markedly increased and the diastolic blood pressure was markedly decreased. Other major changes observed were a highly significant decrease of serum vitamin A levels and a highly significant increase of the white cell count, due primarily to an increase of the neutrophils. An eosinopenic effect observed was believed to be related to the stress of fever treatment. Minor changes were observed in the red cell count and in the serum gamma globulin fraction, which showed a delayed decrease. No changes were observed in carotene, vitamin E, alkaline phosphatase, riboflavin, or ascorbic acid.

Downing JF, Taylor MW.

We have previously demonstrated that artificially induced hyperthermia in man enhances the subsequent production of interferon gamma (IFN-gamma) in isolated leukocyte cultures. The mechanism(s) responsible for this response may involve changes in the circulating lymphocyte populations and may also reflect activation processes occurring in vivo due to hormonal influences. In order to determine whether hyperthermia was associated with other immunostimulatory effects, we measured lymphocyte activation, natural killer cell activity, interleukin-2 (IL-2) production and endotoxin-induced tumor necrosis factor (TNF) activity in blood samples obtained from normothermic (37 degrees C) and hyperthermic (39 degrees C) individuals. Lymphocyte transformation was significantly depressed in post-hyperthermic cultures compared to pre-hyperthermic control cultures. Pre-hyperthermic autologous human plasma was less effective than fetal calf serum in promoting DNA synthesis, while post-hyperthermic plasma suppressed mitogen-induced activation. Natural killer (NK) cell activity was increased by the elevation of core body temperature. Interleukin-2 (IL-2) production in phytohemagglutinin-stimulated mononuclear cell cultures was also elevated when cells were isolated from hyperthermic individuals relative to a paired normothermic control sample. Lipopolysaccharide-induced tumor necrosis factor (TNF) synthesis in monocyte cultures was unchanged by elevation of the core body temperature. This study indicates that in vivo hyperthermia can produce an immunostimulatory effect, an immunosuppressive effect, or no effect on different parameters of the immune system.