Effects of HZE particle on the nigrostriatal dopaminergic system in a future Mars mission.

Because of long duration travel outside the Earth's magnetic field, the effect of iron-rich high charge and energy (HZE) particles in Galactic Cosmic Rays on human body is the major concern in radiation protection. Recently attention has been directed to effects on the central nervous system in addition to mutagenic effects. In particular, a reduction in striatal dopamine content on nigrostriatal dopaminergic system has been reported by investigators using accelerated iron ions in ground-based mammalian studies. In addition, studies of the pathophysiology of Parkinson's disease demonstrated that excess iron cause a reduction in the dopamine content in the substantia nigra. This suggests an intriguing possibility to explain the selective detrimental effects of HZE particles on the dopaminergic system. Should these particles have biochemical effects, possible options for countermeasures are: (1) nutritional prevention, (2) medication, and (3) surgical placement of a stimulator electrode at a specific anatomic site in the basal ganglia.

[Immunity and immunosuppression in childhood idiopathic nephrotic syndrome]. / Immunité cellulaire et traitement immunosuppresseur du syndrome néphrotique idiopathique corticosensible.

Steroid sensitive idiopathic nephrotic syndrome is a T-cell disorder characterized by a functional renal impairment. Concluding a still relevant demonstration involving cellular immunity in the pathogenesis of the disease, R. Shalhoub in 1974 suggested a "special role for the thymus" based on the efficiency of steroids and alkylating agents, dramatic recoveries following measles, sensibility to bacterial infection due to a lack of cooperation between T and B cell and association to Hodgkin disease. As a matter of fact, the selected drugs based on medical empirism somehow enhance thymocytes apoptosis and negative selection of T cell, except cyclosporin. Steroids have been the first historical treatment of idiopathic nephrotic syndrome and have steadily been the first-line treatment for 50 years. Their unavoidable ability to induce rapid recovery of proteinuria and long-lasting or definite remission are dependent to a strict compliance to treatment. Indications of steroids-sparing treatments are not that clearcut in patients with steroids intoxication. Objectively, efficiency of levamisole and cyclophosphamide are much more limited than previously reported and cyclosporin nephrotoxicity might severely impair renal function following long-lasting treatment as well as it may paradoxically increase the activity of the disease. An alternate strategy to those currently adopted would use cyclosporin as the first-line steroids-sparing treatment during a very limited period, awaiting favourable ageing of patients and natural dampening activity of the disease to a full efficiency of alkylating agents. Compared to cyclophosphamide and cyclosporin, the relative safety of levamisole is encouraging to a more frequent uses. Its association to a full dose of prednisone in the treatment of the inaugural episode should be investigated. According to the limitations of those therapies, emerging drugs as mycophenolate might be worthwhile in the treatment of nephrotic patients.

Risky behavior and risk in adolescents with IDDM.

PURPOSE: To determine: (1) the frequency of risky behaviors (alcohol and other drug use, smoking cigarettes, smokeless tobacco use, and unprotected intercourse); (2) the perception of general risks and diabetes-related risks from risky behaviors; (3) if perception of risk is related to engaging in risky behaviors; and (4) if perception of general risks and diabetes-related risks are influenced by age, gender, or race in adolescents with insulin dependent diabetes mellitus (IDDM). Decreasing risky behaviors in youth with IDDM is important because of their increased vulnerability to specific disease related physiologic and pathologic changes. METHODS: A descriptive, cross-sectional design was used. Data on risky behavior and perception of risk were obtained by self-report during a regularly scheduled clinic visit. One hundred and fifty-five adolescents between ages of 10-20 years participated. Correlational and student's t-test analyses were used to test relationships and group differences (age, race, gender). RESULTS: Thirty-nine percent of the sample reported alcohol use, 34% reported smoking cigarettes, 8% reported smokeless tobacco use, 10% reported drug use, and 29% reported unprotected intercourse. Perception of risk to peers from these behaviors was significantly higher (t = 8.1, df 153; p < .001) than risk to self. Females reported significantly lower (t = 3.08, df 52; p < .002) risk to self than males. There was no difference in perception of risk between youth who reported participating in risky behaviors (N = 38%) and those who did not (62%). Not surprisingly, the frequency of risky behavior increased with age (F = 15.46; p < .001). CONCLUSIONS: Compared to community samples of middle school children, our sample had lower rates for most risky behaviors. As with community samples, the physical risks were known and perceived to be higher for peers than self. Perception of risk was not related to self-reports of risky behaviors. The lower rate of risky behaviors might reflect the success of educational efforts directed toward diabetes management or may be due to later initiation of behaviors, especially if personal social development is delayed. Additional research is indicated in order to understand the timing and trajectory of risky behavior and whether or not perception of risk deters youth with IDDM from engaging in risky behavior.

Space research activities during missions of the past.

For over 30 yr, men and women have lived for various periods of time in a weightless (or free-fall) environment while orbiting the Earth. During these years, we have learned that humans function quite well for short periods of weightlessness, that is, for up to a little more than a year. Some space flight missions have provided physiologic data, including cardiovascular data, from the spacefarers. In fact, some missions have provided laboratories for systematic study of cardiovascular responses and adaptation to space flight. However, the opportunity to obtain physiologic data from people in space is a rarity. It is important to remember that the population sample sizes are small, other stresses may confound the effects of weightlessness, and in some situations the crewmembers are subjects for several experiments at the same time. Furthermore, comparison of cardiovascular data from space flight to data obtained on the ground is sometimes difficult because the subject's posture on the ground is not always reported; in a gravity environment, posture influences the hydrostatic gradient. This over view describes what we have learned about cardiovascular function during flight and after return to Earth.

The Neurolab mission and biomedical engineering: a partnership for the future.

NASA: Over the last five years, with the advent of flights of U.S. Shuttle/Spacelab missions dedicated entirely to life sciences research, the opportunities for conducting serious studies that use a fully outfitted space laboratory to better understand basic biological processes have increased. The last of this series of Shuttle/Spacelab missions, currently scheduled for 1998, is dedicated entirely to neuroscience and behavioral research. The mission, named Neurolab, includes a broad range of experiments that build on previous research efforts, as well as studies related to less mature areas of space neuroscience. The Neurolab mission provides the global scientific community with the opportunity to use the space environment for investigations that exploit microgravity to increase our understanding of basic processes in neuroscience. The results from this premier mission should lead to a significant advancement in the field as a whole and to the opening of new lines of investigation for future research. Experiments under development for this mission will utilize human subjects as well as a variety of other species. The capacity to carry out detailed experiments on both human and animal subjects in space allows a diverse complement of studies that investigate functional changes and their underlying molecular, cellular, and physiological mechanisms. In order to conduct these experiments, a wide array of biomedical instrumentation will be used, including some instruments and devices being developed especially for the mission.^ieng

King's framework and theory in Japan, Sweden, and the United States.

In this article, we present our work in extending and testing Imogene King's conceptual framework and theory in Japan, Sweden, and the United States. Comparing and contrasting cultural relevance, methodology, and issues of validity provide examples of international scholarship and knowledge development that result from networking and collaboration.

Use of lower body negative pressure to assess changes in heart rate response to orthostatic-like stress during 17 weeks of bed rest.

This study examined the heart rate response to lower body negative pressure (LBNP) during 17 weeks of horizontal bed rest to estimate the development and duration of orthostatic instability elicited by this model for space flight. Based on data from Skylab, the authors hypothesized that orthostatic (LBNP) instability would appear during the first 3 to 4 weeks, and would then remain constant for the duration of bed rest. Heart rates of four healthy adult male subjects were monitored at rest and during LBNP for 1 week of ambulatory control, 17 weeks of horizontal bed rest, and 5 weeks of recovery. The LBNP protocol consisted of 10 minutes of control (atmospheric pressure) and 5 minutes each at 5, 10, 20, 30, 40, and 50 mm Hg decompression, followed by a 10-minute recovery period; this protocol was repeated weekly to document the progressive changes in heart rate response to LBNP. Lower body negative pressure was terminated early if symptoms compatible with the onset of syncope occurred. Throughout the study, heart rate was unchanged at 5, 10, and 20 mm Hg, but it increased at 30, 40, and 50 mm Hg LBNP. During the pre-bed rest period, peak heart rate was 97 +/- 10 beats/min (mean +/- SE), occurring at 50 mm Hg for all four subjects. After 3 days of bed rest, all monitored heart rate responses, including values after release of LBNP, were only slightly elevated (NS) above pre-bed rest level. Peak heart rate was 118 +/- 21 beats/min at 50 mm Hg decompression (NS; N = 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular responses to standing: effect of hydration.

Many astronauts experience intolerance to orthostatic stress after space flight, despite the ingestion of salt tablets and water equivalent to 0.9% saline just before their return to Earth. Previous research indicates that the ingestion of 1.07% saline solution increased plasma volume more than did 0.9% saline. Therefore, the authors hypothesized that the 1.07% saline would be more effective in reducing orthostatic stress during standing. In this study, six men (22-47 years) performed a 5-minute "stand test" (5 minutes supine followed by 5 minutes standing) under four hydration conditions: 1) hypohydrated (HYPO, 20 mg intravenous [IV] Lasix), 2) euhydrated (EU), 3) rehydrated with 1 L 0.9% saline 2 hours after Lasix, or 4) rehydrated with 1 L 1.07% saline. Stand tests were done 4 5 hours after rehydration. Plasma volume was reduced 10% after Lasix, and was restored by both rehydration solutions. When subjects stood, their diastolic pressure, mean pressure, heart rate (HR), and peripheral resistance increased (P < .05), and their stroke volume (SV), cardiac output (CO), and thoracic fluid (TF, by impedance cardiography) decreased (P < .05). Systolic arterial pressure (SBP) increased when subjects stood after saline, but decreased if subjects were HYPO or EU (P < .05 for 1.07% versus HYPO and EU). Heart rate (HR), another indicator of orthostatic stress, did not differ among hydration states. During the last minute of the stand test, TF was greater if subjects had fluid countermeasures. Stroke volume, CO, and TF were significantly less during minute 5 of standing than during minute 3. Whether they would continue to fall in a longer stand test is not known. The results for SBP indicate that 1.07% saline may have advantages over 0.9% saline as a countermeasure to postspace-flight or postbedrest orthostatic intolerance.

Cardiovascular responses to postural changes: differences with age for women and men.

The cardiovascular responses to postural change, and how they are affected by aging, are inadequately described in women. Therefore, the authors examined the influence of age and sex on the responses of blood pressure, cardiac output, heart rate, and other variables to change in posture. Measurements were made after 10 minutes each in the supine, seated, and standing positions in 22 men and 25 women who ranged in age from 21 to 59 years. Several variables differed, both by sex and by age, when subjects were supine. On rising, subjects' diastolic and mean arterial pressures, heart rate, total peripheral resistance (TPR), and thoracic impedance increased; cardiac output, stroke volume, and mean stroke ejection rate decreased; and changes in all variables, except heart rate, were greater from supine to sitting than sitting to standing. The increase in heart rate was greater in the younger subjects, and increases in TPR and thoracic impedance were greater in the older subjects. Stroke volume decreased less, and TPR and thoracic impedance increased more, in the women than in the men. The increase in TPR was particularly pronounced in the older women. These studies show that the cardiovascular responses to standing differ, in some respects, between the sexes and with age. The authors suggest that the sex differences are, in part, related to greater decrease of thoracic blood volume with standing in women than in men, and that the age differences result, in part, from decreased responsiveness of the high-pressure baroreceptor system.

Effects of spaceflight on the musculoskeletal system: NIH and NASA future directions.

Prolonged bed rest, undertaken by volunteers or resulting from injury and disease, can impair bone and muscle function and structure; extended travel in space also induces these effects. Fluid shifts and disrupted fluid balance may also contribute to observed musculoskeletal aberrations in the weightless environment. Some molecular and cellular events involved in the loading and unloading of the musculoskeletal system are under neural and endocrine influence or control, whereas other events are influenced by local growth factors. Studies are in progress to develop interventions that preserve or improve musculoskeletal integrity in 1g. The NIAMS and NASA are interested in basic and clinical studies of the influence of microgravity on the musculoskeletal system. The interagency workshop results form the basis for new collaborative and cooperative research emphases for the biomedical community under a broad agreement between the National Institutes of Health and NASA.

Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt.

Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of spaceflight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 degrees head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power.

Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake (VO2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6 degrees) head-down tilt (HDT), each subject underwent graded LBNP to -6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither VO2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.

Effect of breakfast on selected serum and cardiovascular variables.

We compared high-density lipoprotein cholesterol (HDL-C) and other blood and cardiovascular variables of subjects when they had been fasting overnight to those values when they had eaten breakfast. The subjects were 47 men (24 to 70 years) and 34 women (23 to 63 years) who visited our laboratory on two occasions, once fasting and once after breakfast, at the same time of the morning, exactly 1 week apart. Systolic (SBP) and diastolic (DBP) pressures and heart rates (HR) were recorded, and 24-ml blood samples were obtained from an antecubital vein and analyzed for hemoglobin (Hgb), hematocrit (Hct), HDL-C, total cholesterol (T Chol), triglycerides (Trig), total calcium (T Ca), ionized calcium (Ca++), and phosphorus (P). When subjects were fasting, their SBP, HR, Trig, T Ca, and Ca++ were lower than when they had eaten breakfast. SBP, DBP, Hgb, and Trig of the women were lower than those of the men; and HDL-C and phosphorus of the women were higher. Several correlations between variables were significant only when subjects were fasting. These were SBP with age, Hct with T Ca, and T Chol with Trig. Several correlations were significant only for one sex. For the women only, SBP, DBP, and HR were correlated with T Chol, and Trig and HDL-C were correlated with T Ca. For the men only, Hgb was correlated with HDL-C, Trig, T Ca, and P; and HDL-C was correlated with Trig.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood and urine responses to ingesting fluids of various salt and glucose concentrations.

Several hours before returning to Earth, Space Shuttle astronauts consume fluid and salt tablets equivalent to a liter of 0.9% saline as a countermeasure to postflight orthostatic intolerance. This countermeasure is not completely successful. Therefore, in search of a countermeasure that would protect against orthostatic intolerance better and for a longer duration, the authors compared the blood and urine responses of five men (21-41 yr) after they drank 1 L of 0.9% saline to their responses after drinking five other solutions: distilled water, 1% glucose, 0.74% saline with 1% glucose, 0.9% saline with 1% glucose, and 1.07% saline. Each subject ingested a different solution on 6 different days and remained seated for the ensuing 4 hours. Heart rate, blood pressures, and urine variables were measured before ingestion of the fluids and every 30 minutes thereafter; blood samples were drawn before, immediately after, and every 60 minutes after ingestion. Change in plasma volume, which was estimated from hemoglobin and hematocrit, was considered the most critical variable. Data for all solutions were compared by analysis of variance. Since plasma volume was increased most after ingestion of 1.07% saline, all variables (at 2 hours, at 3 hours and at 4 hours) were compared between 1.07% saline and 0.9% saline, the current countermeasure. Plasma volume was increased more after 1.07% saline than after 0.9% saline, and this difference was most significant at 4 hours after ingestion (P = .056). Diuresis occurred promptly after ingestion of the two saline-free solutions, water and 1% glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Gender-based differences in the cardiovascular response to standing.

Reduced tolerance to orthostatic stress is a recognized consequence of spaceflight. Both men and women serve as astronauts and are staying longer in space. While there are recognized cardiovascular differences in baseline function based on gender, little is known about any gender-based differences in cardiovascular responses to orthostatic stress. The purpose of this study was to compare the cardiovascular responses of men and women to the stand test. The subjects were 10 men and 10 women, 20-30 years of age. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were monitored during 5 min supine and 5 min standing. Men responded similarly in heart rate (39 vs. 35%); but had significantly greater decreases in stroke volume (-53 vs. -40%), cardiac output (-36 vs. -21%), and pulse pressure (-19 vs. -12%); and greater increases in blood pressure (11 vs. 6%) and total peripheral resistance (77 vs. 34%) than did the women. Men and women demonstrated fundamental differences in cardiovascular responses during standing. Differences in the height of the subjects did not account for these differing cardiovascular responses. The mechanisms for these differences are not yet clear. Men and women should be studied as separate groups until these differences are understood.

Assessing and teaching self-care to youths with diabetes mellitus.

PURPOSE: To investigate the nature of diabetes (health deviation) self-care in youths with IDDM and to relate diabetes self-care to metabolic control, perceived health status, and general (universal) self-care. METHOD: Thirty seven youths with IDDM between the ages of 11-19 completed the Diabetes Self-Care Practices Instrument, Denyes Self-Care Practice Instrument, and Denyes Health Status Instrument. Metabolic control was measured by glycosylated hemoglobin. Data were analyzed by correlational analysis. RESULTS: Diabetes self-care was positively related to general (universal) self-care, health status, and metabolic control. CONCLUSIONS: Results of the study provide clear direction for ongoing assessment and teaching of diabetes self-care in youths with IDDM.

Effect of a central redistribution of fluid volume on response to lower-body negative pressure.

We studied cardiovascular responses to lower-body negative pressure (LBNP) following 1 hour (h) of 6 degrees head-down tilt to determine whether a redistribution of blood volume toward the central circulation modifies the subsequent response to orthostatic stress. Responses of 12 men, ages 30-39 years, were evaluated by electrocardiography, impedance cardiography, sphygmomanometry, and measurement of calf circumference. During the LBNP that followed head-down tilt--as compared with control LBNP (no preceding head-down tilt)--subjects had smaller stroke volume and cardiac output, greater total peripheral resistance, and less calf enlargement. These differences reflect differences in the variables immediately preceding LBNP. Magnitudes of the responses from pre-LBNP to each pressure stage of the LBNP procedure did not differ between protocols. Mean and diastolic arterial pressures were slightly elevated after LBNP-control, but they fell slightly during LBNP post-tilt. These cardiovascular responses to simulated gravitational stress following head-down tilt may reflect the manner in which adaptation to microgravity affects subsequent responses to orthostatic stress on return to Earth.