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PubMed2000

Primary sodium plasma membrane ATPases in salt-tolerant algae: facts and fictions.

For thermodynamic reasons algae growing in media of both high salinity and high alkalinity require active export of sodium. However, experimental evidence for an active Na+-dependent cycle was scarce until recently, in contrast to the situation in marine bacteria (including cyanobacteria), fungi and animals. However, a review of literature reveals that some progress has been made in this respect, recently: data demonstrate that at least in two marine algae, Tetraselmis (Platymonas) viridis and Heterosigma akashiwo (syn. Olisthodiscus luteus), active Na+-export is carried out by means of a plasma membrane localized Na+-pump (apparent molecular mass 100-140 kDa). Biochemical characteristics of this vanadate-sensitive, but ouabain-resistant primary P-type Na+-ATPase are described and compared with the corresponding properties of Na+-ATPase from prokaryotes and animals. Alternative mechanisms for Na+-pumping are discussed.

Adenosine Triphosphate↗
PubMed1996

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

Administration, Inhalation↗
PubMed1982

Lack of synergism and cross tolerance between tactile stimulus- and LSD-induced limb flicking in the cat.

The hypotheses that LSD-induced limb flicking, as well as tolerance to this behavioral effect following repeated drug administration, are due to alterations in somatosensory thresholds were tested by examining the rate of limb flicking to LSD alone, saline plus water on the limbs, or LSD plus water on the limbs, and by comparing the limb flick rate with water on the limbs in drug tolerant versus non-tolerant conditions. Cats exhibited the same rate of limb flicking in response to water on the limbs regardless of whether they were pretreated with saline of LSD. Furthermore, there was no significant difference in the tactile stimulus-induced rate of limb flicking in the tolerant versus non-tolerant states. These data suggest that LSD-induced limb flicking is not simply a function of drug-induced altered somatosensory thresholds, but is apparently reflective of more complex neural processes.

Animals↗
PubMed1983

Assessment of diisopropylfluorophosphate (DFP) toxicity and tolerance in rats.

Single s.c. injection of 1, 2, 3 or 4 mg/kg of DFP in saline was given to male rats. Control rats received saline. Beginning 24 hr after injections, body weights and food and water consumption were measured at 24 hr intervals. The 1 and 2 mg/kg DFP-treated group maintained these parameters at levels equal to those of the controls. The other DFP-treatment groups showed significant depressions in body weights and in food and water consumption, but these groups recovered 48 and 72 hrs after DFP administration of 3 mg/kg or 4 mg/kg, respectively. Daily injections of 2, 3 or 4 mg/kg of DFP, s.c., caused significant depressions of all three parameters, with only 75% of the 2 mg/kg group showing recovery over the 14 day treatment period. Of the 2 mg/kg group, 25% died following the 6th injection, 100% of the 3 mg/kg group were dead following the 4th injection and 100% of the 4 mg/kg group were dead following the 3rd injection. Prior to deaths in all DFP-treatment groups, the decreases in body weights and in food and water consumption were progressive and dose-dependent. The data show dose-dependency of general toxicity during acute and subacute exposure to DFP and of tolerance during subacute exposure.

Animals↗
PubMedDate not supplied

Ceruletide increases threshold and tolerance to experimentally induced pain in healthy man.

UNLABELLED: Previous studies suggested that ceruletide might be endowed with analgesic and sedative properties. To investigate the effects of ceruletide on experimentally induced pain and on central nervous functions, two studies, each involving 24 healthy subjects, were carried out in random double-blind fashion. Every subject participated in three experiments one week apart. In study 1, 120 and 60 ng/kg/hr ceruletide IV increased threshold and tolerance to electrically and threshold to thermally induced cutaneous pain significantly more than saline (p less than 0.001), the higher dose being slightly more active. Only mild sedative effects occurred. Study 2 compared the effects of 60 and 6 ng/kg/hr ceruletide IV to those of 0.4 mg/kg/hr pentazocine IV and investigated whether these effects were naloxone reversible. Both ceruletide doses, 60 ng/kg/hr slightly more than 6 ng/kg/hr, elevated threshold and tolerance to electrically induced and threshold to thermally induced pain markedly, pentazocine acted stronger and longer than ceruletide (p less than 0.001). Naloxone reversed the effects of pentazocine but not of ceruletide. CONCLUSION: ceruletide (1) exerts potent naloxone resistant analgesic effects, which, however, are inferior to those of pentazocine, and (2) produces only mild sedation.

Adult↗
PubMedDate not supplied

A new angiotensin-II- receptor blocker, CGP 48933: local tolerance and effect on intraocular pressure. A pilot study.

CGP 48933, a new angiotensin-II-receptor antagonist, has been shown to lower intraocular pressure (IOP) in two different rabbit glaucoma models in a dose-dependent manner after local application. As a further step a pilot study was performed in human eyes. The trial consisted of three parts. Parts 1 and 2 comprised a double-masked intraindividual trial between CGP 48933 and its vehicle (saline) in five healthy volunteers (Part 1) and five patients with early stages of primary open-angle glaucoma (Part 2), to assess local tolerance and the effect on IOP. Part 3 was a single-masked intraindividual trial between CGP 48933 and saline, to find the effective dose range of the new compound. Local tolerance was assessed as excellent in all subjects. No conjunctival hyperemia burning or itching occurred. There were no significant changes in IOP from baseline in drug or vehicle-treated eyes. In addition, there was no dose-dependent (200 micrograms to 1 mg) effect of CGP 48933 on IOP. Systemic blood pressure, heart rate and pupil size did not change during the observation period. Topical application of CGP 48933 in its present formulation is thus not suitable for lowering IOP in humans.

Administration, Topical↗
PubMed2005

Constructed treatment wetland: a study of eight plant species under saline conditions.

A series of investigations was conducted to evaluate the feasibility of using constructed treatment wetlands to remove pollutants from saline wastewater. Eight emergent plants; cattail, sedge, water grass, Asia crabgrass, salt meadow cordgrass, kallar grass, vetiver grass and Amazon, were planted in experimental plots and fed with municipal wastewater that was spiked with sodium chloride (NaCl) to simulate a saline concentration of approximately 14-16 mScm-1. All macrophytes were found tolerant under the tested conditions except Amazon and vetiver grass. Nutrient assimilation of salt tolerant species was in the range of 0.006-0.061 and 0.0002-0.0024 gm-2d-1 for nitrogen and phosphorus, respectively. Treatment performances of planted units were found to be 72.4-78.9% for BOD5, 43.2-56.0% for SS, 67.4-76.5% for NH3-N and 28.9-44.9% for TP. The most satisfactory plant growth and nitrogen assimilation were found for cattail (Typha angustifolia) though the plant growth was limited, whereas Asia crabgrass (Digitaria bicornis) was superior for BOD5 removal. Both were evaluated again in a continuous flow constructed wetland system receiving saline feed processing wastewater. A high removal rate regularly occurred in long-term operating conditions. The reduction in BOD5, SS, NH3-N and TP was in the range of 44.4-67.9%, 41.4-70.4%, 18.0-65.3% and 12.2-40.5%, respectively. Asia crabgrass often provided higher removal especially for BOD5 and SS removal. Nutrient enriched wastewater promoted flourishing growth of algae and plankton in the surface flow system, which tended to reduce treatment performance.

Biodegradation, Environmental↗
PubMed1978

Tolerance to the hyperthermic effect of morphine in the rat is a learned response.

The results of several experiments indicated that the hyperthermic effect of morphine in rats becomes attenuated over the course of successive administrations by a conditional, compensatory, hypothermic response elicited by cues present at the time of morphine administration, thus accounting for hyperthermic tolerance: (a) Rats with a history of morphine administration display a tolerant response to the hyperthermic effect of the drug and a compensatory hypothermia following a placebo if these substances are administered following cues that previously signaled morphine--neither the tolerant reaction to morphine nor the hypothermic response to the placebo results when animals are injected following cues that previously signaled injection of physiological saline (Experiments 1A and 1B); (b) presenting environmental cues previously associated with morphine, but without the drug, abolished established tolerance, that is, pyretic tolerance can be extinguished (Experiment 2); (c) placebo sessions interspersed between morphine sessions impeded the acquisition of tolerance, that is pyretic tolerance is retarded by partial reinforcement (Experiment 3). These findings, implicating a Pavlovian conditioning process in hyperthermic tolerance, are not readily interpretable by tolerance models that do not attribute any role to drug-associated environmental cues in the acquisition of tolerance.

Animals↗
PubMed2000

Effects of glucosamine infusion on insulin secretion and insulin action in humans.

Glucose toxicity (i.e., glucose-induced reduction in insulin secretion and action) may be mediated by an increased flux through the hexosamine-phosphate pathway. Glucosamine (GlcN) is widely used to accelerate the hexosamine pathway flux, independently of glucose. We tested the hypothesis that GlcN can affect insulin secretion and/or action in humans. In 10 healthy subjects, we sequentially performed an intravenous glucose (plus [2-3H]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 micromol x min(-1) x kg(-1)) or high (5 micromol x min(-1) x kg(-1) [n = 5]) GlcN infusion. Beta-cell secretion, insulin (SI*-IVGTT), and glucose (SG*) action on glucose utilization during the IVGTT were measured according to minimal models of insulin secretion and action. Infusion of GlcN did not affect readily releasable insulin levels, glucose-stimulated insulin secretion (GSIS), or the time constant of secretion, but it increased both the glucose threshold of GSIS (delta approximately 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (delta approximately 0.3-0.5 mmol/l, P < 0.05-0.02). GlcN did not change glucose utilization or intracellular metabolism (glucose oxidation and glucose storage were measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in SI*-IVGTT (delta approximately 30%, P < 0.02) and in SG* (delta approximately 40%, P < 0.05). Thus, in humans, acute GlcN infusion recapitulates some metabolic features of human diabetes. It remains to be determined whether acceleration of the hexosamine pathway can cause insulin resistance at euglycemia in humans.

Adult↗
PubMed1991

Behavioral effects of chronic buspirone administration in the pigeon: comparison to midazolam.

The effects of acute and chronic administration of buspirone and midazolam were examined in White Carneau pigeons (N = 5) responding under a fixed-ratio 30 (FR 30) schedule of food presentation. Each drug was studied in all pigeons. For three pigeons, buspirone was studied before midazolam, while the order was reversed for the other two subjects. For each drug, a dose-response curve was determined before (prechronic) and two weeks after (postchronic) discontinuation of chronic administration. Prior to chronic drug administration, buspirone (0.3-5.6 mg/kg) and midazolam (0.1-3.0 mg/kg) decreased response rates in all subjects, in a dose-dependent manner. Midazolam was more potent than buspirone; midazolam's ED50 (95% C.I.) was 0.53 (0.41-0.69) mg/kg compared to 2.55 (1.48-4.41) mg/kg for buspirone. For each subject, the lowest dose that decreased responding by at least 50% was administered daily, immediately before the session, for up to 6 weeks. At the lowest daily dose of buspirone, complete recovery of baseline rates was observed in 3 pigeons. However, when the buspirone dose was increased, responding remained below control rates in all but one pigeon. During chronic midazolam administration, tolerance developed to the rate-decreasing effects of midazolam in 4 subjects. When saline was substituted for buspirone or midazolam, suppressed responding returned to predrug rates in all subjects. When the dose-response curves were redetermined, the postchronic ED50 for buspirone was 3.79 (2.10-6.82) mg/kg, which was not significantly different from the prechronic ED50, suggesting that tolerance did not develop to buspirone's rate-decreasing effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1966

The effect of an intravenous infusion of hypertonic saline on renal mechanisms and on electrolyte changes in sheep.

1. The ability of the sheep to tolerate excess sodium chloride has been investigated by subjecting sheep to an intravenous infusion of a 10% solution of sodium chloride.2. Inulin and diodrast clearances failed to show any consistent changes in glomerular filtration rate but the effective renal plasma flow was slightly more. Plasma levels of sodium and chloride increased by 20-25% and potassium decreased by 30%. Urinary levels for sodium and chloride showed a corresponding increase and potassium excretion was reduced.3. The rates of re-absorption of sodium and chloride from the renal tubules were found to be proportional to their rates of filtration at the glomerulus, but this ratio was reduced after the hypertonic saline infusion. No such correlation could be established for potassium.4. Osmolar clearances indicated that continued re-absorption of osmotically free water from the kidney tubular fluid occurred during and after the hypertonic saline. Excretion of urine, hyperosmotic to plasma, was thus maintained and water conservation supported.5. Possible renal mechanisms associated with these effects are discussed.

Animals↗
PubMed1996

Neuroendocrine effects of dexmedetomidine: evidence of cross-tolerance between a mu-opioid agonist and an alpha 2-adrenoceptor agonist in growth hormone secretion of the male rat.

The role of alpha 2-adrenergic receptors (adrenoceptors) in the secretion of growth hormone, prolactin and thyrotropin was studied using highly selective agonists and antagonists of the alpha 2-adrenoceptor. The interplay between opiates and alpha 2-adrenergic drugs in the acute secretion of growth hormone and prolactin, as well as the possible cross-tolerance between morphine (mu-opioid receptor agonist) and dexmedetomidine (alpha 2-adrenoceptor agonist) in growth hormone secretion were also evaluated. Dexmedetomidine dose-dependently increased plasma growth hormone and prolactin levels and decreased thyrotropin levels. The enhanced secretion of both growth hormone and prolactin was antagonized by atipamezole (an alpha 2-adrenoceptor antagonist) but not by prazosin (an alpha 1-adrenoceptor antagonist). Morphine (5 mg/kg)-induced stimulation of growth hormone secretion was antagonized by both naloxone (mu-opioid antagonist) and atipamezole. Naloxone, but not atipamezole, antagonized the morphine-induced increase in prolactin secretion. Dexmedetomidine increased growth hormone secretion in the saline pretreated rats, but did not do so in the morphine-tolerant rats. The stimulation of alpha 2-adrenoceptor enhances secretion of both growth hormone and prolactin. The adrenergic regulation of thyrotropin secretion still remains unclear. Evidently, adrenergic mechanisms are involved in the morphine-induced stimulation of growth hormone secretion, but not in the morphine-induced stimulation of prolactin secretion. In addition, there is a clear cross-tolerance between dexmedetomidine and morphine in growth hormone secretion of the rat.

Adrenergic alpha-Agonists↗
PubMed1986

[Amelioration of glucose tolerance and correction of reactive hypoglycemias induced by intravenous calcium infusion cannot be explained by modifications in blood glucagon levels].

Glucagon is not involved in intravenous calcium-induced improvement in glucose tolerance nor in correction of reactive hypoglycemia. Recent investigations have shown that intravenous (IV) calcium infusion improved blood glucose values in patients with moderately impaired glucose tolerance, and suppressed hypoglycemia in patients with isolated reactive hypoglycemia. The aim of this study was to investigate the possibility that these changes were secondary to calcium induced alterations in glucagon (IRG) secretion. Four groups of subjects were studied: group 1: normal controls (n = 7); group 2: patients with isolated hypoglycemia (n = 9); group 3: patients with impaired glucose tolerance without reactive hypoglycemia (n = 9) and group 4: patients with impaired glucose tolerance and reactive hypoglycemia (n = 10). All patients were submitted in randomized order to two 5 hour oral glucose tolerance tests (OGTT, 75 g glucose), during a simultaneous infusion, either of saline or of calcium (calcium gluconate 36.3 mEq/5 h.), starting 30 minutes before the OGTT. In none of the groups did calcium infusion influence basal plasma IRG. In group 1 and 3, oral glucose significantly suppressed IRG, and during IV calcium infusion this suppression disappeared. In group 2, glucose ingestion resulted in a paradoxical increase in IRG both during saline and during calcium infusion. In group 4, oral glucose induced a significant drop in plasma IRG and a rebound rise during hypoglycemia, results which were unaffected by IV calcium infusion. These data suggest that glucagon is not involved in the alterations of blood glucose profiles during OGTT observed during intravenous calcium infusion.

Adult↗
PubMed1990

Behavioral study on mergocriptine (CBM36-733) by ambulatory activity in mice: repeated administration and interaction with methamphetamine.

Effects of repeated administration of mergocriptine (CBM36-733: CBM), a long-acting ergot derivative with an agonistic action on both dopamine D1 and D2 receptors, as well as interaction between CBM and methamphetamine (MAP: 2 mg/kg, s.c.), were investigated by ambulatory activity in mice. CBM at 4 mg/kg significantly suppressed the ambulatory activity, but significantly increased it at 16 mg/kg in the drug-naive mice. However, 4 and 8 mg/kg of CBM were effective for increasing the ambulatory activity when these doses were repeatedly administered for 9 times at intervals of 7 days. The same treatment with 16 mg/kg of CBM produced a reverse tolerance to the ambulation-increasing effect. The mice that had received CBM at 1 and 2 mg/kg, but not 4-16 mg/kg, demonstrated a significantly lower sensitivity to MAP than the saline-experienced mice. On the other hand, the repeated MAP administration induced not only a reverse tolerance to itself, but also a cross reverse tolerance to 8 and 16 mg/kg of CBM. Furthermore, the established reverse tolerance to MAP was scarcely attenuated by the repeated treatment with any doses of CBM, but rather enhanced by 8 and 16 mg/kg of CBM. The present results indicate that, although the dose-effect relations are partially different, the behavioral characteristics of CBM were almost identical with those of bromocriptine, another long-acting ergot derivative having antagonistic and agonistic actions on dopamine D1 and D2 receptors, respectively.

Animals↗
PubMedDate not supplied

The value of saline salpingosonography as a surrogate test of tubal patency in low-resource settings.

BACKGROUND: Tubal factor, which accounts for 15-30% of infertility in all women, is common in developing countries with high rates of pelvic inflammatory disease but limited resources. It is possible to outline the fallopian tubes by injecting isotonic saline transcervically during transvaginal ultrasound scanning of the pelvis, and both color flow Doppler and 3-dimensional scanning modes have been employed to improve visualization of the tubes, with varying success. METHOD: We investigated the value of saline salpingosonography (SSG), using 2-dimensional transvaginal ultrasound scanning, as a screening test of tubal patency in 113 women by comparing SSG findings to those at HSG or laparoscopy. RESULTS: The findings at SSG correlated well with the results of HSG or laparoscopy, with an overall concordance of 82.5%. SSG was more accurate at diagnosing patent tubes than blocked tubes and was well tolerated. The results are, however, unreliable when it is difficult to inject the saline and when the patient experiences severe pain during the procedure. CONCLUSION: SSG is a useful screening tool for investigating infertility, particularly in low-resource settings.

Adult↗
PubMed1990

Defective oral tolerance promotes nephritogenesis in experimental IgA nephropathy induced by oral immunization.

Oral tolerance, an important feature of the mucosal immune system, appears to protect against immune-mediated disease by blunting production of systemic IgG and IgM antibody directed toward immunogens chronically present at mucosal surfaces. In this study, we explored the role of oral tolerance and mucosal immunoregulation in an experimental model of IgA nephropathy (IgAN), an important form of nephritis in humans. Cyclophosphamide and estradiol were used to inhibit the expression of oral tolerance, which otherwise develops after chronic oral presentation of Ag. BALB/c mice given drinking water containing 0.1% bovine gamma globulin (BGG) continuously for 14 wk were randomly assigned to groups given either 2 mg of cyclophosphamide i.p., 2 mg of estradiol s.c. or both drugs. Groups of control mice received neither BGG nor drugs. In three separate experiments, a low percentage of saline-treated orally immunized mice had microscopic hematuria (0 to 20%), as did nonimmunized controls (0 to 20%). However, 58 to 83% of mice given estradiol and/or cyclophosphamide at appropriate times developed significant hematuria. If drugs were given at suboptimal times, only 25 to 56% of mice developed hematuria. Drug-treated immunized mice also had more serum IgG and IgM anti-BGG antibodies than control and saline groups. Immunofluorescence showed significantly more glomerular deposits of IgG, IgM, and C3 in drug-treated immunized mice compared to saline-treated immunized and normal untreated control mice. Hematuria and glomerular deposits of IgG, IgM, and C3 paralleled serum IgG and IgM antibody. All immunized mice showed significant mesangial IgA and BGG deposits and there were no differences in such deposits between saline- and drug-treated immunized mice. We suggest that blunting of oral tolerance with promotion of systemic IgG and IgM antibody production leads to nephritis in chronically orally immunized mice and that glomerular immune complexes containing IgG and/or IgM promote complement deposition and hematuria in IgAN. Analogous defects in oral (or more generally mucosal) tolerance could play a role in the genesis of symptomatic human IgAN.

Administration, Oral↗
PubMed2001

Dichloroacetate reduces diaphragmatic lactate formation but impairs respiratory performance.

Previous studies have found that administration of dichloroacetate (DCA), an agent that reduces lactic acid generation, increases limb muscle endurance. The purpose of the present study was to determine if this agent also improves respiratory muscle performance. To examine this issue, we determined the effect of DCA administration on the response to application of a large inspiratory resistive load (32,000 cm H(2)O/L/s) in unanesthetized decerebrate rats. Studies were carried out in four groups of animals: saline unloaded, DCA unloaded, saline loaded, and DCA loaded. DCA was administered as 100 mg/kg, given intravenously over 30 min, prior to respiratory loading. We found that diaphragm lactate levels were higher in saline-treated loaded animals than in unloaded controls and that DCA administration prevented loading-induced increases in diaphragm lactate (p < 0.001). DCA-treated animals tolerated loading poorly, however, with a more rapid reduction in diaphragm pressure generation and a shorter time to respiratory arrest (42 +/- 3 min) than for saline-treated animals (57 +/- 3 min, p < 0.01). These data indicate that DCA administration decreases the tolerance to loaded breathing despite reductions in diaphragm lactate concentrations. We speculate that suppression of lactate formation by DCA may impair metabolic regulation within the diaphragm during resistive loaded breathing.

Airway Resistance↗
PubMed1977

Reversal of bedrest-induced orthostatic intolerance by lower body negative pressure and saline.

Six healthy male volunteers underwent two 1-week periods of bedrest, each preceded and followed by 2-week control and recovery periods. The daily metabolic diet contained 150 mEq of sodium. Following one 7-d bedrest period, each man was subjected to LBNP at a level of --30 mm Hg for 4 h while consuming 1000 ml of beef bouillon containing 154 mEq of sodium. After the other bedrest period, each man simply consumed the bouillon without LBNP treatment during 4 h of continued bedrest. Measurements of plasma volume and orthostatic tolerance were made before and after each treatment period. After combined LBNP and saline therapy, plasma volume and response to LBNP testing, as measured by heart rate and systolic BP, showed a return to pre-bedrest levels. Saline consumption alone had a lesser effect. With continuation of bedrest in three subjects, the beneficial effects of these measures appeared to be largely gone after 18 h.

Adult↗