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At least 73 records · Page 4

Toxicologic evaluation of the migration of a plasticizer, DI (2-ethylhexyl) phthalate (DEHP) from vinyl plastics

The intravenous administration of DEHP solubilized by means of a number of different detergents leads to respiratory distress and death in rats. At autopsy the lungs are grossly enlarged, edamatous, and hemorrhagic. Light and electron microscopic evaluation of the lungs indicate engorgement of the interalveolar septa with edema fluid and polymorphonuclear leucocytes, degranulation of the leukocytes, and progessive destruction of the endothelial and epithelial cells. Consistent with the conclusion that solubilized DEHP results in a syndrome of "shock lung" is the associated massive fall in arterial blood pressure and the prevention of the lung pathology by pretreatment with pharmacologic doses of an antiinflammatory steroid, methylprednisolone. Evidence is also presented that suggests that the DEHP inadvertently administered to humans during transfusions is also in a solubilized state in the plasma.

Rubin, R. J.↗

The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

Carter, V. L., Jr.↗

A review of available LC/50/ data

Several gaseous products of pyrolysis and combustion have been evaluated for LC/50/, defined as the concentration of toxic gas in the atmosphere being inhaled by test animals that will produce death in 50% of the animals within a given time period. The products tested included CO, HCl, HF, HCN, NO2, and SO2. It was found that HCN and NO2 were consistently the most toxic of the gases reviewed, and that mice were more susceptible than rats to HCl and HF, although less susceptible than rats to NO2. Extrapolation of LC/50/ data to humans indicates that metabolic rate may be a valid basis for extrapolation when the toxicity mechanism is interference with oxygen transport and utilization, or pulmonary edema, but not when it is irritation and damage to the upper respiratory tract.

Hilado, C. J.↗

Structural and Functional Organization of the Vestibular Apparatus in Rats Subjected to Weightlessness for 19.5 Days Aboard the Kosmos-782 Satellite

The vestibular apparatus was investigated in rats subjected to weightlessness for 19.5 days. The vestibular apparatus was removed and its sections were fixed in a glutaraldehyde solution for investigation by light and electron microscopes. Structural and functional charges were noted in the otolith portions of the ear, with the otolith particles clinging to the utricular receptor surface and with the peripheral arrangement of the nucleolus in the nuclei of the receptor cells. It is possible that increased edema of the vestibular tissue resulted in the destruction of some receptor cells and in changes in the form and structure of the otolith. In the horizontal crista, the capula was separated.

Vinnikov, Y. A.↗

Effect of gravitational overloads, hypokinesia and hypodynamia on the vessels of the pulmonary blood circuit

Vessels of the pulmonary circuit are studied under normal conditions, in exposure to single stress or continuous threshold endurable chestspine gravitational stresses, and one to eight weak hypokinesia and hypodynamic effects followed by stress. Examination methods include rentgenography and microrentgenography, clearing, and histology. In exposure to gravitational stress the distal portions of the arterial vessels of the 3 and 4 orders constrict, while all veins dilate. Sinuosity of all vessels is noted. The volume of the capillary bed increases and signs of perivascular edema occur. Due to hypokinesia and hypodynamia the arteries constricted and the arterial bed becomes poor. The veins of all orders dilate and the volume of the capillary bed increases. The changes grew greater the longer the terms of hypodyamic effects. Successive combination of hypokinesia and hypodynamia and gravitational stresses cause more pronounced changes than separate effects of these two factors and result in great deformity of the vascular walls, including their rupture and penetration of formed elements beyond the limits of the vascular bed.

Kasimtsev, A. A.↗

State of the mitral valve in rabbits with hypokinesia

In hypokinesia, edema of all the layers of the mitral value was observed, which resulted in morphological changes of the cellular and noncellular components. An increase in ratio of elastic and collagenic fibers in the value was also observed along with and changes in their structural and staining properties. The observed changes can limit valve mobility and can result in manifestations of cardiac valve insufficiency, which is found clinically.

Strelkovska, V. Y.↗

Morphological changes in neurons of the hind limb reflex arc during long term immobilization

Twelve adult rabbits were immobilized for 9 to 31 days, followed by histological study of the nerve processes of lumbar vertebra 7 and sacral vertebra 1, the sciatic nerve and the motor endings of the thigh muscles. In the spinal ganglia, dystrophic changes of increasing severity with immobilization time were found, including pericellular edema, vacuolized neuroplasm, pycnotic changes, cytolysis and destruction. Chromatophilic matter decreased and was partly bleached, and amitotic division occurred. A portion of the sciatic nerve fibers were argentophilic, and some fragmentary decomposition occurred. Considerable dystrophic changes occurred in the motor nerve endings.

Tkachenko, Z. Y.↗

Tolerance of Lower Body Negative Pressure (LBNP) in endurance runners, weightlifters, swimmers and nonathletes

Thirteen endurance runners (R), 12 weightlifters (WL), 12 swimmers (SW) and 10 nonathletes (NA) were tested for their tolerance of lower body negative pressure (LBNP) in consecutive 5 minute stages at -20, -30, -40, -50 and -60 torr. Each subject also performed an exercise test on a bicycle ergometer with progressive workloads to exhaustion to determined aerobic capacity. The R had a much higher aerobic capacity than any of the other groups, but a significantly lower LBNP tolerance. While responses in heart rate and pulse pressure were quite similar in all 4 groups, the rate of increase in leg volume relative to LBNP stress (leg compliance, LC) was considerably greater in R than in the other athletes and NA. The greater LC in R could be attributed not only to a more rapid shift of blood to the lower extremities but also to a greater tendency for edema formation, both contributing to a more rapid loss in effective central blood volume for a given LBNP stress. These results substantiate earlier observations which led to the conclusion that endurance running is not advisable as a training regimen for astronauts.

Source record↗

Measurement of central venous pressure and determination of hormones in blood serum during weightlessness

A Spacelab experiment is described which proposes to obtain data on the degree of engorgement of the cephalad circulation during weightlessness by recording central venous pressure. Of practical importance is the question of how close the astronauts are to pulmonary edema and whether the pressure falls toward normal during the time of the mission. Another experiment to investigate deviations from normal fluid and mineral metabolism, possibly initiated by the central engorgement of the low pressure system, is discussed. Hormones responsible for the control of water and mineral balance (vasopressin, catecholamines, renin, aldosterone, corticosteroids, and prostaglandin E1) will be analyzed from blood samples.

Kirsch, K.↗

A Pathologist's view on the effects of very long exposure to weightlessness

Speculations concerning the probable consequences of exposure to weightlessness during periods of one year or more and how these effects compare with aging are made. Orthostatic and excercise intolerance, neurological and muscular effects, cell division and DNA synthesis, tissue hypoxia, and edema are discussed in reference to the in-space and return-to-Earth situations.

Bensch, K. G.↗

Fluid shifts in vascular and extravascular compartments of humans during and after simulated weightlessness

A study is presented of the transcapillary pressures and the possible fluid shifts in muscles and subcutaneous tissue of the lower leg before, during, and after head-down tilt. Results showed that the subjects experienced facial edema, headache, nasal congestion, diuresis, and decreased lower-leg volume in response to 8 hours of 5 degree head-down tilt. Also found were significant decreases in systolic and diastolic pressures 2 hours after initiation of tilt, although blood pressure normalized thereafter. The lower-leg volume, urine output and interstitial fluid pressures of the tibialis anterior muscle and overlying subcutaneous tissue also changed significantly. No significant change was found in the colloid osmotic pressures of blood or interstitial fluid. It is concluded that these results indicate the need for countermeasures to maintain precapillary-muscle tone during long space flights in order to prevent swelling of lower-leg tissues upon readjustment to earth's gravity.

Hargens, A. R.↗

Fluid shifts and muscle function in humans during acute simulated weightlessness

The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

Hargens, A. R.↗

Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats

The tail suspension model (head-down tilt) simulates hypogravity in terms of musculoskeletal loss in the rat. However, little is known of tissue fluid shifts and body weight distribution in this model. Tissue fluid pressures were measured by wick catheters in 12 Munich-Wistar rats before, during, and after 48 hrs of tail suspension (about 30 deg head-down tilt). Subcutaneous tissue fluid pressure in the neck increased from -2.2 + or - 0.4 (normal horizontal position) to +4.0 + or - 1.5 cm H2O during tail suspension, indicating a cephalic fluid shift and significant edema during head-down tilt. In a separate study, six rats were suspended at 30-70 deg, and forelimb load and tail tension were measured by a balance and force transducer, respectively. Approximately 50 percent of body weight (BW) was loaded on forelimbs at a head-down tilt angle of 30 deg and forelimb load declined linearly to 10 percent BW at 70 deg. Furthermore, tail tension increased from 50 percent BW at 30 deg to 85 percent BW at 70 deg. These results indicate that less than normal loads are applied to forelimbs of rats suspended at angles of less than 30 deg and that the tail bears an increasing proportion of the rat's body weight at head-down tilt angles of less than 30 deg.

Hargens, A. R.↗

Mechanism for negative water balance during weightlessness An hypothesis

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus, the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.

Greenleaf, J. E.↗

Mechanisms for negative water balance during weightlessness Immersion or bed rest?

Results of bedrest and water immersion studies are of interest when formulating an hypothesis to explain inflight changes in water and electrolyte metabolism. A comparison of the two techniques is made, and it is found that the time course of fluid-electrolyte responses with bedrest occur more slowly than during weightlessness and faster with immersion. Hence, the head-down bedrest is the more appropriate model for simulation studies. The facts lead to the following hypothesis: Because of the head-ward shift of fluid , there is a transient elevation of central venous pressure upon reaching weightlessness that is not sufficiently intense to significantly activate the vasopressin-diuresis mechanism. But the increased pressure is of significant intensity to release atrial natriuretic peptides. A hypotonic fluid moving into the cells contributes to edema and inhibits thirst. In this manner, astronauts gradually lose body water as a result of slightly increased urinary sodium coupled with decreased fluid intake. These responses continue until a new fluid-electrolyte steady state is attained at a reduced level of total body water.

Greenleaf, J. E.↗

Experiment K-6-13. Morphological and biochemical examination of heart tissue. Part 1: Effects of microgravity on the myocardial fine structure of rats flown on Cosmos 1887. Ultrastructure studies. Part 2: Cellular distribution of cyclic ampdependent protein kinase regulatory subunits in heart muscle of rats flown on Cosmos 1887

The left ventricle of hearts from rats flown on the Cosmos 1887 biosatellite for 12.5 days was compared to the same tissue of synchronous and vivarium control animals maintained in a ground based laboratory. The volume density of the mitochondria in the myocardium of the space-flown animals was statistically less (p equal less than 0.01) than that of the synchronous or vivarium control rats. Exposure to microgravity resulted in a certain degree of myocardial degeneration manifested in mitochondrial changes and accumulation of myeloid bodies. Generalized myofibrillar edema was also observed.

Philpott, D. E.↗

Effects of acute hypoxia on cardiopulmonary responses to head-down tilt

Six male subjects were exposed on two separate occasions to simulated microgravity with 28 deg head-down tilt (HD) for 1 h with baseline followed by recovery at + 17 deg head-up. Pulmonary ventilation, gas exchange, spirometry, and central and cerebral blood flow characteristics were compared while breathing ambient air and reduced F(I)O2 equivalent to 14,828 ft. With hypoxia (HY), the increased tidal volume served to attenuate the drop in arterial saturation by reducing deadspace ventilation. Arterial and mixed venous PO2, values, estimated from peripheral venous samples and cardiac output (CO), were both maintained during HD in HY. Mixed venous PO2 was elevated by an increase in CO associated with a reduction in systemic resistance. Changes in spirometric indices during HD were not accentuated by HY, making the presence of interstitial edema unlikely. Cerebral flow and resistance showed minor reductions with HD. Tissue oxygenation and cardiopulmonary function were not notably effected by HD during HY, but a combination of these two stressors may predispose subjects to subsequent orthostatic intolerance during initial recovery.

Loeppky, J. A.↗

Postural responses of head and foot cutaneous microvascular flow and their sensitivity to bed rest

To explore the mechanism for facial puffiness, headache, and nasal congestion associated with microgravity and cephalad fluid shifts, the postural responses of the cutaneous microcirculation (CMC) in the forehead and dorsum of the foot of eight healthy men were studied by changing body position on a tilt table and measuring blood flows with a laser Doppler flowmeter. Increasing arterial pressure in the feet by moving from a -6-deg head-down tilt to a 60-deg head-up posture decreased foot CMC by 46.5 + or - 12.0 percent. Raising arterial pressure in the head increased forehead CMC by 25.5 + or - 0.7 percent (p less than 0.05). To investigate the possibility that these opposite responses could be modified by simulated microgravity, tilt test were repeated after 7 d of -6-deg head-down-tilt bed rest. The responses were not significantly different from those recorded before bed rest. Therefore, CMC in the feet is well regulated to prevent edema when shifting to an upright position, whereas there is less regulation in the head CMC.

Aratow, Michael↗