Rett syndrome: stimulation of endogenous biogenic amines.

Transient hypercapnic hyperoxemia was induced in two Rett syndrome children by the administration of a gaseous mixture of 80% O2 and 20% CO2. Time course studies of neurotransmitters and their metabolites showed an immediate and marked increase in central biogenic amine turnover following inhalation of the gas mixture. The increased turnover of biogenic amines was associated with improved clinical changes. This suggests a coupled relationship and provides further support for an etiological role of neurotransmitter dysfunction in Rett syndrome. In a complementary study, elevation of pulmonary CO2 by application of a simple rebreathing device resulted in improvement of abnormal blood gases and elimination of the Cheyne-Stokes-like respiratory pattern of the Rett syndrome. Near normalization of the EEG occurred when a normal respiratory pattern was imposed by means of a respirator. Taken together, these results lead to the preliminary conclusion that cerebral hypoxemia secondary to abnormal respiratory function may contribute to diminished production of biogenic amines in Rett syndrome.

Effect of weightlessness and centrifugation on red cell survival in rats subjected to space flight.

Rats were flown aboard the Soviet biosatellite Cosmos 936 for 18.5 d during August, 1977. Five rats were subjected to near-weightless space flight, as with Cosmos 782, and five rats were subjected to a 1-G force via an on-board centrifuge. These rats and three control groups were injected with 2-14C glycine 19 d preflight. The flight rats were recovered from orbit after 18.5 d of space flight. Erythrocyte hemolysis and lifespan were evaluated in the five groups of rats by quantitation of radioactive carbon monoxide exhaled in the breath which arises from the breakdown of the previously labeled hemoglobin. The results support our previous findings wherein hemolysis was found to increase as a result of weightless space flight. A comparison to the centrifuged animals indicates that artificial gravity attenuates the effect of weightlessness on hemolysis and appears to normalize the hemolytic rate in the early postflight period.

Extremes of urine osmolality: lack of effect on red blood cell survival.

Rats were allowed a third of normal water intake for 20 days, and food consumption decreased. The reticulocyte count indicated a suppression of erythropoiesis. Urine osmolality increased from 2,000 mosmol/kg to 3,390 mosmol/kg. Random hemolysis and senescence of a cohort of red blood cell (RBC) previously labeled with [2-14C]glycine was monitored via the production of 14CO. Neither hemolysis nor senescence was affected. Following water restriction, the polydipsic rats generated a hypotonic urine. Urine osmolality decreased to 1,300 mosmol/kg for at least 6 days; a reticulocytosis occurred, but RBC survival was unaffected. These results contradict those previously reported, which suggest that RBC survival is influenced by the osmotic stress imposed on the RBC by extremes of urine tonicity. This discrepancy, we conclude, is due to differences in the methods employed for measuring RBC survival. The random-labeling technique employed previously assumes a steady state between RBC production and destruction. The cohort-labeling technique used here measures hemolysis and senescence independent of changes in RBC production, which is known to be depressed by fasting.

Relationship of intracellular creatine concentration and uptake to muscle mass in vivo.

Attempts have been made to evaluate the role of intracellular creatine in conditions leading to increased or decreased amounts of contractile protein in rat skeletal muscles. Resting concentrations of intracellular creatine ([Cr]i) and creatine phosphate ([CrP]i) were compared in gastrocnemius and soleus muscles with those immediately after a 20-s tetanic stimulation. The hydrolysis of creatine phosphate was the same after heavily and lightly loaded contractions, suggesting that hypertrophy of isometric exercise is not mediated by creatine. With atrophy after denervation or interruption of sciatic axoplasmic flow [Cr]i also remained unchanged, though [CrP]i and the rate of Cr uptake fell after denervation. The major change in adult red and white muscle bulk with unaltered [Cr]i suggests that the Cr sensitivity found by others in developing muscle in vitro has been supplemented or replaced by other control mechanisms.

Alterations in erythrocyte survival parameters in rats after 19.5 days aboard Cosmos 782.

Rats were subjected to 19.5 d of weightless space flight aboard the Soviet biosatellite, Cosmos 782. Based on the output of 14CO, survival parameters of a cohort of erythrocytes labeled 15.5 d preflight were evaluated upon return from orbit. These were compared to vivarium control rats injected at the same time. Statistical evaluation indicates that all survival factors were altered by the space flight. The mean potential lifespan, which was 63.0 d in the control rats, was decreased to 59.0 d in the flight rats, and random hemolysis was increased three-fold in the flight rats. The measured size of the cohort was decreased, lending further support to the idea that hemolysis was accelerated during some portion of the flight. A number of factors that might be contributory to these changes are discussed, including forces associated with launch and reentry, atmospheric and environmental parameters, dietary factors, radiation, and weightlessness.

Analysis of the exudate produced by Streptococcus mutans SL-1 colonies of sucrose-containing agar media.

The watery exudate produced by Streptococcus mutans SL-1 colonies on sucrose-containing agar media was found to contain about 7% (wt/vol) of a water-soluble, branched dextran, 4% sucrose, and smaller (less than 1%) amounts of fructose, Folin-phenol-positive material, and lactic acid.

The effects of cosmic Particle radiation on pocket mice aboard Apollo XVII: V. Preflight studies on tolerance of pocket mice to oxygen and heat. Part I. physiological studies.

Tests were carried out on pocket mice to ascertain their tolerance to elevated oxygen pressures alone and to a combination of hyperoxta and heat in excess of that expected during the flight of the mice on Apollo XVII. the mice withstood oxygen partial pressures up to 12 pst at normal room temperature (24 degrees C, 75 degrees F) over a period of 7 days. A few mice previously exposed to increased PO2 died in the course of exposure to an oxygen pressure of 10 pst or 12 psi (517 mm or 620 mm Hg) for 13 d in ambient heat of 32 degrees C (90 degrees F). Supplemental vitamin E and physiological saline loading given prior to exposure had no apparent protective effect. The overall conclusion was that the pocket mice which were to go on Apollo XVII could readily survive the ambient atmosphere to which they would be exposed.

The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: X. Results of ear examination.

In the five pocket mice flown on Apollo XVII, no evidence was found that the inner ear had been damaged, though poor fixation precluded detailed study. On the other hand, the middle ear cavity was involved in all the mice, hemorrhage having occurrred in response to excursions in pressure within the canister that housed the mice during their flight. The same occurred in flight control mice which had been subjected to pressure excursions of much the same magnitude. A greater degree of exudation into air cells and greater leukotaxis were noted in the flight animals than in the control animals. There was no increase in leukocyte population along the paths of the 23 cosmic ray particles registered in the subscalp dosimeters that traversed the middle ear cavities of the flight mice. The increased exudation and the greater response by leukocytes in the flight mice may have been causally related to the lesions found in their olfactory mucosa but there were no data in support of this possibility.

The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: IV. engineering aspects of the experiment and results of animal tests.

A closed passive system independent of support from the spacecraft or its crew was developed to house five pocket mice for their flight on Apollo XVII. The reaction of potassium superoxide with carbon dioxide and water vapor to produce oxygen provided a habitable atmosphere within the experiment package. The performance of the system and the ability of the mice to survive the key preflight tests gave reasonable assurance that to mice would also withstand the Apollo flight.

Changes in haptoglobin and other plasma proteins of rats during exposure to pure oxygen at 760 torr.

Changes in plasma haptoglobin, total protein, hematocrit, and hemoglobin content of blood were studied in rats at various times during a 7-d exposure to oxygen at 760 torr. Plasma haptoglobin and other plasma proteins were fractionated and quantitatively evaluated for a 3-d exposure period. Total protein and haptoglobin were depressed after 7 d of exposure. Significant changes were not noted before this time. With a 3-d exposure, for which plasma proteins were fractionated, fibrinogen showed a considerable increase whereas albumin, gamma globulins, and the beta 1 globulin fraction decreased significantly. Individual variations in albumin and haptoglobin were correlated inversely to the hematocrit. These variations indicate that the altered composition of the plasma protein is due, in part, to a variable loss of the various plasma protein fractions as a result of increased vascular permeability.