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Biomedical subjects

S F Gottlieb

Publications and source records attributed to S F Gottlieb.

At least 19 recordsLinked to original sources

Identification of hypometabolic areas in the brain using brain imaging and hyperbaric oxygen.

Current neurologic assessments consider idling neurons and ischemic penumbras to be metabolically lethargic and electrically nonfunctional or nonviable. Diagnosis, prognosis, and therapeutics of central nervous system dysfunctions require differentiation between viable and nonviable neurons. It is necessary to develop and document efficacious and safe techniques for reactivating idling neurons. The authors present a case study of a near drowning 12 years earlier. Areas of cortical hypometabolism were identified by using SPECT imaging in conjunction with hyperbaric oxygen therapy (HBOT). Delayed imaging after HBOT (1 hour, 1.5 atm abs) suggested viable but metabolically lethargic neurons. After HBOT (80 1-hour treatments, monoplace chamber, 1.5 atm abs), marked improvements in cognitive and motor functioning were demonstrated. The data support the hypothesis that idling neurons and ischemic penumbras, when given sufficient oxygen, are capable of reactivation. Thus, changes in tracer distribution after a single exposure to HBOT may be a good prognostic indicator of viable neurons. HBOT may be valuable not only in recovery from anoxic encephalopathy but also from other traumatic and nontraumatic dysfunctions of the central nervous system, including stroke. HBOT in conjunction with physical and rehabilitative therapy may help reactivated idling neurons to remain permanently active.

Adolescent

The etiology of multiple sclerosis: a new and extended vascular-ischemic model.

It is hypothesized that multiple sclerosis is a disease of the cerebro-vascular system. The basic defect is visualized as a wound in the CNS due to a focal hypertension of genetically susceptible vessels which results in vascular injury and the initiation of a series of biochemical and physiological events culminating in an ischemic hypoxia leading to demyelination and a secondary damaging process associated with the immune system.

Brain Ischemia

The effect of allopurinol on oxygen-induced seizures in mice.

Prolonged exposure to hyperbaric oxygen causes central nervous system (CNS) oxygen toxicity manifested by grand mal seizures. The superoxide anion is believed to be a cause of tissue damage in CNS oxygen toxicity and it is proposed that xanthine oxidase activity is one of the prime sources of superoxide. Groups of mice were given equivalent doses of allopurinol, hypoxanthine, or saline, and exposed to five atmospheres absolute of oxygen. It was proposed that allopurinol, a xanthine oxidase inhibitor, would decrease the rate of superoxide formation thus delaying the onset of oxygen-induced seizures. It was further proposed that hypoxanthine would increase the rate of superoxide formation decreasing the preconvulsive latency. The data indicated that neither allopurinol nor hypoxanthine altered susceptibility to the CNS manifestations of oxygen toxicity. The results do not support the theory that xanthine oxidase is a prime source of superoxide anions in mouse brain.

Allopurinol

Enhancement of cortical Na+,K+-ATPase by increased oxygen tensions: evidence of a new controlling mechanism.

This study describes the preliminary isolation of substances from beef brain cortex which are required to produce an oxygen-induced enhancing effect on Na, K-ATPase. Evidence is presented that at least 3 fractions--a heat stable, low molecular weight proteinaceous substance, a cholesterol rich, membranous component, and an as yet unidentified substance--are required to produce oxygen enhancement of Na, K-ATPase activity. These findings have specific ramifications in neurocellular physiology, especially as related to seizures.

Adenosine Triphosphatases

Pregnant mare serum and human chorionic gonadotropin stimulate ovarian delta5-3beta-hydroxysteroid dehydrogenase in aged mice.

Aged (12- to 14-month-old) estrous and diestrous C57BL mice exhibited lower histochemically demonstrable ovarian delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity in thecal, luteal, and interstitial cells, and lower (P less than 0.01) ovarian 3beta-HSD concentration and total content than did young (3-month-old) estrous animals. Administration of pregnant mare serum (PMS, 10 IU subcutaneously), followed in 40 hours by human chorionic gonadotropin (HCG, 5 IU subcutaneously) or HCG (2 IU daily for 4 days) alone, restored luteal and interstitial 3beta-HSD in aged mice. Follicular, lutea, and interstitial 3beta-HSD activity was increased in aged mice by a single PMS injection (10 IU). The total ovarian dehydrogenase concentration was increased 100% in aged animals by PMS and/or HCG administration. Restoration of histochemically demonstrable ovarian 3beta-HSD and total enzyme content in aged mice by PMS and/or HCG indicates ovarian sensitivity to gonadotropin and subnormal tropic hormone stimulation of the ovary in situ.

Animals

Effect of increased pressures of oxygen, nitrogen, and helium on activity of a Na-K-Mg ATPase of beef brain.

Increased pressure of O2, N2,or He exert inhibitory or stimulatory effects on activity of Na-K-Mg ATPase obtained from beef brain cortex. Oxygen at 2 ATA and N2 at 4 ATA exert significant inhibitory effects whereas 3 & 4 ATA O2, 1-3 ATA N2 exert significant stimulatory effects. Effects of He on ATPase activity are qualitatively similar to those of N2. The effects of the gases are not qualitatively altered by the presence or absence of ATP. A pressure compensated analysis reveals that at the same pressures, O2 and N2 exert different effects of ATPase activity.

Adenosine Triphosphatases

Ageing and ovarian delta 5-3 beta-hydrosteroid dehydrogenase in the pregnant mouse.

Aged (12- to 14-month-old) C57BL oestrous mice exhibited significantly lower (P less than 0-001) ovarian delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) concentration, specific activity and total content than young (3-month-old) oestrous mice, suggesting a decrease in the potential of the older animals to produce ovarian delta 4-3-oxosteroids. Mice in both age groups maintaining pregnancy to 10 or 18 days post coitum (p.c.) had similar values for activity of ovarian 3 beta-HSD. In the aged females in which foetal resorption had occurred, the majority of foetuses had been resorbed by 10 days p.c. However, ovarian 3 beta-HSD activity in these animals was not significantly different from that of young or aged mice maintaining pregnancy. By day 18, however, ovarian dehydrogenase activity in aged females failing to maintain pregnancy had decreased significantly. It is suggested that foetal death in aged mice is not the result of a deficiency in ovarian 3 beta-HSD, but rather may initiate luteal regression and consequently a decline in 3 beta-HSD.

Aging

Effects of increased pressures of oxygen and air on short-term memory in mice.

The purpose of this study was to determine the effects of increased oxygen tensions on short-term memory in mice following one-trial, passive-avoidance learning. Neither increased oxygen tensions per se nor 6 ATA air had any measurable deleterious effects on retention of the learned task. Interference with memory of the learned task occurred only when the animals were subjected to oxygen-induced convulsions. Oxygen-induced convulsions did not result in permanent brain damage such that the animals were incapable of learning. Oxygen-induced convulsions following a 2-h interval after learning did not result in a retrograde amnesia. It appears that oxygen-induced convulsions interferes with the consolidation process of memory.

Air Pressure

Effects of increased partial pressures of oxygen on the embryonic and post-embryonic development of drosophila melanogaster.

The objective of this investigation was to study the effects of increased oxygen pressures on the development of Drosophila melanogaster. Oxygen is a potent inhibitor of embryonic and post-embryonic development of Drosophila. The lowest partial pressure of O2 (Po2) found to elicit measurable inhibitory effects on development is 0.6 ATA. Continuous exposure of developing Drosophila to 0.6 ATA O2 elicits primarily a larvicidal effect; surviving larvae exhibit delays in initial puparium formation and in mean day of adult eclosion: several resultant adults exhibit the effects of O2-induced teratogenesis in that body and wing abnormalities become manifest which do not breed true on matings and back crosses. Continuous exposure to 0.8 or 1.0 ATA O2 results in developmental arrest in the second larval instar followed by death. This development arrest is reversible depending upon the duration of exposure. As concerns lethality, early larval stages are more sensitive to O2 than late larval stages which, in turn, are more sensitive than early or late pupal stages: the embryo is the more resistant of the development stages. As concerns sensitivity for teratogenesis, the embryo is the most sensitive stage.

Animals

Effect of high oxygen tensions on the growth of selected, aerobic, gram-negative, athogenic bacteria.

The in vitro effects of high O(2) tensions (P(O2)) on aerobic, enteric pathogens were examined at pressures of up to 3 atm absolute. Organisms from the genera Salmonella, Shigella, and Vibrio were usually subjected to 24-hr exposures. Tensions of 0.87, 1.87, and 2.87 atm absolute of O(2) (plus traces of CO(2) and N(2)) became progressively inhibitory for Salmonella and Shigella growth, but were bactericidal only for V. comma strains at tensions greater than 0.87 atm absolute of O(2). Growth inhibition of enteric organisms resulted from increased P(O2), rather than pressure per se, and could be mitigated nutritionally; an appropriate carbohydrate source is at least partially involved. Further studies with vibrios indicated that such mitigation was independent of medium pH. In addition, a synergistic relationship existed between O(2) and sulfisoxazole when tensions from 0.87 to 2.87 atm absolute of O(2) were maintained for 3 to 24 hr. Synergism occurred even under nutritional conditions which negated growth inhibition by O(2) alone. Bactericidal concentrations of sulfisoxazole, in the presence of increased P(O2), were reducible up to 4,000-fold. The combined procedure employed in this investigation, by use of an antimicrobial drug of known action, which also synergizes with O(2), plus nutritional studies, suggests a means for establishing a site of O(2) toxicity. These data support the concept that O(2) inhibition of growth represents a metabolic disturbance and that metabolic pathways involving p-aminobenzoic acid may be O(2)-labile. Such an approach could also guide development of antimicrobial agents as O(2) substitutes for promoting synergism.

Carbohydrate Metabolism