Effects of dexamethasone on the development of radiation nephropathy in the rat.

Low-dose, chronic administration of the synthetic glucocorticoid, dexamethasone, to male CD-I rats in the drinking water or by osmotic minipumps implanted subcutaneously after supralethal irradiation of the kidneys (20 Gy) was studied. The effectiveness of treatment with dexamethasone in the drinking water at concentrations of 23 micrograms/l to 188 micrograms/l and treatment times varying from 33 to 166 days was evaluated. At monthly intervals kidney function was assayed by measuring the clearance of 51Cr-ethylenediaminetetraacetic acid. All dexamethasone treatment regimens increased survival times significantly and delayed the development of kidney dysfunction. The most effective combination of concentration of dexamethasone in drinking water and treatment interval after irradiation with respect to survival was 94 micrograms/l and 88 days. However, a slightly longer survival and a better functional result was obtained if an equivalent amount of dexamethasone was administered by minipumps. Shielding the adrenal glands during kidney irradiation did not prolong survival. This shows that the beneficial effect of dexamethasone is not due to compensation for reduced adrenal glucocorticoid production resulting from concomitant exposures of these glands during kidney irradiation.     

Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization

In addition to being critical for apoptosis, components of the apoptotic pathway, such as caspases, are involved in other physiological processes in many types of cells, including neurons. However, very little is known about their role in dynamic, nonphysically destructive processes, such as axonal arborization and synaptogenesis. We show that caspases were locally active in vivo at the branch points of young, dynamic retinal ganglion cell axonal arbors but not in the cell body or in stable mature arbors. Caspase activation, dependent on Caspase-3, Caspase-9, and p38 mitogen-activated protein kinase (MAPK), rapidly increased at branch points corresponding with branch tip addition. Time-lapse imaging revealed that knockdown of Caspase-3 and Caspase-9 led to more stable arbors and presynaptic sites. Genetic analysis showed that Caspase-3, Caspase-9, and p38 MAPK interacted with Slit1a-Robo2 signaling, suggesting that localized activation of caspases lie downstream of a ligand receptor system, acting as key promoters of axonal branch tip and synaptic dynamics to restrict arbor growth in vivo in the central nervous system.     

The Performance of Respirators Used in the Treatment of Respiratory Insufficiency

Mechanical ventilators may be required for the treatment of inadequate ventilation, intractable left heart failure and cerebral edema. Each situation requires different ventilator characteristics. The performance of the Blease P3, Engström, Mörch Piston, Bird Mark 7 and 8 and Bennett PR1 and PR2 respirators has been studied. The factors governing choice of respirator in specific clinical situations are described.     

Affinity partitioning of membranes. Cholinergic receptor-containing membranes from Torpedo californica.

Affinity partitioning has been employed in the purification of membranes rich in cholinergic receptor from Torpedo californica electric organs. The procedure involves a modification of poly(ethylene oxide)-dextran aqueous phase partitioning systems where a ligand selective for the receptor is conjugated to the poly(ethylene oxide). Specific partitioning of the receptor-containing membranes into the poly(ethylene oxide)-rich phase occurs when bis-alpha,omega-trimethylamino poly(ethylene oxide) or bis-rho-tri-methylammonium phenylamino poly(ethylene oxide) was added to the phase system in low mole ratio. bis-alpha,omega-Methylamino poly(ethylene oxide), which should impart equivalent interfacial electromotive potential to the system but bind poorly to the receptor sites, was much less effective in producing phase distribution changes. The ligand-polymer-dependent phase distribution shifts were blocked by bisquaternary methonium ligands at concentrations consistent with their relative affinities for the cholinergic receptor. Titration or receptor sites with cobra alpha-toxin decreased the phase distribution changes in a linear fashion up to the point of stoichiometry. These observations are consistent with the phase distribution changes being consequent to ligand-polymer association with the pharmacologically important site on the receptor. The affinity partitioning procedure, when employed following an initial purification of the membranes by differential and density gradient centrifugation, yields membrane preparations with a high degree of morphological uniformity and a specific activity between 2.9 and 4.6 nmol of bound cobra alpha-toxin/mg of protein.     

Hospital Medical Staff By-laws: An Instrument for Self-Government

Hospital medical staff by-laws are important. By them the governing board of a hospital can and does confer on the medical staff the power to set up a form of organization by which that staff can give assurance of quality hospital medical care. The form of medical staff organization is patterned on familiar concepts of democratic self-government as we know it on this continent. Within the ordered society of the hospital medical staff, as in society at large, there is control of citizenship, classification of citizens as to their citizen rights, licence to do differing kinds of work, election of representatives, definition of rules for conduct, application of the cabinet principle, law enforcement by appointed judges, the right of appeal and, importantly, incentive for voluntary effort. Traditional professional freedom, self-determination and voluntary association of colleagues are guarded by this method of hospital conduct which is unique to the voluntary hospital system on this continent. Knowledge of the democratic process and of the motivation required to make it work well are essential for its preservation.     

Biochemical and electropharmaceutical studies with tricyclic antidepressants in rat and guinea-pig cerebral cortex.

Chopped guinea pig cerebral cortex was incubated with a series of antidepressant drugs which produced increases in the cyclic AMP content of the tissue. These effects were partially or wholly blocked by theophylline, suggesting that they were mediated by endogenous production, release and action of adenosine. A similar series of drugs was iontophoretically ejected on rat cerebral cortical neurons where augmentation of concurrently ejected adenosine was observed as slowing of the rate of cell firing. Pharmacological correlations between the two sets of data suggest a common mechanism of action.