Transient mass transfer processes during the perfusion of a biological organ with a cryophylactic agent solution

An analytical study was performed for the mass transfer processes which occurs during a typical CPA introduction protocol in a biological organ. In such a protocol the concentration of CPA in the perfusate changes linearly with time to a maximal value and is then kept at that value for an additional period of time. Numerical solutions to the Kedem-Katchalsky equations for mass transfer processes in an organ modeled by a large number of typical Krogh tissue units were found. The solutions indicate that several phenomena possibly harmful to the organ occur in the tissue as a function of H, the rate of increase in the CPA concentration.     

Inhibition of tubulin polymerization with ribose-modified analogs of GDP and GTP reduced inhibition with microtubule-associated proteins and magnesium

Inhibitory effects of ribose-modified GDP and GTP analogs on tubulin polymerization were examined to explore nucleotide structural requirements at the exchangeable GTP binding site. With microtubule-associated proteins and Mg²⁺, GTP-supported polymerization was only modestly inhibited by GDP, and still weaker inhibitory activity was found with two analogs, dGDP and 9-β-D-arabinofuranosylguanine-5′-diphosphate (araGDP). Omission of Mg²⁺ significantly enhanced the inhibitory effects of GDP, dGDP and araGDP and resulted in weak inhibition of the reaction by several other GDP analogs. The relative inhibitory activity of the GDP analogs had no discernable relationship to the relative activity of cognate GTP analogs in supporting microtubule-associated protein-dependent polymerization. One GTP analog, 2′,3′-dideoxyguanosine 5′-triphosphate (ddGTP), supports polymerization both with and without microtubule-associated proteins. The inhibitory activity of GDP and GDP analogs in ddGTP-supported polymerization was much greater in the absence of microtubule-associated proteins than in their presence; and both reactions were more readily inhibited than was microtubule-associated protein-dependent, GTP-supported polymerization. Microtubule-associated protein-independent, ddGTP-supported polymerization was also potently inhibited by GTP and a number of GTP analogs. GTP was in fact twice as inhibitory as GDP. The relative inhibitory activity of the GTP analogs was comparable to the relative inhibitory activity of the cognate GDP analogs and very different from their relative activity in supporting polymerization.     

FIELD IMMOBILIZATION OF FREE-RANGING IMPALA IN NORTHERN KENYA

Two drug combinations were tested during 18 field captures of 14 individual impala in northern Kenya in 1966–67. Nine additional impala, eight females and one male, were darted but not captured. Dosages of 0.45 mg M.99+10.0 mg acepromazine+4.5 mg hyoscine were adequate for males, but did not completely immobilize them. Females proved more difficult to capture, and all attempts using the acepromazine mixture were unsuccessful. The substitution of phencyclidine for acepromazine, and the deletion of hyoscine, proved a more suitable mixture. A dosage of 0.32 mg M.99+90 mg phencyclidine per animal completely immobilized both sexes. The phencyclidine-M.99 mixture was judged an improvement over other common field immobilizing drugs, but the long recovery time limits the usefulness of this drug combination for large-scale capturing operations.     

Fluctuation Analysis of Tetanic Rundown (Short-Term Depression) at a Corticothalamic Synapse

Hypothetical scenarios for “tetanic rundown” (“short-term depression”) of synaptic signals evoked by stimulus trains differ in evolution of quantal amplitude (Q) and covariances between signals. With corticothalamic excitatory postsynaptic currents (EPSCs) evoked by 2.5- to 20-Hz trains, we found Q (estimated using various corrections of variance/mean ratios) to be unchanged during rundown and close to the size of stimulus-evoked “miniatures”. Except for covariances, results were compatible with a depletion model, according to which incomplete “refill” after probabilistic quantal release entails release-site “emptying”. For five neurons with 20 train repetitions at each frequency, there was little between-neuron variation of rundown; pool-refill rate increased with stimulus frequency and evolved during rundown. Covariances did not fit the depletion model or theoretical alternatives, being excessively negative for adjacent EPSCs early in trains, absent at equilibrium, and anomalously positive for some nonadjacent EPSCs. The anomalous covariances were unaltered during pharmacological blockade of receptor desensitization and saturation. These findings suggest that pool-refill rate and release probability at each release site are continually modulated by antecedent outputs in its neighborhood, possibly via feedback mechanisms. In all data sets, sampling errors for between-train variances were much less than theoretical, warranting reconsideration of the probabilistic nature of quantal transmitter release.