SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

In this report, we describe the clinical, topographical and immunohistochemical characteristics of neurofilament (NF) inclusion formation induced by the intracisternal inoculation of young adult New Zealand white rabbits at 28-day intervals with 100 micrograms AlCl3 over the course of 267 days. The ability to recover following cessation of aluminum exposure has also been assessed. The extent of neurofilamentous inclusion formation was proportionate to the cumulative amount of AlCl3 inoculated and initially consisted of fusiform axonal distention in the ventral spinal cord at day 51 following the initial inoculum. Spinal motor neuron perikaryal inclusions and discrete axonal spheroids were observed at day 107 and supraspinal neurofilamentous pathology by day 156. Perikaryal inclusions were immunoreactive to antibodies recognizing both poorly phosphorylated (SMI 32) and more highly phosphorylated high molecular weight NF (NFH). In contrast, axonal spheroids were intensely immunoreactive at all stages with antibodies recognizing highly phosphorylated NFH and an age-dependent NFH phosphorylation state (SMI 34) with only faint SMI 32 immunoreactivity. Immunoreactivity to an antibody recognizing ubiquitin-protein conjugates did not appear until day 156, whereas inclusions were not immunoreactive to antibodies recognizing either phosphatase-dependent or -independent microtubule-associated protein tau at any stage. Upon withdrawal from further AlCl3 exposure after intervals of 51, 107 or 156 days following the initial inoculum, clinical recovery ensued in all rabbits. In all but the most severely affected rabbits, perikaryal neurofilamentous inclusions resolved. However, axonal spheroids continued to be prominent. These studies demonstrate that the repetitive intracisternal inoculation of AlCl3 in New Zealand white rabbits induces a reversible process of neurofilamentous inclusion formation that preferentially affects motor neurons, and in which recovery will occur in those inclusions containing an admixture of both poorly and highly phosphorylated NFH.

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SummaryPlatelet responses stimulated by a range of concentrations of ADP or collagen were studied in platelet-rich plasma (PRP) from alcoholics 24-36 h and 6 days after cessation of drinking, and in PRP from age- and sex-matched controls. The studies were done using plasma from blood anticoagulated with the specific thrombin inhibitor D-pheny1a1any1-T,-prolyl-L-arginyl chloromethyl ketone (FPRCH2Cl, PPACK); the use of this compound permits the study of platelet responses in plasma at physiological concentrations of ionized calcium. Responses of platelets to ADP (primary aggregation) and collagen (aggregation, secretion of [14C]serotonin from prelabelled platelets, and thromboxane formation) were lower in alcoholics 24-36 h after withdrawal of alcohol compared with controls. This inhibition of platelet function was not due to the presence of alcohol in the blood of the alcoholics. Aggregation in response to ADP did not change during the withdrawal period studied, while collagen-induced aggregation and secretion increased significantly and collagen-induced thromboxane formation tended to increase towards control values. The reduced platelet responses observed in alcoholics and the different rates of “recovery” of different pathways of aggregation towards control values must be due to alterations either in the platelets themselves and/or in the plasma brought about by the chronic presence of ethanol, and its withdrawal.