Amfonelic acid (AFA), a non-amphetamine central stimulant dose-dependently reduced the hypnotic effect of ethanol in C57B1/6 mice. It did not enhance the elimination of ethanol. Amfonelic acid failed to modify the duration of pentobarbitone-induced hypnosis or the ethanol-induced hypothermia in these animals. Combined treatment with amfonelic acid and a lipophilic alpha 1-adrenoceptor agonist was not more effective than amfonelic acid alone in blocking ethanol hypnosis. The stimulation of locomotor activity by amfonelic acid in C57B1/6 mice was more sensitive to the blocking effect of ethanol than stimulation induced by d-amphetamine. The blocking effect of amfonelic acid, but not that of d-amphetamine, on the effects of ethanol developed tolerance. In pimozide-pretreated mice, amfonelic acid failed to reduce the ethanol-induced hypnosis. Hence it appears that dopamine (DA) released by amfonelic acid is responsible for its antagonism of ethanol. However, though amfonelic acid acted as a strong releaser of DA in Swiss-Webster, CD-1, DBA-2 and BALB/c mice, in these strains it failed to reduce the effect of ethanol. Moreover, methylphenidate, a dopaminergic stimulant, which acts by a mechanism similar to that of amfonelic acid was not effective in reducing the hypnotic effect of ethanol in C57B1/6 mice. For these reasons, additional mechanisms may have to be considered to explain this strain-dependent effect of amfonelic acid.

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PubMedDate not supplied

Stem cell plasticity: an overview.

The capacity of adult bone marrow cells to convert to cells of other tissues, referred to by many as stem cell plasticity, was the focus of the meeting in Providence entitled "Challenges in the Era of Stem Cell Plasticity". The meeting provided a showcase for the many impressive positive results on tissue restoration including the capacity of purified marrow stem cells to restore heart, skin, and liver function in impaired mice or humans. This area of research has become a center of controversy, although it is not clear why. Calls for clonality, robustness, and function have been shown to be erroneous or premature. A call for clonality (which has been shown nicely in one study) is meaningless on a predefined stem cell population which is intrinsically heterogeneous, as they all are. Robustness means nothing; it all depends on the details of the situation. Function on an organ level is, of course, the goal of many investigators and should not be raised as a limiting consideration. Lastly, fusion has been highlighted as undermining studies with adult stem cells. It, of course, does not. Fusion is simply a means to a final goal, which occurs in certain settings of marrow conversions (transdifferentiation) and not in others. We hypothesize that the conversion phenomena may, in fact, be due to one or several marrow stem cells with broad differentiation potential which can be expressed when the cell is placed in an environment with the appropriate inductive signals. Furthermore, initial events may be relatively rare and significant conversion numbers may be obtained with massive or ongoing selection. Fusion appears in an initial mechanism in some cases and not in others. Overall, the therapeutic potential of adult marrow stem cells is very intriguing, and successful use therapeutically will probably depend on definition of the most appropriate transplant model and tissue injury.

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PubMedDate not supplied

Tissue injury in marrow transdifferentiation.

Recent findings indicate that adult BM contains cells that can differentiate into mature, nonhematopoietic cells of multiple tissues including cells of the kidney, lung, liver, skin and GI tract and fibers of heart and skeletal muscle. Recently the number of these observations has substantially increased, but there is a lack of information on the mechanistic issues in stem cell plasticity. In three different models for skin, liver and skeletal muscle plasticity, we have shown that following transplantation of the marrow cells from green fluorescent protein (GFP) transgenic mice, high levels of conversion of marrow cells can be identified. Injury to the tissue was the single most important factor for this phenomenon since the incidence of marrow to other tissue conversions significantly increased after tissue injury was implemented. Our studies also demonstrate the effect of radiation on the extent of marrow conversion.

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