AIDS impact.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
F van den Boom
Publications and source records attributed to F van den Boom.
In rat hepatocytes, the hypertonic activation of Na(+) conductance and Na(+)-K(+)-2Cl(-) symport--but not Na(+)-H(+) antiport--is mediated by protein kinase C.
1. The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an import of extracellular Na(+) via Na(+) conductance, Na(+)-K(+)-2Cl(-) symport, and Na(+)-H(+) antiport. 2. Here, the protein kinase inhibitors staurosporine (100 nmol l(-1)) and bis-indolyl-maleimide I (400 nmol l(-1)) were used to test for a possible contribution of protein kinase C (PKC) to the hypertonic activation of these transporters in confluent primary cultures. 3. Stimulation of Na(+) conductance was monitored: (i) by use of a differential approach based on Na(+) fluxes, (ii) by means of cable analysis, and (iii) in experiments with low Na(+) pulses. All three experimental protocols in concert demonstrated a block of the activation of Na(+) conductance by staurosporine and bis-indolyl-maleimide I. 4. In addition, both compounds significantly reduced the hypertonic activation of Na(+)-K(+)-2Cl(-) symport (quantified on the basis of furosemide-sensitive (86)Rb(+) uptake) to approximately 30 %. 5. In contrast, neither staurosporine nor bis-indolyl-maleimide I had any detectable effect on the hypertonicity-induced alkalinization of cell pH via Na(+)-H(+) antiport (determined fluorometrically). 6. Staurosporine and bis-indolyl-maleimide I completely blocked the RVI of rat hepatocytes (quantified by means of confocal laser-scanning microscopy). The high efficiency of the block suggests an additional inhibitory effect of both compounds on the activity of Na(+)/K(+)-ATPase (determined as ouabain-sensitive (86)Rb(+) uptake). 7. It is concluded that the hypertonic activation of rat hepatocyte Na(+) conductance and Na(+)-K(+)-2Cl(-) symport--but not Na(+)-H(+) antiport--is probably mediated by PKC.
Algorithms↗
The hypertonicity-induced Na(+) conductance of rat hepatocytes: physiological significance and molecular correlate.
The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an uptake of extracellular Na(+) that is then exchanged for K(+) via stimulation of Na(+)/K(+)-ATPase. While it was generally assumed that this Na(+) uptake is mediated by the activation of Na(+)/H(+) antiport and Na(+)-K(+)-2Cl(-) symport it could be shown recently that, in addition to these transporters, hypertonic stress also stimulates conductive Na(+) entry. In a quantitative study, it was found that the relative contribution of Na(+) conductance, Na(+)/H(+) antiport, and Na(+)-K(+)-2Cl(-) symport to the initial Na(+) import as well as to the RVI process (at 300 --> 400 mosmol/l) is approximately 4 : 1 : 1. When the osmotic sensitivity of these Na(+) importers was tested (at 300 mosmol/l --> 327, 360, 400, 450 mosmol/l) it became clear that Na(+) conductance is the prominent mechanism of RVI from 360 mosmol/l upwards whereas Na(+)/H(+) antiport is the most sensitive transporter with 65 % of its maximal activation at 327 mosmol/l already. Concerning the intracellular regulation of the Na(+) importers involved in RVI it was found that Na(+) concuctance as well as Na(+)-K(+)-2Cl(-) symport - but not Na(+)/H(+) antiport - are activated via PKC. With respect to the molecular correlate of the volume activated Na(+) conductance it could be shown that it exhibits a rather low affinity to amiloride (IC(50) = 6.0 micromol/l) and an overall sensitivity profile of EIPA > amiloride > benzamil = phenamil that, at first sight, would not speak in favor of a typical epithelial type of Na(+) channel (ENaC). Western-blot analysis and RT-PCR techniques, however, revealed that alpha-, beta-, as well as gamma-ENaC are, in fact, expressed in rat hepatocytes. Moreover, by use of an antisense-DNA based approach it could be shown that at least alpha-ENaC is part of the hypertonicity induced Na(+) conductance.
Animals↗
AIDS, euthanasia and grief.
Almost 50% of people with AIDS in the Netherlands make the necessary arrangements for a possible death by the administration of thanatic drugs. In approximately 50% of those who arranged for it, euthanasia is performed. Euthanasia is a well-considered decision. By means of euthanasia people with AIDS want to prevent unbearable suffering and a degrading existence. Those who have arranged for euthanasia were proven to have adapted to the disease better than those who had not. No relationship was found between ending life by means of euthanasia and complicated grief in survivors. However, if the euthanasia process itself was complicated, the risk of complicated grief increased.
Acquired Immunodeficiency Syndrome↗