Linked Life Data

7512989

Source:http://linkedlifedata.com/resource/pubmed/id/7512989

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-5-20
pubmed:abstractText
Prevention of red cell K+ and water loss is a therapeutic strategy for sickle cell disease. We have investigated in vitro and in vivo the effects of clotrimazole (CLT) and miconazole (MIC) on transgenic mice red cells expressing hemoglobin SAD. CLT blocked the Gardos channel (ID50 75 +/- 22 nM; n = 3) and the A23187-induced dehydration of Hbbs/Hbbthal SAD 1 mouse erythrocytes in vitro. Oral treatment with CLT (160 mg/kg per d) and MIC (100 mg/kg per d) inhibited the Gardos channel in both SAD 1 and control (Hbbs/Hbbthal) mice. In the SAD 1 mice only, cell K+ content increased, and mean corpuscular hemoglobin concentration and cell density decreased. After 7 d of treatment, the hematocrit of SAD 1, CLT-treated animals also increased. All changes were fully reversible. Long-term treatments of SAD 1 mice with oral CLT (80 mg/kg per d for 28 d) lead to sustained increases in cell K+ content and hematocrit and sustained decreases in mean corpuscular hemoglobin concentration and cell density, with no changes in animals treated with vehicle alone. Thus, CLT and MIC can reverse dehydration and K+ loss of SAD 1 mouse erythrocytes in vitro and in vivo, further supporting the potential utility of these drugs in the treatment of sickle cell anemia.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-13618284, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-14233155, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-1465455, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-1702096, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-1732017, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-1915288, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-2081015, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-3311198, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-3699160, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-3961486, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-4146621, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-638256, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-6999348, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-7296001, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-7430265, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-8325974, http://linkedlifedata.com/resource/pubmed/commentcorrection/7512989-8326017
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1670-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Treatment with oral clotrimazole blocks Ca(2+)-activated K+ transport and reverses erythrocyte dehydration in transgenic SAD mice. A model for therapy of sickle cell disease.
pubmed:affiliation
Department of Internal Medicine, University of Verona, Italy.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't