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C Hershko

Publications and source records attributed to C Hershko.

210 records · Page 12Linked to original sources
PubMedDate not supplied

Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells.

Cardiac dysfunction is a well known but poorly understood complication of iron overload. We have previously shown that cultured myocardial cells are able to assimilate large amounts of iron. In the present study, the effect of iron on the rate and amplitude of beating in monolayer cultures of rat ventricular myocytes was studied. Iron had negative chronotropic and inotropic effects, both reversible upon washout. The negative chronotropic effect developed earlier and could be reversed by adrenaline. The negative inotropic effect took longer to develop and was completely reversed by caffeine. Elevated [Ca++] also partially restored impaired contractility, while adrenaline or ouabain did not show any significant effect. These results indicate that iron toxicity in cultured heart cells impairs cellular function at both sarcolemmal and intracellular sites.

Animals↗
PubMedDate not supplied

The antimalarial effect of iron chelators: studies in animal models and in humans with mild falciparum malaria.

In this study we explore the antimalarial effects of 3-hydroxypyridin-4-ones (CP compounds), a family of bidentate orally effective iron chelators in experimental animal systems in vivo and in vitro, and examine whether the iron chelator deferoxamine (DF) is active against human infection with P. falciparum. There was direct relation between lipid solubility of the CP compounds, which would facilitate membrane transit, and their in vivo antimalarial action, suggesting direct intracellular iron chelation as the most likely explantation for the antimalarial effect of iron chelators. Results of the double-blind, placebo controlled trial of DF in humans with asymptomatic parasitemia provided unequivocal evidence that this iron-chelating agent has antimalarial activity. Depriving the parasite of a metabolically important source of iron may represent a novel approach to antimalarial drug development. DF is a relatively ineffective intraerythrocytic chelator, and our data indicate that other orally effective iron chelators may have superior antimalarial activity in vivo. A systematic screening of available iron chelating drugs may result in the identification of potentially useful antimalarial compounds.

Animals↗
PubMedDate not supplied

Re-emergence of lead poisoning from contaminated flour in a West Bank Palestinian village.

Although contaminated flour was first described as an important source of endemic lead poisoning in the Middle East almost 20 years ago, the use of lead in community flour mills has not been eliminated and continues to represent a significant environmental risk. The authors describe an outbreak of lead poisoning in a West Bank Palestinian family and draw attention to this unusual but important source of lead exposure. All 13 members of the family (two children and 11 adults), were found to have lead poisoning following hospitalization for "gastroenteritis," headache, joint pain, weight loss, and vision difficulties. Seven females had low hemoglobin levels. Blood lead concentrations ranged from 42 to 84 microg/dL. Household flour samples obtained from a stone mill, previously closed because of lead contamination, contained 2,000 ppm lead. Flour from traditional stone mills reinforced with lead joints remains a potential source for lead poisoning.

Adolescent↗
PubMedDate not supplied

Lead poisoning by contaminated flour.

Between October 1982 and June 1983, 43 patients were identified with symptomatic lead poisoning in three Arab villages of the Nablus district. Because of the clustering of clinical poisoning by household units, investigation was focussed on potential sources common to all members of the households. After excluding water, olive oil and a variety of foodstuff, lead in high concentrations was discovered in locally ground flour in all affected households. The source of poisoning was lead poured into the fissures between the metal housing and the driveshaft of the millstone. Significant lead contamination of freshly ground flour was demonstrated in 23% of the 146 community flour mills operating in West Bank villages. Since the completion of these studies, similar outbreaks of lead poisoning caused by contaminated flourmills have been identified in the Upper Galilee and in Spain. As the methods of milling in the Mediterranean area are similar, a coordinated international effort is needed in order to eliminate this health hazard from countries where similar community stone mills are still in use.

Adult↗