ABSTRACT
A new benzimidazole anthelmintic, triclabendazole (CGA-89317) was found to be highly efficient against mature and early immature Fasciola hepatica infections in sheep. At the dose rate of 2.5 mg/kg the efficiency was 90 and 98 per cent against flukes aged eight and 12 weeks respectively. At 5 mg/kg the drug was 92 and 98 per cent efficient against flukes aged four and eight weeks respectively and 100 per cent against 12-week-old flukes. An efficiency of 93 and 98 per cent was achieved against one-week-old flukes and 99 to 100 per cent against flukes aged two to four weeks at 10 mg/kg. At this dose rate the drug had 100 per cent efficiency against six-week-old flukes. If the dose was increased to 15 mg/kg, 98 per cent efficiency was achieved one day after infection. Triclabendazole was equally efficient when administered orally or by intraruminal or intra-abomasal injection. The maximum tolerated dose of 200 mg/kg was established.
Subject(s)
Benzimidazoles/therapeutic use , Fascioliasis/veterinary , Sheep Diseases/drug therapy , Animals , Anthelmintics/therapeutic use , Benzimidazoles/administration & dosage , Chemical Phenomena , Chemistry , Dose-Response Relationship, Drug , Fasciola hepatica/drug effects , Fascioliasis/drug therapy , Fascioliasis/parasitology , Safety , Sheep , Sheep Diseases/parasitology , TriclabendazoleSubject(s)
Mitochondria/metabolism , Phospholipids/biosynthesis , Saccharomyces cerevisiae/metabolism , Cytochromes/metabolism , DNA, Mitochondrial/metabolism , Enzyme Repression , Glucose/pharmacology , Glycerides/biosynthesis , Microsomes/metabolism , Mutation , Phosphatidylinositols/biosynthesis , Phosphatidylserines/biosynthesis , Saccharomyces cerevisiae/ultrastructureABSTRACT
Yeast cell cytosol stimulated the exchange of phospholipids between yeast mitochondria and microsomes in vitro, and also between organelles isolated from rat liver. The major phospholipids exchanged in both cases were phosphatidylinositol and phosphatidylcholine, together with smaller amounts of phosphatidylethanolamine. Evidence was also obtained that interconversion of phospholipids occurred during the incubation, probably via base exchange mechanisms.
Subject(s)
Cytosol/metabolism , Microsomes/metabolism , Mitochondria/metabolism , Phospholipids/metabolism , Saccharomyces cerevisiae/metabolism , Animals , Leucine/metabolism , Microsomes, Liver/metabolism , Mitochondria, Liver/metabolism , Phosphates/metabolism , RatsSubject(s)
Fatty Acids, Unsaturated/physiology , Fungal Proteins/biosynthesis , Mitochondria/metabolism , Saccharomyces cerevisiae/metabolism , Adenosine Triphosphatases/metabolism , Centrifugation, Density Gradient , Cytochromes/metabolism , Enzyme Activation , Kinetics , NADH, NADPH Oxidoreductases/metabolism , Protein Biosynthesis , RNA/biosynthesis , Ribosomal Proteins/biosynthesis , Ribosomes/metabolism , Succinate Dehydrogenase/metabolism , Temperature , Thermodynamics , Transcription, GeneticABSTRACT
The ability in vitro of yeast mitochondrial and microsomal fractions to synthesize lipid de novo was measured. The major phospholipids synthesized from sn-[2-(3)H]glycerol 3-phosphate by the two microsomal fractions were phosphatidylserine, phosphatidylinositol and phosphatidic acid. The mitochondrial fraction, which had a higher specific activity for total glycerolipid synthesis, synthesized phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine and phosphatidic acid, together with smaller amounts of neutral lipids and diphosphatidylglycerol. Phosphatidylcholine synthesis from both S-adenosyl[Me-(14)C]methionine and CDP-[Me-(14)C]choline appeared to be localized in the microsomal fraction.
Subject(s)
Microsomes/metabolism , Mitochondria/metabolism , Phospholipids/biosynthesis , Chromatography, Thin Layer , Cytidine Diphosphate Choline/metabolism , Glycerophosphates/metabolism , In Vitro Techniques , Phosphatidic Acids/biosynthesis , Phosphatidylcholines/biosynthesis , Phosphatidylethanolamines/biosynthesis , Phosphatidylinositols/biosynthesis , Phosphatidylserines/biosynthesis , Phospholipids/analysis , S-Adenosylmethionine/metabolism , Saccharomyces cerevisiae/metabolism , Subcellular FractionsABSTRACT
Turnover of phospholipids occurred continuously in a fatty acid auxotroph of Escherichia coli, but in the wild-type parent strain significant turnover occurred only under conditions where protein synthesis was inhibited but lipid synthesis continued. Both strains gave a stringent response of ribonucleic acid accumulation to amino acid starvation, but only in the wild type was lipid synthesis also inhibited. A revertant strain of the auxotroph resembled the wild type in this respect. The phospholipid that accumulates in the culture medium as a result of the lipid turnover appears to be part of a loosely bound low-density complex arising from the cell envelope.
Subject(s)
Bacterial Proteins/biosynthesis , Escherichia coli/metabolism , Phospholipids/metabolism , Acetates/metabolism , Carbon Isotopes , Centrifugation, Density Gradient , Chloramphenicol/pharmacology , Chlortetracycline/pharmacology , Chromatography, Gel , Escherichia coli/analysis , Fatty Acids/analysis , Fatty Acids, Unsaturated/metabolism , Genes, Regulator , Leucine/metabolism , Lipids/biosynthesis , Mutation , Oleic Acids/metabolism , Phospholipids/analysis , Phospholipids/biosynthesis , RNA, Bacterial/biosynthesis , Tritium , Ultracentrifugation , Uracil/metabolismABSTRACT
The membrane phospholipids of an unsaturated fatty acid auxotroph of Escherichia coli were found to undergo turnover. These phospholipids were excreted into the culture medium, and were replaced in the cell with newly synthesized phospholipids. Phospholipids of growing cells supplemented with elaidic acid underwent rapid turnover, while those of cells supplemented with oleate, or cis-vaccenate plus palmitoleate, underwent slow turnover. Starvation for required amino acids stimulated this turnover in the latter two cases. Protein was also lost from growing cells. However, after amino acid starvation this loss ceased while phospholipid turnover continued. Electron micrographs of growing cells indicated that large pieces of membrane-like material were separating from the cell surface.