succimer and Schistosomiasis

Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective against S. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi's equation up to approximately 80% release, with exponentially decreasing release rates thereafter.

Topics: Antimony; Capsules; Humans; Lactates; Lactic Acid; Organometallic Compounds; Polyesters; Polymers; Schistosoma mansoni; Schistosomiasis; Schistosomicides; Succimer; Sulfhydryl Compounds

The effects of Astiban, Lucanthone, Hycanthone and Niridazole on autophagic activities in the gastrodermis of Schistosoma mansoni were determined in vivo, using different dosage levels and dosage times. With Astiban, high levels of autophagy were observed in the gastrodermis 2 hours after an injection of the drug into the mouse, and this response had declined by 20 hours, marking a recovery by the parasite from the drug. Hycanthone and Lucanthone produced an autophagic response several days after the onset of treatment, and no recovery was observed in the morphology of the gastrodermis after the drug was discontinued. The effects of Niridazole on the gastrodermis were to produce the most dramatic ultrastructural changes after high doses and over several days of treatment. With all the drugs examined, gastrodermal autophagy was characterized by the formation of vacuoles containing cell components, lipid droplets and sometimes hydrolytic enzyme reaction product. The autophagic vacuoles appeared to be formed by the sequestration of cytoplasmic material by the basal membrane infoldings, and the transfer of enzymes into the vacuole from within the limiting membrane. The residues from intracellular digestion appeared to be emptied into the caecal lumen.

Topics: Animals; Antimony; Hycanthone; Lucanthone; Mice; Niridazole; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Schistosomicides; Succimer

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Succimer; Sulfhydryl Compounds; Time Factors

Topics: Aged; Antimony; Child, Preschool; Female; Humans; Organometallic Compounds; Schistosomiasis; Succimer; Sulfhydryl Compounds

Topics: Animals; Antimony; Glucuronidase; Kidney; Liver; Mice; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Spleen; Succimer; Sulfhydryl Compounds; Time Factors; Urinary Bladder

Topics: Africa; Africa, Western; Antimony; Child; Drug Therapy; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Humans; Ions; Organometallic Compounds; Schistosomiasis; Sodium; Sodium, Dietary; Succimer; Succinates; Succinic Acid

Topics: Antimony; Body Fluids; Organometallic Compounds; Polarography; Schistosomiasis; Succimer; Toxicology; Urine

Topics: Animals; Antimony; Cricetinae; Dosage Forms; Mice; Organometallic Compounds; Pharmacology; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Adolescent; Antimony; Biomedical Research; Drug Therapy; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer; Toxicology

Topics: Adolescent; Africa; Africa, Western; Antimony; Child; Drug Therapy; Ghana; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Toxicology

Topics: Antimony; Antiprotozoal Agents; Emetine; Mice; Organometallic Compounds; Pharmacology; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Animals; Antimony; Blood; Chemical Phenomena; Chemistry; Cricetinae; Intestines; Kidney; Liver; Mice; Organometallic Compounds; Pharmacology; Radioisotopes; Research; Schistosomiasis; Schistosomiasis mansoni; Sodium; Succimer; Succinates

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer

Topics: Animals; Antimony; Antiparasitic Agents; Humans; Organometallic Compounds; Schistosoma mansoni; Schistosomiasis; Sodium; Succimer

Topics: Acids, Noncarboxylic; Antimony; Humans; Organometallic Compounds; Schistosomiasis; Sodium; Sodium, Dietary; Succimer; Succinates; Toxicology

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Electrocardiography; Organometallic Compounds; Schistosomiasis; Succimer; Succinates; Succinic Acid

Topics: Antimony; Humans; Iraq; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Hepatitis; Hepatitis A; Organometallic Compounds; Schistosomiasis; Shock, Septic; Succimer; Succinates; Succinic Acid

Topics: Antimony; Iraq; Lucanthone; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Urinary Tract Infections

Topics: Antimony; Heart; Humans; Liver Diseases; Organometallic Compounds; Schistosomiasis; Succimer; Succinates; Sulfhydryl Compounds

Topics: Animals; Antimony; Humans; Organometallic Compounds; Schistosoma haematobium; Schistosomiasis; Schistosomiasis haematobia; Sodium; Sodium, Dietary; Succimer

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Succimer

Topics: Antimony; Antimony Potassium Tartrate; Organometallic Compounds; Schistosomiasis; Schistosomiasis mansoni; Succimer

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Somalia; Succimer; Urinary Tract Infections

Topics: Acids, Noncarboxylic; Antimony; Organometallic Compounds; Schistosomiasis; Schistosomiasis japonica; Sodium; Sodium, Dietary; Succimer; Succinates

Topics: Antimony; Humans; Organometallic Compounds; Schistosomiasis; Schistosomiasis haematobia; Succimer; Succinates; Urologic Diseases

Topics: Antimony; Organometallic Compounds; Schistosomiasis; Succimer