ABSTRACT
Reactions of antimalarial beta-sulfonyl endoperoxides 9 and 10, which, like yingzhaosu A (2), derive from the 2,3-dioxabicyclo[3.3.1]nonane system 3, with iron(II) salts were studied. Product analysis of the iron(II)-induced degradations provided evidence for the intermediacy of carbon-centered cyclohexyl radicals 20 and 31 and their possible oxidation to the corresponding carbocations 21 and 32. It is conceivable that the antimalarial activity of beta-sulfonyl endoperoxides of type 5 may derive from alkylation of vital intraparasitic biomolecules by free radicals and/or carbocations, generated within the malaria parasite through a similar iron(II)-induced degradation process.
Subject(s)
Antimalarials/metabolism , Iron/pharmacology , Peroxides/metabolism , Antimalarials/chemistry , Free Radicals/chemistry , Free Radicals/metabolism , Oxidation-Reduction , Peroxides/chemistry , Peroxides/therapeutic use , Prodrugs/chemistry , Prodrugs/metabolism , Sulfinic Acids/chemistryABSTRACT
A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).
Subject(s)
Antimalarials/chemical synthesis , Plasmodium falciparum/drug effects , Sulfones/chemical synthesis , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Chloroquine/pharmacology , Drugs, Chinese Herbal , Models, Molecular , Molecular Conformation , Molecular Structure , Peroxides , Sesquiterpenes/chemistry , Structure-Activity Relationship , Sulfones/chemistry , Sulfones/pharmacologyABSTRACT
New concepts are needed for the still increasing number of geriatric patients who require long term institutional care and for the often difficult situation of caregiving relatives. We investigated the possibility to integrate relatives of institutionalized patients in the nursing care. 323 geriatric patients were randomly selected and the relatives contacted. Only four (1%) had no relatives or friends. Of 86% of the patients it was possible to interview 343 relatives or close friends. Of those 147 (43%) were favorably disposed towards a cooperation in the care with the ward staff. Persons willing to cooperate were characterized by female sex, middle class status, good health, not too demanding jobs, and close contacts prior to institutionalization of their next of kin. In a second part 29 of 196 relatives were willing to take part in a pilot project. Unfortunately, for technical reasons only five patients could be hospitalized on the experimental ward in the given time. The practical experience demonstrated that relatives can cooperate on a part time basis with the nursing staff in the care of institutionalized geriatric patients. It is estimated that probably 12% of the geriatric patients in institutions have relatives willing and capable to take part in the nursing or other activities on the ward. Smaller nursing facilities appear more suitable than large geriatric clinics for this type of cooperation.
Subject(s)
Chronic Disease/therapy , Home Nursing , Aged , Combined Modality Therapy , Female , Homes for the Aged , Humans , Male , Middle Aged , Nursing Homes , Patient Care Team , Pilot Projects , SwitzerlandABSTRACT
Eight spasmolytic drugs commonly used in the treatment of the irritable bowel syndrome were compared to verapamil with respect to their effects (all drugs injected i.v.) on the contraction of duodenum, ileum and colon induced by high K+ topical application in the anaesthetized rat. Verapamil greater than rociverine greater than papaverine greater than mebeverine greater than dicyclomine antagonized dose-dependently the contraction of duodenum and colon, the activity on duodenum being from 2 (rociverine) to 10 (verapamil) fold higher. Verapamil and rociverine, but not the other drugs mentioned above, were also active on ileum. N-Butylscopolammonium bromide, phloroglucinol and trimebutine were inactive against the contraction of the three intestinal tracts and prifinium bromide was inactive on duodenum and ileum, while it had remarkable activity on colon, unrelated to its antimuscarinic activity. The results are discussed briefly with reference to the pharmacological therapy of the irritable bowel syndrome.
