ABSTRACT
A sensitive enzyme immunoassay (EIA) for galactomannan antigenemia that avoids the use of radioisotopes was devised. Three carbohydrate-rich antigenic fractions were purified from Aspergillus fumigatus 2085: a cold alkali extract (CA) from mycelium, an acetone-precipitated pyridine extract (APSK-66) from mycelium, and a methanol precipitate from culture filtrate. CA and APSK-66 were further purified by gel filtration and ion-exchange chromatography, respectively. An acid hydrolysate of CA contained only mannose and galactose, as determined by gas-liquid chromatography. Rabbit antisera were raised against conidia, mycelia, and cell walls of A. fumigatus. By indirect EIA, the best immunoglobulin G response (1/8,000) was obtained against CA in rabbits immunized intravenously with cell walls. Antigenemia was detected by indirect EIA inhibition in heat-dissociated sera of four immunosuppressed rabbits that were infected intravenously but was absent in two uninfected controls. The circulating antigen was resistant to pronase, was adsorbed onto concanavalin A, and had a molecular size of 50 to 100 kilodaltons.
Subject(s)
Antigens, Fungal/analysis , Aspergillosis/diagnosis , Aspergillus fumigatus/immunology , Mannans/immunology , Animals , Antibodies, Fungal/biosynthesis , Chromatography, Affinity , Chromatography, Gas , Chromatography, Gel , Chromatography, Ion Exchange , Female , Galactose/analogs & derivatives , Immunoenzyme Techniques , Immunoglobulin G/biosynthesis , Immunosuppression Therapy , Mannans/analysis , Rabbits , UltrafiltrationABSTRACT
The synthesis and the antihypertensive activity in rats of a series of 6-methylergolin-8 beta-yl-propionic acid derivatives are reported. The prolactin lowering activity (nidation inhibition test) in rats and the acute toxicity in mice were also studied as a measure of the specificity and safety of the potential antihypertensive compounds. From the structure-activity considerations reported here it is clear how modifications at the C8 side chain can improve the selectivity of the antihypertensive effects, whilst introducing substituents in other positions of the ergoline skeleton afforded unfavourable results in this respect. Compound 5, namely 2(R,S)-cyano-3-(6-methylergolin-8 beta-yl)-propionamide, emerged as the most interesting antihypertensive derivative.
Subject(s)
Antihypertensive Agents/chemical synthesis , Ergolines/chemical synthesis , Animals , Blood Pressure/drug effects , Chemical Phenomena , Chemistry , Embryo Implantation/drug effects , Ergolines/pharmacology , Ergolines/toxicity , Female , Lethal Dose 50 , Male , Mice , Pregnancy , Prolactin/antagonists & inhibitors , Rats , Rats, Inbred StrainsABSTRACT
The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.
Subject(s)
Ergolines/chemical synthesis , Nicergoline/chemical synthesis , Sympatholytics/chemical synthesis , Administration, Oral , Animals , Delayed-Action Preparations , Dihydroergotamine/pharmacology , Guinea Pigs , Injections, Intravenous , Male , Nicergoline/administration & dosage , Nicergoline/analogs & derivatives , Receptors, Adrenergic, alpha/drug effects , Structure-Activity RelationshipABSTRACT
The synthesis and the pharmacological activities of 24 analogues of the alpha-adrenergic blocking drug, nicergoline (I b), are reported. The majority of the new compounds were found to be less active than (I b): the structure-activity relationships are presented and discussed.
