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We examined the effects of adenosine A 1 and A 2 receptor agonists on LPS-stimulated TNFα production by human monocytes isolated from peripheral blood. We have demonstrated that CGS-21680, a highly selective A 2 agonist inhibited production of TNFα at the protein level by 75% whereas the A 1 selective agonist N 6 reduced TNFα production by only 25%. The action of CGS-21680 was mediated via the A 2 receptors since its effect on TNF production was blocked by 3,7-dimethyl-l-propargylxanthine (DMPX) but not by xanthine amine cogener (XAC), antagonists selective for the A 2 and A 1 receptors, respectively. Thus intervention with A 2 -selective agonists or compounds that can elevate endogenously released adenosine may be beneficial in TNFα-mediated diseases.

Immature salivary gland (SG) infections averaging 10(3) parasites per fly can apparently develop into mature gland infections averaging 10(5) parasites per fly in as little as 4 days. Frequently flies which extrude parasites in their saliva prove to have no parasites in the SG, but often show trypanosomes in the esophagus, cibarial pump, and proboscis. In some instances, SG infections have cleared, resulting in a loss of infectivity. Results of studying numbers of parasites regurgitated upon feeding or probing have shown that number to be highly variable and not necessarily related either to previous feeding status or the total number of parasites in the glands. Cloning of metacyclics in mice has been achieved, indicating that the minimum effective dose is one parasite. To date, no infections in mice have resulted from inoculation of extraglandular parasites. Histological and dissection studies support both the classical route and an alternate route of infection development in flies. No SG-infected flies have been found which did not also have proventricular and anterior and posterior midgut (AMG and PMG) infections. Although the AMG is where the heaviest MG infections occur, the PMG seems to support the last survivors in a moribund MG infection. No parasites have been found in the hindgut.

Starved mature male tsetse flies (21 to 25 days old) are capable of developing salivary gland (SG) infections of Trypanosoma brucei rhodesiense at rates nearly comparable to teneral males less than 24 hours old when given an infective meal containing parasites, horse red cells and culture medium. Although the over-all SG infection rate for mature males starved for three, four or five days before infection was about half that for teneral males less than 48 hours old (8.0% v. 15.6%), males starved for four days developed infection rates (12.3%) that were comparable to those of teneral flies less than 24 hours old (11.8%). It is suggested that the acquisition of infection by mature flies should be considered when evaluating factors contributing either to maintenance of endemic infections or perhaps even epidemic infections of human sleeping sickness.