In the rat, somatodendritic application of the NMDA antagonist AP-5, within the Substantia Nigra Zona Compacta and Ventral Tegmental Area, either by micro-iontophoresis or pressure ejection, reduces burst firing of dopamine neurons. Similar local application of the non-NMDA antagonist CNQX does not affect their firing pattern. These results indicate that, in vivo, excitatory amino acid afferents participate through NMDA receptors in the control of the spontaneous burst firing of midbrain dopamine neurons.
Abnormal delayed-type hypersensitivy to Candida albicans, since it results in an excessive reaction of the immune system, is very difficult to diagnose. This study shows that the syndromic reaction observed after intradermal injection of an extract of Candida albicans, in patients suspected of abnormal delayed-type hypersensitivy to this antigen, is associated with the presence of specific circulating T cells, detectable through cell culture in the presence of Candida albicans. There is a very significant correlation between the clinical symptoms, the cutaneous tests, and the lymphocyte activation tests. This abnormal reactivity essentially involves the CD8 cells.
By measuring the activation of different cell models (lymphocytes and lymphocytic subsets) in the presence of Candida albicans with flow cytometry reading, it is possible to show that successive dilutions of Candida albicans can lead to lymphocyte activation in abnormally-sensitized subjects. In a first trial, 10 subjects were tested in duplicate. The decrease of activity of the dilutions does not appear to be regular in relation to the progression of the dilutions. The activity of the dilutions wanes relatively rapidly with the first dilutions, then recurs later very distinctly, at the 6th dilution, then ebbs, then reappears in similar manner at the 9th, the 14th, and finally, the 19th dilution. Cell reactivity appears to differ depending on the subject. It can be represented through the calculated slope of the regression line, for each series of data. It therefore appears feasible to determine a threshold of reactivity and a scale of sensitivity, to make it possible to specify the degree of abnormal reactivity existing at a given time for a given subject. The constancy of the activity of the different dilutions tested, on 10 cultures of a single cell suspension, is especially well demonstrated in the second trial, showing unusually small standard deviations. Thus, the question arises as to the exact nature of the observed phenomenon and of its analysis from a physical-chemical point of view, with regard to the pharmacological effect of successive dilutions of Candida albicans.
Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome. Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans albicans, and then monitoring for a systemic reaction over the following six to forty-eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25. Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other. This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".
