Studies in vitro on the effects of rhein on the chemotaxis of human leukocytes

Rhein (R: 1,8-dihydroxy-3-carboxyanthraquinone) is the active metabolite of the drug diacetylrhein (DAR), an anthraquinone molecule which has recently been proposed for the long-term treatment of osteoarthrosis. Its action mechanism in rheumatic pathology has not been fully explained. It is known that DAR, while not inhibiting the formation of prostaglandins, inhibits certain proteolytic enzymes, and acts on phlogistic cells by lysosomal enzymic and superoxide-anion modifications. Moreover DAR modifies phagocytic functions and the motility of cells. This paper is a contribution to the clarification of the last point, namely the effect of rhein on cell motility. It reports that in vitro no effect of R on random migration was found, but instead a double inhibiting effect on chemotaxis (i.e. a low-dosage and a high-dosage effect). Furthermore, R did not modify the inhibition or induce modification of chemotaxis by vinblastine. Finally R cancelled the stimulating effect of ionic potassium. The results thus indicate that R acts on the chemotaxis of the leukocytes with a complex action at different doses. The action mechanism is probably due to a membrane effect, since rhein (R) did not modify the chemotaxis-inhibiting activity of vinblastine but did interfere with the stimulating effect of K+.     

Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease

Peripheral arterial disease (PAD) is a predictor of cardiovascular risk. However, it is unknown whether PAD severity influences inflammatory status and endothelial function, which play a major role in atherosclerosis. Accordingly, we measured brachial artery flow-mediated dilation (FMD), and plasma levels of several inflammatory markers in 15 control subjects, and 19 asymptomatic and 19 symptomatic PAD patients. Each symptomatic patient was matched to an asymptomatic patient for age, sex, risk factors, presence of cardiovascular disease, and pharmacological treatments. Asymptomatic patients had similar inflammatory profiles as controls, but lower median FMD (11.7% vs 8.5%, p < 0.01). Compared with asymptomatic patients, symptomatic patients had higher median C-reactive protein (1.5 mg/l vs 6.0 mg/l, p < 0.05) and interleukine-6 (1.5 pg/ml vs 3.5 pg/ml, p < 0.05), and lower FMD (8.5% vs 5.1%, p < 0.01). In the 38 PAD patients, the ankle/brachial pressure index correlated positively with FMD (p < 0.01), and negatively with C-reactive protein (p < 0.05), soluble intercellular adhesion molecule-1 (p < 0.05) and soluble vascular cell adhesion molecule-1 (p < 0.05). Thus, in PAD, endothelial function and inflammatory status are related to the severity of the circulatory impairment. This finding may contribute to the explanation of the increasingly poor prognosis with increased PAD severity.     

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h ² = 0.79, P = 3.97e−15) and AVP (h ² = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.Key words: oxytocin, vasopressin, schizophrenia, bipolar disorder, emotion recognition