Macrolides and immunity: effects of erythromycin and spiramycin on human mononuclear cell proliferation

Macrolides are actively concentrated by leucocytes. The dose-effect responses of spiramycin (Sp) and erythromycin (Er) on phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) stimulated human mononuclear leucocytes (MNL) were studied. Cell viability was not altered at any antibiotic concentration (1-100 mg/l). Both Sp and Er showed dose-related inhibition of the proliferative response of PHA and PWM stimulated MNL. Very marked effects were observed at high antibiotic concentrations and the effects observed at low concentrations (1-10), although small, were also significant. Similar results were observed for the mitogen PWM. A decrease in tritiated thymidine (3H-TdR) incorporation occurred only if Sp and Er were added during the first 8 h of culture. Sp and Er also induced a decrease in tritiated uridine (3H-UdR) uptake. These data suggest that Sp and Er interfered with an early event in the cell cycle. However Sp did not affect PHA binding to MNL. The clinical significance of these findings is discussed.     

Diethyldithiocarbamate provides partial protection against pulmonary and lymphoid oxygen toxicity

Prolonged exposure of C57B16 mice to pure O2 at 1 ATA induced pulmonary edema associated with involution of lymphoid system and depressed immunity. The consequences of these toxic events were evaluated by 1) mortality rate, 2) determination of pulmonary water, 3) thymic and splenic cellularity, and 4) humoral (primary antibodies) and cellular (mitogenic) immune responses. Pretreatment of mice with 125 mg kg-1 of diethyldithiocarbamate (DDC) several days before exposure to O2 resulted in 1) an increase in animal survival (92-100% vs. 59% O2 controls), 2) a reduction in pulmonary edema, 3) partial stabilization of thymus and spleen lymphocyte populations, and 4) restoration of the humoral response (specific antibodies appeared earlier than in O2 control animals) and improvement of the mitogenic proliferative response of the spleen cells after hyperoxia. None of these effects were observed when DDC treatment coincided with the beginning of exposure. Our results indicated that DDC protects mice from both pulmonary and lymphoid hyperoxic injury, but only in a partial manner. It is suggested that the mechanism of this antioxidative property is indirect.     

The relationship between blood-lead concentrations,intelligence, attainment and behaviour in a school population: the second London study

Summary This study replicates an earlier one carried out in London in which an association was found between lead and intelligence, reading and spelling. In the present study 194 children living near an urban motorway were given the same battery of tests as well as an extensive family interview to determine background variables. Before social factors were taken into account there were no significant associations between lead and outcome variable. Possible reasons for the negative results from this study are discussed.     

Contact allergy to corticosteroids

Conclusion Contact allergy to corticosteroids is not infrequent. The diagnosis is not easy because of the atypical clinical picture and difficulties encountered in testing these anti-inflammatory drugs. As in all cases of contact dermatitis, the therapy of choice is avoidance, but here also one has to keep in mind the frequent crossreactions between several corticosteroids. Groups of corticosteroids that behave in similar ways regarding contact allergy have been identified, but this does not relieve us from the need for testing all the other corticosteroid molecules.     

Ascorbate-copper induced DNA lesions and repair in Escherichia coli K12 cells

Multiple lines of evidence show that oxidation products of ascorbicacid (vitamin C) are capable of inducing a variety of geneticalterations in microbial and mammalian cells. We have studiedthe inactivation kinetics in repair proficient and deficientEscherichia coli K12 cells treated with oxidized solutions ofascorbic acid, in the presence of catalytic amounts of copper.Our results suggest that the repair pathways controlled by therecA and uvrA gene products (the latter in a recA strain) contributeto cell survival. However, the lack of ß-galactosidaseinduction, in the SOS chromotest, implies a role for the RecAprotein other than SOS induction. Catalase and thiourea suppressthe toxic effects of oxidized ascorbate solutions, confirmingthat H₂O₂ and hydroxyl radicals are intermediate agents in thedamaging action. Single-strand breaks were detected in DNA fromtreated cells.     

Priming study of human phagocytes oxidative burst by using flow cytometry

In response to a variety of stimuli, eg pathogens, phagocytes release reactive oxygen species which are essential for bacterial killing and also potentiate inflammatory reactions. We have used flow cytometry measurements to study the priming process of phagocyte oxidative burst in whole blood, in order to avoid introducing artefacts due to the purification process and to simulate the in vivo situation more closely. In these conditions, we examined the in vitro effects of proinflammatory cytokines (TNF alpha, IL-1 alpha, IL-1 beta, IL-6, IL-8 and GM-CSF) on the PMN oxidative burst. We found that none of the cytokine tested directly activated the PMN oxidative burst. In contrast, TNF, GM-CSF and IL-8 strongly primed PMN in HIV-infected patients. This impairment, which correlated with the clinical stage of the disease, could contribute to the increased susceptibility to bacterial infections in HIV-infected patients. In addition, we reported the case of a child with severe recurrent infections due to intracellular microorganisms which could be related to an impairment of the phagocyte priming process of the oxidative burst.