BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

Use of LPC antagonist, choline, in the management of bronchial asthma.

The present study was conducted to compare the effects of disodium cromoglycate (DSCG) and choline, a lipotropic factor, in management of bronchial asthma. Two groups taking DSCG and choline were compared between themselves and with a control group (on bronchodilators only) in a three month trial. A significant improvement in average symptoms scores was observed in all groups but was clinically significant only in the groups taking choline. Percent asymptomatic days increased in all the groups, but was not significant. The additional drug requirement decreased significantly only in the group taking choline. All groups showed an improvement in SGaw at FRC and percent fall in specific airways conductance (SGaw) at RV, but non-significant. A significant fall in bronchial hyperreactivity (BHR) was observed in the group taking choline, which was not consistent, whereas a marginal increase in BHR in the control and DSCG groups was observed. It is concluded that choline, an anti-inflammatory agent which acts by lowering lipophosphatidyl choline (LPC), plays an active role in subjective as well as functional improvement in bronchial asthma. However, a dose related response is yet to be established.