EFFECTS OF PENTOXIFYLLINE OR DEXAMETHASONE IN COMBINATION WITH AMPHOTERICIN-B IN EXPERIMENTAL MURINE CEREBRAL CRYPTOCOCCOSIS - EVIDENCE OF NEUROEXCITATORY PATHOGENIC MECHANISMS
L. Ostroskyzeichner et al., EFFECTS OF PENTOXIFYLLINE OR DEXAMETHASONE IN COMBINATION WITH AMPHOTERICIN-B IN EXPERIMENTAL MURINE CEREBRAL CRYPTOCOCCOSIS - EVIDENCE OF NEUROEXCITATORY PATHOGENIC MECHANISMS, Antimicrobial agents and chemotherapy, 40(5), 1996, pp. 1194-1197
In a murine model of intracerebral infection by Cryptococcus neoforman
s the therapeutic effects of pentoxifylline or dexamethasone were stud
ied alone and in combination with amphotericin B. Assessed parameters
were mean survival time, brain histopathology index, amounts of glutam
ate and gamma-aminobutyric acid in the brain, and yeast CFU per brain.
Survival increased significantly in mice treated with dexamethasone,
amphotericin B, amphotericin B plus dexamethasone, and amphotericin B
plus pentoxifylline; the latter had significantly longer survival than
other treated groups. Indices of histopathological damage were simila
r in all treated groups. In infected untreated mice, the amounts of gl
utamate in the brain were decreased, presumably by depletion. In mice
treated with amphotericin B plus dexamethasone, glutamate levels retur
ned to the range of control mice. No differences in the amounts of gam
ma-aminobutyric acid were found between control and treatment groups.
Brain fungal counts were significantly lower in mice treated with amph
otericin B, amphotericin B plus dexamethasone, and amphotericin B plus
pentoxifylline than in untreated animals. In this model, pentoxifylli
ne in combination with amphotericin B improved survival, decreasing th
e fungal burden, and has potential as adjuvant therapy in cerebral cry
ptococcosis.