No abstract

Visceral leishmaniasis caused by Leishmania donovani is a life-threatening disease involving uncontrolled parasitization of liver, spleen, and bone marrow. Most available drugs are toxic. Moreover, relapse after seemingly successful therapy remains a chronic problem. In this study, we evaluated a new therapeutic approach based on combination of a low dose of amphotericin B (AmB) in association with suboptimum dose of stearylamine (SA)-bearing cationic liposomes, itself having leishmanicidal activity. We demonstrate that a single-shot therapy with this formulation caused clearance of parasites from liver and spleen below the level of detection in the selected piece of the organs of BALB/c mice. The combination was superior to free AmB and AmBisome for therapy, as well as for prevention of relapse and reinfection. Besides having better killing activity, AmB in SA liposomes, in contrast to AmBisome, maintained the immunomodulatory effect of free AmB on CD4+ and CD8+ T cells for IFN-γ production, at the same time reducing the toxic effects of the drug, reflected through decline in TNF-α. In addition, IL-10 was down-regulated to almost negligible levels, most efficiently through therapy with SA-bearing cationic liposomes-AmB. This IL-10-deficient environment of IFN-γ-secreting T cells probably up-regulated the enhanced IL-12 and NO production observed in splenic culture supernatants of these mice, correlating with prolonged disease suppression better than free AmB and AmBisome. The ability of the formulation to elicit protective immunity was reconfirmed in a prophylactic model. Our results emphasize the requirement of effective immune stimulation, additionally, by antileishmanials for persistent disease protection, demonstrated by this liposomal AmB formulation.

No abstract

We report on the first demonstration of a diode-pumped, gas cooled, cryogenic multislab Yb:YAG amplifier. The performance was characterized over a temperature range from 88 to 175 K. A maximum small-signal single-pass longitudinal gain of 11.0 was measured at 88 K. When amplifying nanosecond pulses, recorded output energies were 10.1 J at 1 Hz in a four-pass extraction geometry and 6.4 J at 10 Hz in a three-pass setup, corresponding to optical to optical conversion efficiencies of 21% and 16%, respectively. To our knowledge, this represents the highest pulse energy so far obtained from a cryo-cooled Yb-laser and the highest efficiency from a multijoule diode pumped solid-state laser system.

Visceral leishmaniasis (VL) caused by the parasite