Efficacy of miltefosine therapy against subcutaneous experimental pythiosis in rabbits.

We evaluated the in vitro activity of miltefosine against 29 Pythium spp. and the in vivo therapeutic response of 2mg/kg/day of miltefosine given orally to rabbit with pythiosis induced experimentally. The MICs (in µg/mL) of miltefosine was medium-dependent and ranged from 0.5 to 2 and 32-64 on RPMI 1640 and Mueller Hinton broth, respectively. The treatment with miltefosine demonstrated significantly lower subcutaneous lesion areas compared to the control group but was not sufficient for the complete remission of the lesions. This study indicates that miltefosine has limited efficacy against pythiosis and furthers in vitro and in vivo studies are necessary to determine the possible potential of this drug in the treatment of pythiosis.

In vitro activity of essential oils extracted from condiments against fluconazole-resistant and -sensitive Candida glabrata.

In the present study, the antifungal activity of essential oils obtained from Origanum vulgare (oregano), Cinnamomum zeylanicum (cinnamon), Lippia graveolens (Mexican oregano), Thymus vulgaris (thyme), Salvia officinalis (sage), Rosmarinus officinalis (rosemary), Ocimum basilicum (basil) and Zingiber officinale (ginger) were assessed against Candida glabrata isolates. One group contained 30 fluconazole-susceptible C. glabrata isolates, and the second group contained fluconazole-resistant isolates derived from the first group after the in vitro induction of fluconazole-resistance, for a total of 60 tested isolates. The broth microdilution methodology was used. Concentrations of 50µg/mL, 100µg/mL, 200µg/mL, 400µg/mL, 800µg/mL, 1600µg/mL and 3200µg/mL of the essential oils were used, and the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined. Thyme, sage, rosemary, basil and ginger essential oils showed no antifungal activity at the tested concentrations. Antimicrobial activity less than or equal to 3200µg/mL was observed for oregano, Mexican oregano and cinnamon essential oils. Both the oregano and Mexican oregano essential oils showed high levels of antifungal activity against the fluconazole-susceptible C. glabrata group, whereas the cinnamon essential oil showed the best antifungal activity against the fluconazole-resistant C. glabrata isolates.

Micafungin alone and in combination therapy with deferasirox against Pythium insidiosum.

This study evaluated the in vitro and in vivo activity of micafungin alone and in combination with the iron chelator deferasirox against Pythium insidiosum. Micafungin showed a poor in vitro activity when it was used alone, but synergistic interactions were observed for 88.2% of the strains when the drug was combined with deferasirox. Smaller lesions were observed in infected rabbits receiving the combination therapy, although it favored disease dissemination to the lungs. The present results show that micafungin alone is ineffective against P. insidiosum, and the combination micafungin-deferasirox might have deleterious effects for the host.

Efficacy of a Brazilian calcium montmorillonite against toxic effects of dietary aflatoxins on broilers reared to market weight.

1. The protective effect of a natural Brazilian calcium montmorillonite (CaMont) against aflatoxins was studied in broiler chickens. 2. A total of 1056-d-old Cobb male broilers were housed in experimental pens (22 chickens per pen) for 42 d. Three levels of CaMont (0, 2.5 and 5 g/kg) and two levels of aflatoxins (0 and 3 mg/kg) were assayed. Each treatment had 8 replicate pens of 22 broiler chickens each. 3. Of all the chickens tested in the experiment, the ones treated with aflatoxins were the most adversely affected. CaMont treatment at concentrations of 2.5 and 5 g/kg improved body weight of chickens at 42 d of age by 13.3% and 22.7%, increased daily feed intake by 9.7% and 24.7%, and improved the productive efficiency index of chickens by 53% and 66.5%, respectively. 4. Dietary CaMont positively affected parameters such as weight of liver, heart and gizzard; however, serum potassium concentration decreased by 15.3% compared with that of chickens given only the aflatoxin-contaminated diet. 5. CaMont did not cause adverse effects in chickens that did not receive aflatoxins. 6. CaMont at pH 8.5 partially reduced the toxic effects of aflatoxins in broilers when included at levels of 2.5 and 5 g/kg in the diet.

Iron chelation therapy as a treatment for Pythium insidiosum in an animal model.

OBJECTIVES: Iron plays an important role in the pathogenesis of Pythium insidiosum. Human pythiosis frequently occurs in iron-overloaded thalassaemic patients and experimentally infected animals develop iron deficiency anaemia. Therefore, we sought to determine the in vitro and in vivo activities of the iron chelator deferasirox against P. insidiosum. METHODS: In vitro, the MIC and minimum fungicidal concentration (MFC) values of deferasirox for 17 strains of P. insidiosum were determined in accordance with CLSI document M38-A2. In vivo studies were carried out in 20 inoculated rabbits divided into four groups: placebo, immunotherapy obtained from vortexed P. insidiosum cultures (14 day intervals), deferasirox (15 mg/kg/day) and a combination of immunotherapy and deferasirox. Five non-infected animals were used as controls. RESULTS: The MIC and MFC values of deferasirox for P. insidiosum ranged from 12.5 to 50 mg/L and from 50 to 100 mg/L, respectively. Treatment with deferasirox alone ameliorated anaemia and normalized the serum iron levels and hepatic iron concentration in the animals. However, the mean lesion size, although decreased, did not differ significantly from that in the placebo group. The results of immunotherapy plus iron chelation therapy were worse than those of immunotherapy alone. Moreover, the disease spread to the lung tissue in 5 out of 10 deferasirox-treated animals. CONCLUSIONS: Despite its limited in vitro and in vivo activity, deferasirox improved iron deficiency anaemia in P. insidiosum-infected rabbits. Further studies are needed to investigate the immunomodulatory properties observed in this study and the benefits and drawbacks of using iron-chelating drugs as an adjuvant therapy in pythiosis.