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- W2556960478 abstract "Background: Reports of yeast isolates resistant to traditional antifungal drugs have become common. Similarly, refractory clinical cases treated with these traditional antifungal drugs have also been reported. These cases ‘may or may not be related to pregnancy. Newly developed therapeutic approaches, such as the immunostimulant β-glucan combined with the traditional antifungal agents show promising results. Therefore, knowledge of the effects of these new associations is essential. The aims of this study were to evaluate the effects of the combination of itraconazole and β (1-3) glucan on fertility in female rats and its interference in the development of their offspring, including teratogenic potential. Materials, Methods & Results: A total of 180 female Wistar rats (90 days old) separated into six groups were used (n = 30 per group): Negative Control treated daily with the volume corresponding to 10 mL.kg of sterile distilled water orally, and 0.25 mL of sterile 0.9% NaCl solution subcutaneously weekly; IT treated daily with itraconazole at a dose of 10 mg.kg orally, and 0.25 ml of sterile 0.9% NaCl solution subcutaneously weekly; Beta treated daily with the volume corresponding to 10 mL.kg of sterile distilled water orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT treated daily with itraconazole at a dose of 10 mg.kg orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT5x treated daily with itraconazole at a dose of 50 mg.kg orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT10x treated daily with itraconazole at a dose of 100 mg.kg orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly. The rats were treated before (14 days) and during the mating period (up to 21 days), pregnancy (21 days) and lactation (21 days). The reproductive index of females, including maternal behavior, fetal skeletal abnormalities, and indicators of physical and neuromotor development in the offspring, including behavior in the open field and sexual behavior, were evaluated. The main differences (P < 0.05) between groups were the mating index, birth index and post-implantation loss index, the body mass of pups at birth and skeletal abnormalities of fetuses. Among the fetal skeletal abnormalities, statistical differences (P < 0.05) were observed in the percentage of: thoracolumbar supernumerary ribs (apparent and rudimentary); incomplete ossification of the parietal, interparietal, supraoccipital, sternebrae, cervical spine and tail; enlarged fontanel; lateral ossification centrum in the 7th cervical vertebra; misshapen and absent sternebrae; and misshapen vertebral centrum. No statistically significant differences in weight development of the pups and in open field test and sexual behavior test were observed. Discussion: The results of this study showed that high doses of itraconazole in combination with s (1-3) glucan have embryotoxic potential, including teratogenic effects. The embryotoxicity is also possibly related to s (1-3) glucan, which showed the same effect even when administered alone. Delays in some physical indicators, though discreet, indicate effects of higher doses of itraconazole on offspring development. The data demonstrate that the combination of itraconazole and β (1-3) glucan have potential interference in the fertility of mothers and the development of fetuses /pups. Although the combination of itraconazole and s (1-3) glucan seem safe at therapeutic doses, caution is advised in the administration of these drugs, alone or combined, during pregnancy, with special attention needed for higher doses of itraconazole." @default.
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- W2556960478 date "2015-01-01" @default.
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- W2556960478 title "Reproductive toxicity of itraconazole in combination with beta-glucan in female rats and their offspring." @default.
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