Browsing by Autor "Davies, Carolina"

Now showing 1 - 5 of 5

Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection.
(2020) Davies, Carolina; Simonazzi, Analía; Micheloud, Juan Francisco; Ragone, Paula Gabriela; Cid, Alicia Graciela; Negrette, Olga Sánchez; Bermúdez, José María; Parada, Luis Antonio
Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.
[Comparison of nucleic acid extraction efficiency using different commercial kits and qPCR. Effect of inhibitors].
(2012) Poma, Hugo R; Davies, Carolina; Gutiérrez Cacciabue, Dolores; Mora, María C; Basombrío, Miguel Á; Rajal, Verónica B
The detection of specific nucleic acid (NA) sequences by PCR has revolutionized the biological and medical sciences. Real-time PCR (qPCR) opened up the possibility of obtaining quantitative results. NA extraction is a decisive step prior to qPCR since it may produce either the removal or co-extraction of inhibitory substances of the enzymatic reaction, which in turn affects the amplification efficiency. In the present work we compared the commercial NA extraction kits from Qiagen, Invitrogen and Macherey-Nagel, which were used to extract DNA from mice blood artificially infected with Trypanosoma cruzi and PP7 RNA, Pseudomonas aeruginosa bacteriophage, in spiked aqueous matrices. NA recovery efficiency in samples without inhibitors was similar for the three extraction kits. However, the Invitrogen kit was the only one that remained unaffected in the presence of inhibitors in the samples.
Hydroxymethylnitrofurazone is active in a murine model of Chagas' disease.
(2010) Davies, Carolina; Marino Cardozo, Rubén; Sánchez Negrette, Olga; Mora, María Celia; Chung, Man Chin; Basombrío, Miguel Angel
The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.
Morphological and ITS2 Molecular Characterization of Ribeiroia Cercariae (Digenea: Psilostomidae) from Biomphalaria spp. (Gastropoda: Planorbidae) in Northern Argentina.
(2015) Davies, Dora; Davies, Carolina; Lauthier, Juan José; Hamann, Monika; Ostrowski de Núñez, Margarita
Species of Ribeiroia use planorbid snails as intermediate host. Since there is little information about these digenean parasites in South America, we aimed to assess whether Ribeiroia cercariae from 3 north Argentina locations belonged to the same species and differed from Ribeiroia cercariae described elsewhere. Specimens were obtained from Biomphalaria tenagophila and Biomphalaria orbignyi (Salta Province), and Biomphalaria occidentalis (Corrientes Province). Morphological traits of cercariae were analyzed, as well as their sequence of the ribosomal internal transcribed spacer 2 (ITS2). The ITS2 region consisted of 426 nucleotides identical in all samples, suggesting that all specimens belong to the same species in spite of their morphological differences and first intermediate host species. Comparison of the ITS2 region with GenBank database records showed that specimens from Argentina were different from Ribeiroia ondatrae (0.9% divergence), Ribeiroia marini (0.7% divergence), and Cercaria lileta (0.2% divergence). In summary, morphological, ecological, and ITS2 molecular data suggest that specimens from Argentina belong to a different species.
The life cycle of Magnivitellinum saltaensis n. sp. (Digenea: Alloglossidiidae) in Salta Province, Argentina.
(2021) Davies, Dora; Liquin, Florencia; Lauthier, Juan José; Párraga, Regina; Saravia, José; Davies, Carolina; Ostrowski de Núñez, Margarita
We describe the alloglossiid trematode Magnivitellinum saltaensis n. sp., a parasite of the characiform fish Psalidodon endy, and its life cycle from Salta, northwest of Argentina. This is the first life cycle described for a species belonging to the genus Magnivitellinum. Cercariae emerged naturally from Biomphalaria tenagophila snails and infected experimentally exposed larvae of Diptera and Ephemeroptera as second intermediate hosts. These larvae in turn were exposed to commercially raised fish, and adults were recovered from characiform albino fish Gymnocorymbus ternetzi. Molecular analysis of natural and experimental adults showed the same genetic sequence for the partial region of 28S rDNA, thus confirming conspecificity. Comparison of these sequences with those published for M. simplex from Mexico showed 1.45% divergence, indicating that the specimens found in Salta belong to a different species, the third described of Magnivitellinum, in agreement with morphological data, geographical location, and host species composition. The new species is distinguished by its small body, vitelline follicles extending from the mid-level of the ventral sucker, Y-shaped excretory vesicle, and presence of papillae around the mouth.