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Dive into the research topics where Silvia R. B. Uliana is active.

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Featured researches published by Silvia R. B. Uliana.


Antimicrobial Agents and Chemotherapy | 2005

Antileishmanial Activity of the Terpene Nerolidol

Denise C. Arruda; Fabio L. D'Alexandri; Alejandro M. Katzin; Silvia R. B. Uliana

ABSTRACT The activity of nerolidol, a sesquiterpene used as a food-flavoring agent and currently under testing as a skin penetration enhancer for the transdermal delivery of therapeutic drugs, was evaluated against Leishmania species. Nerolidol inhibited the growth of Leishmania amazonensis, L. braziliensis, and L. chagasi promastigotes and L. amazonensis amastigotes with in vitro 50% inhibitory concentrations of 85, 74, 75, and 67 μM, respectively. The treatment of L. amazonensis-infected macrophages with 100 μM nerolidol resulted in 95% reduction in infection rates. Inhibition of isoprenoid biosynthesis, as shown by reduced incorporation of [2-14C]mevalonic acid (MVA) or [1-14C]acetic acid precursors into dolichol, ergosterol, and ubiquinone, was observed in nerolidol-treated promastigotes. This drug effect can be attributed to the blockage of an early step in the mevalonate pathway, since incorporation of the precursor [1(n)-3H]farnesyl pyrophosphate in polyisoprenoids is not inhibited by nerolidol. L. amazonensis-infected BALB/c mice were treated with intraperitoneal doses of 100 mg/kg/day for 12 days or topically with 5 or 10% ointments for 4 weeks. Significant reduction of lesion sizes in nerolidol treated mice was observed for both treatment routes. However, long-term follow up indicated that the disease was not cured in this highly susceptible animal model. Nonetheless, the in vitro activity of nerolidol against these parasites may prove a useful tool for the development of new drugs for the treatment of leishmaniasis. In addition, biosynthesis of dolichols with 11 and 12 isoprene units was identified in Leishmania, as described for other trypanosomatids and Apicomplexa.


Journal of Eukaryotic Microbiology | 1994

Discrimination Amongst Leishmania by Polymerase Chain Reaction and Hybridization with Small Subunit Ribosomal DNA Derived Oligonucleotides

Silvia R. B. Uliana; Kimberlyn Nelson; Stephen M. Beverley; Erney P. Camargo; Lucile Maria Floeter-Winter

ABSTRACT. A method for discriminating among Leishmania is described, based upon small subunit ribosomal DNA sequence differences. The method was to amplify the entire 2.2 kb small subunit rDNA by polymerase chain reaction using conserved primers specific for the 5′ and 3′ termini of the small subunit ribosomal RNA, and then hybridize the product dotted onto nylon membranes with labeled oligonucleotides. The design of the hybridization probes was based upon complete small subunit rDNA sequences from L. amazonensis, L. major and L. guyanensis and partial sequences of L. mexicana, L. braziliensis, L. tropica and L. chagasi. A high degree of sequence similarity (> 99%) among species was found. However, sufficient sequence divergence occurred to permit the design of internal oligonucleotide probes specific for species complexes. This procedure successfully discriminated amongst a wide range of Leishmania isolates. The method detected as few as 10 cultured organisms and detected parasites in tissue samples from experimentally infected animals. Non‐radioactive labeling showed the same specificity and sensitivity as radioactive probes.


Journal of Antimicrobial Chemotherapy | 2008

Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections

Danilo C. Miguel; Rogéria C. Zauli-Nascimento; Jenicer K. U. Yokoyama-Yasunaka; Simone Katz; Clara Lúcia Barbiéri; Silvia R. B. Uliana

OBJECTIVES The aim of this study was to evaluate the efficacy of tamoxifen in vivo in experimental models of cutaneous (CL) and visceral leishmaniasis (VL) caused by Leishmania braziliensis and Leishmania chagasi, respectively. METHODS Drug activity was assessed against intracellular amastigotes by treating infected macrophage cultures and evaluating the number of infected cells. In vivo efficacy of tamoxifen was tested in L. braziliensis-infected BALB/c mice and in L. chagasi-infected hamsters. Treatment with 20 mg/kg/day tamoxifen was administered for 15 days by the intraperitoneal route. Efficacy was evaluated through measurements of lesion size, parasite burden at the lesion site or liver and spleen and survival rate. RESULTS Tamoxifen killed L. braziliensis and L. chagasi intracellular amastigotes with 50% inhibitory concentrations (IC(50)) of 1.9 +/- 0.2 and 2.4 +/- 0.3 microM, respectively. Treatment of L. braziliensis-infected mice with tamoxifen resulted in significant reductions in lesion size and 99% decrease in parasite burden, compared with mock-treated controls. L. chagasi-infected hamsters treated with tamoxifen showed significant reductions in liver parasite load expressed as Leishman-Donovan units and 95% to 98% reduction in spleen parasite burden. All animals treated with tamoxifen survived while 100% of the mock-treated animals had died by 11 weeks after the interruption of treatment. CONCLUSIONS Tamoxifen is effective in the treatment of CL and VL in rodent models.


Journal of Parasitology | 1992

RIBOSOMAL DNA RESTRICTION ANALYSIS AND SYNTHETIC OLIGONUCLEOTIDE PROBING IN THE IDENTIFICATION OF GENERA OF LOWER TRYPANOSOMATIDS

Erney P. Camargo; Clizete Sbravate; Marta M. G. Teixeira; Silvia R. B. Uliana; Marcelo B. Soares; Heloiza T. Affonso; Lucile Maria Floeter-Winter

Fifty-four species or isolates of insect trypanosomatids were examined for the presence of selected restriction enzyme sites in the small (SSU) and large (LSU) rRNA coding units of ribosomal genes. In the SSU, sites for Eco RI, Bgl II, Pst I, and Hind III were found to occur at the same location for all species examined, thus displaying a universal distribution among trypanosomatids. In the LSU, a site for Bgl II in the 24S-alpha sequence and sites for Hind III and Pst I in the 24S-beta sequence were found in all species examined. In contrast, a site for Pvu II in the SSU exhibited a genus-related distribution, being present in Crithidia and Herpetomonas but absent in Phytomonas. A site for Hind III in the 24S-alpha sequence of the LSU also exhibited genus-restricted distribution. The site was present in Crithidia but absent in Phytomonas and Herpetomonas. These findings were confirmed by dot hybridization with a synthetic oligonucleotide complementary to the 18S rRNA sequence containing the Pvu II site. Results point to the usefulness of restriction markers as diagnostic tools for distinguishing the lower trypanosomatid genera Crithidia, Herpetomonas, and Phytomonas at the same time revealing a marked complexity within the genus Leptomonas.


Biomedicine & Pharmacotherapy | 2009

Inhibitory activity of limonene against Leishmania parasites in vitro and in vivo.

Denise Costa Arruda; Danilo C. Miguel; Jenicer K. U. Yokoyama-Yasunaka; Alejandro M. Katzin; Silvia R. B. Uliana

Limonene is a monoterpene that has antitumoral, antibiotic and antiprotozoal activity. In this study we demonstrate the activity of limonene against Leishmania species in vitro and in vivo. Limonene killed Leishmania amazonensis promastigotes and amastigotes with 50% inhibitory concentrations of 252.0+/-49.0 and 147.0+/-46.0 microM, respectively. Limonene was also effective against Leishmania major, Leishmania braziliensis and Leishmania chagasi promastigotes. The treatment of L. amazonensis-infected macrophages with 300 microM limonene resulted in 78% reduction in infection rates. L. amazonensis-infected mice treated topically or intrarectally with limonene had significant reduction of lesion sizes. A significant decrease in the parasite load was shown in the lesions treated topically with limonene by histopathological examination. The intrarectal treatment was highly effective in decreasing the parasite burden, healing established lesions and suppressing the dissemination of ulcers. Limonene presents low toxicity in humans and has been shown to be effective as an agent for enhancing the percutaneous permeation of drugs. Our results suggest that limonene should be tested in different experimental models of infection by Leishmania.


Tropical Medicine & International Health | 2009

In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B

Rogéria C. Zauli-Nascimento; Danilo C. Miguel; Jenicer K. U. Yokoyama-Yasunaka; Ledice Inácia de Araújo Pereira; Milton Adriano Pelli de Oliveira; Fátima Ribeiro-Dias; Miriam Leandro Dorta; Silvia R. B. Uliana

Resistance of Leishmania parasites to specific chemotherapy has become a well‐documented problem in the Indian subcontinent in recent years but only a few studies have focused on the susceptibility of American Leishmania isolates. Our susceptibility assays to meglumine antimoniate were performed against intracellular amastigotes after standardizing an in vitro model of macrophage infection appropriate for Leishmania (Viannia) braziliensis isolates. For the determination of promastigote susceptibility to amphotericin B, we developed a simplified MTT‐test. The sensitivity in vitro to meglumine antimoniate and amphotericin B of 13 isolates obtained from Brazilian patients was determined. L. (V.) braziliensis isolates were more susceptible to meglumine antimoniate than Leishmania (Leishmania) amazonensis. EC50, EC90 and activity indexes (calculated over the sensitivity of reference strains), suggested that all isolates tested were susceptible in vitro to meglumine antimoniate, and did not show association with the clinical outcomes. Isolates were also uniformly susceptible in vitro to amphotericin B.


PLOS Neglected Tropical Diseases | 2008

Tamoxifen Is Effective in the Treatment of Leishmania amazonensis Infections in Mice

Danilo C. Miguel; Jenicer K. U. Yokoyama-Yasunaka; Silvia R. B. Uliana

Background Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America. Methodology/Principal Findings BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 108.5±0.7 in control untreated animals to 105.0±0.0 in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 1015.5±0.5 parasites were quantified from untreated animals, as opposed to 105.1±0.1 parasites detected in treated mice. Conclusions/Significance Treatment of BALB/c mice infected with L. amazonensis for 15 days with tamoxifen resulted in significant decrease in lesion size and parasite burden. BALB/c mice infected with L. amazonensis represents a model of extreme susceptibility, and the striking and sustained reduction in the number of parasites in treated animals supports the proposal of further testing of this drug in other models of leishmaniasis.


Molecular and Biochemical Parasitology | 1996

Structural and functional characterization of the Leishmania amazonensis ribosomal RNA promoter

Silvia R. B. Uliana; Wolfgang Fischer; Valeska de Andrade Stempliuk; Lucile Maria Floeter-Winter

The promoter region of the ribosomal RNA (rRNA) genes of Leishmania amazonensis was characterised and the transcription start point, defined by primer extension, was shown to be a T residue, 1048 nucleotides upstream of the beginning of the 18S sequence. A repetitive element of 60 bp was identified in the intergenic spacer. This element did not show sequence similarity with the region around the transcription start point. Conserved sequences were found in the external transcribed spacer of L. amazonensis, Trypanosoma cruzi and Crithidia fasciculata rRNA genes, 150 nucleotides downstream of the transcription start point. These sequences might be involved in processing events of the rRNA precursor molecule. The general organisation of the gene resembles the pattern observed for the ribosomal cistron in eukaryotic cells. Constructs containing the L. amazonensis promoter region upstream of the chloramphenicol acetyltransferase (cat) gene were able to drive the expression of the reporter gene in transient transfection experiments. CAT expression could be detected even when no trans-splicing acceptor sequence was added to the constructs, although its presence enhanced 5-fold the level of CAT activity. Species-specificity of the RNA polymerase I promoter activity was also demonstrated since constructs containing the L. amazonensis promoter region were unable to drive CAT expression when transfected into the related trypanosomatids, T. cruzi, C. fasciculata and Endotrypanum schaudini.


European Journal of Medicinal Chemistry | 2010

Synthesis and in vitro activity of limonene derivatives against Leishmania and Trypanosoma

Cedric Stephan Graebin; Maria de Fátima Madeira; Jenicer K. U. Yokoyama-Yasunaka; Danilo C. Miguel; Silvia R. B. Uliana; Diego Benítez; Hugo Cerecetto; Mercedes González; Ricardo Gomes da Rosa; Vera Lucia Eifler-Lima

The synthesis and in vitro activity of R(+)-Limonene derivatives against Leishmania and Trypanosoma cruzi strains are reported. Seven compounds have shown better in vitro activity against Leishmania (V.)braziliensis than the standard drug pentamidine. Additionally, we have identified two promising new anti-T. cruzi limonene derivatives.


Vaccine | 2002

Evaluation of the murine immune response to Leishmania meta 1 antigen delivered as recombinant protein or DNA vaccine

Carlos H. Serezani; Amanda Richards Franco; Mariana Wajc; Jenicer K. U. Yokoyama-Yasunaka; Gerhard Wunderlich; Monamaris Marques Borges; Silvia R. B. Uliana

The meta 1 gene of Leishmania is conserved across the genus and encodes a protein upregulated in metacyclic promastigotes. Meta 1 constitutive overexpressing mutants show increased virulence to mice. In this paper, both meta 1 recombinant protein and plasmids bearing the meta 1 gene were tested for their antigenicity and potential for inducing protective immunity in mice. Vaccination with the recombinant protein induced a predominant Th2-type of response and did not result in protection upon challenge with live parasites. Surprisingly, the expected reversal to a CD4(+) Th1-type of response upon genetic immunisation by the intramuscular route was not observed. Instead, vaccination with either the meta 1 gene alone or in fusion with the monocyte chemotactic protein (MCP)-3 cDNA induced a Th2-type of response that correlated with lack of protection against infection.

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