Alvaro Romanha - Academia.edu (original) (raw)

Papers by Alvaro Romanha

Memórias do Instituto Oswaldo Cruz, 2015

We describe herein the antitrypanosomal activity of 20 novel 1,3-bis(aryloxy)propan-2-amine deriv... more We describe herein the antitrypanosomal activity of 20 novel 1,3-bis(aryloxy)propan-2-amine derivatives. Compounds 2, 4, 6, 12, 15, 16 and 19 were significantly active against amastigote and trypomastigote forms, with half maximal inhibitory concentrationvalues in the range of 6-18 µM. In the cytotoxicity tests against L929 cells, only compound 4 presented selectivity index value above 10, indicating low toxicity.

Antimicrobial Agents and Chemotherapy, 2015

Cysteine metabolism is considered as essential for the crucial maintenance of a reducing environm... more Cysteine metabolism is considered as essential for the crucial maintenance of a reducing environment in trypanosomatids due to its importance as a precursor of trypanothione biosynthesis. Expression, activity assays, functional rescue and overexpression of cysteine synthase (CS) and cystathionine β-synthase (CβS) were evaluated in Leishmania braziliensis promastigotes and intracellular amastigotes under in vitro stress conditions induced by hydrogen peroxide (H2O2), SNAP or antimonial compounds. Our results demonstrate a stage-specific increase of protein expression and activity levels of LbrCS and LbrCβS, resulting on the increment of total thiols levels in response to both oxidative and nitrosative stress. The rescue of the CS activity in T. rangeli, a trypanosome that does not perform cysteine biosynthesis de novo, resulted in increased survival rates of epimastigotes expressing the LbrCS under stress conditions when compared to wild-type parasites. We also found a significantly enhanced ability of L. braziliensis promastigotes and amastigotes overexpressing LbrCS and LbrCβS to resist oxidative stress when compared to non-transfected cells, resulting in a phenotype far more resistant to Sb(V) treatment in vitro. In conclusion, up-regulation of the protein expression and increment of the activity levels of LbrCS and LbrCβS alters the parasite resistance to antimonials and may influence the efficacy of antimony treatment of New World leishmaniasis.

The American journal of tropical medicine and hygiene, 2001

The role of reinfection in the evolution of Chagas' disease was evaluated in dogs alternately... more The role of reinfection in the evolution of Chagas' disease was evaluated in dogs alternately infected with the 147 and SC-1 strains of Trypanosoma cruzi. A parasitologic, serologic, clinical, and electrocardiographic follow-up was carried out on the infected and noninfected dogs. The dogs were reinfected five times over a period of 38 months. No deaths were observed during the experiment. They presented a brief oligosymptomatic acute phase. The level of parasitemia decreased progressively with the number of reinfections. Bloodstream parasites were not detectable after the fifth reinfection. All parasite samples isolated during the follow-up were zymodeme B, corresponding to strain 147, irrespective of the strain with which the dogs were first infected and of the triatomine species used for isolation. Conversely, amplification by the polymerase chain reaction of a segment of the T. cruzi mini-exon gene showed the simultaneous presence of both strains in three of the eight reinfe...

Journal of medical entomology, 2000

Isoenzymes, random amplified polymorphic DNA (RAPD), and morphometry were used to compare genetic... more Isoenzymes, random amplified polymorphic DNA (RAPD), and morphometry were used to compare genetic variability within and between three populations of Triatoma brasiliensis Neiva, 1911 from northeast Brazil. The isoenzyme profiles were identical for the three populations, whereas the complex RAPD patterns allowed clear discrimination between the three. Morphometric analysis, using characters of the head capsule, also showed discrimination between the three populations but only in comparisons of males, not females. The results show considerable genetic heterogeneity in T. brasiliensis, with an indication of geographic structuring possibly resulting from a recent series of domestication events.

The American journal of tropical medicine and hygiene, 2000

We examined intraspecific variability in the genus Rhodnius using starch gel electrophoresis of s... more We examined intraspecific variability in the genus Rhodnius using starch gel electrophoresis of salivary heme proteins. Salivary protein profiles of 8 Rhodnius species (R. prolixus, R. robustus, R. neglectus, R. nasutus, R. ecuadoriensis, R. pallescens, R. pictipes, and R. domesticus) were compared. All species could be distinguished by this technique. The greatest protein polymorphism was found in R. ecuadoriensis, R. nasutus, R. robustus, and R. pictipes, followed by R. prolixus, R. neglectus, R. pallescens, and R. domesticus. This approach was able to distinguish R. prolixus from R. robustus and R. neglectus from R. nasutus, species with extreme phenotypical similarity.

Infection and immunity, 1999

To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control... more To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control of Trypanosoma cruzi or Toxoplasma gondii replication, we used human fibroblasts and a fibrosarcoma cell line (2C4). The cells were cultured in the presence or absence of recombinant gamma interferon (rIFN-gamma) and/or recombinant tumor necrosis factor alpha (rTNF-alpha) for 24 h and were then infected with either T. cruzi or T. gondii. Intracellular parasite replication was evaluated 24 or 48 h after infection. Treatment with rIFN-gamma and/or rTNF-alpha had no inhibitory effect on T. cruzi replication. In contrast, 54, 73, or 30% inhibition of T. gondii replication was observed in the cells treated with rIFN-gamma alone, rIFN-gamma plus rTNF-alpha, or TNF-alpha alone, respectively. The replication of T. gondii tachyzoites in cytokine-activated cells was restored by the addition of extra tryptophan to the culture medium. Similarly, T. gondii tachyzoites transfected with bacterial tryp...

Cadernos De Saude Publica, 2000

We evaluated the genetic variability of Triatoma brasiliensis, the main vector of Cha- gas diseas... more We evaluated the genetic variability of Triatoma brasiliensis, the main vector of Cha- gas disease in Northeast Brazil, using specimens from three populations. Regions of genomic DNA were amplified by RAPD (Random Amplified Polimorphic DNA), using two primers. The products were visualized after polyacrylamide gel electrophoresis followed by silver staining. A dendrogram constructed through the Dice similarity coefficient allowed for

Experimental parasitology, 2015

Cyclophilin (CyP), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biologic... more Cyclophilin (CyP), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, CyP could serve as a potential drug target in disease-causing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZ-resistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending ...

Antimicrobial agents and chemotherapy, Jan 23, 2015

The pressing need for better drugs against Chagas disease, African sleeping sickness and schistos... more The pressing need for better drugs against Chagas disease, African sleeping sickness and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain and SmCB1, the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei and Schistosoma mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain and 5 SmCB1 inhibitors with IC50 ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside ( 4I: ) was discovered as a potent rhodesain inhibitor (IC50= 1.2 ± 1.0 μM). The impact of a range of modifications was determined: removal of thiosemicarbazone or its replacement by semicar...

Four Leishmania sp. samples were isolated from autochthonous human cases of American cutaneous le... more Four Leishmania sp. samples were isolated from autochthonous human cases of American cutaneous leishmaniasis (ACL) in Santa Catarina State, southern Brazil. These strains were characterized using indirect immunofluorescence with a panel of Leishmania-specific monoclonal antibodies (MAbs), and by PCR amplification and hybridization assay of the mini-exon gene with group specific probes. The results obtained with the MAbs were in agreement

Jornal de Pediatria, 2005

To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed thr... more To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed through specific interviews. A total of 73 patients who had concluded the maintenance phase of chemotherapy were enrolled on the study. Eighty-one percent of the interviews were conducted with the patients' mothers; 92% of the families stated that medical instructions had been understood well. Interviews indicated that 27% of the patients did not receive their medication twice or more during the maintenance phase, without medical direction for this. These children were considered non-compliant. Sixteen percent of the children failed to receive their medication three times or more. The main reason for non-compliance was forgetfulness. In ten cases the reported dosage of drugs was not that which was prescribed. No significant associations of non-compliance with parents' schooling level, number of family members or per capita family income were detected. The 8.5-year estimated probability of event free survival was 72.4% (95% CI: 59.2-82.3). The event free survival curves for non-compliant children were not statistically different from those for the compliant group. Results suggest that comprehensive approaches to the problem of non-compliance are urgently needed.

The Journal of Protozoology, 1991

While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test ... more While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%).

Jornal de Pediatria, 2005

To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed thr... more To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed through specific interviews. A total of 73 patients who had concluded the maintenance phase of chemotherapy were enrolled on the study. Eighty-one percent of the interviews were conducted with the patients' mothers; 92% of the families stated that medical instructions had been understood well. Interviews indicated that 27% of the patients did not receive their medication twice or more during the maintenance phase, without medical direction for this. These children were considered non-compliant. Sixteen percent of the children failed to receive their medication three times or more. The main reason for non-compliance was forgetfulness. In ten cases the reported dosage of drugs was not that which was prescribed. No significant associations of non-compliance with parents' schooling level, number of family members or per capita family income were detected. The 8.5-year estimated probability of event free survival was 72.4% (95% CI: 59.2-82.3). The event free survival curves for non-compliant children were not statistically different from those for the compliant group. Results suggest that comprehensive approaches to the problem of non-compliance are urgently needed.

Memórias do Instituto Oswaldo Cruz, 2008

Taxonomic markers (head structure morphometry, isoenzymes and randon amplified polymorphism of DN... more Taxonomic markers (head structure morphometry, isoenzymes and randon amplified polymorphism of DNA - RAPD) were used to understand the population dynamics of Triatoma vitticeps, predominant triatomine species in Itanhomi district, using samples obtained from domestic, peridomiciliary and sylvatic habitats. Morphometric analysis revealed sexual dimorphism within the three samples although specimens could not be separated according to the habitat in which they were captured. Forty-two bands were analyzed from RAPD profiles generated using four primers. A dendrogram constructed from Dice's similarity coefficient values showed that migration of the insects between the habitats has occurred, without structuring of populations. Moreover, the dendrogram obtained from the genetic distance values showed an important gene flow between the sylvatic and domestic habitats. No polymorphism was found in the electrophoretic mobility of proteins for the ten enzymes studied. Our results revealed movement of triatomines between the three habitats, suggesting that the presence of T. vitticeps in houses should not be ignored. As invasion of houses by sylvatic insects is frequent and the natural infection indices of this species are among the highest known, epidemiological vigilance studies may reveal possible changes in T. vitticeps behaviour which could present future risks to public health.

Molecular and Biochemical Parasitology, 1998

Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivative... more Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivatives benznidazole and nifurtimox, were analyzed using the following molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic variability assayed by randomly amplified polymorphic DNA (RAPD) with two different primers; and (iii) gene probes for P-glycoprotein (TcPGP), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the ribosomal RNA gene (rDNA) and the mini-exon gene

PLoS Neglected Tropical Diseases, 2014

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other... more Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.

Memórias do Instituto Oswaldo Cruz, 2006

The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma... more The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC 50 of 48.5 µM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60% at 20 µg/ml (59 and 90 µM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 µg/ml (0.6-1.5 mM).

Revista da Sociedade Brasileira de Medicina Tropical, 2003

A new case of spontaneous cure of human Chagas' disease is described in Uruguay. An 87-year-old m... more A new case of spontaneous cure of human Chagas' disease is described in Uruguay. An 87-year-old man who had a typical acute phase of Trypanosoma cruzi infection in 1947 and never received specific treatment against the disease, when examined in 1998 revealed several completely negative parasitological and serological tests, including traditional serology, PCR and flow cytometry. As a whole, such findings fulfill the current criteria to define the cure of Chagas' disease. Clinical data suggest the possibility of a benign evolution of Chagas' disease in this case, but the basic findings (slight cardiac and esophageal impairment) could also be due to the advanced age of the patient.

Cadernos de saúde pública, 2008

The article begins by describing a dog with characteristic symptoms of visceral leishmaniasis. A ... more The article begins by describing a dog with characteristic symptoms of visceral leishmaniasis. A serum sample from this animal was positive by indirect immunofluorescence (IIF) performed in anti-Leishmania total IgG in 1999. Tissues from the same dog were also positive by polymerase chain reaction (PCR) in 2004, identifying Leishmania DNA in the cerebellum, liver, kidney, and intestine. This is the first report of a dog with autochthonous visceral leishmaniasis in the county of Bom Sucesso, Minas Gerais State, Brazil. The finding of this IIF-positive dog led to a canine visceral leishmaniasis epidemiological investigation in the county. The investigation was conducted from March 1999 to December 2005. IIF was positive for Leishmania in 22 (3%) of 734 examined dogs. Among the 22 IIF-positive dogs, six presented characteristic symptoms of canine visceral leishmaniasis. The results of this epidemiological investigation were sent to local and State public health authorities, requesting ...

Memórias do Instituto Oswaldo Cruz, 2015

We describe herein the antitrypanosomal activity of 20 novel 1,3-bis(aryloxy)propan-2-amine deriv... more We describe herein the antitrypanosomal activity of 20 novel 1,3-bis(aryloxy)propan-2-amine derivatives. Compounds 2, 4, 6, 12, 15, 16 and 19 were significantly active against amastigote and trypomastigote forms, with half maximal inhibitory concentrationvalues in the range of 6-18 µM. In the cytotoxicity tests against L929 cells, only compound 4 presented selectivity index value above 10, indicating low toxicity.

Antimicrobial Agents and Chemotherapy, 2015

Cysteine metabolism is considered as essential for the crucial maintenance of a reducing environm... more Cysteine metabolism is considered as essential for the crucial maintenance of a reducing environment in trypanosomatids due to its importance as a precursor of trypanothione biosynthesis. Expression, activity assays, functional rescue and overexpression of cysteine synthase (CS) and cystathionine β-synthase (CβS) were evaluated in Leishmania braziliensis promastigotes and intracellular amastigotes under in vitro stress conditions induced by hydrogen peroxide (H2O2), SNAP or antimonial compounds. Our results demonstrate a stage-specific increase of protein expression and activity levels of LbrCS and LbrCβS, resulting on the increment of total thiols levels in response to both oxidative and nitrosative stress. The rescue of the CS activity in T. rangeli, a trypanosome that does not perform cysteine biosynthesis de novo, resulted in increased survival rates of epimastigotes expressing the LbrCS under stress conditions when compared to wild-type parasites. We also found a significantly enhanced ability of L. braziliensis promastigotes and amastigotes overexpressing LbrCS and LbrCβS to resist oxidative stress when compared to non-transfected cells, resulting in a phenotype far more resistant to Sb(V) treatment in vitro. In conclusion, up-regulation of the protein expression and increment of the activity levels of LbrCS and LbrCβS alters the parasite resistance to antimonials and may influence the efficacy of antimony treatment of New World leishmaniasis.

The American journal of tropical medicine and hygiene, 2001

The role of reinfection in the evolution of Chagas' disease was evaluated in dogs alternately... more The role of reinfection in the evolution of Chagas' disease was evaluated in dogs alternately infected with the 147 and SC-1 strains of Trypanosoma cruzi. A parasitologic, serologic, clinical, and electrocardiographic follow-up was carried out on the infected and noninfected dogs. The dogs were reinfected five times over a period of 38 months. No deaths were observed during the experiment. They presented a brief oligosymptomatic acute phase. The level of parasitemia decreased progressively with the number of reinfections. Bloodstream parasites were not detectable after the fifth reinfection. All parasite samples isolated during the follow-up were zymodeme B, corresponding to strain 147, irrespective of the strain with which the dogs were first infected and of the triatomine species used for isolation. Conversely, amplification by the polymerase chain reaction of a segment of the T. cruzi mini-exon gene showed the simultaneous presence of both strains in three of the eight reinfe...

Journal of medical entomology, 2000

Isoenzymes, random amplified polymorphic DNA (RAPD), and morphometry were used to compare genetic... more Isoenzymes, random amplified polymorphic DNA (RAPD), and morphometry were used to compare genetic variability within and between three populations of Triatoma brasiliensis Neiva, 1911 from northeast Brazil. The isoenzyme profiles were identical for the three populations, whereas the complex RAPD patterns allowed clear discrimination between the three. Morphometric analysis, using characters of the head capsule, also showed discrimination between the three populations but only in comparisons of males, not females. The results show considerable genetic heterogeneity in T. brasiliensis, with an indication of geographic structuring possibly resulting from a recent series of domestication events.

The American journal of tropical medicine and hygiene, 2000

We examined intraspecific variability in the genus Rhodnius using starch gel electrophoresis of s... more We examined intraspecific variability in the genus Rhodnius using starch gel electrophoresis of salivary heme proteins. Salivary protein profiles of 8 Rhodnius species (R. prolixus, R. robustus, R. neglectus, R. nasutus, R. ecuadoriensis, R. pallescens, R. pictipes, and R. domesticus) were compared. All species could be distinguished by this technique. The greatest protein polymorphism was found in R. ecuadoriensis, R. nasutus, R. robustus, and R. pictipes, followed by R. prolixus, R. neglectus, R. pallescens, and R. domesticus. This approach was able to distinguish R. prolixus from R. robustus and R. neglectus from R. nasutus, species with extreme phenotypical similarity.

Infection and immunity, 1999

To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control... more To study the role of tryptophan degradation by indoleamine 2, 3-dioxygenase (INDO) in the control of Trypanosoma cruzi or Toxoplasma gondii replication, we used human fibroblasts and a fibrosarcoma cell line (2C4). The cells were cultured in the presence or absence of recombinant gamma interferon (rIFN-gamma) and/or recombinant tumor necrosis factor alpha (rTNF-alpha) for 24 h and were then infected with either T. cruzi or T. gondii. Intracellular parasite replication was evaluated 24 or 48 h after infection. Treatment with rIFN-gamma and/or rTNF-alpha had no inhibitory effect on T. cruzi replication. In contrast, 54, 73, or 30% inhibition of T. gondii replication was observed in the cells treated with rIFN-gamma alone, rIFN-gamma plus rTNF-alpha, or TNF-alpha alone, respectively. The replication of T. gondii tachyzoites in cytokine-activated cells was restored by the addition of extra tryptophan to the culture medium. Similarly, T. gondii tachyzoites transfected with bacterial tryp...

Cadernos De Saude Publica, 2000

We evaluated the genetic variability of Triatoma brasiliensis, the main vector of Cha- gas diseas... more We evaluated the genetic variability of Triatoma brasiliensis, the main vector of Cha- gas disease in Northeast Brazil, using specimens from three populations. Regions of genomic DNA were amplified by RAPD (Random Amplified Polimorphic DNA), using two primers. The products were visualized after polyacrylamide gel electrophoresis followed by silver staining. A dendrogram constructed through the Dice similarity coefficient allowed for

Experimental parasitology, 2015

Cyclophilin (CyP), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biologic... more Cyclophilin (CyP), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, CyP could serve as a potential drug target in disease-causing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZ-resistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending ...

Antimicrobial agents and chemotherapy, Jan 23, 2015

The pressing need for better drugs against Chagas disease, African sleeping sickness and schistos... more The pressing need for better drugs against Chagas disease, African sleeping sickness and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain and SmCB1, the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei and Schistosoma mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain and 5 SmCB1 inhibitors with IC50 ≤ 10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside ( 4I: ) was discovered as a potent rhodesain inhibitor (IC50= 1.2 ± 1.0 μM). The impact of a range of modifications was determined: removal of thiosemicarbazone or its replacement by semicar...

Four Leishmania sp. samples were isolated from autochthonous human cases of American cutaneous le... more Four Leishmania sp. samples were isolated from autochthonous human cases of American cutaneous leishmaniasis (ACL) in Santa Catarina State, southern Brazil. These strains were characterized using indirect immunofluorescence with a panel of Leishmania-specific monoclonal antibodies (MAbs), and by PCR amplification and hybridization assay of the mini-exon gene with group specific probes. The results obtained with the MAbs were in agreement

Jornal de Pediatria, 2005

To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed thr... more To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed through specific interviews. A total of 73 patients who had concluded the maintenance phase of chemotherapy were enrolled on the study. Eighty-one percent of the interviews were conducted with the patients' mothers; 92% of the families stated that medical instructions had been understood well. Interviews indicated that 27% of the patients did not receive their medication twice or more during the maintenance phase, without medical direction for this. These children were considered non-compliant. Sixteen percent of the children failed to receive their medication three times or more. The main reason for non-compliance was forgetfulness. In ten cases the reported dosage of drugs was not that which was prescribed. No significant associations of non-compliance with parents' schooling level, number of family members or per capita family income were detected. The 8.5-year estimated probability of event free survival was 72.4% (95% CI: 59.2-82.3). The event free survival curves for non-compliant children were not statistically different from those for the compliant group. Results suggest that comprehensive approaches to the problem of non-compliance are urgently needed.

The Journal of Protozoology, 1991

While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test ... more While relapses following clinical cure of American cutaneous leishmaniasis are frequent, no test has been described until now to predict such relapses. A cohort of 318 American cutaneous leishmaniasis patients was followed up for two years after treatment with meglumine antimoniate, during which time 32 relapses occurred, 30 in the first year and two in the second (accumulated risk: 10.5%).

Jornal de Pediatria, 2005

To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed thr... more To evaluate compliance in children with acute lymphoblastic leukemia. Compliance was assessed through specific interviews. A total of 73 patients who had concluded the maintenance phase of chemotherapy were enrolled on the study. Eighty-one percent of the interviews were conducted with the patients' mothers; 92% of the families stated that medical instructions had been understood well. Interviews indicated that 27% of the patients did not receive their medication twice or more during the maintenance phase, without medical direction for this. These children were considered non-compliant. Sixteen percent of the children failed to receive their medication three times or more. The main reason for non-compliance was forgetfulness. In ten cases the reported dosage of drugs was not that which was prescribed. No significant associations of non-compliance with parents' schooling level, number of family members or per capita family income were detected. The 8.5-year estimated probability of event free survival was 72.4% (95% CI: 59.2-82.3). The event free survival curves for non-compliant children were not statistically different from those for the compliant group. Results suggest that comprehensive approaches to the problem of non-compliance are urgently needed.

Memórias do Instituto Oswaldo Cruz, 2008

Taxonomic markers (head structure morphometry, isoenzymes and randon amplified polymorphism of DN... more Taxonomic markers (head structure morphometry, isoenzymes and randon amplified polymorphism of DNA - RAPD) were used to understand the population dynamics of Triatoma vitticeps, predominant triatomine species in Itanhomi district, using samples obtained from domestic, peridomiciliary and sylvatic habitats. Morphometric analysis revealed sexual dimorphism within the three samples although specimens could not be separated according to the habitat in which they were captured. Forty-two bands were analyzed from RAPD profiles generated using four primers. A dendrogram constructed from Dice's similarity coefficient values showed that migration of the insects between the habitats has occurred, without structuring of populations. Moreover, the dendrogram obtained from the genetic distance values showed an important gene flow between the sylvatic and domestic habitats. No polymorphism was found in the electrophoretic mobility of proteins for the ten enzymes studied. Our results revealed movement of triatomines between the three habitats, suggesting that the presence of T. vitticeps in houses should not be ignored. As invasion of houses by sylvatic insects is frequent and the natural infection indices of this species are among the highest known, epidemiological vigilance studies may reveal possible changes in T. vitticeps behaviour which could present future risks to public health.

Molecular and Biochemical Parasitology, 1998

Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivative... more Twenty-seven Trypanosoma cruzi strains, susceptible or naturally resistant to the nitroderivatives benznidazole and nifurtimox, were analyzed using the following molecular markers: (i) isoenzyme patterns of six enzymes; (ii) genetic variability assayed by randomly amplified polymorphic DNA (RAPD) with two different primers; and (iii) gene probes for P-glycoprotein (TcPGP), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the ribosomal RNA gene (rDNA) and the mini-exon gene

PLoS Neglected Tropical Diseases, 2014

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other... more Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.

Memórias do Instituto Oswaldo Cruz, 2006

The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma... more The natural lignans veraguensin and grandisin have been reported to be active against Trypanosoma cruzi bloodstream forms. Aiming at the total synthesis of these and related compounds, we prepared three 2-arylfurans and eight 2,5-diarylfurans. They were evaluated for their potential as T. cruzi trypanothione reductase (TR) inhibitors as well against the parasite's intracellular (amastigote) and bloodstream (trypomastigote) forms. Compound 12 was the most effective against TR with an IC 50 of 48.5 µM while 7 and 14 were active against amastigotes, inhibiting the parasite development by 60% at 20 µg/ml (59 and 90 µM, respectively). On the other hand, none of the compounds was significantly active against the parasite bloodstream forms even at 250 µg/ml (0.6-1.5 mM).

Revista da Sociedade Brasileira de Medicina Tropical, 2003

A new case of spontaneous cure of human Chagas' disease is described in Uruguay. An 87-year-old m... more A new case of spontaneous cure of human Chagas' disease is described in Uruguay. An 87-year-old man who had a typical acute phase of Trypanosoma cruzi infection in 1947 and never received specific treatment against the disease, when examined in 1998 revealed several completely negative parasitological and serological tests, including traditional serology, PCR and flow cytometry. As a whole, such findings fulfill the current criteria to define the cure of Chagas' disease. Clinical data suggest the possibility of a benign evolution of Chagas' disease in this case, but the basic findings (slight cardiac and esophageal impairment) could also be due to the advanced age of the patient.

Cadernos de saúde pública, 2008

The article begins by describing a dog with characteristic symptoms of visceral leishmaniasis. A ... more The article begins by describing a dog with characteristic symptoms of visceral leishmaniasis. A serum sample from this animal was positive by indirect immunofluorescence (IIF) performed in anti-Leishmania total IgG in 1999. Tissues from the same dog were also positive by polymerase chain reaction (PCR) in 2004, identifying Leishmania DNA in the cerebellum, liver, kidney, and intestine. This is the first report of a dog with autochthonous visceral leishmaniasis in the county of Bom Sucesso, Minas Gerais State, Brazil. The finding of this IIF-positive dog led to a canine visceral leishmaniasis epidemiological investigation in the county. The investigation was conducted from March 1999 to December 2005. IIF was positive for Leishmania in 22 (3%) of 734 examined dogs. Among the 22 IIF-positive dogs, six presented characteristic symptoms of canine visceral leishmaniasis. The results of this epidemiological investigation were sent to local and State public health authorities, requesting ...