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1.
Pharm Res ; 36(8): 122, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218556

RESUMO

PURPOSE: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. METHODS: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. RESULTS: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. CONCLUSION: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Nanopartículas Metálicas/química , Prata/química , Sulfadiazina/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Queimaduras/patologia , Queimaduras/fisiopatologia , Composição de Medicamentos/métodos , Quimioterapia Combinada , Emulsões , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Masculino , Camundongos , Óleos/química , Tamanho da Partícula , Permeabilidade , Pele/efeitos dos fármacos , Pele/patologia , Pele/fisiopatologia , Staphylococcus aureus/efeitos dos fármacos , Sulfadiazina/administração & dosagem , Tensoativos/química
2.
Exp Parasitol ; 202: 7-14, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31077733

RESUMO

Toxoplasmosis in South America presents great health impacts and is a topic of research interest not only because of the severity of native cases but also due to the predominant atypical genotypes of the parasite circulating in this continent. Typically, symptomatic toxoplasmosis is treated with a combination of sulfadiazine (SDZ) and pyrimethamine (PYR). However, some clinical cases present treatment failures due to an inability of the drugs to control the infection or their significant adverse effects, which can lead to treatment interruption. Although resistance/susceptibility to the aforementioned drugs has been well described for clonal strains of Toxoplasma gondii spread to the Northern Hemisphere, less is known about the South American atypical strains. In this study, the effectiveness of SDZ and PYR for the treatment of mice during acute infection with different atypical T. gondii strains was evaluated. Swiss mice were infected with seven T. gondii strains obtained from newborn patients with congenital toxoplasmosis in Brazil. The infected mice were treated with 10-640 mg/kg per day of SDZ, 3-200 mg/kg per day of PYR, or a combination of both drugs with a lower dosage. The mice were evaluated for parameters including mortality, anti-T. gondii IgG production by ELISA and the presence of brain cysts. In addition, the presence of polymorphisms in the dhps gene was verified by gene sequencing. A descriptive analysis was used to assess the association between susceptibility to SDZ and/or PYR and the genotype. The TgCTBr4 and TgCTBr17 strains (genotype 108) presented lower susceptibility to SDZ or PYR treatment. The TgCTBr1 and TgCTBr25 strains (genotype 206) presented similar susceptibility to PYR but not SDZ treatment. The TgCTBr9 strain (genotype 11) was the only strain with high susceptibility to treatment with both drugs. The TgCTBr13 strain (genotype 208) was not susceptible to treatment with the lower PYR or SDZ doses. The TgCTBR23 strain (genotype 41) was more susceptible to PYR than to SDZ treatment. However, the association of low SDZ and PYR doses showed good efficacy for the treatment of experimental toxoplasmosis with T. gondii atypical strains obtained from newborns in Brazil. A new mutation in the T. gondii dhps gene (I347M) was identified that might be associated with the SDZ low sensitivity profile observed for the TgCTBr4 and TgCTBr17 isolates.


Assuntos
Antiprotozoários/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasmose Animal/tratamento farmacológico , Toxoplasmose Congênita/parasitologia , Álcool Desidrogenase/genética , Animais , Antiprotozoários/farmacologia , Feminino , Genótipo , Humanos , Recém-Nascido , Camundongos , Pirimetamina/farmacologia , Sulfadiazina/farmacologia , Toxoplasma/classificação , Toxoplasma/efeitos dos fármacos , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasmose Animal/parasitologia , Toxoplasmose Congênita/tratamento farmacológico , Virulência
3.
Molecules ; 24(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022878

RESUMO

Employing a simple synthetic protocol, a series of highly effective halogen-substituted imidazole-thiosemicarbazides with anti-Toxoplasma gondii effects against the RH tachyzoites, much better than sulfadiazine, were obtained (IC50s 10.30-113.45 µg/mL vs. ~2721.45 µg/mL). The most potent of them, 12, 13, and 15, blocked the in vitro proliferation of T. gondii more potently than trimethoprim (IC50 12.13 µg/mL), as well. The results of lipophilicity studies collectively suggest that logP would be a rate-limiting factor for the anti-Toxoplasma activity of this class of compounds.


Assuntos
Semicarbazidas/síntese química , Relação Estrutura-Atividade , Toxoplasma/efeitos dos fármacos , Toxoplasmose/tratamento farmacológico , Animais , Halogênios/química , Humanos , Imidazóis/química , Imidazóis/farmacologia , Semicarbazidas/química , Sulfadiazina/farmacologia , Toxoplasma/patogenicidade , Toxoplasmose/parasitologia
4.
Chemosphere ; 219: 305-312, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30543966

RESUMO

Extensive studies on anaerobic fermentation of waste activated sludge (WAS) for volatile fatty acids (VFAs) production focused on the effects of operating parameters and pretreatment methods, and little information is available for those of organic pollutants which were absorbed on sludge. The influence of sulfadiazine (SDZ), a typical antibiotic pollutant in WAS, on VFAs production during anaerobic fermentation was investigated in this study. The accumulation of VFAs was remarkably affected in the presence of SDZ. When the content of SDZ was 50 mg per kilogram dry sludge the concentration of VFAs from sludge was 2032.8 mg COD/L, much higher than that of control (1540.2 mg COD/L). Mechanism investigation revealed that the content of extracellular polymeric substances (EPS) from sludge was increased due to the presence of SDZ, which provided more substrates, i.e., protein and carbohydrate, and created a favorable environment for anaerobes. The hydrolysis and acidification of WAS were stimulated by SDZ, and the functional microorganisms were advantageous to VFAs production. The activities of protease, α-glucosidase and acetate kinase were promoted when SDZ occurred, which were beneficial for hydrolysis and acidification. The effect of SDZ on pure strains further confirmed that the formation of VFAs during anaerobic fermentation was stimulated by SDZ.


Assuntos
Ácidos Graxos Voláteis/biossíntese , Fermentação/efeitos dos fármacos , Esgotos/microbiologia , Sulfadiazina/farmacologia , Bactérias Anaeróbias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise/efeitos dos fármacos , Esgotos/química , Sulfadiazina/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-29620436

RESUMO

The cross-contamination of non-medicated feed with residues of anti-microbials (AM) causes a public and animal health concern associated with the potential for selection and dissemination of resistance. To analyse the associated risks, a probabilistic model was built using @Risk® (Palisade Corporation®) to show the potential extent of the effect of cross-contaminated pig feed on resistance selection. The results of the model include estimations of the proportion of pigs per production stage with residues of doxycycline, chlortetracycline, sulfadiazine and trimethoprim in their intestinal contents, as a result of exposure to cross-contaminated feed with different carry-over levels, in Belgium. By using a semi-quantitative approach, these estimations were combined with experimental data on AM concentrations associated with potential for resistance-selection pressure. Based on this model, it is estimated that 7.76% (min = 1.67; max = 36.94) of sows, 4.23% (min = 1.01%; max = 18.78%) of piglets and 2.8% (min = 0.51%; max = 14.9%) of fatteners in Belgium have residues of doxycycline in their intestinal tract due to consumption of feed with at least 1% carry-over. These values were estimated to be almost triple for sulfadiazine, but substantially lower for chlortetracycline and trimethoprim. Doxycycline concentrations as low as 1 mg/L (corresponding to consumed feed with at least 1% carry-over) can select for resistant porcine commensal Escherichia coli in vitro and in vivo. Conclusions on this risk could not be drawn for other AM at this stage, due to the lack of data on concentrations associated with resistance development. However, since the possibility of resistance mechanisms (e.g. co-selection) occurring cannot be excluded, the results of this model highlight that the use of AM medicated feed should be minimised where possible. In case of medicated feed production, good practice should be followed thoroughly at all levels of production, distribution, storage and administration, with a special focus on the feed distributed to piglets and sows.


Assuntos
Ração Animal , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Contaminação de Alimentos/análise , Modelos Estatísticos , Suínos/microbiologia , Animais , Antibacterianos/análise , Clortetraciclina/análise , Clortetraciclina/farmacologia , Doxiciclina/análise , Doxiciclina/farmacologia , Escherichia coli/efeitos dos fármacos , Conteúdo Gastrointestinal/química , Conteúdo Gastrointestinal/efeitos dos fármacos , Conteúdo Gastrointestinal/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Risco , Sulfadiazina/análise , Sulfadiazina/farmacologia , Trimetoprima/análise , Trimetoprima/farmacologia
6.
Int J Antimicrob Agents ; 51(5): 775-783, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29421171

RESUMO

The recent emergence of colistin (COL) resistance, particularly mcr-1 plasmid-mediated COL resistance in Gram-negative bacteria, has led to renewed interest in antibiotic combinations to overcome clinical therapeutic impasses. The aim of this study was to evaluate the potential of the synergistic and bactericidal activity of COL in combination with sulphonamide compounds, including sulfadiazine (SDI), sulfamethoxazole (SMX) and trimethoprim/sulfamethoxazole (SXT), as well as trimethoprim (TMP) against clinical COL-resistant bacterial strains, including strains with the plasmid-encoded mcr-1 gene. A collection of 55 COL-resistant and -susceptible strains from different origins (Laos, Thailand and France) was used in this study. Several in vitro methods were used to determine the potential of the synergistic activity of these combinations, including Etest on agar pre-treated plates, the Etest cross method and the chequerboard assay. A time-kill assay was performed to evaluate the potential bactericidal activity of combinations in addition to synergistic activity. Significant synergistic activity was observed with all combinations tested. The combination of COL + SDI presented the highest synergistic effect against the various species of COL-resistant strains (92.7%). For the other combinations, a synergistic effect was also observed but with lower frequency for COL + SMX (33.3%), COL + TMP (47.3%) and COL + SXT (31.5%). Synergy was observed independently of the COL resistance mechanism. These in vitro results suggest that the combination of COL + SDI would appear to be justifiable in patients with multidrug-resistant bacterial infections that cannot be treated with COL monotherapy.


Assuntos
Antibacterianos/farmacologia , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Sulfadiazina/farmacologia , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Proteínas de Escherichia coli/genética , França , Bactérias Gram-Negativas/genética , Humanos , Laos , Testes de Sensibilidade Microbiana , Tailândia , Trimetoprima/farmacologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia
7.
Int J Antimicrob Agents ; 51(2): 235-238, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28711677

RESUMO

In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one 'Mycobacterium simulans' and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium kansasii/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Cloranfenicol/farmacologia , Clofazimina/farmacologia , Djibuti , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Minociclina/farmacologia , Mycobacterium kansasii/isolamento & purificação , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Sulfadiazina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia
8.
Int J Antimicrob Agents ; 51(1): 123-127, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28668675

RESUMO

Pig feed may contain various levels of antimicrobial residues due to cross-contamination. A previous study showed that a 3% carry-over level of doxycycline (DOX) in the feed results in porcine faecal concentrations of approximately 4 mg/L. The aim of this study was to determine the effect of residual DOX concentrations (1 and 4 mg/L) in vitro on selection of DOX-resistant porcine commensal Escherichia coli and transfer of their resistance plasmids. Three different DOX-resistant porcine commensal E. coli strains and their plasmids were characterised. These strains were each brought in competition with a susceptible strain in a medium containing 0, 1 and 4 mg/L DOX. Resistant bacteria, susceptible bacteria and transconjugants were enumerated after 24 h and 48 h. The tet(A)-carrying plasmids showed genetic backbones that are also present among human E. coli isolates. Ratios of resistant to susceptible bacteria were significantly higher at 1 and 4 mg/L DOX compared with the blank control, but there was no significant difference between 1 and 4 mg/L. Plasmid transfer frequencies were affected by 1 or 4 mg/L DOX in the medium for only one of the resistance plasmids. In conclusion, DOX concentrations of 1 and 4 mg/L can select for resistant E. coli in vitro. Further research is needed to determine the effect of these concentrations in the complex environment of the porcine intestinal microbiota.


Assuntos
Ração Animal/análise , Antibacterianos/administração & dosagem , Clortetraciclina/análise , Doxiciclina/análise , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Sulfadiazina/análise , Trimetoprima/análise , Animais , Antibacterianos/farmacologia , Antiporters/genética , Proteínas de Bactérias/genética , Clortetraciclina/farmacologia , Doxiciclina/farmacologia , Combinação de Medicamentos , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Transferência Genética Horizontal/genética , Intestinos/microbiologia , Plasmídeos/genética , Sulfadiazina/farmacologia , Suínos , Trimetoprima/farmacologia
9.
Exp Parasitol ; 181: 111-118, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28803905

RESUMO

Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2. Two antibiotic protocols were evaluated, as follow: i) pre-treatment of T. gondii-tachyzoites with selected antibiotics prior trophoblast infection and ii) post-treatment of infected trophoblasts. The infection index/replication and the impact of the antibiotic therapy on the cytokine milieu were characterized. It was observed that TgChBrUD2 infection induced lower infection index/replication as compared to TgChBrUD1. Regardless the therapeutic protocol, azithromycin was more effective to control the trophoblast infection with both genotypes when compared to conventional antibiotics. Azithromycin induced higher IL-12 production in TgChBrUD1-infected cells that may synergize the anti-parasitic effect. In contrast, the effectiveness of azithromycin to control the TgChBrUD2-infection was not associated with the IL-12 production. BeWo-trophoblasts display distinct susceptibility to T. gondii genotypes and the azithromycin treatment showed to be more effective than conventional antibiotics to control the T. gondii infection/replication regardless the parasite genotype.


Assuntos
Antiprotozoários/farmacologia , Azitromicina/farmacologia , Toxoplasma/efeitos dos fármacos , Trofoblastos/parasitologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Combinação de Medicamentos , Genótipo , Humanos , Interleucina-12/metabolismo , Pirimetamina/farmacologia , Espiramicina/farmacologia , Sulfadiazina/farmacologia , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasma/imunologia , Trofoblastos/efeitos dos fármacos
10.
Exp Parasitol ; 181: 75-81, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28774497

RESUMO

Due to the toxicity of conventional medication in toxoplasmosis, some drugs are being studied for treating this infection, such as statins, especially rosuvastatin compound, which is efficient in inhibiting the initial isoprenoid biosynthesis processes in humans and the parasite. The goal of this study was to assess the activity of rosuvastatin in HeLa cells infected with the RH strain of T. gondii. In the experiment, HeLa cells (1 × 105) were infected with tachyzoites of T. gondii (5 × 105). After the experimental infection, we assessed the number of infected cells and the amount of intracellular tachyzoites. In addition, culture supernatants were collected to determine the amount of cytokines by cytometric bead array. We observed that there was no cytotoxicity in the concentrations tested in this cell line. The effect of rosuvastatin showed a significant reduction in both the number of infected cells and the proliferation index of the intracellular parasite, when compared with the conventional treatment combining sulfadiazine and pyrimethamine for toxoplasmosis. There were also reduced levels of cytokines IL-6 and IL-17. Therefore, it was concluded that rosuvastatin exhibited antiproliferative activity. The data presented are significant to promote further studies and the search for alternative treatment for toxoplasmosis.


Assuntos
Células HeLa/parasitologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Rosuvastatina Cálcica/farmacologia , Toxoplasma/efeitos dos fármacos , Análise de Variância , Antiprotozoários/farmacologia , Meios de Cultura , Células HeLa/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Pirimetamina/farmacologia , Rosuvastatina Cálcica/toxicidade , Sulfadiazina/farmacologia , Toxoplasma/imunologia
11.
Sci Rep ; 7: 45871, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28361906

RESUMO

The evolutionary relationship between plants and the malarial parasite Plasmodium falciparum is well established and underscored by the P. falciparum apicoplast, an essential chloroplast-like organelle. As a result of this relationship, studies have demonstrated that herbicides active against plants are also active against P. falciparum and thus could act as antimalarial drug leads. Here we show the converse is also true; many antimalarial compounds developed for human use are highly herbicidal. We found that human antimalarial drugs (e.g. sulfadiazine, sulfadoxine, pyrimethamine, cycloguanil) were lethal to the model plant Arabidopsis thaliana at similar concentrations to market herbicides glufosinate and glyphosate. Furthermore, the physicochemical properties of these herbicidal antimalarial compounds were similar to commercially used herbicides. The implications of this finding that many antimalarial compounds are herbicidal proffers two novel applications: (i) using the genetically tractable A. thaliana to reveal mode-of-action for understudied antimalarial drugs, and (ii) co-opting antimalarial compounds as a new source for much needed herbicide lead molecules.


Assuntos
Antimaláricos/farmacologia , Arabidopsis/efeitos dos fármacos , Herbicidas/farmacologia , Arabidopsis/parasitologia , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/parasitologia , Proguanil/farmacologia , Pirimetamina/farmacologia , Sulfadiazina/farmacologia , Sulfadoxina/farmacologia , Triazinas/farmacologia
12.
Appl Biochem Biotechnol ; 183(1): 374-384, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28285355

RESUMO

Bacterial infection is one of the vital reasons of morbidity and mortality, especially in developing countries. It appears silently without bothering the geological borders and imposes a grave threat to humanity. Nuclear medicine technique has an important role in helping early diagnosis of deep-seated infections. The aim of this study was to develop a new radiopharmaceutical 99mTc-labeling sulfadiazine as an infection imaging agent. Radiolabeling of sulfadiazine with technetium-99m (99mTc) was carried out using stannous tartrate as a reducing agent in the presence of gentistic acid at pH = 5. The quality control tests revealed ~98% labeling efficiency. Paper chromatographic (PC) and instant thin-layer chromatographic (ITLC) techniques were used to analyze radiochemical yield. Biodistribution and infection specificity of the radiotracer were performed with Escherichia coli (E. coli) infection-induced rats. Scintigraphy and glomerular filtration rate (GFR) study was performed in E. coli-infected rabbits. Scintigraphy indicated E. coli infection targeting potential of 99mTc-SDZ, while biodistribution study showed minimal uptake of 99mTc-SDZ in non-targeted tissues. The uptake in the kidneys was found 2.56 ± 0.06, 2.09 ± 0.10, and 1.68 ± 0.09% at 30 min, 1 h, and 4 h, respectively. The infected muscle (target) to non-infected muscle (non-target) ratio (T/NT) was found 4.49 ± 0.04, 6.78 ± 0.07, and 5.59 ± 0.08 at 30 min, 1 h, and 4 h, respectively.


Assuntos
Infecções por Escherichia coli/diagnóstico por imagem , Escherichia coli , Marcação por Isótopo/métodos , Sulfadiazina , Tecnécio , Animais , Infecções por Escherichia coli/tratamento farmacológico , Camundongos , Coelhos , Cintilografia , Ratos , Ratos Sprague-Dawley , Sulfadiazina/química , Sulfadiazina/farmacocinética , Sulfadiazina/farmacologia , Tecnécio/química , Tecnécio/farmacocinética , Tecnécio/farmacologia
13.
PLoS One ; 12(1): e0170689, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28118394

RESUMO

BACKGROUND: Previous Toxoplasma gondii studies revealed that mutations in the dhps (dihydropteroate synthase) gene are associated with resistance to sulfonamides. Although Brazilian strains are genotypically different, very limited data are available regarding the susceptibility of strains obtained from human to sulfonamides. The aim of this study was to evaluate the efficacy of sulfadiazine (SDZ) against Brazilian isolates of T. gondii and verify whether isolates present polymorphisms in the dhps gene. We also investigated whether the virulence-phenotype and/or genotype were associated with the profile of susceptibility to SDZ. METHODS: Five T. gondii isolates obtained from newborns with congenital toxoplasmosis were used to verify susceptibility. Mice were infected with 104 tachyzoites and orally treated with different doses of SDZ. The mortality curve was evaluated by the Log-rank test. The presence of polymorphisms in the dhps gene was verified using sequencing. A descriptive analysis for 11 Brazilian isolates was used to assess the association between susceptibility, genotype, and virulence-phenotype. RESULTS: Statistical analysis showed that TgCTBr03, 07, 08, and 16 isolates were susceptible to SDZ, whereas TgCTBr11 isolate presented a profile of resistance to SDZ. Nineteen polymorphisms were identified in dhps exons. Seven polymorphisms corresponded to non-synonymous mutations, with four being new mutations, described for the first time in this study. No association was found between the profile of susceptibility and the virulence-phenotype or genotype of the parasite. CONCLUSIONS: There is a high variability in the susceptibilities of Brazilian T. gondii strains to SDZ, with evidence of drug resistance. Despite the large number of polymorphisms identified, the profile of susceptibility to SDZ was not associated with any of the dhps variants identified in this study. Other genetic factors, not yet determined, may be associated with the resistance to SDZ; thus, further studies are needed as a basis for a more adequate toxoplasmosis treatment.


Assuntos
Antiprotozoários/farmacologia , Di-Hidropteroato Sintase/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Protozoários/genética , Sulfadiazina/farmacologia , Toxoplasma/genética , Toxoplasmose Congênita/parasitologia , Animais , Antiprotozoários/uso terapêutico , Sequência de Bases , Brasil/epidemiologia , Resistência a Medicamentos/genética , Feminino , Estudos de Associação Genética , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Mutação , Alinhamento de Sequência , Sulfadiazina/uso terapêutico , Toxoplasma/efeitos dos fármacos , Toxoplasma/patogenicidade , Toxoplasmose Animal/tratamento farmacológico , Toxoplasmose Congênita/tratamento farmacológico , Toxoplasmose Congênita/epidemiologia , Virulência/genética
14.
Plant Cell Environ ; 40(6): 789-801, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27620674

RESUMO

The role of some aquaporins as CO2 permeable channels has been controversial. Low CO2 permeability of plant membranes has been criticized because of unstirred layers and other limitations. Here we measured both water and CO2 permeability (Pos , PCO2 ) using stopped flow on plasma membrane vesicles (pmv) isolated from Pisum sativum (pea) and Arabidopsis thaliana leaves. We excluded the chemical limitation of carbonic anhydrase (CA) in the vesicle acidification technique for PCO2 using different temperatures and CA concentrations. Unstirred layers were excluded based on small vesicle size and the positive correlation between vesicle diameter and PCO2 . We observed high aquaporin activity (Pos 0.06 to 0.22 cm s-1 ) for pea pmv based on all the criteria for their function using inhibitors and temperature dependence. Inhibitors of Pos did not alter PCO2 . PCO2 ranged from 0.001 to 0.012 cm s-1 (mean 0.0079 + 0.0007 cm s-1 ) with activation energy of 30.2 kJ mol-1 . Intrinsic variation between pmv batches from normally grown or stressed plants revealed a weak (R2 = 0.27) positive linear correlation between Pos and PCO2 . Despite the low PCO2 , aquaporins may facilitate CO2 transport across plasma membranes, but probably via a different pathway than for water.


Assuntos
Aquaporinas/metabolismo , Dióxido de Carbono/metabolismo , Membrana Celular/metabolismo , Folhas de Planta/metabolismo , Água/metabolismo , Acetazolamida/farmacologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Ervilhas/metabolismo , Folhas de Planta/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Sulfadiazina/farmacologia
15.
J Clin Microbiol ; 55(1): 326-330, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27847375

RESUMO

Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim-sulfamethoxazole and/or trimethoprim-sulfadiazine with S. equi This study indicates trimethoprim-sulfamethoxazole as an acceptable surrogate for trimethoprim-sulfadiazine with S. equi.


Assuntos
Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana/normas , Streptococcus equi/efeitos dos fármacos , Sulfadiazina/farmacologia , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Trimetoprima/farmacologia , Medicina Veterinária/normas , Animais , Combinação de Medicamentos , Testes de Sensibilidade Microbiana/métodos , Medicina Veterinária/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-27933277

RESUMO

Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of T. gondii infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs) were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from T. gondii. The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL, or sulfadiazine, and the following parameters analyzed: Cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus ArtinM treatment induced production of pro-inflammatory and anti-inflammatory cytokines, showing differential but complementary profiles. Moreover, when compared with non-treated mice, the parasite burden was significantly lower and survival rates higher in mice treated with ScLL or ScLL plus ArtinM, similarly with sulfadiazine treatment. In conclusion, the results demonstrated the suitable potential immunotherapeutic effect of ScLL and ArtinM lectins to control acute toxoplasmosis in this experimental murine model.


Assuntos
Adjuvantes Imunológicos/farmacologia , Artocarpus/química , Lectinas/farmacologia , Extratos Vegetais/farmacologia , Toxoplasma/imunologia , Toxoplasmose/tratamento farmacológico , Toxoplasmose/imunologia , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/imunologia , Encéfalo/parasitologia , Citocinas/sangue , Citocinas/efeitos dos fármacos , Testes Imunológicos de Citotoxicidade , DNA Bacteriano , Modelos Animais de Doenças , Relação Dose-Resposta Imunológica , Feminino , Lectinas/administração & dosagem , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/análise , Carga Parasitária , Vacinas Protozoárias/imunologia , Sulfadiazina/farmacologia , Análise de Sobrevida , Toxoplasma/efeitos dos fármacos , Toxoplasma/patogenicidade
17.
PLoS One ; 11(10): e0165013, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27755578

RESUMO

This study is aimed to assess the biodegradation of sulfadiazine (SDZ) and characterization of heavy metal resistance in three pure bacterial cultures and also their chemotactic response towards 2-aminopyrimidine. The bacterial cultures were isolated from pig manure, activated sludge and sediment samples, by enrichment technique on SDZ (6 mg L-1). Based on the 16S rRNA gene sequence analysis, the microorganisms were identified within the genera of Paracoccus, Methylobacterium and Kribbella, which were further designated as SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47. The three identified pure bacterial strains degraded up to 50.0, 55.2 and 60.0% of SDZ (5 mg L-1), respectively within 290 h. On the basis of quadrupole time-of-flight mass spectrometry and high performance liquid chromatography, 2-aminopyrimidine and 4-hydroxy-2-aminopyrimidine were identified as the main intermediates of SDZ biodegradation. These bacteria were also able to degrade the metabolite, 2-aminopyrimidine, of the SDZ. Furthermore, SDZ-PM2-BSH30, SDZ-W2-SJ40 and SDZ-3S-SCL47 also showed resistance to various heavy metals like copper, cadmium, chromium, cobalt, lead, nickel and zinc. Additionally, all three bacteria exhibited positive chemotaxis towards 2-aminopyrimidine based on the drop plate method and capillary assay. The results of this study advanced our understanding about the microbial degradation of SDZ, which would be useful towards the future SDZ removal in the environment.


Assuntos
Anti-Infecciosos/metabolismo , Bactérias/metabolismo , Sulfadiazina/metabolismo , Actinobacteria/classificação , Actinobacteria/efeitos dos fármacos , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Animais , Anti-Infecciosos/análise , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Quimiotaxia , Cromatografia Líquida de Alta Pressão , Farmacorresistência Bacteriana , Sedimentos Geológicos/microbiologia , Esterco/microbiologia , Espectrometria de Massas , Metais Pesados/toxicidade , Methylobacterium/classificação , Methylobacterium/efeitos dos fármacos , Methylobacterium/genética , Methylobacterium/isolamento & purificação , Testes de Sensibilidade Microbiana , Paracoccus/classificação , Paracoccus/efeitos dos fármacos , Paracoccus/genética , Paracoccus/isolamento & purificação , Filogenia , Pirimidinas/análise , Pirimidinas/isolamento & purificação , RNA Ribossômico 16S/química , RNA Ribossômico 16S/metabolismo , Análise de Sequência de DNA , Esgotos/microbiologia , Sulfadiazina/análise , Sulfadiazina/farmacologia , Suínos
18.
Parasitol Int ; 65(5 Pt A): 494-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27380994

RESUMO

An anti-malarial candidate, 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251), was studied to characterize its potential as a novel anti-Toxoplasma gondii drug. In the present study, IC50 and LC50 of N-251 on host cells and T. gondii were compared to those of artemisinin and sulfadiazine. The IC50 on Huh-7 cells was 10.19µg/ml, 67.69µg/ml and 310.17µg/ml for N-251, artemisinin, and sulfadiazine, respectively. The LC50 for anti-T. gondii effect was shown to be 1.11µg/ml, 5.79µg/ml, and 5.45µg/ml for N-251, artemisinin and sulfadiazine, respectively. N-251 concentration causing complete parasiticidal effect with minimal cytotoxicity on host cells was determined to be 5µg/ml. Additionally, the anti-T. gondii effect of N-251 was confirmed by ultrastructural changes, loss of organelles, degenerated morphology and the increase of amylopectin as detected by transmission electron microscope (TEM). Accordingly, the present study suggests that the anti-malarial synthetic endoperoxide, N-251, is an emerging drug candidate more effective than artemisinin and sulfadiazine.


Assuntos
Antimaláricos/farmacologia , Compostos de Espiro/farmacologia , Tetraoxanos/farmacologia , Toxoplasma/efeitos dos fármacos , Artemisininas/farmacologia , Linhagem Celular , Humanos , Testes de Sensibilidade Parasitária , Sulfadiazina/farmacologia
19.
Mem Inst Oswaldo Cruz ; 111(6): 391-8, 2016 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-27276184

RESUMO

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities.


Assuntos
Gado/parasitologia , Sulfadiazina/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/patogenicidade , Animais , DNA de Protozoário/isolamento & purificação , Feminino , Genótipo , Camundongos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Parasitária , Fenótipo , Filogenia , Polimorfismo de Fragmento de Restrição , Fatores de Tempo , Virulência
20.
Mem. Inst. Oswaldo Cruz ; 111(6): 391-398, June 2016. graf
Artigo em Inglês | LILACS | ID: lil-784250

RESUMO

Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities.


Assuntos
Animais , Feminino , Camundongos , Gado/parasitologia , Sulfadiazina/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/patogenicidade , DNA de Protozoário/isolamento & purificação , Genótipo , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Parasitária , Fenótipo , Filogenia , Polimorfismo de Fragmento de Restrição , Fatores de Tempo , Virulência
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