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1.
Toxicol In Vitro ; 74: 105158, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823240

RESUMO

BACKGROUND: Leishmaniasis is a parasitosis with a wide incidence in developing countries. The drugs which are indicated for the treatment of this infection usually are able to promote high toxicity. PURPOSE: A combination of limonene and carvacrol, monoterpenes present in plants with antiparasitic activity may constitute an alternative for the treatment of these diseases. METHODS: In this study, the antileishmania activity against Leishmania major, cytotoxicity tests, assessment of synergism, parasite membrane damage tests as well as molecular docking and immunomodulatory activity of limonene-carvacrol (Lim-Car) combination were evaluated. RESULTS: The Lim-Car combination (5:0; 1:1; 1:4; 2:3; 3:2; 4:1 and 0:5) showed potential antileishmania activity, with mean inhibitory concentration (IC50) ranging from 5.8 to 19.0 µg.mL-1. They demonstrated mean cytotoxic concentration (CC50) ranging from 94.1 to 176.0 µg.mL-1, and did not show significant hemolytic effect. In the investigation of synergistic interaction, the 4:1 Lim-Car combination showed better fractional inhibitory concentration (FIC) index as well as better activity on amastigotes and IS. The samples caused considerable damage to the parasite membrane this monoterpene activity seems to be more related to Trypanothione Reductase (TryR) enzyme interaction, demonstrated in the molecular docking assay. In addition, the 4:1 Lim-Car combination stimulated macrophage activation, and showed at was the best association, with reduction of infection and infectivity of parasitized macrophages. CONCLUSION: The 4:1 Lim-Car combination appears to be a promising candidate as a monotherapeutic antileishmania agent.

2.
Int Immunopharmacol ; : 107124, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33168414

RESUMO

Leishmaniasis is caused by several protozoan species of Leishmania, and being endemically present in 98 countries around the world, it is also a severe public-health problem. The available antileishmanial drugs are toxic and yet present risks of recurrent infection. Efforts to find new, effective, and safe oral agents for the treatment of leishmaniasis are continuing throughout the world. This work aimed to evaluate the antileishmania activity of cordiaquinone E (CORe), isolated from the roots of Cordia polycephala (Lam.) I. M. Johnston. Cytotoxicity, and possible mechanisms of action against promastigote and amastigote forms of Leishmania amazonensis were examined. CORe was effective in inhibiting promastigote (IC50 4.5 ± 0.3 µM) and axenic amastigote (IC50 2.89 ± 0.11 µM) growth in concentrations found non-toxic for the host cell (CC50 246.81 ± 14.5 µM). Our results revealed that CORe presents direct activity against the parasite, inducing cell death by apoptosis. CORe present greater activity against intracellular amastigotes (EC50 1.92 ± 0.2 µM), yet with much higher selectivity indexes than the reference drugs, being respectively more benign towards RAW 264.7 macrophages than meglumine antimoniate and amphotericin B, (respectively by 4.68 and 42.84 fold). The antiamastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels, as well as decreased IL-10 levels. These results encourage the progression of studies on this compound for the development of new leishmanicidal agents.

3.
Antimicrob Agents Chemother ; 64(12)2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-32928735

RESUMO

In this study, we demonstrated the potential associative effect of combining conventional amphotericin B (Amph B) with gallic acid (GA) and with ellagic acid (EA) in topical formulations for the treatment of cutaneous leishmaniasis in BALB/c mice. Preliminary stability tests of the formulations and in vitro drug release studies with Amph B, GA, Amph B plus GA, EA, and Amph B plus EA were carried out, as well as assessment of the in vivo treatment of BALB/c mice infected with Leishmania major After 40 days of infection, the animals were divided into 6 groups and treated twice a day for 21 days with a gel containing Amph B, GA, Amph B plus GA, EA, or Amph B plus EA, and the negative-control group was treated with the vehicle. In the animals that received treatment, there was reduction of the lesion size and reduction of the parasitic load. Histopathological analysis of the treatments with GA, EA, and combinations with Amph B showed circumscribed lesions with the presence of fibroblasts, granulation tissue, and collagen deposition, as well as the presence of activated macrophages. The formulations containing GA and EA activated macrophages in all evaluated parameters, resulting in the activation of cells of the innate immune response, which can generate healing and protection. GA and EA produced an associative effect with Amph B, which makes them promising for use with conventional Amph B in the treatment of cutaneous leishmaniasis.

4.
Chem Biol Interact ; 320: 109026, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112863

RESUMO

Leishmaniasis is a widespread tropical infection caused by different species of Leishmania protozoa. Many of the available drugs against the disease are toxic and in certain cases parasite drug resistance is developed. The discovery of drugs for the treatment of leishmaniasis is a pressing concern. In the present work, we describe in vitro studies of the phenolic compound methyl gallate (MG) against Leishmania (Leishmania) amazonensis and its possible mechanisms of action. The in vitro activity of MG was assayed against L. amazonensis (promastigotes, axenic amastigotes, and intramacrophagic amastigotes). Cytotoxicity tests were performed with J774A.1 macrophages and THP-1 cell derived macrophages. To evaluate mechanisms of action, we analyzed cellular TNF-α, IL-12, IFN-γ, IL-10, IL-6, NO, ROS levels, arginase activity, and structural mechanisms (phagocytic and lysosomal activities) involving macrophage activation. Meglumine antimoniate and amphotericin B were used as reference drugs. It was observed that MG effectively inhibited the growth of both promastigote (IC50 5.71 µM) and amastigote-like forms (EC50 5.39 µM), with much higher selectivity indexes than the reference drugs, being more benign towards J774A.1 macrophages than meglumine antimoniate and amphotericin B, at 1631- and 70.92-fold respectively, with respect to the promastigote form. Additionally, MG proved to be even more active against intracellular amastigotes of the parasite (EC50 4.24 µM). Our results showed that antileishmania activity was associated with increased TNF-α, IL-12, NO and ROS levels, as well as decreased IL-6 and decreased arginase activity. In addition, MG induced increased phagocytic capability, and lysosomal volume in macrophages; structural parameters of microbicidal activity. Taken together, our results suggest that MG may be a promising candidate for new drug development against leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Ácido Gálico/análogos & derivados , Leishmania/efeitos dos fármacos , Anfotericina B/farmacologia , Antiprotozoários/química , Ácido Gálico/efeitos adversos , Ácido Gálico/química , Ácido Gálico/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Antimoniato de Meglumina/farmacologia , Estrutura Molecular , Espécies Reativas de Oxigênio
5.
Toxicol In Vitro ; 63: 104750, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31862617

RESUMO

The present study was directed to the in vitro antileishmanial, cytotoxic and immunomodulatory effects of Garcinielliptone FC (GFC) against promastigote and macrophage-internalized amastigote forms of Leishmania amazonensis. GFC showed in vitro cytotoxicity against BALB/c peritoneal macrophages with CC50 of 74.90 µM. The hemolytic activity against sheep erythrocytes only demonstrated a decrease of 20.42% in cell viability at the highest tested concentration tested (1326.0 µM). GFC promoted in vitro growth inhibition of both promastigote and intracellular amastigotes with IC50 values of 14.06 and 1.91 µM, respectively, with 7.3-fold higher Selectivity Index (SI) for intracellular amastigotes (SI = 39.21) than for promastigotes (SI = 5.33). Interestingly, the pre-treatment of macrophages or promastigotes with GFC promoted decrease of infected macrophages and number of recovered amastigotes, respectively. Also, GFC was able to markedly promote macrophages activation by increase of phagocytic capability and nitrite production at concentrations able to solve infection of macrophages by L. amazonensis, suggesting the possible involvement of immunomodulatory modulation of macrophages leading to solve the infection. GFC is an emerging and promising chemical compound for the studies focused on the assessment of its therapeutic potential on in vivo experimental models of leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Fatores Imunológicos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Leishmania , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/parasitologia , Camundongos Endogâmicos BALB C , Nitritos/metabolismo , Fagocitose/efeitos dos fármacos , Ovinos
6.
Drug Dev Ind Pharm ; 44(10): 1713-1723, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29961344

RESUMO

OBJECTIVE: This work aimed to develop and characterize a topical emulgel of amphotericin B (AmB) with bacuri butter (Platonia insignis Mart.) and evaluate its antileishmanial activity using in vitro assays. SIGNIFICANCE: Leishmaniasis is considered an infectious disease, with high incidence and capacity to produce deformities. The first-line treatment recommended by WHO, with pentavalent antimonials, is aggressive and very toxic. Therefore, the development of topical treatments can emerge as a promising and less offensive alternative. METHODS: The developed formulations were evaluated for organoleptic characteristics, centrifugation resistance, globule size, pH, electrical conductivity, viscosity, spreadability, drug content, preliminary stability, in vitro release profile, evaluation of antileishmanial activity using promastigotes forms of Leishmania major as infecting agents, macrophage cytotoxicity and selectivity index (IS). RESULTS: Formulated emulsions presented organoleptic characteristics compatible with its constituents; pH values were suitable for topical application, ranging from 4.73 to 5.02; introduced non-Newtonian shear thinning system; drug content was within the established standards, and the most suitable kinetic model of release was the first order. Regarding the in vitro assays, formulations containing both 1% and 3% of AmB presented similar outcomes, indicating a synergism between the bacuri butter and the drug, possibly showing a reduction on cytotoxicity to host cells. CONCLUSIONS: It was concluded that the formulations developed showed promising antileishmanial action and high potential for topical use.


Assuntos
Anfotericina B/química , Antiprotozoários/química , Leishmaniose Cutânea , Extratos Vegetais/química , Administração Tópica , Anfotericina B/administração & dosagem , Animais , Antiprotozoários/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Emulsões/administração & dosagem , Emulsões/química , Feminino , Géis , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/administração & dosagem
7.
Int J Biol Macromol ; 117: 640-647, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29852231

RESUMO

The search for natural antibacterial agents to treat diseases caused by resistant microorganisms has been gaining increasing attention. Chitosan has been studied in several areas due to its particular properties. The grafting of hydrophobic chains into the chitosan molecule, turning it amphiphilic, may improve its antimicrobial activity by increasing electrostatic interaction with the bacterial cell wall. The objective of this work was to enhance the antimicrobial activity of chitosan by the reaction of N-acylation with maleic anhydride. For this purpose, molar ratios of 1:2, 1:5 and 1:10 chitosan: anhydride were investigated, and the obtained derivatives were characterized by elemental analysis, FTIR, thermal analysis and XRD where it was possible to prove the chemical modification of chitosan. The modified materials presented excellent antibacterial action against Staphylococcus aureus and Escherichia coli, evidencing no activity against the protozoan Leishmania amazonensis. Cytotoxicity assays by the MTT analysis and hemolysis indicated that the derivatives did not show toxicity in mammalian cells. The proposed modified chitosan compounds showed to be promising for biomedical applications since they allied excellent antibacterial activity and absence of cytotoxicity.


Assuntos
Anti-Infecciosos/síntese química , Quitosana/síntese química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Quitosana/química , Quitosana/farmacologia , Escherichia coli/patogenicidade , Hemólise , Humanos , Interações Hidrofóbicas e Hidrofílicas , Leishmania/efeitos dos fármacos , Leishmania/patogenicidade , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/patogenicidade , Eletricidade Estática , Difração de Raios X
8.
PeerJ ; 6: e4656, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736332

RESUMO

Background: Tissue engineering has been shown to exhibit great potential for the creation of biomaterials capable of developing into functional tissues. Cellular expansion and integration depends on the quality and surface-determinant factors of the scaffold, which are required for successful biological implants. The objective of this research was to characterize and evaluate the in vitro characteristics of rabbit bone marrow mesenchymal stem cells (BM-MSCs) associated with a bacterial cellulose membrane (BCM). We assessed the adhesion, expansion, and integration of the biomaterial as well as its ability to induce macrophage activation. Finally, we evaluated the cytotoxicity and toxicity of the BCM. Methods: Samples of rabbit bone marrow were collected. Mesenchymal stem cells were isolated from medullary aspirates to establish fibroblast colony-forming unit assay. Osteogenic, chondrogenic, and adipogenic differentiation was performed. Integration with the BCM was assessed by scanning electron microscopy at 1, 7, and 14 days. Cytotoxicity was assessed via the production of nitric oxide, and BCM toxicity was assessed with the MTT assay; phagocytic activity was also determined. Results: The fibroblastoid colony-forming unit (CFU-F) assay showed cells with a fibroblastoid morphology organized into colonies, and distributed across the culture area surface. In the growth curve, two distinct phases, lag and log phase, were observed at 15 days. Multipotentiality of the cells was evident after induction of osteogenic, chondrogenic, and adipogenic lineages. Regarding the BM-MSCs' bioelectrical integration with the BCM, BM-MSCs were anchored in the BCM in the first 24 h. On day 7 of culture, the cytoplasm was scattered, and on day 14, the cells were fully integrated with the biomaterial. We also observed significant macrophage activation; analysis of the MTT assay and the concentration of nitric oxide revealed no cytotoxicity of the biomaterial. Conclusion: The BCM allowed the expansion and biointegration of bone marrow progenitor cells with a stable cytotoxic profile, thus presenting itself as a biomaterial with potential for tissue engineering.

9.
Artigo em Inglês | MEDLINE | ID: mdl-28852412

RESUMO

Platonia insignis Mart., popularly known as "bacurizeiro," is used in traditional medical practices based on its diverse biological properties. This study was aimed at evaluating the antileishmanial effects of the ethanol extract (EtOH-Ext), hexane fraction (Hex-F), and its main isolated Lupeol obtained from stem barks of P. insignis against Leishmania (Leishmania) amazonensis, as well as their cytotoxicity and possible mechanisms of action. The EtOH-Ext, Hex-F, and Lupeol inhibited the growth of L. amazonensis promastigote forms at IC50 of 174.24, 45.23, and 39.06 µg/mL, respectively, as well as L. amazonensis axenic amastigote forms at IC50 of 40.58, 35.87, and 44.10 µg/mL, respectively. The mean cytotoxic concentrations for macrophages (CC50) were higher than those for amastigotes (341.95, 71.65, and 144.0 µg/mL, resp.), indicating a selective cytotoxicity towards the parasite rather than the macrophages. Interestingly, all treatments promoted antileishmanial effect against macrophage-internalized amastigotes at concentrations lower than CC50. Furthermore, increases of lysosomal volume of macrophages treated with EtOH-Ext, Hex-F, and Lupeol were observed. On the other hand, only Lupeol stimulated increase of phagocytic capability of macrophages, suggesting this compound might be characterized as the biomarker for the antileishmanial effect of P. insignis stem bark, as well as the involvement of immunomodulatory mechanisms in this effect.

10.
Naunyn Schmiedebergs Arch Pharmacol ; 390(9): 893-903, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28643086

RESUMO

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Ácido Elágico/farmacologia , Ácido Gálico/farmacologia , Leishmaniose Cutânea/tratamento farmacológico , Animais , Antiprotozoários/administração & dosagem , Cálcio/metabolismo , Relação Dose-Resposta a Droga , Ácido Elágico/administração & dosagem , Feminino , Ácido Gálico/administração & dosagem , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Leishmania major/efeitos dos fármacos , Leishmania major/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
11.
J Ethnopharmacol ; 160: 32-40, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25460590

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as "jambolão" in Brazil is widely used in folk medicine against leishmaniasis, inflammation, chronic diarrhea, and ulcers. It is one of the most commonly used plants for the treatment of diabetes worldwide. In previous studies, Syzygium cumini was shown to possess antihyperlipidemic and anti-allergic properties, and to exhibit good performance as an antimicrobial agent against bacteria, fungi, and protozoa parasites of the genus Leishmania and Trypanosoma. This study was aimed at evaluating the effects of S. cumini essential oil (ScEO) and its major component α-pinene on Leishmania (Leishmania) amazonensis, as well as their cytotoxicity and possible mechanisms of action. MATERIALS AND METHODS: To evaluate the anti-proliferative effect on Leishmania, effects on promastigote and axenic amastigote forms were assessed using tetrazolium salt (MTT) assay. The intramacrophagic amastigotes were exposed to ScEO and α-pinene to determine the survival index. To gain insight into the mechanism of action involved in the effect on the samples, we evaluated the modulation of macrophage activation state by observing structural (phagocytic and lysosomal activities) and cellular (nitric oxide increase) changes. To assess the safety profile of ScEO and α-pinene, murine macrophages and human red blood cells were treated with ScEO and α-pinene and the selectivity index was calculated for each treatment. RESULTS: α-Pinene was effective against Leishmania amazonensis promastigote forms, with a half-maximal inhibitory concentration (IC50) value of 19.7µg/mL. α-Pinene was more active (IC50 values of 16.1 and 15.6µg/mL against axenic and intracellular amastigotes, respectively) than ScEO (IC50 values of 43.9 and 38.1µg/mL against axenic and intracellular amastigotes, respectively). Our results showed that the anti-Leishmania effects were mediated by immunomodulatory activity, as evidenced by the observed increases in both phagocytic and lysosomal activity, and the elevated NO levels. ScEO and α-pinene exhibited low cytotoxicity against murine macrophages and human erythrocytes. The 50% cytotoxicity concentration (CC50) values for the macrophages in the MTT assay were 614.1 and 425.2µg/mL for ScEO and α-pinene, respectively, while the corresponding half-maximal hemolytic concentration (HC50) values were 874.3 and 233.3µg/mL. CONCLUSIONS: Taken together, the results demonstrate that ScEO and its major constituent α-pinene have significant anti-Leishmania activity, modulated by macrophage activation, with acceptable levels of cytotoxicity in murine macrophages and human erythrocytes. Further work is warranted, involving more in-depth mechanistic studies and in vivo investigations.


Assuntos
Imunomodulação/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Syzygium , Animais , Monoterpenos Bicíclicos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Concentração Inibidora 50 , Leishmania/citologia , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Monoterpenos/efeitos adversos , Óleos Voláteis/efeitos adversos
12.
Pharmacogn Mag ; 10(Suppl 3): S456-62, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25298660

RESUMO

BACKGROUND: Mimosa caesalpiniifolia Benth. (Leguminosae) is widely found in the Brazilian Northeast region and markedly contributes to production of pollen and honey, being considered an important honey plant in this region. OBJECTIVE: To investigate the chemical composition of the ethanol extract of leaves from M. caesalpiniifolia by GC-MS after derivatization (silylation), as well as to evaluate the in vitro and in vivo toxicological effects and androgenic activity in rats. MATERIALS AND METHODS: The ethanol extract of leaves from Mimosa caesalpiniifolia was submitted to derivatization by silylation and analyzed by gas chromatography-mass spectrometry (GC-MS) to identification of chemical constituents. In vitro toxicological evaluation was performed by MTT assay in murine macrophages and by Artemia salina lethality assay, and the in vivo acute oral toxicity and androgenic evaluation in rats. RESULTS: Totally, 32 components were detected: Phytol-TMS (11.66%), lactic acid-2TMS (9.16%), α-tocopherol-TMS (7.34%) and ß-sitosterol-TMS (6.80%) were the major constituents. At the concentrations analyzed, the ethanol extract showed low cytotoxicity against brine shrimp (Artemia salina) and murine macrophages. In addition, the extract did not exhibit any toxicological effect or androgenic activity in rats. CONCLUSIONS: The derivatization by silylation allowed a rapid identification of chemical compounds from the M. caesalpiniifolia leaves extract. Besides, this species presents a good safety profile as observed in toxicological studies, and possess a great potential in the production of herbal medicines or as for food consumption.

13.
Artigo em Inglês | MEDLINE | ID: mdl-23533469

RESUMO

Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%), with curzerene (47.3%), γ -elemene (14.25%), and trans- ß -elemenone (10.4%) being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04 µ g·mL(-1)) and amastigotes (IC50, 1.92 µ g·mL(-1)) suggested significant anti-Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400 µ g·mL(-1)); however, there appeared to be no toxicity at 50 µ g·mL(-1). While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmania activity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determine in vivo activity as well as additional mechanisms of the anti-Leishmania activity.

14.
Epidemiol. serv. saúde ; 18(4): 365-374, out.-dez. 2009. tab, graf
Artigo em Português | LILACS | ID: lil-534316

RESUMO

O objetivo deste estudo é descrever os indicadores epidemiológicos e vetoriais da dengue em Teresina-PI, de 2002 a 2006. Utilizou-se dados referentes à ocorrência da doença, do Sistema de Informação de Agravos de Notificação (Sinan), monitoramento do Aedes aegypti do Sistema de Informação de Febre Amarela e Dengue (FAD), além de dados populacionais e do meio ambiente. A relação entre o número de casos notificados, precipitação pluviométrica e temperatura e entre o índice de infestação predial e índice de pendência foi analisada pela correlação de Spearman. Nesse período, foram notificados 11.003 casos de dengue, com coeficiente de incidência variando de 592,7/100.000 habitantes em 2002 e 19,5/100.000 habitantes em 2004, com maior incidência na faixa etária de 15 a 49 anos (305,5/100.000 habitantes) e maior proporção no sexo feminino (60 por cento). A menor taxa de letalidade ocorreu em 2003 (6,25 por cento) e a maior em 2006 (20 por cento), com predomínio na faixa etária de 20 a 49 anos (36,36 por cento). Foi encontrada correlação positiva entre o número de casos, pluviosidade e temperatura e não houve associação entre índice de infestação predial e índice de pendência por estrato. Os depósitos de armazenamento de água para consumo predominaram como principais criadouros. A dengue na cidade de Teresina apresentou maior incidência no primeiro semestre de cada ano, coincidindo com o período de maior índice pluviométrico e de infestação predial. As estratégias de combate ao Ae. aegypti não têm sido eficazes, pois tais medidas não têm produzido o efeito epidemiológico desejado, sendo necessária ênfase especial na redução de criadouros artificiais, principalmente aqueles utilizados para armazenamento de água nos domicílios, com a diminuição dos riscos domésticos da proliferação do vetor.


This study aims at describing dengue fever epidemiological and vector-related indicators in Teresina, State of Piaui, Brazil from 2002 to 2006. The analysis has included cases registered in the Information System for Notifiable Diseases (Sinan), data on the monitoring of the Aedes aegypti in the Information System for Yellow Fever and Dengue Fever (FAD), and population and environmental data. The relation among notified cases, rainfall and temperature as well as between house infestation rate and pendency rate was analyzed using the Spearman correlation coefficient. In that period, 11,003 dengue fever cases were notified. Incidence rate varied from 592.7/100,000 population in 2002 to 19.5/100,000 population in 2004, with greater incidence in the 15-to 49-year-old group (305.5/100,000 population) and in females (60 percent). The lowest and highest lethality rate occurred, respectively, in 2003 (6.25 percent) and 2006 (20 percent), predominantly in the 20-to 49-year-old group (36.36 percent). There was a positive correlation among the number of cases, rainfall and temperature and there was no association between house infestation rate and pendency rate by stratum. Water storage reservoirs have predominated as the main breeding site. Each year, dengue fever incidence in the city of Teresina was higher during the first semester, which is the period of both higher rainfall and house infestation rate. The strategies for fighting the Ae. aegypti have not been efficacious, because the measures taken are not producing the expected epidemiological effects. It is necessary to adopt control measures with a special focus on the reduction of artificial breeding sites, mainly those used for house water storage, which lowers domestic risks associated with the proliferation of vectors.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Vírus da Dengue , Notificação de Doenças , Dengue/epidemiologia , Dengue/mortalidade , Brasil/epidemiologia , Relatos de Casos , Dengue/diagnóstico , Estudos Epidemiológicos , Incidência
15.
Epidemiol. serv. saúde ; 17(2): 87-96, 2008. ilus, graf
Artigo em Português | LILACS | ID: lil-488080

RESUMO

Este artigo apresenta e discute as implicações dos resultados do inquérito inicial de um estudo de intervenção comunitária para avaliar a efetividade de medidas de controle para a leishmaniose visceral. O estudo foi realizado em dez localidades da cidade de Teresina, Estado do Piauí, Brasil. As localidades foram subdivididas em quadras, quatro delas selecionadas e alocadas aleatoriamente para diferentes intervenções a serem implementadas após o inquérito inicial. No inquérito inicial, realizado no primeiro semestre de 2004, os participantes (n=1.105) responderam a um questionário e tiveram avaliada sua reação ao teste de intradermorreação com antígeno de Montenegro (IDRM). A prevalência global de infecção foi de 36,7 por cento – com tendência a aumentar com a idade –, significativamente mais alta nos homens. A prevalência variou de 24,0 a 47,0 por cento entre localidades. O processo de randomização mostrou-se relativamente satisfatório para variáveis sociodemográficas; houve, entretanto, diferenças significativas na prevalência de positividade na IDRM entre áreas de intervenção. A não-comparabilidade das áreas, no que diz respeito às taxas basais de transmissão, elemento fundamental para inferência causal em doenças infecciosas, pode afetar a validade do estudo de intervenção...


Assuntos
Humanos , Masculino , Feminino , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Inquéritos de Morbidade
16.
Belo Horizonte; s.n; 2001. 110 p. ilus.
Tese em Português | LILACS | ID: lil-521765

RESUMO

A leishmaniose é uma doença causada por protozoários do gênero Leishmania e nas Américas eles se agrupam em duas categorias: Leishmaniose Visceral Americana (LVA) e Leishmaniose Tegumentar Americana (LTA). A profilaxia da LTA baseia-se no combate aos transmissores, na redução das fontes de infecção e no tratamento de pacientes com agentes quimioterápicos, os quais são muito limitados, tóxicos e requerem um longo período de tratamento. Em virtude dos problemas associados ao tratamento convencional com antimoniais, uma grande diversidade de tratamentos alternativos, de uso tópico ou sistêmico, vem sendo estudados para essa doença. Dentre eles destaca-se a paromomicina que tem mostrado resultados surpreendentes no tratamento das várias formas da doença. Utilizamos a paromomicina em formulações de uso tópico para o tratamento de lesões ulceradas causadas por Leishmania major em camundongos BALB/c. Nossos resultados mostraram que das formulações utilizadas (emulsão e pomada), administradas duas vezes ao dia por doze dias, a emulsão foi mais eficaz que a pomada e que o tratamento conduzido com a remoção das crostas mostrou que essa formação funciona como uma barreira fisica interferindo na eficácia do tratamento. A associação com a uréia, como agente promotor da absorção cutânea, não aumentou a eficácia da pomada. O aumento da concentração de paromomicina nas formulações foi capaz de aumentar a eficiência do tratamento sendo insuficiente para a cura completa dos animais. A utilização da interleucina 12 como adjuvante ao tratamento foi fundamental para a modulação da resposta imunológica e para a cura clínica dos animais. Dessa forma, concluímos que o tratamento com a emulsão a 5 por cento de paromomicina associado a IL-12 durante e após o tratamento é eficaz para a cura clínica da doença neste modelo experimental.


Assuntos
Animais , Camundongos , Imunoterapia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/terapia , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Experimentação Animal , /administração & dosagem , /uso terapêutico
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