Nanostructured Lipid Carriers as Robust Systems for Lupeol Delivery in the Treatment of Experimental Visceral Leishmaniasis.

Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 ± 4.6 nm, a polydispersity index of <0.25 and a zeta potential of -37.2 ± 0.84 mV; the efficacy of encapsulation was 84.04 ± 0.57%. Studies on hamsters showed that Lu-NLC (5 mg/kg) administered intraperitoneally for 10 consecutive days caused a reduction of 99.9% in the number of parasites in the spleen and liver compared to the untreated infected control. On the contrary, Lu-treated animals (5 mg/kg) had 94.4 and 90.2% less parasites in the spleen and liver, respectively, than the infected group. Additionally, a significant preservation of splenic and hepatic tissues was observed in animals treated with Lu-NLC or Lu. Furthermore, Lu-NLC-treated animals produced high levels of anti-Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.

Therapeutic Activity of a Topical Formulation Containing 8-Hydroxyquinoline for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis exhibits a wide spectrum of clinical manifestations; however, only a limited number of drugs are available and include Glucantime® and amphotericin B, which induce unacceptable side effects in patients, limiting their use. Thus, there is an urgent demand to develop a treatment for leishmaniasis. Recently, it was demonstrated that 8-hydroxyquinoline (8-HQ) showed significant leishmanicidal effects in vitro and in vivo. Based on that, this work aimed to develop a topical formulation containing 8-HQ and assess its activity in experimental cutaneous leishmaniasis. 8-HQ was formulated using a Beeler base at 1 and 2% and showed an emulsion size with a D50 of 25 and 51.3 µm, respectively, with a shear-thinning rheological behaviour. The creams were able to permeate artificial Strat-M membranes and excised porcine skin without causing any morphological changes in the porcine skin or murine skin tested. In BALB/c mice infected with L. (L.) amazonensis, topical treatment with creams containing 1 or 2% of 8-HQ was found to reduce the parasite burden and lesion size compared to infected controls with comparable efficacy to Glucantime® (50 mg/kg) administered at the site of the cutaneous lesion. In the histological section of the skin from infected controls, a diffuse inflammatory infiltrate with many heavily infected macrophages that were associated with areas of necrosis was observed. On the other hand, animals treated with both creams showed only moderate inflammatory infiltrate, characterised by few infected macrophages, while tissue necrosis was not observed. These histological characteristics in topically treated animals were associated with an increase in the amount of IFN-γ and a reduction in IL-4 levels. The topical use of 8-HQ was active in decreasing tissue parasitism and should therefore be considered an interesting alternative directed to the treatment of leishmaniasis, considering that this type of treatment is non-invasive, painless, and, importantly, does not require hospitalisation, improving patient compliance by allowing the treatment to be conducted.

Chromoblastomycosis: New Perspective on Adjuvant Treatment with Acitretin.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient's quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.

High Selectivity of 8-Hydroxyquinoline on Leishmania (Leishmania) and Leishmania (Viannia) Species Correlates with a Potent Therapeutic Activity In Vivo.

Leishmaniasis is a neglected disease caused by protozoa of the genus Leishmania, which causes different clinical manifestations. Drugs currently used in the treatment such as pentavalent antimonial and amphotericin B cause severe side effects in patients, and parasite resistance has been reported. Thus, it is necessary and urgent to characterize new and effective alternative drugs to replace the current chemotherapy of leishmaniasis. In this regard, it has been experimentally demonstrated that quinoline derivatives present significative pharmacological and parasitic properties. Thus, the aim of this work was to demonstrate the leishmanicidal activity of 8-hydroxyquinoline (8-HQ) in vitro and in vivo. The leishmanicidal activity (in vitro) of 8-HQ was assayed on promastigote and intracellular amastigote forms of L. (L.) amazonensis, L. (L.) infantum chagasi, L. (V.) guyanensis L. (V.) naiffi, L. (V.) lainsoni, and L. (V.) shawi. Additionally, the levels of nitric oxide and hydrogen peroxide were analyzed. The therapeutic potential of 8-HQ was analyzed in BALB/c mice infected with a strain of L. (L.) amazonensis that causes anergic cutaneous diffuse leishmaniasis. In vitro data showed that at 24 and 72 h, 8-HQ eliminated promastigote and intracellular amastigote forms of all studied species and this effect may be potentialized by nitric oxide. Furthermore, 8-HQ was more selective than miltefosine. Infected animals treated with 8-HQ by the intralesional route dramatically reduced the number of tissue parasites in the skin, and it was associated with an increase in IFN-γ and decrease in IL-4, which correlated with a reduction in inflammatory reaction in the skin. These results strongly support the idea that 8-HQ is an alternative molecule that can be employed in the treatment of leishmaniasis, given its selectivity and multispectral action in parasites from the Leishmania genus.

Reviewing the Etiologic Agents, Microbe-Host Relationship, Immune Response, Diagnosis, and Treatment in Chromoblastomycosis.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause subcutaneous infections. This disease has been considered an occupational disease, occurring among people working in the field of agriculture, particularly in low-income countries. In 1914, the first case of CBM was described in Brazil, and although efforts have been made, few scientific and technological advances have been made in this area. In the field of fungi and host cell relationship, a very reduced number of antigens were characterized, but available data suggest that ectoantigens bind to the cell membrane of host cells and modulate the phagocytic, immunological, and microbicidal responses of immune cells. Furthermore, antigens cleave extracellular proteins in tissues, allowing fungi to spread. On the contrary, if phagocytic cells are able to present antigens in MHC molecules to T lymphocytes in the presence of costimulation and IL-12, a Th1 immune response will develop and a relative control of the disease will be observed. Despite knowledge of the resistance and susceptibility in CBM, up to now, no effective vaccines have been developed. In the field of chemotherapy, most patients are treated with conventional antifungal drugs, such as itraconazole and terbinafine, but these drugs exhibit limitations, considering that not all patients heal cutaneous lesions. Few advances in treatment have been made so far, but one of the most promising ones is based on the use of immunomodulators, such as imiquimod. Data about a standard treatment are missing in the medical literature; part of it is caused by the existence of a diversity of etiologic agents and clinical forms. The present review summarizes the advances made in the field of CBM related to the diversity of pathogenic species, fungi and host cell relationship, antigens, innate and acquired immunity, clinical forms of CBM, chemotherapy, and diagnosis.

Managing chromoblastomycosis with acitretin plus imiquimod: A case report on the improvement of cutaneous lesions and reduction of the treatment time.

Chromoblastomycosis (CBM) is an infectious disease caused by fungi that is prevalent in tropical and subtropical countries. Besides few therapeutic options, the classical treatment of CBM needs to be administrated for a long period of time, and unfortunately some patients do not show improvement of the lesions. Thus, it becomes urgent to develop new strategies for the treatment of CBM. This work reports a successful treatment, performed with the combination of oral acitretin (50 mg/kg, once a day) plus topical imiquimod (50 mg/g, five times per week) for 5 months in a patient with CBM. A significant improvement of the lesions was observed in the 1st month, and in the 5th a complete regression of lesions was recorded. Changes in the biochemical parameters were not observed. These data suggest that the combination of acitretin and imiquimod may be effective at treating CBM.

Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis.

Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (-29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis.

A case of tuberculosis verrucosa cutis in Brazil undiagnosed for 15 years.

Tuberculosis verrucosa cutis is a rare medical condition that is caused by the inoculation of Mycobacterium tuberculosis into the skin of a previously sensitized individual. This clinical form of tuberculosis corresponds to 1-2% of all cases of tuberculosis and due to the paucibacillary characteristic of the lesions, patients can be misdiagnosed, accounting for the chronification of the skin infection. Herein, we report the case of a 26-year-old male farmer, presenting plaques with verrucosa and hyperkeratosis features in the left thigh and buttocks during 15 years. M. tuberculosis was identified by PCR and the patient was treated with standard anti-tuberculosis drugs, with subsequent improvement of the skin lesions.

Related Pentacyclic Triterpenes Have Immunomodulatory Activity in Chronic Experimental Visceral Leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the flagellated protozoa of the genus Leishmania that affects millions of people around the world. Drugs employed in the treatment of leishmaniasis have limited efficacy and induce local and systemic side effects to the patients. Natural products are an interesting alternative to treat leishmaniasis, because some purified molecules are selective toward parasites and not to the host cells. Thus, the aim of the present study was to compare the in vitro antileishmanial activity of the triterpenes betulin (Be), lupeol (Lu), and ursolic acid (UA); analyze the physiology and morphology of affected organelles; analyze the toxicity of selected triterpenes in golden hamsters; and study the therapeutic activity of triterpenes in hamsters infected with L. (L.) infantum as well as the cellular immunity induced by studied molecules. The triterpenes Lu and UA were active on promastigote (IC50 = 4.0 ± 0.3 and 8.0 ± 0.2 µM, respectively) and amastigote forms (IC50 = 17.5 ± 0.4 and 3.0 ± 0.2 µM, respectively) of L. (L.) infantum, and their selectivity indexes (SI) toward amastigote forms were higher (≥13.4 and 14, respectively) than SI of miltefosine (2.7). L. (L.) infantum promastigotes treated with Lu and UA showed cytoplasmic degradation, and in some of these areas, cell debris were identified, resembling autophagic vacuoles, and parasite mitochondria were swelled, fragmented, and displayed membrane potential altered over time. Parasite cell membrane was not affected by studied triterpenes. Studies of toxicity in golden hamster showed that Lu did not alter blood biochemical parameters associated with liver and kidney functions; however, a slight increase of aspartate aminotransferase level in animals treated with 2.5 mg/kg of UA was detected. Lu and UA triterpenes eliminated amastigote forms in the spleen (87.5 and 95.9% of reduction, respectively) and liver of infected hamster (95.9 and 99.7% of reduction, respectively); and UA showed similar activity at eliminating amastigote forms in the spleen and liver than amphotericin B (99.2 and 99.8% of reduction). The therapeutic activity of both triterpenes was associated with the elevation of IFN-γ and/or iNOS expression in infected treated animals. This is the first comparative work showing the in vitro activity, toxicity, and therapeutic activity of Lu and UA in the chronic model of visceral leishmaniasis caused by L. (L.) infantum; additionally, both triterpenes activated cellular immune response in the hamster model of visceral leishmaniasis.

A case of tuberculosis verrucosa cutis in Brazil undiagnosed for 15 years

ABSTRACT Tuberculosis verrucosa cutis is a rare medical condition that is caused by the inoculation of Mycobacterium tuberculosis into the skin of a previously sensitized individual. This clinical form of tuberculosis corresponds to 1-2% of all cases of tuberculosis and due to the paucibacillary characteristic of the lesions, patients can be misdiagnosed, accounting for the chronification of the skin infection. Herein, we report the case of a 26-year-old male farmer, presenting plaques with verrucosa and hyperkeratosis features in the left thigh and buttocks during 15 years. M. tuberculosis was identified by PCR and the patient was treated with standard anti-tuberculosis drugs, with subsequent improvement of the skin lesions.

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis.

Ursolic acid (UA) is a triterpene with a broad array of pharmacological activities. In leishmaniasis, UA killed different species of parasites, and it was active in the experimental model of cutaneous and visceral leishmaniasis. Thus, the objective of this work was to study the therapeutic efficacy of the conventional drugs amphotericin B (AmB) or glucantime (Glu) combined with UA in experimental visceral and cutaneous leishmaniasis, respectively. L. (L.) infantum-infected hamsters were treated with AmB alone or combined with UA. L. (L.) amazonensis-infected BALB/c mice were treated with Glu alone or combined with UA. Animals were treated for 15 consecutive days by intraperitoneal or intralesional routes. Following one week after the last dose, the tissue parasitism and cellular immune responses were analyzed. Hamsters treated with 0.2 and 1.0 mg/kg of AmB plus 1.0 mg/kg of UA showed low hepatic and splenic parasitisms; however, AmB given as monotherapy did not reduce the number of viable parasites in the spleen of treated animals. In cutaneous leishmaniasis, Glu given as monotherapy was inactive at 2.0 mg/kg, showed mild activity at 10.0 mg/kg, and at 50.0 mg/kg was highly active at eliminating parasites in the skin. When animals were treated with Glu plus UA, higher leishmanicidal activity was observed in comparison to all groups treated with monotherapy schemes, and such activity was related to lesion improvement and upregulation of IFN-γ production. Altogether, data suggest that the association of drugs for the treatment of leishmaniasis can increase the efficiency of the treatment and decrease the toxicity associated to the conventional drugs.

Reactivity of purified and axenic amastigotes as a source of antigens to be used in serodiagnosis of canine visceral leishmaniasis.

Although there is a great diversity of techniques and antigens used in the serodiagnosis of canine visceral leishmaniasis (CVL), total sensitivity and specificity have not yet been found. Since the use of amastigote forms in the indirect immunofluorescence assay has shown an improvement in the specificity of the test for the diagnosis of CVL, the performance of amastigotes forms of L. (L.) infantum chagasi as antigen source were evaluated in automatized ELISA test using crude antigen of axenic amastigote and purified amastigote from spleen of hamster chronically infected comparing with ELISA using total antigen produced with promastigote forms of L. (L.) infantum chagasi. One hundred and fifteen sera from dogs with positive parasitological diagnosis by PCR were used. The animals were classified into 2 groups: symptomatic (n = 67) and asymptomatic (n = 48) animals, in accordance with the clinical signs and laboratory tests were. As control, ninety-four sera from dogs with negative parasitological diagnosis were included. No significant difference was found in sensitivity, specificity, predictive values and accuracy between ELISA using whole antigens produced with both axenic and purified amastigotes in comparison with promastigotes forms. Correlation and concordance between the three total antigens tested in ELISA was observed. According to the similar performance among antigens, data pointed out to use antigen from promastigote forms for diagnosing canine leishmaniasis, especially due the easily in the production, lower cost and the abundance of correlative literature.

Tolnaftate inhibits ergosterol production and impacts cell viability of Leishmania sp.

Leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania. The treatment of all forms of leishmaniasis relies on first-line drug, pentavalent antimonial, and in cases of drug failure, the second-line drug amphotericin B has been used. Besides the high toxicity of drugs, parasites can be resistant to antimonial in some areas of the World, making it necessary to perform further studies for the characterization of new antileishmanial agents. Thus, the aim of the present work was to evaluate the leishmanicidal activity of tolnaftate, a selective reversible and non-competitive inhibitor of the fungal enzyme squalene epoxidase, which is involved in the biosynthesis of ergosterol, essential to maintain membrane physiology in fungi as well as trypanosomatids. Tolnaftate eliminated promastigote forms of L. (L.) amazonensis, L. (V.) braziliensis and L. (L.) infantum (EC50 ~ 10 µg/mL and SI ~ 20 for all leishmanial species), and intracellular amastigote forms of all studied species (EC50 ~ 23 µg/mL in infections caused by dermatotropic species; and 11.7 µg/mL in infection caused by viscerotropic species) with high selectivity toward parasites [SI ~ 8 in infections caused by dermatotropic species and 17.4 for viscerotropic specie]. Promastigote forms of L. (L.) amazonensis treated with the EC50 of tolnaftate displayed morphological and physiological changes in the mitochondria and cell membrane. Additionally, promastigote forms treated with tolnaftate EC50 reduced the level of ergosterol by 5.6 times in comparison to the control parasites. Altogether, these results suggest that tolnaftate has leishmanicidal activity towards Leishmania sp., is selective, affects the cell membrane and mitochondria of parasites and, moreover, inhibits ergosterol production in L. (L.) amazonensis.

Successful treatment of chromoblastomycosis caused by Fonsecaea pedrosoi using imiquimod.

Chromoblastomycosis (CBM) is a fungal infection caused by fungi belonging to the order Chaetothyriales, and caused mainly by Fonsecaea pedrosoi. The classic treatment, based on itraconazole and/or terbinafine as well as physical approaches, is considered complex and ineffective due to the high rate of relapses. Thus, new strategies are needed to manage CBM; in this regard, the present work reports the evolution of lesions in patients successfully treated with imiquimod. Of note, classic treatment was not effective in healing the lesions of two of them, but single topical treatment with imiquimod healed the lesions.

Participatory ethnobotany and conservation: a methodological case study conducted with quilombola communities in Brazil's Atlantic Forest.

BACKGROUND: Although multiple studies advocate the advantages of participatory research approaches for ethnoscience, few provide solid contributions from case studies that involve residents in all of the project phases. We present a case study of a participatory approach whose aim is to register ethnobotanical knowledge on the use of plants in two quilombola communities (maroon communities), an important biodiversity hotspot in the Atlantic Forest, Southeast Brazil. Our aim is to provide tools that will empower decision-making related to sustainable use and management among residents. METHODS: In phase I, the objectives and activities were defined in meetings with residents to carry out ethnobotanical surveys between two quilombola communities-the Quilombo da Fazenda (QF) and Quilombo do Cambury (QC). In phase II, we offered community partners training courses on how to collect plants and ethnobotanical data. In coordination with the university team and using ethnobotanical methods, community partners interviewed specialists on plants and their uses. In phase III, using the participatory mapping method, residents indicated plot locations and collected plants to calculate the Conservation Priority Index for native species recorded in phase II. RESULTS: In 178 days of fieldwork, two community partners from the QF and three from the QC selected 8 and 11 respondents who reported 175 and 195 plant species, respectively, corresponding to 9 ethnobotanical categories. Based on requests from the local community, booklets and videos with these data were collaboratively produced. A large percentage of species were found to be of great conservation priority-82.1% in the QC and 62.5% in the QF. Virola bicuhyba, Cedrela fissilis, Plinia edulis, and Tabebuia cassinoides are the species most at risk and will be the focus of phase IV, when a participatory management plan will be carried out. Additionally, we present both challenges and opportunities with the hope that others can learn from our successes and failures. CONCLUSIONS: Our experience shows that it is possible to train community members who wish to document their knowledge to support the process of ensuring that local knowledge is highly regarded, further ensuring its perpetuation. In this context, the project may be of great interest to development programs in promoting community-based management strategies for useful plants.

Ethnopharmacology Study of Plants from Atlantic Forest with Leishmanicidal Activity.

Leishmaniasis is an infectious disease caused by a protozoan belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and patient's health condition. The outcomes can range from single cutaneous lesions to lethal visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and, in some cases, the second-line drug, amphotericin B, is used. Beside the toxicity of both classes of drugs, in some areas of the world, parasites are resistant to antimonial. These detrimental features make fundamental the discovery and characterization of new drugs or plant extracts with leishmanicidal effects. Brazil is a well-known country for its biodiversity. Additionally, the common knowledge inherited for generations in small villages makes Brazil a source of new information and resources for the discovery and development of new drugs. Based on ethnopharmacology, elderlies were interviewed about plants they commonly used for skin diseases and infections. Five native plants from Atlantic forest were indicated; EtOH and n-hexane extracts were prepared with the vegetative organs of the plants and assayed against promastigote and amastigote forms of L. (L.) amazonensis. The major molecules of each extract were detected using qualitative nuclear magnetic resonance. Among all tested extracts, the n-hexane extract from the leave of Eugenia uniflora (Myrtaceae), enriched in myricitrin and quercitrin flavonoids, was the most effective against L. (L.) amazonensis amastigotes. This data supports the ethnopharmacology approach as a successful tool for the discovery of new drugs with leishmanicidal effects.

Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species.

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis.

Conventional Versus Natural Alternative Treatments for Leishmaniasis: A Review.

Leishmaniasis is a neglected disease caused by protozoan belonging to the Leishmania genus. There are at least 16 pathogenic species for humans that are able to cause different clinical forms, such as cutaneous or visceral leishmaniasis. In spite of the different species and clinical forms, the treatment is performed with few drug options that, in most cases, are considered outdated. In addition, patients under classical treatment show serious side effects during drug administration, moreover parasites are able to become resistant to medicines. Thus, it is believed and well accepted that is urgent and necessary to develop new therapeutic options to overpass these concerns about conventional therapy of leishmaniasis. The present review will focus on the efficacy, side effects and action mechanism of classic drugs used in the treatment of leishmaniasis, as well as the importance of traditional knowledge for directing a rational search toward the discovery and characterization of new and effective molecules (in vivo assays) from plants to be used against leishmaniasis.

Dynamic of the cellular immune response at the dermal site of Leishmania (L.) amazonensis and Leishmania (V.) braziliensis infection in Sapajus apella primate.

The purpose of this study was to characterize the immunopathological response in the skin of S. apella infected with Leishmania (L.) amazonensis and L. (V.) braziliensis parasites, the main causative agents of localized cutaneous leishmaniasis in South America. In infected animals, amastigote forms of L. (L.) amazonensis could be detected till 120 days postinfection (PI), while, in L. (V.) braziliensis infection, parasites could be detected until 180 days PI in the skin sections. CD20(+) cells were detected throughout the experimental time in both groups as well as in CD3(+) cells, which appeared to be activated because high densities of inducible nitric oxide synthase (iNOS(+)) cells were detected at 60 and 90 days PI in both studied groups. After 60 and 120 days PI, decrease in iNOS(+) cells was observed in L. (L.) amazonensis and L. (V.) braziliensis, respectively, which was associated with parasite clearance. Increase in lysozyme(+) cells was observed during the experimental infections, which also can be associated with parasite killing.

Plants used in traditional medicine: extracts and secondary metabolites exhibiting antileishmanial activity.

Plants and their extracts have been used traditionally against different pathologies, and in some poor regions they are the only therapeutic source for treatments. Moreover, the identification of specific active secondary metabolites can be account for amelioration of clinical status of suffering individual. A series of ethnopharmacological surveys conducted in Brazil recorded the traditional use of plants against different pathologies and interestingly, some of them presented antileishmanial activity in vitro and in vivo, possibly due to their immunostimulatory, healing and microbicidal properties. Of note, Leishmania parasites can alter patient's immunological status, leading to the development of extensive skin and/or visceral alterations. Therefore, the extracts or secondary metabolites presented in plants that might be capable of improving the pathological conditions can be attractive candidates in the development of new chemotherapeuticals against leishmaniosis.