The anti-Leishmania potential of bioactive compounds derived from naphthoquinones and their possible applications. A systematic review of animal studies.

Leishmaniasis affects millions of people worldwide, and available treatments have severe limitations. Natural and derivative products are significant sources of innovative therapeutic agents. Naphthoquinones are natural or synthetic chemical compounds with broad biological activity. This systematic review aimed to evaluate the potential anti-Leishmania activity of bioactive compounds derived from naphthoquinones in animal models. Conducted in accordance with PRISMA guidelines, two blocks of MeSH terms were assembled: group I, Leishmania OR Leishmaniasis; group II, Atovaquone OR Lapachol OR Beta lapachone OR Naphthoquinones. The search was performed on PubMed, Web of Science, SCOPUS, EMBASE, and Lilacs databases. Twenty-four articles were retrieved and submitted for quality assessment using the SYRCLE critical appraisal tool. The in vivo anti-Leishmania potential of naphthoquinones was evaluated in visceral and cutaneous leishmaniasis using several measurement parameters. Analyzed compounds varied in structure, association with reference drugs, and encapsulation using a drug delivery system. The study design, including treatment protocol, differed between studies. The findings of the studies in this systematic review indicate the anti-Leishmania potential of naphthoquinones in vivo, with different treatment regimens directed against different Leishmania species. The employed drug delivery systems improve the results concerning selectivity, distribution, and required therapeutic dose. The immunomodulatory action was shown to be beneficial to the host, favoring an adequate immune response against infection by Leishmania parasites since it favored Th1 responses. All studies presented a moderate to high risk of bias. These findings suggest that more studies are needed to assess the overall effectiveness and safety of these treatments.

Three decades of clinical trials on immunotherapy for human leishmaniases: a systematic review and meta-analysis.

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.

Genetic variations in the human immune system influence susceptibility to tegumentary leishmaniasis: a systematic review and meta-analysis.

OBJECTIVES: The outcomes of tegumentary leishmaniasis (TL) rely on a complex interaction between the host immune system and the parasite. This study assessed the influence of polymorphisms in immune-related genes on TL. METHODS: Web of Science, Scopus, PubMed, and Embase databases were searched systemically. The meta-analysis used a retrospective model in examining alleles, heterozygotes, and homozygotes. A quality assessment and an analysis of cumulative evidence were performed. RESULTS: A total of 29 genes (encoding for cytokines, chemokines, and other immune receptors) and 84 polymorphisms were analyzed. The IL-1ß_rs16944 (OR = 1.341, p = 0.003), TNF-α_rs1800629 (OR = 3.804, p = 0.004), MIF_rs755622 (OR = 3.357, p = 0.001), and INF- γ_rs243056 (OR = 1.670, p = 0.028) polymorphisms were speculated as risk factor for TL. They decrease the expression of the corresponding genes crucial for TL control. The quality assessment score was approximately 50%, suggesting the need for a clear method and polymorphism characterization for further comparison. The relevant risk of bias and other considerations resulted in low and moderate cumulative evidence confidence. CONCLUSIONS: IL-1ß_rs16944, TNF-α_rs1800629, MIF_rs755622, and INF-γ_rs2430561 polymorphisms were speculated as risk factor for TL, corroborating that IL-1ß, TNF-α, INF-γ, and MIF are involved in the TL pathogenesis.

Effect of essential oils on Leishmania amazonensis: a systematic review.

This systematic review investigated the evidence for the therapeutic potential of essential oils (EOs) against Leishmania amazonensis. We searched available scientific publications from 2005 to 2019 in the PubMed and Web of Science electronic databases, according to PRISMA statement. The search strategy utilized descriptors and free terms. The EOs effect of 35 species of plants identified in this systematic review study, 45.7% had half of the maximal inhibitory concentration (IC50) 10 < IC50 ⩽ 50 µg mL-1 and 14.3% had a 10 < IC50µg mL-1 for promastigote forms of L. amazonensis. EOs from Cymbopogon citratus species had the lowest IC50 (1.7 µg mL-1). Among the plant species analyzed for activity against intracellular amastigote forms of L. amazonensis, 39.4% had an IC50 10 < IC50 ⩽ 50 µg mL-1, and 33.3% had an IC50 10 < IC50µg mL-1. Aloysia gratissima EO showed the lowest IC50 (0.16 µg mL-1) for intracellular amastigotes. EOs of Chenopodium ambrosioides, Copaifera martii and Carapa guianensis, administered by the oral route, were effective in reducing parasitic load and lesion volume in L. amazonensis-infected BALB/c mice. EOs of Bixa orellana and C. ambrosioides were effective when administered intraperitoneally. Most of the studies analyzed in vitro and in vivo for the risk of bias showed moderate methodological quality. These results indicate a stimulus for the development of new phytotherapy drugs for leishmaniasis treatment.

Photodynamic therapy in wound healing in vivo: a systematic review.

Wounds constitute severe problems in public health. Inappropriate manipulation to promote wound healing and indiscriminate use of antibiotics may contribute to failure in wound treatment, leading to bacterial growth and resistance. Appropriate and correct approaches to wound treatment are crucially important. Further, the development of new and effective treatment modalities is important to decrease infection-related mortality and to reduce patient suffering and side effects. Photodynamic therapy (PDT) could be a promising approach to ameliorate this global health problem. We researched articles that used PDT in wound healing in vivo. The systematic review included articles that investigated the effect of PDT on wound healing in animals, published from May 2008 through 2018, in the databases PubMed and Web of Science. The main types of wounds described in the selected articles were burns, abrasions, and excisional wounds. Most of the studies tested PDT in wounds infected by methicillin-resistant Staphylococcus aureus, S. aureus standard strain, or Pseudomonas aeruginosa. The studies demonstrated that PDT contributes in several ways to the wound healing process, such as killing bacterial cells and stimulating the proliferation of fibroblasts and consequently of collagen and elastin. Based on these studies, PDT provided excellent results for the wound healing process, acting in several steps and accelerating tissue repair. PDT has proven to be a promising therapeutic modality, able to inhibit bacterial regrowth or kill bacteria, contributing significantly to accelerate the wound healing process.

Potential of Pluronics® P-123 and F-127 as nanocarriers of anti-Leishmania chemotherapy.

Leishmaniasis is a neglected disease and drugs approved for its treatment often lead to abandonment, failure of therapy and even death. Photodynamic therapy (PDT) has been shown to be a promising, non-invasive and selective for a target region without requiring high-cost technology. Usually, it is employed a photosensitizing agent (PS) incorporated into nanoparticles (NP). Pluronics® P-123 and F-127 micelles are very interesting aqueous NP promoting efficient and selective delivery and less adverse effects. This study aimed to detect the activity of Pluronics® P-123 and F-127 themselves since there is a scarcity of data on these NP activities without drugs incorporation. This study evaluated, in vitro, the activity of Pluronics® against promastigotes and amastigotes of Leishmania amazonensis and also their cytotoxicities. Additionally, the determination of the mitochondria membrane potential in promastigotes, internalization of these Pluronics® in the parasite membrane and macrophages and its stability in the culture medium was evaluated. Results showed that Pluronics® did not cause significant damage to human red cells and promastigotes. The P-123 and F-127 inhibited the survival rate of L. amazonensis amastigotes, and also presented loss of mitochondrial membrane potential on promastigotes. The Pluronics® showed low cytotoxic activity on J774A.1 macrophages, while only P-123 showed moderate cytotoxicity for BALB/c macrophages. The stability of P-123 and F-127 in culture medium was maintained for ten days. In conclusion, the NP studied can be used for incorporating potent leishmanicidal chemotherapy, due to their selectivity towards macrophages, being a promising system for the treatment of cutaneous leishmaniasis.

American tegumentary leishmaniasis: diagnostic and treatment challenges in a clinical case.

This clinical case presents a patient with a raised and ulcerative lesion with erythematous edges in the mouth, on the lower lip that was unsuccessfully treated as herpes labialis. Clinical data and laboratory tests (Montenegro skin test, indirect immunofluorescence, direct parasite search and polymerase chain reaction) led to the diagnosis of American tegumentary leishmaniasis caused by Leishmania (Viannia) sp. Treatment with pentavalent antimonial (Glucantime®) for 120 days was not effective and administration of amphotericin B for 30 days resulted in wound healing. Glucantime® treatment protocol was longer than the recommended by the Brazilian Ministry of Health in the handbook of mucosal leishmaniasis. This suggests that amphotericin B should have been administered earlier, preventing the psychological and social problems faced by the patient. This study reports a rare clinical case of primary mucosal leishmaniasis on the lip that had a delayed diagnosis, highlighting the precariousness in the management of disease and showing that, despite the importance of leishmaniasis in Brazil, it is still neglected by health professionals.

Contribution of photodynamic therapy in wound healing: A systematic review.

OBJECTIVE: We researched articles that used photodynamic therapy (PDT) for skin wound healing in humans. METHODS: The systematic review was conducted through scientific articles that investigated the action of PDT on wound healing in humans, published from July 2005 to March 2017, in the data bases PubMed and LILACS. RESULTS: The main types of wound described in selected articles in this review were chronic ulcer and non-melanoma skin cancer. For accomplishing the PDT, second generation of photosensitizing agents with laser or light emitting diode were used. The studies demonstrated that PDT contribute in several ways to the wound healing process: leading to cellular death; reducing or increasing inflammation; stimulating fibroblasts proliferation and, consequently, of collagen and elastin; raising transforming growth factor beta and metalloproteinases. Based on this, PDT provided good results in wound healing process, acting in several steps and accelerating tissue repair. CONCLUSIONS: PDT improved healing in many wound models in humans, revealing itself as a promising therapeutic modality for stimulating wound healing and remodelling.

Qualidade microbiológica da água para consumo humano em instituição de ensino de Maringá-PR / Microbiological quality of human consumption water in a school in Maringa-PR

A água contaminada associada à falta de saneamento básico mata anualmente cerca de 1,6 milhões de pessoas no mundo.A falta da potabilidade da água nem sempre é perceptível à visão ou olfato, sendo necessária uma análise laboratorial paradetectá-la. Torna-se importante o controle microbiológico da água devido sua característica de veículo de transmissão debactérias, dentre estas, coliformes totais e termotolerantes, protozoários, vírus e fungos causadores de inúmeras doençasao homem. Esses micro-organismos são responsáveis pela ocorrência de diarreias, disenterias, hepatites, cólera, entreoutras enfermidades graves. Esta pesquisa teve por finalidade analisar a presença de coliformes totais e termotolerantesem amostras de água mineral engarrafada e água tratada. No presente estudo foram selecionados 50 locais para coleta deágua para consumo humano, todos localizados em uma instituição de ensino na cidade de Maringá-PR. Das amostras coletadas,13 foram provenientes de bebedouros de água mineral natural engarrafada e 37 amostras de bebedouros de pressãode água tratada na própria instituição de ensino. A metodologia empregada para pesquisa de coliformes foi o métodode fermentação em tubos múltiplos. O resultado deste trabalho revelou, por meio de análise microbiológica, que as amostrasde água tratada dos bebedouros de pressão apresentaram-se próprias para consumo humano. Entretanto, 15,38% dasamostras de água mineral apresentaram-se contaminadas por coliformes totais. Esses resultados demonstraram que a águatratada com cloro apresentou melhor qualidade microbiológica quando comparada à água mineral natural engarrafada.(AU)

Contaminated water associated with poor sanitation kills about 1.6 million people worldwide annually. Lack of potabilityin water is not always perceptible to the sight or smell, requiring laboratory analysis to detect it. Because of that it is importantto control microbiologically water since it is a vehicle of transmission of bacteria such as total and fecal coliforms,protozoa, viruses and fungi that cause numerous humans diseases. These microorganisms cause diarrhea, dysentery, hepatitis,cholera, among other serious illnesses. This research aimed at examining the presence of total and fecal coliformsin samples from bottled mineral water and treated water. In the present study 50 sites of drinking water were selected, alllocated in an educational institution in Maringá-PR. 13 of the collected samples were from water drinker dispensers withbottled natural mineral water and 37 samples were from water dispensers with water treated in their own institution. Themethodology used for detecting coliforms was the method of Multiple Tube Fermentation. The result of this study revealed– through microbiological analysis – that the samples of treated water were fit for human consumption. However, 15.38%of the analyzed mineral water samples were contaminated with total coliforms. These results showed that water treatedwith chlorine showed better microbiological quality when compared to bottled natural mineral water.(AU)

Qualidade microbiológica da água paraconsumo humano em instituição de ensino deMaringá-PR / Microbiological quality of human consumption water in aschool in Maringa-PR

A água contaminada associada à falta de saneamento básico mata anualmente cerca de 1,6 milhões de pessoas no mundo.A falta da potabilidade da água nem sempre é perceptível à visão ou olfato, sendo necessária uma análise laboratorial paradetectá-la. Torna-se importante o controle microbiológico da água devido sua característica de veículo de transmissão debactérias, dentre estas, coliformes totais e termotolerantes, protozoários, vírus e fungos causadores de inúmeras doençasao homem. Esses micro-organismos são responsáveis pela ocorrência de diarreias, disenterias, hepatites, cólera, entreoutras enfermidades graves. Esta pesquisa teve por finalidade analisar a presença de coliformes totais e termotolerantesem amostras de água mineral engarrafada e água tratada. No presente estudo foram selecionados 50 locais para coleta deágua para consumo humano, todos localizados em uma instituição de ensino na cidade de Maringá-PR. Das amostras coletadas,13 foram provenientes de bebedouros de água mineral natural engarrafada e 37 amostras de bebedouros de pressãode água tratada na própria instituição de ensino. A metodologia empregada para pesquisa de coliformes foi o métodode fermentação em tubos múltiplos. O resultado deste trabalho revelou, por meio de análise microbiológica, que as amostrasde água tratada dos bebedouros de pressão apresentaram-se próprias para consumo humano. Entretanto, 15,38% dasamostras de água mineral apresentaram-se contaminadas por coliformes totais. Esses resultados demonstraram que a águatratada com cloro apresentou melhor qualidade microbiológica quando comparada à água mineral natural engarrafada.

Contaminated water associated with poor sanitation kills about 1.6 million people worldwide annually. Lack of potabilityin water is not always perceptible to the sight or smell, requiring laboratory analysis to detect it. Because of that it is importantto control microbiologically water since it is a vehicle of transmission of bacteria such as total and fecal coliforms,protozoa, viruses and fungi that cause numerous humans diseases. These microorganisms cause diarrhea, dysentery, hepatitis,cholera, among other serious illnesses. This research aimed at examining the presence of total and fecal coliformsin samples from bottled mineral water and treated water. In the present study 50 sites of drinking water were selected, alllocated in an educational institution in Maringá-PR. 13 of the collected samples were from water drinker dispensers withbottled natural mineral water and 37 samples were from water dispensers with water treated in their own institution. Themethodology used for detecting coliforms was the method of Multiple Tube Fermentation. The result of this study revealed– through microbiological analysis – that the samples of treated water were fit for human consumption. However, 15.38%of the analyzed mineral water samples were contaminated with total coliforms. These results showed that water treatedwith chlorine showed better microbiological quality when compared to bottled natural mineral water.