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1.
J Zoo Wildl Med ; 52(1): 206-216, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827178

RESUMO

Sarcocystosis was diagnosed in a captive flock of thick-billed parrots (Rhynchopsitta pachyrhyncha) at the Wildlife Conservation Society's Queens Zoo. Since the index case in 2005, 45% of mortalities in birds over 30 days of age were due to sarcocystosis. Sarcocystis falcatula was repeatedly identified as the causative agent. The disease predominantly affected younger adult parrots. Administration of antiparasitic medications prior to development of respiratory signs prolonged life in infected birds, but disease was fatal until utilization of a three-drug combination (pyrimethamine, trimethoprim-sulfamethoxazole, and ponazuril). This protocol may require in excess of 6 mo of therapy to achieve clinical resolution of active disease. Plasma creatine kinase activity was found to be the most useful test in diagnosing infection and monitoring response to therapy. Polymerase chain reaction (PCR) for apicomplexan organisms on antemortem whole blood, blood smears, or dried blood spots helped confirm suspected cases, but due to the poor sensitivity was sometimes misleading when assessing response to therapy or resolution of clinical disease. Preventive measures, focusing on exclusion and removal of Virginia opossums (Didelphis virginiana) from zoo grounds failed to curtail the occurrence of sarcocystosis in the flock. Other preventative steps, such as modification of feeding stations to exclude potential arthropod paratenic hosts and prophylaxis trials with diclazuril, appeared to successfully mitigate new infections. Given the diagnostic and therapeutic challenges, prevention of exposure to S. falcatula is essential to ex-situ conservation efforts for thick-billed parrots.


Assuntos
Antiprotozoários/uso terapêutico , Doenças das Aves/parasitologia , Papagaios/parasitologia , Sarcocistose/veterinária , Animais , Animais de Zoológico , Doenças das Aves/tratamento farmacológico , Doenças das Aves/mortalidade , Sarcocistose/tratamento farmacológico , Sarcocistose/mortalidade
2.
Parasite ; 28: 38, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851916

RESUMO

Current treatments of visceral leishmaniasis face limitations due to drug side effects and/or high cost, along with the emergence of parasite resistance. Novel and low-cost antileishmanial agents are therefore required. We report herein the antileishmanial activity of ß-acetyl-digitoxin (b-AD), a cardenolide isolated from Digitalis lanata leaves, assayed in vitro and in vivo against Leishmania infantum. Results showed direct action of b-AD against parasites, as well as efficacy for the treatment of Leishmania-infected macrophages. In vivo experiments using b-AD-containing Pluronic® F127 polymeric micelles (b-AD/Mic) to treat L. infantum-infected mice showed that this composition reduced the parasite load in distinct organs in more significant levels. It also induced the development of anti-parasite Th1-type immunity, attested by high levels of IFN-γ, IL-12, TNF-α, GM-CSF, nitrite and specific IgG2a antibodies, in addition to low IL-4 and IL-10 contents, along with higher IFN-γ-producing CD4+ and CD8+ T-cell frequency. Furthermore, low toxicity was found in the organs of the treated animals. Comparing the therapeutic effect between the treatments, b-AD/Mic was the most effective in protecting animals against infection, when compared to the other groups including miltefosine used as a drug control. Data found 15 days after treatment were similar to those obtained one day post-therapy. In conclusion, the results obtained suggest that b-AD/Mic is a promising antileishmanial agent and deserves further studies to investigate its potential to treat visceral leishmaniasis.


Assuntos
Antiprotozoários , Digitalis , Leishmania infantum , Leishmaniose Visceral , Animais , Antiprotozoários/uso terapêutico , Cardenolídeos/uso terapêutico , Digitoxina/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C
3.
Prog Chem Org Nat Prod ; 115: 115-176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33797642

RESUMO

Secondary metabolites (SM) from organisms have served medicinal chemists over the past two centuries as an almost inexhaustible pool of new drugs, drug-like skeletons, and chemical probes that have been used in the "hunt" for new biologically active molecules with a "beneficial effect on human mind and body." Several secondary metabolites, or their derivatives, have been found to be the answer in the quest to search for new approaches to treat or even eradicate many types of diseases that oppress humanity. A special place among SM is occupied by lignans and neolignans. These phenolic compounds are generated biosynthetically via radical coupling of two phenylpropanoid monomers, and are known for their multitarget activity and low toxicity. The disadvantage of the relatively low specificity of phenylpropanoid-based SM turns into an advantage when structural modifications of these skeletons are made. Indeed, phenylpropanoid-based SM previously have proven to offer great potential as a starting point in drug development. Compounds such as Warfarin® (a coumarin-based anticoagulant) as well as etoposide and teniposide (podophyllotoxin-based anticancer drugs) are just a few examples. At the beginning of the third decade of the twenty-first century, the call for the treatment of more than a dozen rare or previously "neglected" diseases remains for various reasons unanswered. Leishmaniasis, a neglected disease that desperately needs new ways of treatment, is just one of these. This disease is caused by more than 20 leishmanial parasites that are pathogenic to humans and are spread by as many as 800 sandfly species across subtropical areas of the world. With continuing climate changes, the presence of Leishmania parasites and therefore leishmaniasis, the disease caused by these parasites, is spreading from previous locations to new areas. Thus, leishmaniasis is affecting each year a larger proportion of the world's population. The choice of appropriate leishmaniasis treatment depends on the severity of the disease and its form of manifestation. The success of current drug therapy is often limited, due in most cases to requiring long hospitalization periods (weeks to months) and the toxicity (side effects) of administered drugs, in addition to the increasing resistance of the parasites to treatment. It is thus important to develop new drugs and treatments that are less toxic, can overcome drug resistance, and require shorter periods of treatment. These aspects are especially important for the populations of developing countries. It was reported that several phenylpropanoid-based secondary metabolites manifest interesting antileishmanial activities and are used by various indigenous people to treat leishmaniasis. In this chapter, the authors shed some light on the various biological activities of phenylpropanoid natural products, with the main focus being on their possible applications in the context of antileishmanial treatment.


Assuntos
Antiprotozoários , Leishmaniose , Lignanas , Preparações Farmacêuticas , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Humanos , Leishmaniose/tratamento farmacológico , Lignanas/farmacologia , Lignanas/uso terapêutico , Fenóis/farmacologia , Fenóis/uso terapêutico
4.
Rev Soc Bras Med Trop ; 54: e0514-2020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759920

RESUMO

A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Compostos Organometálicos , Adulto , Antiprotozoários/uso terapêutico , Brasil , Genitália , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Reação em Cadeia da Polimerase
5.
Rev Soc Bras Med Trop ; 54: e0633-2020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33759923

RESUMO

In this study, we present two cases of cutaneous leishmaniasis in patients with end-stage renal disease, who were treated solely with intramuscular pentamidine. In such cases, treatment implies a fine line between therapeutic efficacy and toxicity. This is suggestive of a knowledge gap; however, findings indicate that this is still the fastest and safest alternative to the treatment with antimonials. Also, it can help avoid the side effects that occur upon using antimonials.


Assuntos
Antiprotozoários , Falência Renal Crônica , Leishmaniose Cutânea , Antiprotozoários/uso terapêutico , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Pentamidina/uso terapêutico , Diálise Renal
6.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672753

RESUMO

The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24-31 µM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4-20 µM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.


Assuntos
Antibacterianos/farmacologia , Antiprotozoários/farmacologia , Quinolonas/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Quinolonas/síntese química , Quinolonas/química , Staphylococcus aureus/efeitos dos fármacos , Trypanosoma brucei brucei/efeitos dos fármacos
7.
Chem Biol Interact ; 339: 109429, 2021 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-33713644

RESUMO

Leishmaniasis is considered as one of the most Neglected Tropical Diseases (NTDs) in the world, caused by protozoan parasites of the genus Leishmania. Treatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. The search for new therapeutic agents from natural sources has been a constant for the treatment of diseases such as leishmaniasis. The objective of this study was to evaluate the biological activity of Eugenia piauhiensis Vellaff. essential oil (EpEO) and its major constituent γ-elemene on promastigote and amastigote forms of Leishmania (Leishmania) amazonensis, its cytotoxicity, and possible mechanisms of action. EpEO was more active (IC50 6.43 ± 0.18 µg/mL) against promastigotes than γ-elemene [9.82 ± 0.15 µg/mL (48.05 ± 0.73 µM)] and the reference drug miltefosine [IC50 17.25 ± 0.26 µg/mL (42.32 ± 0.64 µM)]. EpEO and γ-elemene exhibited low cytotoxicity against J774.A1 macrophages, with CC50 225.8 ± 3.57 µg/mL and 213.21 ± 3.3 µg/mL (1043 ± 16.15 µM), respectively. Additionally, EpEO and γ-elemene present direct activity against the parasite, decreasing plasma membrane integrity. EpEO and γ-elemene also proved to be even more active against intracellular amastigotes of the parasite [IC50 4.59 ± 0.07 µg/mL and 8.06 ± 0.12 µg/mL (39.44 ± 0.59 µM)], respectively), presenting indirect effects through macrophage activity modulation. Anti-amastigote activity was associated with increased TNF-α, IL-12, NO, and ROS levels. In conclusion, our results suggest EpEO and γ-elemene as promising candidates for new drug development against leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Membrana Celular/efeitos dos fármacos , Eugenia/química , Imunomodulação/efeitos dos fármacos , Leishmania mexicana/efeitos dos fármacos , Óleos Voláteis/farmacologia , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Macrófagos/parasitologia , Camundongos , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia
8.
Molecules ; 26(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670791

RESUMO

Betulinic acid (BA, 3ß-hydroxy-lup-20(29)-en-28-oic acid) is a pentacyclic triterpene acid present predominantly in Betula ssp. (Betulaceae) and is also widely spread in many species belonging to different plant families. BA presents a wide spectrum of remarkable pharmacological properties, such as cytotoxic, anti-HIV, anti-inflammatory, antidiabetic and antimicrobial activities, including antiprotozoal effects. The present review first describes the sources of BA and discusses the chemical strategies to produce this molecule starting from betulin, its natural precursor. Next, the antiprotozoal properties of BA are briefly discussed and the chemical strategies for the synthesis of analogues displaying antiplasmodial, antileishmanial and antitrypanosomal activities are systematically presented. The antiplasmodial activity described for BA was moderate, nevertheless, some C-3 position acylated analogues showed an improvement of this activity and the hybrid models-with artesunic acid-showed the most interesting properties. Some analogues also presented more intense antileishmanial activities compared with BA, and, in addition to these, heterocycles fused to C-2/C-3 positions and amide derivatives were the most promising analogues. Regarding the antitrypanosomal activity, some interesting antitrypanosomal derivatives were prepared by amide formation at the C-28 carboxylic group of the lupane skeleton. Considering that BA can be produced either by isolation of different plant extracts or by chemical transformation of betulin, easily obtained from Betula ssp., it could be said that BA is a molecule of great interest as a starting material for the synthesis of novel antiprotozoal agents.


Assuntos
Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Triterpenos Pentacíclicos/síntese química , Triterpenos Pentacíclicos/farmacologia , Antiprotozoários/química , Modelos Moleculares , Triterpenos Pentacíclicos/química , Triterpenos/química
9.
Molecules ; 26(4)2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33672916

RESUMO

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC50 values of 12.35, 13.53 and 12.93 µg/mL and with IC90 values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-ß-d-galactopyranoside (6) and myricetin-3'-O-ß-d-glucopyranoside (7). Myricetin-3'-O-ß-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC50 and IC90 values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.


Assuntos
Antiprotozoários/farmacologia , Flavonoides/farmacologia , Hypericum/química , Modelos Moleculares , Compostos Fitoquímicos/farmacologia , Quercetina/farmacologia , Trypanosoma/efeitos dos fármacos , Sequência de Aminoácidos , Antiprotozoários/química , Sítios de Ligação , Morte Celular/efeitos dos fármacos , Sequência Conservada , Flavonoides/química , Flavonoides/isolamento & purificação , Ligantes , Simulação de Dinâmica Molecular , Compostos Fitoquímicos/química , Estrutura Secundária de Proteína , Proteínas de Protozoários/química , Quercetina/química , Quercetina/isolamento & purificação , Água/química
10.
Exp Parasitol ; 224: 108103, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33771537

RESUMO

In this work the effect of (-)-epicatechin on the development of amebic liver abscess in hamsters was evaluated. (-)-epicatechin is a flavonoid present in plants that possesses various biological properties, including its activity against some protozoal parasites; however its antiamebic activity in a living model had not been evaluated. Syrian golden hamsters were intrahepatically inoculated with 1x106E. histolytica trophozoites, three days after inoculation they received nine intraperitoneal doses of (-)-epicatechin (10 mg/100 g) every 48 h. Animals without treatments and treated with metronidazole were included as controls. Macroscopic characteristics of the hepatic abscess, histopathological analysis of the tissue and the levels of inflammatory cytokines were determined. (-)-epicatechin produced a decrease in liver abscess progression being observed only 9.49% of damage compared to 84% shown by untreated animals. During treatment with (-)-epicatechin hepatic tissue showed signs of liver repair and absence of amoebae. Additionally, (-)-epicatechin produced a modulating effect on inflammatory cytokines TNF-α, IL-1ß and IL-10. All these events observed in animals treated with (-)-epicatechin could contribute to the elimination of trophozoites and liver healing.


Assuntos
Catequina/uso terapêutico , Abscesso Hepático Amebiano/prevenção & controle , Análise de Variância , Animais , Antiprotozoários/uso terapêutico , Antiprotozoários/toxicidade , Catequina/toxicidade , Cricetinae , Citocinas/análise , Citocinas/metabolismo , Dimetil Sulfóxido/toxicidade , Modelos Animais de Doenças , Fígado/imunologia , Abscesso Hepático Amebiano/tratamento farmacológico , Masculino , Mesocricetus , Metronidazol/uso terapêutico , Metronidazol/toxicidade , Reação em Cadeia da Polimerase em Tempo Real
12.
Medicine (Baltimore) ; 100(10): e24890, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725845

RESUMO

RATIONALE: Cystoisosporiasis is an intestinal infectious disease caused by a coccidian protozoa, Cystoisospora belli (C. belli). It can cause prolonged and refractory diarrhea most commonly in immunocompromised patients, while immunocompetent individuals usually exhibit no symptoms or self-limited diarrhea. PATIENT CONCERNS: We herein report a case of chronic cystoisosporiasis in an immunocompetent patient. A 62-year-old man, who had been first diagnosed with cystoisosporiasis 15 years ago and had been treated with oral administration of trimethoprim-sulfamethoxazole (TMP-SMX), complained of persistent watery diarrhea. He was negative for anti-human immunodeficiency virus antibody and anti-human T-cell leukemia virus type 1 (HTLV-1) antibody. DIAGNOSIS: Biopsy specimens from the duodenum revealed oocysts in the atrophic absorptive epithelium and protozoa were detected through stool examination, indicating the recurrence of cystoisosporiasis. Capsule endoscopy showed diffuse atrophic mucosa with white villi in the entire small intestine. We diagnosed him with chronic cystoisosporiasis that occurred in an immunocompetent adult. INTERVENTIONS: Since oral administration of TMP-SMX and ciprofloxacin were ineffective, the intravenous administration of TMP-SMX was initiated. OUTCOMES: Intravenous TMP-SMX exhibited a significant improvement. LESSONS: This case indicates that even immunocompetent individuals may develop recurrent and refractory cystoisosporiasis. Furthermore, intravenous treatment of antibiotic agents should be considered when the impaired absorptive ability from the small intestine is suspected.


Assuntos
Antiprotozoários/administração & dosagem , Enteropatias Parasitárias/diagnóstico , Enteropatias Parasitárias/tratamento farmacológico , Isosporíase/diagnóstico , Isosporíase/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Administração Intravenosa , Administração Oral , Antiprotozoários/uso terapêutico , Endoscopia por Cápsula , Doença Crônica , Diarreia/parasitologia , Humanos , Imunocompetência , Masculino , Pessoa de Meia-Idade , Recidiva , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
13.
Molecules ; 26(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525706

RESUMO

Polycyclic endoperoxides are rare natural metabolites found and isolated in plants, fungi, and marine invertebrates. The purpose of this review is a comparative analysis of the pharmacological potential of these natural products. According to PASS (Prediction of Activity Spectra for Substances) estimates, they are more likely to exhibit antiprotozoal and antitumor properties. Some of them are now widely used in clinical medicine. All polycyclic endoperoxides presented in this article demonstrate antiprotozoal activity and can be divided into three groups. The third group includes endoperoxides, which show weak antiprotozoal activity with a reliability of up to 70%, and this group includes only 1.1% of metabolites. The second group includes the largest number of endoperoxides, which are 65% and show average antiprotozoal activity with a confidence level of 70 to 90%. Lastly, the third group includes endoperoxides, which are 33.9% and show strong antiprotozoal activity with a confidence level of 90 to 99.6%. Interestingly, artemisinin and its analogs show strong antiprotozoal activity with 79 to 99.6% confidence against obligate intracellular parasites which belong to the genera Plasmodium, Toxoplasma, Leishmania, and Coccidia. In addition to antiprotozoal activities, polycyclic endoperoxides show antitumor activity in the proportion: 4.6% show weak activity with a reliability of up to 70%, 65.6% show an average activity with a reliability of 70 to 90%, and 29.8% show strong activity with a reliability of 90 to 98.3%. It should also be noted that some polycyclic endoperoxides, in addition to antiprotozoal and antitumor properties, show other strong activities with a confidence level of 90 to 97%. These include antifungal activity against the genera Aspergillus, Candida, and Cryptococcus, as well as anti-inflammatory activity. This review provides insights on further utilization of polycyclic endoperoxides by medicinal chemists, pharmacologists, and the pharmaceutical industry.


Assuntos
Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Produtos Biológicos/farmacologia , Peróxidos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos/química , Antiprotozoários/química , Produtos Biológicos/química , Humanos , Peróxidos/química
14.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33625354

RESUMO

Introduction. Cryptosporidium parvum causes intestinal parasitic infections affecting both immunosuppressed and immunocompetent individuals.Gap statement. Given the absence of effective treatments for cryptosporidiosis, especially in immunodeficient patients, the present study was designed to assess the therapeutic efficacy of secnidazole (SEC) and its combination with nitazoxanide (NTZ) in comparison to single NTZ treatment in relation to the immune status of a murine model of C. parvum infection.Methodology. The infected groups were administered NTZ, SEC or NTZ-SEC for three or five successive doses. At days 10 and 12 post-infection (p.i.), the mice were sacrificed, and the efficacy of the applied drugs was evaluated by comparing the histopathological alterations in ileum and measuring the T helper Th1 (interferon gamma; IFN-γ), Th2 [interleukin (IL)-4 and IL-10] and Th17 (IL-17) cytokine profiles in serum.Results. The NTZ-SEC combination recorded the maximal reduction of C. parvum oocyst shedding, endogenous stages count and intestinal histopathology, regardless of the immune status of the infected mice. The efficacy of NTZ-SEC was dependent on the period of administration, as the 5 day-based treatment protocol was also more effective than the 3 day-based one in terms of immunocompetence and immunosuppression. The present treatment schedule induced an immunomodulatory effect from SEC that developed a protective immune response against C. parvum infection with reduced production of serum IL-17, IFN-γ, IL-4 and IL-10.Conclusions. Application of NTZ-SEC combined therapy may be useful in treatment of C. parvum, especially in cases involving immunosuppression.


Assuntos
Antiprotozoários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Metronidazol/análogos & derivados , Nitrocompostos/uso terapêutico , Tiazóis/uso terapêutico , Animais , Criptosporidiose/imunologia , Criptosporidiose/parasitologia , Criptosporidiose/patologia , Cryptosporidium parvum/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Esquema de Medicação , Quimioterapia Combinada , Íleo/efeitos dos fármacos , Íleo/parasitologia , Íleo/patologia , Hospedeiro Imunocomprometido , Masculino , Metronidazol/uso terapêutico , Camundongos , Carga Parasitária
15.
BMC Infect Dis ; 21(1): 168, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568075

RESUMO

BACKGROUND: Human alveolar echinococcosis (AE) caused by Echinococcus multilocularis is an underreported, often misdiagnosed and mistreated parasitic disease mainly due to its low incidence. The aim of this study was to describe the epidemiological and clinical characteristics of human AE patients in Hungary for the first time. METHOD: Between 2003 and 2018, epidemiological and clinical data of suspected AE patients were collected retrospectively from health database management systems. RESULTS: This case series included a total of 16 AE patients. The mean age of patients was 53 years (range: 24-78 years). The sex ratio was 1:1. Four patients (25%) revealed no recurrence after radical surgery and adjuvant albendazole (ABZ) therapy. For five patients (31.3%) with unresectable lesions, a stabilization of lesions with ABZ treatment was achieved. In seven patients (43.8%), progression of AE was documented. The mean diagnostic delay was 33 months (range: 1-122 months). Three AE related deaths (fatality rate 18.8%) were recorded. CONCLUSIONS: AE is an emerging infectious disease in Hungary with a high fatality rate since based on our results, almost every fifth AE patient died in the study period. Differential diagnosis and appropriate surgical and medical therapy for AE is an urging challenge for clinicians in Hungary, as well as in some other European countries where E. multilocularis is prevalent.


Assuntos
Equinococose/diagnóstico , Adulto , Idoso , Albendazol/uso terapêutico , Animais , Antiprotozoários/uso terapêutico , Diagnóstico Tardio , Diagnóstico Diferencial , Equinococose/tratamento farmacológico , Equinococose/epidemiologia , Equinococose/parasitologia , Echinococcus multilocularis/isolamento & purificação , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Rev Soc Bras Med Trop ; 54: e04542020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533816

RESUMO

INTRODUCTION: The objective of this study was to estimate the direct medical costs of the treatment for mucosal leishmaniasis (ML) using three therapeutic approaches in the Brazilian context. METHODS: We performed this economic assessment from the perspective of the Brazilian public healthcare system. The following therapeutic approaches were evaluated: meglumine antimoniate, liposomal amphotericin B, and miltefosine. Direct medical costs were estimated considering four treatment components: a) drug, b) combined medical products, c) procedures, and d) complementary tests. RESULTS: Treatment with meglumine antimoniate had the lowest average cost per patient (US$ 167.66), followed by miltefosine (US$ 259.92) in the outpatient treatment regimen. The average cost of treatment with liposomal amphotericin B was US$ 715.35 both in inpatient regimen. In all estimates, the drugs accounted for more than 60% of the total cost for each treatment approach. CONCLUSIONS: These results demonstrate the marked differences in costs between the therapeutic alternatives for ML. In addition to efficacy rates and costs related to adverse events, our data have the potential to support a complete cost-effectiveness study in the future. Complete analyses comparing costs and benefits for interventions will assist health managers in choosing drugs for ML treatment in Brazil as well as in establishing effective public health policies.


Assuntos
Antiprotozoários , Leishmaniose Mucocutânea , Antiprotozoários/uso terapêutico , Brasil , Análise Custo-Benefício , Humanos , Leishmaniose Mucocutânea/tratamento farmacológico , Antimoniato de Meglumina/uso terapêutico
17.
SAR QSAR Environ Res ; 32(1): 71-83, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33455460

RESUMO

Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, was selected to develop the computational model. Dragon software was used to calculate the molecular descriptors and WEKA software to obtain the classification tree. The best model shows accuracy greater than 93.4% for the training set; the tree was also validated using a 10-fold cross-validation procedure and through a test set, achieving accuracy values over 90.5% and 92.2%, correspondingly. The values of sensitivity and specificity were around 90% in all series; also the false alarm rate values were under 10.5% for all sets. In addition, a simulated ligand-based virtual screening for several compounds recently reported as promising anti-chagasic agents was carried out, yielding good agreement between predictions and experimental results. Finally, the present work constitutes an example of how this rational computer-based method can help reduce the cost and increase the rate in which novel compounds are developed against Chagas disease.


Assuntos
Antiprotozoários/farmacologia , Relação Quantitativa Estrutura-Atividade , Trypanosoma cruzi/efeitos dos fármacos , Doença de Chagas/tratamento farmacológico , Ligantes , Estrutura Molecular , Software
18.
Parasitol Res ; 120(3): 785-796, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33409640

RESUMO

Leishmania spp. and Trypanosoma cruzi are parasites belonging to the Trypanosomatidae family and the causative agents for two very important neglected tropical diseases (NTDs), namely leishmaniasis and trypanosomiasis, respectively. Together, they affect millions of people worldwide and the number of cases is constantly rising; thus, further effort on identifying and developing non-toxic, affordable and effective new drug is urgently needed to overcome this alarming situation. Exploring natural products from fungal and bacterial origin remains hitherto a valuable approach to find new hits and candidates for the development of new drugs against these protozoal human infections. Endophytes, which are microorganisms (fungal and bacterial) inhabiting plant tissues, represent a promising source, as they hold potential to produce a high number of distinct chemical scaffolds. These structurally diverse natural products have previously been successfully tested against a wide range of pathogenic microorganisms. The present review provides an update of endophytic compounds exerting anti-trypanosomal and anti-leishmanial effects and their predicted pharmacokinetic properties.


Assuntos
Antiprotozoários/farmacologia , Bactérias/química , Produtos Biológicos/farmacologia , Endófitos/química , Fungos/química , Leishmania/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Animais , Humanos , Leishmania/fisiologia , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Plantas/microbiologia , Trypanosoma cruzi/fisiologia , Tripanossomíase/tratamento farmacológico , Tripanossomíase/parasitologia
19.
Parasitol Res ; 120(2): 705-713, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415404

RESUMO

Leishmaniasis is one of the most neglected parasitic infections of the world and current therapeutic options show several limitations. In the search for more effective drugs, plant compounds represent a powerful natural source. Artemisinin is a sesquiterpene lactone extracted from Artemisia annua L. leaves, from which dihydroartemisinin (DQHS) and artesunic acid (AA)/artesunate are examples of active derivatives. These lactones have been applied successfully on malaria therapy for decades. Herein, we investigated the sensitivity of Leishmania braziliensis, one of the most prevalent Leishmania species that cause cutaneous manifestations in the New World, to artemisinin, DQHS, and AA. L. braziliensis promastigotes and the stage that is targeted for therapy, intracelular amastigotes, were more sensitive to DQHS, showing EC50 of 62.3 ± 1.8 and 8.9 ± 0.9 µM, respectively. Cytotoxicity assays showed that 50% of bone marrow-derived macrophages cultures were inhibited with 292.8 ± 3.8 µM of artemisinin, 236.2 ± 4.0 µM of DQHS, and 396.8 ± 6.7 µM of AA. The control of intracellular infection may not be essentially attributed to the production of nitric oxide. However, direct effects on mitochondrial bioenergetics and H2O2 production appear to be associated with the leishmanicidal effect of DQHS. Our data provide support for further studies of artemisinin and derivatives repositioning for experimental leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Artemisininas/farmacologia , Leishmania braziliensis/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Animais , Metabolismo Energético/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Leishmania braziliensis/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Mitocôndrias/metabolismo , Succinatos/farmacologia
20.
Eur J Med Chem ; 212: 113101, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385837

RESUMO

The kinetoplastid parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are the causative agents of neglected tropical diseases with a serious burden in several parts of the world. These parasites are incapable of synthesizing purines de novo, and therefore rely on ingenious purine salvage pathways to acquire and process purines from their host. Purine nucleoside analogs that may interfere with these pathways therefore constitute a privileged source of new antikinetoplastid agents. In this study, we synthetized a collection of C-nucleosides employing five different heterocyclic nucleobase surrogates. C-nucleosides are chemically and enzymatically stable and allow for extensive structural modification. Inspired by earlier 7-deazaadenosine nucleosides and known antileishmanial C-nucleosides, we introduced different modifications tailored towards antikinetoplastid activity. Both adenosine and inosine analogs were synthesized with the aim of discovering new antikinetoplastid hits and expanding knowledge of structure-activity relationships. Several promising hits with potent activity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum were discovered, and the nature of the nucleobase surrogate was found to have a profound influence on the selectivity profile of the compounds.


Assuntos
Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Nucleosídeos/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma cruzi/efeitos dos fármacos , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/química , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
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