Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis.

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O2N-BZM7 and O2N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O2N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O2N-BZM9 being the most potent, with an IC50 value of 4.8 µM. These results are promising for potential future therapeutic applications.

Trichomonicidal activity of a new anthraquinone isolated from the roots of Morinda panamensis Seem.

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. vaginalis. Antimicrobial activity of anthraquinone compounds has been reported by a number of authors. The genus Morinda is well known for the diversity of anthraquinones with numerous biological activities. A new anthraquinone, lucidin-ω-isopropyl ether, was isolated from the roots of Morinda panamensis Seem. The structure of the compound was determined by 1 H and 13 C Nuclear Magnetic Resonance (NMR) analyses, in addition to comparison with literature reports. Using in vitro susceptibility assay, the half inhibitory concentration (IC50 ) of lucidin-ω-isopropyl ether for T. vaginalis (1.32 µg/mL) was found similar to that of metronidazole concentration tested (6 µM = 1.03 µg/mL). In addition, this anthraquinone was capable of inhibiting the parasite's ability to kill HeLa cells and decreased proteolytic activity of the proteinase TvMP50 from T. vaginalis. This was associated with the decreased expression of the mp50 gene. These results demonstrate the trichomonicidal potential by lucidin-ω-isopropyl ether. Further action-mode studies are necessary to elucidate the antiparasitic mechanism of this new anthraquinone to develop a more potent antitrichomonal agent.

Anti-Trichomonas vaginalis activity of ursolic acid derivative: a promising alternative.

Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 µM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 µM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent.

The Caatinga endemic Manilkara rufula possesses remarkable activity against Trichomonas vaginalis and Tritrichomonas foetus.

Tritrichomonas foetus infects the bovine urogenital tract, causing bovine trichomoniasis. Significant economic losses may occur due to infertility and abortion among cattle. Trichomonas vaginalis is the causative agent of trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. Human and bovine trichomoniasis present treatment restrictions and efforts to identify new alternatives are essential. The present study evaluated the anti-trichomonads activities of seven fractions from northwest endemic plant Manilkara rufula. Flavonoids and condensed tannins were identified from these fractions by LC-DAD-MS/MS and MALDI-MS/MS. Altogether, the results demonstrated for the first time the structural description of tannins from leaves of M. rufula and the relation of these compounds with anti-T. vaginalis and anti-T. foetus activities. Overall, this report reveals the potential of M. rufula fractions against both parasites and shows new alternatives to treat the infection caused by trichomonads.

Natural and synthetic compound anti-Trichomonas vaginalis: an update review.

Trichomonas vaginalis is a flagellate protozoan that causes trichomonosis, a sexually transmitted disease of worldwide importance. However, the infection has long received much less attention than other parasitic and sexually transmitted diseases. This negligence leads to poor diagnosis and underestimated prevalence values, and consequently, it has been associated to increasing acquisition and transmission of HIV, pregnancy outcomes, infertility, pelvic inflammatory disease, and cervical and prostate cancer. In view of increased resistance to drugs belonging to the nitroimidazole class, new treatment alternatives are urgently needed. Natural products provide an immeasurable wealth of active molecules, and a great number of new drugs have been originated from these compounds. In addition, new synthetic products or derivatives from old drugs also provide an alternative to treat trichomonosis. Albeit many studies have been performed with natural products against T. vaginalis, none of them progressed to clinical trials. Overall, inadequate financial investments are made, and no alternative treatment for trichomonosis has been discovered; meanwhile, hundreds of thousands of people will remain infected and suffering the serious consequences of this nonviral STD. Thus, it is highlighted that clinical trials for better understanding the potential in vitro are necessary and urgent in order to furnish a new therapeutic alternative for trichomonosis treatment. The current review attempts to give an overview on the potential of natural and synthetic products as antitrichomonal.

Anti-Trichomonas vaginalis activity from triterpenoid derivatives.

Trichomonas vaginalis is a flagellated parasite that causes trichomonosis, the most common non-viral sexually transmitted disease (STD) in the world. Worryingly, trichomonosis is associated to increased transmission of HIV. Due to high frequency of the infection during pregnancy and the development of metronidazole-resistant isolates, therapeutic alternatives to 5-nitroimidazole are being searched. Triterpenes are natural products presenting several biological activities such as anti-protozoal activity. The aim of this study was to evaluate the in vitro anti-T. vaginalis activity from betulinic and ursolic acids, as well as semisynthetic derivatives obtained. Compounds obtained from betulinic acid presented better activity than those from ursolic acid. Piperazine derivatived from betulinic acid presented minimum inhibitory concentration (MIC) value of 91.2 µM, and the kinetic growth curve performed with parasites treated with this most active compound revealed complete inhibition of trophozoite proliferation at 2 h of incubation and total abolition of trophozoite growth in 24 h, revealing that the piperazine derivative is an efficient trichomonacidal molecule. The same compound promoted total erythrocyte lysis and lactate dehydrogenase (LDH) liberation of 83 and 100% (at 45.6 and 91.2 µM, respectively), indicating parasite membrane damage. The piperazine derivative demonstrated cytotoxic effect against the HMVII and HeLa cell lineages at the MIC value. This is the first report of semisynthetic triterpenoid derivatives with anti-T. vaginalis activity, revealing the high potential of these compounds as trichomonacidal agents.

Investigating the dissolution profiles of amoxicillin, metronidazole, and zidovudine formulations used in Trinidad and Tobago, West Indies.

Trinidad and Tobago is a twin-island Republic in the Caribbean and like many developing countries, it has included generic drugs on the national drug formulary to decrease the financial burden of pharmaceutical medications. However, to ensure that medications received by patients are beneficial, generic drugs need to be interchangeable with the innovator which has demonstrated safety, efficacy, and quality. The objective of the study was to compare the dissolution profiles and weight variations for different formulations of amoxicillin, metronidazole, and zidovudine that are on the national drug formulary and marketed in Trinidad and Tobago. All the products investigated are categorized as class 1 drugs according to the Biopharmaceutics Classification System (BCS) and the dissolution profiles were assessed according to the World Health Organization (WHO) criteria for interchangeability between products. The similarity factor, f 2, was used to determine sameness between the products. No generic formulation was found to be similar to Amoxil® 500-mg capsules. The two generic products for metronidazole 200-mg tablets demonstrated more than 85% drug release within 15 min in all three of the buffers; however, their 400-mg counterparts did not fulfill this requirement. The zidovudine 300-mg tablet complied with the requirements in buffer pH 4.5 and simulated gastric fluid (SGF) but not for simulated intestinal fluid (SIF). Some Class 1 pharmaceutical formulations may possess the same active ingredient and amount of drug but may show significant differences to in vitro equivalence requirements. Nevertheless, the dissolution process is suitable to detect these variations.

Atividade citotóxica do extrato de Vitis labrusca em culturas de Trichomonas vaginalis / Cytotoxic activity of Vitis labrusca extract in cultures of Trichomonas vaginalis

Objetivos: Avaliar a atividade anti-Trichomonas vaginalis do extrato de folhas de videira (Vitis labrusca) provenientes de cultivo convencional e orgânico.Métodos: Extratos de folhas secas de videira, orgânico e convencional, foram elaborados com extrator Sohxlet. A composição fenólica total dos extratos foi avaliada por Folin-Cicoalteau e Cromatografia Líquida de Alta Eficiência. A atividade antiparasitária dos extratos foi realizada em cultura de T. vaginalis. Os testes foram realizados em três concentrações finais: 5, 10 e 20 mg/mL. Os trofozoítos foram contados em hemocitômetro e sua densidade foi ajustada em meio de cultura Trypticase-Yeast Extract-Maltose (TYM), de forma a se obter a concentração final de 1×105 trofozoítos/mL. Após incubação com os extratos por 24 horas a 37°C, foi feita a contagem dos trofozoítos com motilidade em hemocitômetro. Os controles do veículo foram realizados, adicionando-se água em substituição aos extratos.Resultados: O extrato de folhas convencionais é rico em catequina e os orgânicos, em resveratrol. Os extratos de V. labrusca não apresentaram atividade anti-T. vaginalis nas concentrações de 5 e 10 mg/mL. Entretanto na concentração de 20 mg/L, o extrato de folhas secas convencionais reduziu em 100% e o extrato orgânico em 48% a sobrevivência dos trofozoítos. Os polifenóis catequina, quercetina e rutina estavam em maior concentração no extrato com maior eficácia, os quais podem ser os responsáveis pela ação anti-T. vaginalis do extrato convencional.Conclusões: O extrato de folha de videira pode ser uma alternativa no combate a T. vaginalis. Estudos pré-clínicos e clínicos são necessários para comprovar eficácia e segurança desta intervenção...

AIMS: To evaluate the anti-Trichomonas vaginalis activity of the extract of organic and conventional leaves of Vitis labrusca.METHODS: Organic and conventional grapevine leaf extracts were prepared with extractor Sohxlet. The total phenolic extracts were evaluated by Folin-Cicoalteau and High-Performace Liquid Chromatography. The antiparasitic activity of the extracts was performed on growth of T. vaginalis. Tests were conducted at three final concentrations of 5, 10 and 20 mg/mL. The trophozoites were counted by hemocytometer and their density was adjusted in Trypticase-Yeast Extract-Maltose (TYM) growth environment in order to obtain a final concentration of 1x105 trophozoites/ml. After incubated with the extracts for 24 hours at 37 �C, the count of motile trophozoites was taken by hemocytometer. The vehicle controls were performed by substituting the extract by water.RESULTS: The conventional leaf extract is rich in catechin and the organic in resveratrol. The extracts of V. labrusca showed no anti-T.vaginalis activity at concentrations of 5 and 10 mg/mL. However in the concentration of 20 mg/L conventional grapevine leaf extracts reduced by 100% and the organic extract by 48% the survival of trophozoites. Catechin polyphenols, quercetin and rutin were in higher concentration in the extract with greater efficacy, which may be the responsible for the anti-T. vaginalis action of the conventional extract.CONCLUSIONS: The vine leaf extract may be an alternative to combat T. vaginalis. Pre-clinical and clinical studies are needed to confirm efficacy and safety of this intervention...

[Clinical efficacy of fluconazole, tinidazole and clindamycin vs fluconazole, tinidazole and azithromycin in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis]. / Eficacia clínica de fluconazol, tinidazol y clindamicina vs fluconazol, tinidazol y azitromicina en el tratamiento de infecciones cérvico- vaginales mixtas, incluidas las causadas por Mycoplasma y Chlamydia trachomatis.

BACKGROUND: In the United States 19 million people acquire a sexually transmitted disease every year. Sexually transmitted diseases impact in gynecological terms because they may cause sterility, infertility and ectopic pregnancy. OBJECTIVE: To compare the effectiveness of two combinations of three oral antimicrobial drugs in the treatment of mixed cervical-vaginal infections, included those caused by Mycoplasma and Chlamydia trachomatis. MATERIAL AND METHOD: Aclinical, random, comparative, double-blind study included 50 patients assisting to infectology consult with diagnosis of mixed cervical-vaginal infection. Patients were divided into two groups: Group A (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and azithromycin 250 mg; group B (n = 25): fluconazole 37.5 mg, tinidazole 500 mg and clindamycin 312.5 mg. Patients of both groups received two tablets twice p.o. for one day. Cultures were performed to corroborate the diagnosis and then to demonstrate effectiveness of the schemes studied. For the analysis of the data we used measures of central tendency, dispersion and inferential statistics for comparison of proportions by c2 and Fisher's exact tests with a significance level of p < 0.05. RESULTS: All patient got clinical cure; however, regarding the microbiologic eradication a positive case was identified in group A, requiring rescue treatment. The compliance in both groups was of 100%. In both groups, statistical analysis did not show significant differences. Three patients in group A had mild adverse effects. Patients mean age was 33.4 +/- 5.3 years. CONCLUSIONS: Both treatments showed similar effectiveness against mixed cervical-vaginal infections. Microbiological efficacy was of 96% and 100% in group A and B, respectively, besides, scheme of group B was better tolerated.

Antiprotozoal and antimycobacterial activities of Persea americana seeds.

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC50 <0.634 µg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 µg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 µg/ml). CONCLUSIONS: The CHCl3 and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl3 extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 µg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 µg/ml.

Validation of a modified fluorimetric assay for the screening of trichomonacidal drugs.

A fluorimetric microassay that uses a redox dye to determine the viability of the flagellate Trichomonas vaginalis has been optimised to provide a more sensitive method to evaluate potential trichomonacidal compounds. Resazurin has been used in recent years to test drugs against different parasites, including trichomonadid protozoa; however, the reproducibility of these resazurin-based methods in our laboratory has been limited because the flagellate culture medium spontaneously reduces the resazurin. The objective of this work was to refine the fluorimetric microassay method previously developed by other research groups to reduce the fluorescence background generated by the media and increase the sensitivity of the screening assay. The experimental conditions, time of incubation, resazurin concentration and media used in the microtitre plates were adjusted. Different drug sensitivity studies against T. vaginalis were developed using the 5-nitroimidazole reference drugs, new 5-nitroindazolinones and 5-nitroindazole synthetic derivatives. Haemocytometer count results were compared with the resazurin assay using a 10% solution of 3 mM resazurin dissolved in phosphate buffered saline with glucose (1 mg/mL). The fluorimetric assay and the haemocytometer counts resulted in similar percentages of trichomonacidal activity in all the experiments, demonstrating that the fluorimetric microtitre assay has the necessary accuracy for high-throughput screening of new drugs against T. vaginalis.

Metronidazole immediate release formulations: a fasting randomized open-label crossover bioequivalence study in healthy volunteers.

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters Cmax, Tmax, AUC0-t, AUC0-∞, ke, and t1/2 were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of Cmax, AUC0-t, and AUC0-∞ values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for Cmax (0.92-1.06), AUC0-t (0.97-1.02), and AUC0-∞ (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements.

Validation of a modified fluorimetric assay for the screening of trichomonacidal drugs

A fluorimetric microassay that uses a redox dye to determine the viability of the flagellate Trichomonas vaginalis has been optimised to provide a more sensitive method to evaluate potential trichomonacidal compounds. Resazurin has been used in recent years to test drugs against different parasites, including trichomonadid protozoa; however, the reproducibility of these resazurin-based methods in our laboratory has been limited because the flagellate culture medium spontaneously reduces the resazurin. The objective of this work was to refine the fluorimetric microassay method previously developed by other research groups to reduce the fluorescence background generated by the media and increase the sensitivity of the screening assay. The experimental conditions, time of incubation, resazurin concentration and media used in the microtitre plates were adjusted. Different drug sensitivity studies against T. vaginalis were developed using the 5-nitroimidazole reference drugs, new 5-nitroindazolinones and 5-nitroindazole synthetic derivatives. Haemocytometer count results were compared with the resazurin assay using a 10% solution of 3 mM resazurin dissolved in phosphate buffered saline with glucose (1 mg/mL). The fluorimetric assay and the haemocytometer counts resulted in similar percentages of trichomonacidal activity in all the experiments, demonstrating that the fluorimetric microtitre assay has the necessary accuracy for high-throughput screening of new drugs against T. vaginalis.

Efficacy of the Mentha crispa in the treatment of women with Trichomonas vaginalis infection.

PURPOSE: The aim of this study was to evaluate the efficacy of Mentha crispa in the treatment of women with Trichomonas vaginalis infection (TVI). METHODS: This was a randomized, double-blind, and controlled clinical trial consisting of three phases, pre-treatment, treatment, and post-treatment. Sixty female patients were randomized to a treatment group, M. crispa (24 mg) or secnidazole (2,000 mg), both consisting of single dose. RESULTS: After treatment the proportion of patients without TVI in secnidazole group was 96.6% and in the M. crispa group was 90%, no difference was found between groups (P = 0.6120). We observed improvement in vaginal discharge, malodorous vaginal secretion, dyspareunia, dysuria, pelvic pain, and burning and itching in the genital area in patients of both groups of treatment, with no statistically significant differences between them (P > 0.05). Adverse effects were significantly higher (P = 0.0006) in the secnidazole group (66.6%) than in the M. crispa group (20%), that being mostly nausea and metallic taste with statistically significant differences between treatment groups (P < 0.001). CONCLUSION: This study is the first to show that M. crispa is effective and safe, representing an alternative for the treatment of TVI in women.

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of some benzimidazole derivatives with trichomonicidal activity.

Trichomonosis is a common sexually transmitted infectious disease linked to reproductive health complications. Recently, the benzimidazole nucleus has emerged as a promising scaffold to develop new trichomonicidal agents. Despite the fact that large amounts of experimental data have been accumulated over the past eight years, no quantitative studies have yet been reported on this class of compounds. In our effort to develop new antiparasitic benzimidazole derivatives, we report in this paper CoMFA and CoMSIA studies with an initial set of 70 benzimidazole derivatives with trichomonicidal activity. Four CoMFA models and eight CoMSIA models were generated; ten of these models had values of r(2) > 0.6 and q(2) > 0.5. The best CoMFA model had r(2) = 0.936 and q(2) = 0.634, and the best CoMSIA model had r(2) = 0.858 and q(2) = 0.642. These models were generated by using two conformer selection methodologies (minimum energy conformations and 3D similarity), and three charge types (Mulliken, Gasteiger-Hükel and electrostatic potential atomic charges). The putative active tautomers of 1H-benzimidazole derivatives were selected using 3D-QSAR calculations. All models were validated via an external test set with 13 molecules. The best models satisfied additional validation criteria. The contour maps generated show the most important features that a benzimidazole derivative should have for trichomonicidal activity; they also, suggest that substituents at the 2- and 6-positions are important in the generation of derivatives with strong activity.

Screening and bioguided fractionation of Amaryllidaceae species with anti-Trichomonas vaginalis activity.

The Amaryllidaceae family is known by its ornamental and medicinal value and has attracted considerable attention due to the content of alkaloids of its species, which showed interesting biological properties. The present study evaluated the anti-Trichomonas vaginalis activity of eighteen extracts (12.5 to 0.19 mg/mL) and six isolated alkaloids (125 to 1.9 µg/mL) from Amaryllidaceae species. The alkaloids diminished the trophozoites viability (from 15 to 40 %). The extracts from Hippeastrum breviflorum demonstrated the highest anti-T. vaginalis activity (viability was 60 % reduced), and a bioguided study was conducted. Six fractions with antiprotozoal activity had lycorine and lycosinine as major components suggesting a synergistic effect, taking into account the higher anti-T. vaginalis activity of extracts when compared to isolated alkaloids. Our results point out the antiprotozoal potential of the Amaryllidaceae species against T. vaginalis. This parasite causes trichomonosis, the most prevalent nonviral sexually transmitted diseases (STD) worldwide and a public health problem that requires new therapeutic alternatives as well bioactive natural products.

Ultrastructural alterations induced by Δ(24(25))-sterol methyltransferase inhibitors on Trichomonas vaginalis.

Trichomonas vaginalis is an important human parasite that causes trichomoniasis, a cosmopolitan sexually transmitted disease. Currently, the treatment of choice for T. vaginalis infections is metronidazole. The increase in metronidazole-resistant parasites and undesirable side effects of this drug make the search for alternative chemotherapeutic approaches a priority for the management of trichomoniasis. Here, the antiproliferative and ultrastructural effects of sterol biosynthesis inhibitors against T. vaginalis were investigated. It was found that 22,26-azasterol (5 µM) and 24(R,S),25-epiminolanosterol (10 µM), known inhibitors of Δ(24(25))-sterol methyltransferase, exhibited antiproliferative effects on T. vaginalis trophozoites cultured in vitro. Morphological analyses showed that azasterols induced changes in the ultrastructure of T. vaginalis. The most significant alterations were (1) membrane blebbing and disruption, (2) wrinkled cells and (3) the formation of cell clusters. In addition, autophagic vacuoles, Golgi duplication arrest, an abnormal Golgi enlargement and damaged hydrogenosomes were also observed. Nonspecific cytotoxicity assays using the cultured mammalian cell lines Madin-Darby canine kidney cells showed no effect of the azasterols on the viability and proliferation of these cells at a concentration that significantly inhibited the proliferation of T. vaginalis, indicating a selective antiparasitic action. Taken together, these results suggest that azasterols could be important compounds in the development of novel chemotherapeutic approaches against T. vaginalis.

Empiema pleural causado por tricomonas: caso clínico / Pleural empyema caused by trichomonas: case report

Pleural empyema formation is one of the potential complications of lower respiratory tract infections and it is characterized by bacterial organisms seen on gram stain or the aspiration of pus on thoracentesis. Very rarely empyema can be caused by trichomonas species, of which Trichomonas Tenax appears to be the most common cause. In this article we report the case of a 51-year-old man who developed a pleural empyema caused by trichomonas, and review the available literature of this rare infection of unknown incidence and uncertain pathogenetic significance. Our patient was treated with metronidazole, however complete cure was not achieved and pulmonary decortication was necessary for the successful outcome. As far as we know, this is the first case of pleural empyema caused by trichomonas reported in Chile.

La formación de un empiema pleural es una de las potenciales complicaciones de las infecciones de la vía aérea inferior, y se caracteriza por la observación de bacterias en la tinción de Gram, o la aspiración de pus en la toracocentesis. Muy infrecuentemente el empiema puede ser causado por alguna de las especies de tricomonas, de las cuales Trichomonas Tenax parece ser la causa más común. En este artículo, reportamos el caso de un hombre de 51 años que desarrolló un empiema pleural causado por tricomonas, y revisamos la literatura disponible de esta rara infección, de incidencia desconocida, y significancia patogénica incierta. Nuestro paciente fue tratado con metronidazol, observándose sólo una respuesta parcial, necesitándose decorticación pulmonar para una recuperación completa. Hasta donde sabemos, este es el primer caso de empiema pleural causado por tricomonas reportado en Chile.