RESUMO
Leishmania braziliensis (L. braziliensis) causes cutaneous leishmaniasis (CL) in the New World. The costs and the side effects of current treatments render imperative the development of new therapies that are affordable and easy to administer. Topical treatment would be the ideal option for the treatment of CL. This underscores the urgent need for affordable and effective treatments, with natural compounds being explored as potential solutions. The alkaloid piperine (PIP), the polyphenol curcumin (CUR), and the flavonoid quercetin (QUE), known for their diverse biological properties, are promising candidates to address these parasitic diseases. Initially, the in vitro cytotoxicity activity of the compounds was evaluated using U-937 cells, followed by the assessment of the leishmanicidal activity of these compounds against amastigotes of L. braziliensis. Subsequently, a golden hamster model with stationary-phase L. braziliensis promastigote infections was employed. Once the ulcer appeared, hamsters were treated with QUE, PIP, or CUR formulations and compared to the control group treated with meglumine antimoniate administered intralesionally. We observed that the three organic compounds showed high in vitro leishmanicidal activity with effective concentrations of less than 50 mM, with PIP having the highest activity at a concentration of 8 mM. None of the compounds showed cytotoxic activity for U937 macrophages with values between 500 and 700 mM. In vivo, topical treatment with QUE daily for 15 days produced cured in 100% of hamsters while the effectiveness of CUR and PIP was 83% and 67%, respectively. No failures were observed with QUE. Collectively, our data suggest that topical formulations mainly for QUE but also for CUR and PIP could be a promising topical treatment for CL. Not only the ease of obtaining or synthesizing the organic compounds evaluated in this work but also their commercial availability eliminates one of the most important barriers or bottlenecks in drug development, thus facilitating the roadmap for the development of a topical drug for the management of CL caused by L. braziliensis.
Assuntos
Alcaloides , Antiprotozoários , Benzodioxóis , Curcumina , Leishmania braziliensis , Leishmaniose Cutânea , Piperidinas , Alcamidas Poli-Insaturadas , Cricetinae , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Curcumina/farmacologia , Leishmaniose Cutânea/parasitologia , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Mesocricetus , Antiprotozoários/farmacologiaRESUMO
BACKGROUND: Epstein-Barr virus (EBV) is a human gammaherpesvirus etiologically linked to several benign and malignant diseases. EBV-associated malignancies exhibit an unusual global distribution that might be partly attributed to virus and host genetic backgrounds. OBJECTIVES: To assemble a new genome of EBV (CEMO3) from a paediatric Burkitt's lymphoma from Rio de Janeiro State (Southeast Brazil). In addition, to perform global phylogenetic analysis using complete EBV genomes, including CEMO3, and investigate the genetic relationship of some South American (SA) genomes through EBV subgenomic targets. METHODS: CEMO3 was sequenced through next generation sequencing and its coverage and gaps were corrected through the Sanger method. CEMO3 and 67 EBV genomes representing diverse geographic regions were evaluated through maximum likelihood phylogenetic analysis. Further, the polymorphism of subgenomic regions of some SA EBV genomes were assessed. FINDINGS: The whole bulk tumour sequencing yielded 23,217 reads related to EBV, which 172,713 base pairs of the newly EBV genome CEMO3 was assembled. The CEMO3 and most SA EBV genomes clustered within the SA subclade closely related to the African Raji strain, forming the South American/Raji clade. Notably, these Raji-related genomes exhibit significant genetic diversity, characterised by distinctive synapomorphies at some gene levels absent in the original Raji strain. CONCLUSION: The CEMO3 represents a new South American EBV genome assembled. Albeit the majority of EBV genomes from SA are Raji-related, it harbours a high diversity different from the original Raji strain.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Criança , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Filogenia , Genoma Viral/genética , BrasilRESUMO
In this study, six analogs of 2-arylquinoline were synthesized and evaluated for their in vitro and in vivo antiplasmodial and leishmanicidal activity. At a later stage, hemolytic activity and druggability were tested in vitro and in silico, respectively, observing as a result: firstly, compounds showed half-maximal effective concentration (EC50) values between 3.6 and 19.3 µM. Likewise, a treatment using the compounds 4a-f caused improvement in most of the treated hamsters and cured some of them. Regarding the antiplasmodial activity, the compounds showed moderate to high activity, although they did not show hemolytic activity. Furthermore, 4e and 4f compounds were not able to control P. berghei infection when administered to animal models. Molecular dynamic simulations, molecular docking and ligand binding affinity indicate good characteristics of the studied compounds, which are expected to be active. And lastly, the compounds are absorbable at the hematoencephalic barrier but not in the gastrointestinal tract. In summary, ADMET properties suggest that these molecules may be used as a safe treatment against Leishmania.
Assuntos
Antimaláricos , Antiprotozoários , Leishmania , Animais , Antimaláricos/farmacologia , Antimaláricos/química , Simulação de Acoplamento Molecular , Antiprotozoários/farmacologia , Antiprotozoários/química , Relação Estrutura-AtividadeRESUMO
Cutaneous leishmaniasis (CL) is a neglected disease caused by an intracellular parasite of the Leishmania genus. CL lacks tools that allow its understanding and treatment follow-up. This article presents the use of metrical and optical tools for the analysis of the temporal evolution of treated skin ulcers caused by CL in an animal model. Leishmania braziliensis and L. panamensis were experimentally inoculated in golden hamsters, which were treated with experimental and commercial drugs. The temporal evolution was monitored by means of ulcers' surface areas, as well as absorption and scattering optical parameters. Ulcers' surface areas were obtained via photogrammetry, which is a procedure that allowed for 3D modeling of the ulcer using specialized software. Optical parameters were obtained from a spectroscopy study, representing the cutaneous tissue's biological components. A one-way ANOVA analysis was conducted to identify relationships between both the ulcers' areas and optical parameters. As a result, ulcers' surface areas were found to be related to the following optical parameters: epidermis thickness, collagen, keratinocytes, volume-fraction of blood, and oxygen saturation. This study is a proof of concept that shows that optical parameters could be associated with metrical ones, giving a more reliable concept during the assessment of a skin ulcer's healing.
Assuntos
Leishmaniose Cutânea , Úlcera Cutânea , Cricetinae , Animais , Úlcera , Leishmaniose Cutânea/tratamento farmacológico , Pele , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/parasitologia , Mesocricetus , Modelos Animais de DoençasRESUMO
BACKGROUND Epstein-Barr virus (EBV) is a human gammaherpesvirus etiologically linked to several benign and malignant diseases. EBV-associated malignancies exhibit an unusual global distribution that might be partly attributed to virus and host genetic backgrounds. OBJECTIVES To assemble a new genome of EBV (CEMO3) from a paediatric Burkitt's lymphoma from Rio de Janeiro State (Southeast Brazil). In addition, to perform global phylogenetic analysis using complete EBV genomes, including CEMO3, and investigate the genetic relationship of some South American (SA) genomes through EBV subgenomic targets. METHODS CEMO3 was sequenced through next generation sequencing and its coverage and gaps were corrected through the Sanger method. CEMO3 and 67 EBV genomes representing diverse geographic regions were evaluated through maximum likelihood phylogenetic analysis. Further, the polymorphism of subgenomic regions of some SA EBV genomes were assessed. FINDINGS The whole bulk tumour sequencing yielded 23,217 reads related to EBV, which 172,713 base pairs of the newly EBV genome CEMO3 was assembled. The CEMO3 and most SA EBV genomes clustered within the SA subclade closely related to the African Raji strain, forming the South American/Raji clade. Notably, these Raji-related genomes exhibit significant genetic diversity, characterised by distinctive synapomorphies at some gene levels absent in the original Raji strain. CONCLUSION The CEMO3 represents a new South American EBV genome assembled. Albeit the majority of EBV genomes from SA are Raji-related, it harbours a high diversity different from the original Raji strain.
RESUMO
Malnutrition is one of the main public health problems affecting early childhood development, compromising the health and quality of life of thousands of Peruvian children. The main contribution of this work is the analysis of the nutritional status of the infant population of the Chirikyacu Indigenous Community of Peru in order to evaluate current and future food policies. It is a cross-sectional study with a sample of 19 children between 6 months and 6 years of age. Sociodemographic, anthropometric, clinical variables and dietary habits were analyzed from 7 January to 4 February 2018. The mean age of the children was 29.74 months (SD = 23.91). We found statistically significant differences between the BMI values of boys and girls (p < 0.05; Mann−Whitney test). According to the z-scores, 35.29% suffer from malnutrition, although in no case is it severe. Hair, nails and skin were in good condition in general, except for some cases showing signs of nutritional deficiency. Dietary patterns are based on legumes, vegetables, dairy products, ice cream, cookies and sweets, and are considered insufficient to cover basic needs; water intake was also insufficient. Breastfeeding lasted an average of 14 months (SD = 2.9). We found a prevalence of malnutrition higher than that established by the WHO in Latin America among the children of Chirikyacu. The dietary pattern is insufficient to cover basic needs, so it is necessary to continue with nutritional educational interventions to improve it.
Assuntos
Desnutrição , Avaliação Nutricional , Masculino , Criança , Feminino , Humanos , Lactente , Pré-Escolar , Peru/epidemiologia , Estudos Transversais , Qualidade de Vida , Estado Nutricional , Desnutrição/epidemiologia , AntropometriaRESUMO
Leishmaniasis may occur in three different clinical forms, namely, visceral, mucocutaneous and cutaneous, which are caused by different species of trypanosomatid protozoans of the genus Leishmania. Pentavalent antimonials are the leading treatment for cutaneous leishmaniasis despite the hepatic, renal, and cardiac toxicity. In addition, the response of some Leishmania species to pentavalent antimonials is increasingly poorer, and therefore new and more potent therapeutic alternatives are needed. Arnica montana L., Asteraceae, is a traditional medicinal plant of Europe and preparations of its flowers are commonly used externally to treat disorders of the musculoskeletal system as well as superficial inflammatory conditions. Previous studies have shown that Arnica tincture (AT), an ethanolic extract prepared from the flowerheads of Arnica montana as well as isolated Arnica sesquiterpene lactones (STLs) have antileishmanial activity in vitro against L. donovani and L. infantum, as well as in vivo against L. braziliensis. In this work, we studied the in vitro cytotoxicity and antileishmanial activity of AT and STLs against both L. braziliensis and L. tropica. The in vivo therapeutic effect of AT was studied in hamsters with cutaneous Leishmaniasis (CL) caused by experimental infection with L. braziliensis and L. tropica. Furthermore, various semisolid Arnica preparations were also evaluated against L. braziliensis. The STLs and the AT possess a very high in vitro activity against both Leishmania species with median effective concentrations (EC50) ranging from 1.9 to 5.9 µg/mL. The AT was not cytotoxic for human tissue macrophages, skin fibroblasts, and hepatic cells. The therapeutic response of hamsters infected with L. braziliensis to the topical treatment with AT was 87.5% at a dose of 19.2 µg STL/2× day/60 d, 72.7% at doses of 19.2 µg STL/1× d/60 d and 67% at a dose of 38.4 µg STL/2× d/60 d. In turn, the therapeutic response in hamsters infected with L. tropica was 100% when treated at a dose of 19.2 µg STL/2× day/60 d and 71% at a dose of 38.4 µg STL/2× d/60 d. On the other hand, the effectiveness of treatment with glucantime administered intralesionally at a dose of 200 mg/every three days for 30 days was 62.5% for L. braziliensis and 37.5% for L. tropica infection. These results are promising and encourage the implementation of clinical trials with AT in CL patients as a first step to using AT as a drug against CL.
RESUMO
Abstract Rabbits have played an important role in ophthalmological research processes, however in the environment there has been a deficiency of sensitive equipment in measurement of intraocular pressure for this species. To compare intraocular pressure (IOP) measured with rebound (TONOVET Plus®) and applanation (TONO-PEN VET®) tonometry in healthy New Zealand rabbits treated with Amlodipine. Twelve healthy male New Zealand white rabbits, 5 months old; two groups with 6 individuals were used in this study. The experimental group was given Amlodipine® at a dose of 5 mg/kg, once a day for a month. Blood pressure and intraocular pressure were measurement before treatment and 6 h after treatment in a period of one month. A trend is noted where the group of animals treated with amlodipine® presents lower values than the control group, both in systolic and diastolic pressure. The systolic pressure of the control group showed an average of 116.5 ± 7.9 mmHg and 117.4 ± 8.9 mmHg and the treatment group showed an average of 113.6 ± 7.9 mmHg and 111.8 ± 10.0 mmHg (pretreatment and posttreatment respectively). Tonometry: the values obtained using the TONOVET Plus® (19 ± 3 mmHg) are on average higher than the values obtained using the TONO-PEN VET® (17 ± 3 mmHg). It was possible to demonstrate the relationship between systemic blood pressure and intraocular pressure in New Zealand white rabbits. Rebound tonometry showed less variability in results than applanation tonometry. This study confirmed that both tonometers are reliable for measuring IOP in rabbits.
Resumen Los conejos han jugado un papel importante en los procesos de investigación oftalmológica, sin embargo, en el medio ha existido una deficiencia de equipos sensibles en la medición de la presión intraocular para esta especie. Para comparar la presión intraocular (PIO) medida con la tonometría de rebote (TONOVET Plus®) y aplanación (TONO-PEN VET®) en conejos Nueva Zelanda sanos y tratados con Amlodipino, fueron usados doce conejos Nueva Zelanda, machos, sanos, de 5 meses de edad y distribuidos en dos grupos con 6 individuos cada uno. El grupo experimental recibió Amlodipino® en una dosis de 5 mg/kg, una vez al día durante un mes. La presión arterial y la presión intraocular se midieron antes del tratamiento y 6 h después del tratamiento en un período de un mes. Se observa una tendencia donde el grupo de animales tratados con amlodipino® presenta valores más bajos que el grupo control, tanto en presión sistólica como diastólica. La presión sistólica del grupo control mostró un promedio de 116,5 ± 7,9 mmHg y 117,4 ± 8,9 mmHg y el grupo de tratamiento mostró un promedio de 113,6 ± 7,9 mmHg y 111,8 ± 10,0 mmHg (pretratamiento y postratamiento respectivamente). Tonometría: los valores obtenidos con el TONOVET Plus® (19 ± 3 mmHg) son en promedio superiores a los valores obtenidos con el TONO-PEN VET® (17 ± 3 mmHg). Fue posible demostrar la relación entre la presión arterial sistémica y la presión intraocular en conejos blancos Nueva Zelanda. La tonometría de rebote mostró menos variabilidad en los resultados que la tonometría de aplanamiento. Este estudio confirmó que ambos tonómetros son confiables para medir la PIO en conejos.
Resumo Os coelhos têm desempenhado um papel importante nos processos de pesquisa oftalmológica, porém no meio tem havido uma deficiência de equipamentos sensíveis na medida da pressão intraocular para esta espécie. Comparar a pressão intraocular (PIO) medida com tonometria de rebote (TONOVET Plus®) e de aplanação (TONO-PEN VET®) em coelhos saudáveis da Nova Zelândia tratados com Amlodipina®. Foram utilizados neste estudo doze coelhos brancos da Nova Zelândia, machos saudáveis, 5 meses de idade; distribuído em dois grupos com 6 indivíduos cada um. O grupo experimental recebeu Amlodipina® na dose de 5 mg / kg, uma vez ao dia durante um mês. A pressão arterial e a pressão intraocular foram medidas antes do tratamento e 6 horas após o tratamento em um período de um mês. Nota-se uma tendência onde o grupo de animais tratados com amlodipina® apresenta valores inferiores ao grupo controle, tanto na pressão sistólica quanto na diastólica. A pressão sistólica do grupo controle apresentou média de 116,5 ± 7,9 mmHg e 117,4 ± 8,9 mmHg e o grupo tratamento apresentou média de 113,6 ± 7,9 mmHg e 111,8 ± 10,0 mmHg (pré-tratamento e pós-tratamento, respectivamente). Tonometria: os valores obtidos com o TONOVET Plus® (19 ± 3 mmHg) são em média superiores aos valores obtidos com o TONO-PEN VET® (17 ± 3 mmHg). Foi possível demonstrar a relação entre a pressão arterial sistêmica e a pressão intraocular em coelhos brancos da Nova Zelândia. A tonometria de rebote mostrou menos variabilidade nos resultados do que a tonometria de aplanação. Este estudo confirmou que ambos os tonômetros são confiáveis para medir a PIO em coelhos.
RESUMO
Cutaneous leishmaniasis (CL) is a parasitic disease that produces chronic skin ulcers. Although it has a worldwide presence, it is a neglected disease that still requires novel tools for its management. In order to study the use of optical tools in CL, this article presents a preliminary study of the correlation between CL histopathological and optical parameters. Optical parameters correspond to absorption and scattering coefficients obtained from diffuse reflectance spectra of treated CL in golden hamsters. Independently, histopathological data were collected from the same hamsters. As a result, after Spearman correlation and the Kruskal-Wallis test, inverse correlation was found between absorption/scattering optical parameters and inflammatory histopathological values, such as the scattering parameter related to the diameter of fibroblasts with the histopathological parameters of fibrosis, polymorphonuclear neutrophils, lymphocytes, plasmocytes, hyperplasia, and Leishmania, and the absorption parameter oxygen saturation showed a relation with the granulation tissue histopathological parameter. These correlations agree with the expected behavior of tissue composition during the healing process in CL. The results correspond to a proof of concept that shows that optical diffuse reflectance-based tools and methods could be considered as an alternative to assist in CL diagnosis and treatment follow-up.
Assuntos
Leishmaniose Cutânea , Úlcera Cutânea , Animais , Cricetinae , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Linfócitos , Saturação de Oxigênio , ÚlceraRESUMO
The study of long non-coding RNAs (lncRNAs), greater than 200 nucleotides, is central to understanding the development and progression of many complex diseases. Unlike proteins, the functionality of lncRNAs is only subtly encoded in their primary sequence. Current in-silico lncRNA annotation methods mostly rely on annotations inferred from interaction networks. But extensive experimental studies are required to build these networks. In this work, we present a graph-based machine learning method called FGGA-lnc for the automatic gene ontology (GO) annotation of lncRNAs across the three GO subdomains. We build upon FGGA (factor graph GO annotation), a computational method originally developed to annotate protein sequences from non-model organisms. In the FGGA-lnc version, a coding-based approach is introduced to fuse primary sequence and secondary structure information of lncRNA molecules. As a result, lncRNA sequences become sequences of a higher-order alphabet allowing supervised learning methods to assess individual GO-term annotations. Raw GO annotations obtained in this way are unaware of the GO structure and therefore likely to be inconsistent with it. The message-passing algorithm embodied by factor graph models overcomes this problem. Evaluations of the FGGA-lnc method on lncRNA data, from model and non-model organisms, showed promising results suggesting it as a candidate to satisfy the huge demand for functional annotations arising from high-throughput sequencing technologies.
RESUMO
Leishmaniasis is a neglected, parasitic tropical disease caused by an intracellular protozoan from the genus Leishmania. Quinoline alkaloids, secondary metabolites found in plants from the Rutaceae family, have antiparasitic activity against Leishmania sp. N-methyl-8-methoxyflindersin (1), isolated from the leaves of Raputia heptaphylla and also known as 7-methoxy-2,2-dimethyl-2H,5H,6H-pyran[3,2-c]quinolin-5-one, shows antiparasitic activity against Leishmania promastigotes and amastigotes. This study used in silico tools to identify synthetic quinoline alkaloids having structure similar to that of compound 1 and then tested these quinoline alkaloids for their in vitro antiparasitic activity against Leishmania (Viannia) panamensis, in vivo therapeutic response in hamsters suffering from experimental cutaneous leishmaniasis (CL), and ex vivo immunomodulatory potential in healthy donors' human peripheral blood (monocyte)-derived macrophages (hMDMs). Compounds 1 (natural), 2 (synthetic), and 8 (synthetic) were effective against intracellular promastigotes (9.9, 3.4, and 1.6 µg/mL medial effective concentration [EC50], respectively) and amastigotes (5.07, 7.94, and 1.91 µg/mL EC50, respectively). Compound 1 increased nitric oxide production in infected hMDMs and triggered necrosis-related ultrastructural alterations in intracellular amastigotes, while compound 2 stimulated oxidative breakdown in hMDMs and caused ultrastructural alterations in the parasite 4 h posttreatment, and compound 8 failed to induce macrophage modulation but selectively induced apoptosis of infected hMDMs and alterations in the intracellular parasite ultrastructure. In addition, synthetic compounds 2 and 8 improved the health of hamsters suffering from experimental CL, without evidence of treatment-associated adverse toxic effects. Therefore, synthetic compounds 2 and 8 are potential therapeutic candidates for topical treatment of CL.
Assuntos
Antiprotozoários/farmacologia , Compostos Heterocíclicos com 3 Anéis/farmacologia , Leishmania guyanensis/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Alcaloides/farmacologia , Animais , Antiprotozoários/química , Cricetinae , Modelos Animais de Doenças , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Leishmania guyanensis/patogenicidade , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Óxido Nítrico/genética , Folhas de Planta/química , Quinolinas/química , Quinolonas/farmacologia , Rutaceae/químicaRESUMO
Single nucleotide variants (SNVs) occurring in a protein coding gene may disrupt its function in multiple ways. Predicting this disruption has been recognized as an important problem in bioinformatics research. Many tools, hereafter p-tools, have been designed to perform these predictions and many of them are now of common use in scientific research, even in clinical applications. This highlights the importance of understanding the semantics of their outputs. To shed light on this issue, two questions are formulated, (i) do p-tools provide similar predictions? (inner consistency), and (ii) are these predictions consistent with the literature? (outer consistency). To answer these, six p-tools are evaluated with exhaustive SNV datasets from the BRCA1 gene. Two indices, called K a l l and K s t r o n g , are proposed to quantify the inner consistency of pairs of p-tools while the outer consistency is quantified by standard information retrieval metrics. While the inner consistency analysis reveals that most of the p-tools are not consistent with each other, the outer consistency analysis reveals they are characterized by a low prediction performance. Although this result highlights the need of improving the prediction performance of individual p-tools, the inner consistency results pave the way to the systematic design of truly diverse ensembles of p-tools that can overcome the limitations of individual members.
Assuntos
Proteína BRCA1 , Biologia Computacional , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , HumanosRESUMO
OBJECTIVE: To develop an analog visual instrument to diagnose patients with erectile dysfunction, to establish the ability to understand it in the population and to compare it with the "gold standard" scale for the disease, providing a basis for its future validation. MATERIAL AND METHODS: Cross-sectional study that included all 18 years old men and older, of the urology service of Juarez Hospital of Mexico City, whose reason for consultation was erectile dysfunction. The patients were assessed using two clinical tools: the International Index of Erectile Function and the Erectile Function Pineda Visual Analog Scale consecutively. The sociodemographic features of the patients included age, language, educational level, location and marital status. The comprehension, the response time and the degree of dysfunction were assessed. The qualitative variables were analyzed with Pearson's chi square and the quantitative variables with the Mann-Whitney U test. RESULTS: The final registry included 227 patients, finding an average age of 55.6±14 years. The majority of the population (94.7%) communicated through the Spanish language. There are statistically significant differences between both scales, in the understanding, the degree of dysfunction, the final score and the response time, all with a p=,0001. The patients with lower educational level were able to respond completely and more quickly the Erectile Function Pineda Visual Analog Scale questionnaire than the International Index of Erectile Function. However, we cannot assume that they understand it better. CONCLUSIONS: The Erectile Function Pineda Visual Analog Scale is a prototype of a visual scale that can be used as an alternative to the International Index of Erectile Function questionnaire, especially in patients with academic and linguistic limitations.
Assuntos
Disfunção Erétil/diagnóstico , Inquéritos e Questionários , Adulto , Idoso , Estudos Transversais , Escolaridade , Humanos , Masculino , México , Pessoa de Meia-Idade , Escala Visual AnalógicaRESUMO
American visceral leishmaniasis (VL) is a vector-borne disease caused by Leishmania infantum (syn. chagasi) and transmitted by Lutzomyia longipalpis and Lutzomyia evansi phlebotomine sand flies. Dogs not only are the main host reservoirs of the parasite but also suffer the disease; therefore, canine VL (CVL) has assumed an important role in public health. In Colombia, human and CVL are restricted to two transmission foci: one in the north region (Caribbean coast) and other in the central south region (middle Magdalena River Valley). We present a CVL case involving a 2-year-old male dog with a history of lack of appetite, general weakness, and progressive loss of weight. A diagnosis of CVL was obtained using the direct parasitological examination in spleen and bone marrow samples stained with Giemsa and RT-qPCR. The infecting Leishmania species was identified as L. infantum by PCR-restriction fragment length polymorphism amplifying the Hsp70 gene from bone marrow and spleen samples and confirming by sequencing. The patient responded favorably to treatment with intramuscular meglumine antimoniate at a dose of 100 mg/kg daily for 8 weeks and oral allopurinol at a dose of 10 mg/kg every 12 hours until new indication. This is the first report of urban CVL in the city of Cali, Colombia, highlighting the need for surveillance and control programs in the municipalities of the department of Valle del Cauca, a region where VL has not been informed before. The findings also indicate the need to reinforce the surveillance programs in other rural and urban regions of the country where favorable eco-epidemiological conditions exist.
Assuntos
Doenças do Cão/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/veterinária , Alopurinol/uso terapêutico , Animais , Antimetabólitos/uso terapêutico , Antiprotozoários/uso terapêutico , Sequência de Bases , Cidades/epidemiologia , Colômbia/epidemiologia , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Doenças do Cão/epidemiologia , Cães , Leishmania infantum/genética , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/epidemiologia , Masculino , Antimoniato de Meglumina/uso terapêuticoRESUMO
Through bioguided in vitro assays, the leishmanicidal and trypanocidal effects of an ethanol extract, seven fractions, and two pure substances obtained from Clathrotropis brunnea Amshoff sawdust were established. The effectiveness of the two metabolites was confirmed in a hamster model of cutaneous Leishmaniasis by Leishmania braziliensis and in Balb/c mice infected by Trypanosoma cruzi. In vitro, 3,5-dimethoxystilbene was the most active against L. braziliensis amastigotes, with a median lethal concentration (LC50) of 4.18 µg/ml (17.40 µM) and a selectivity index of 3.55, but showed moderate activity for T. cruzi, with a median effective concentration (EC50) value of 27.7 µg/ml (115.36 µM). Flavanone pinostrobin, meanwhile, showed high activity against L. braziliensis, with an EC50 of 13.61 µg/ml (50.39 µM), as well as for T. cruzi, with an EC50 of 18.2 µg/ml (67.38 µM). The animal model assay of cutaneous Leishmaniasis showed that 50% of the hamsters treated with pinostrobin were definitively cured the cutaneous ulcer, and 40% showed an improvement, with a reduction in the size of the of 84-87%. Moreover, Balb/c mice experimentally infected with T. cruzi and treated for 25 days with pinostrobin experienced a reduction in their parasitemia by 71%. These results demonstrate the high potential of C. brunnea Amshoff against cutaneous Leishmaniasis and American trypanosomiasis and indicate the pharmacological potential of waste from the wood industry, which has tons of potentially useful chemicals for the development of new medicines.
RESUMO
Cutaneous leishmaniasis (CL) is a neglected tropical disease that requires novel tools for its understanding, diagnosis, and treatment follow-up. In the cases of other cutaneous pathologies, such as cancer or cutaneous ulcers due to diabetes, optical diffuse reflectance-based tools and methods are widely used for the investigation of those illnesses. These types of tools and methods offer the possibility to develop portable diagnosis and treatment follow-up systems. In this article, we propose the use of a three-layer diffuse reflectance model for the study of the formation of cutaneous ulcers caused by CL. The proposed model together with an inverse-modeling procedure were used in the evaluation of diffuse-reflectance spectral signatures acquired from cutaneous ulcers formed in the dorsal area of 21 golden hamsters inoculated with Leishmanisis braziliensis. As result, the quantification of the model's variables related to the main biological parameters of skin were obtained, such as: diameter and volumetric fraction of keratinocytes, collagen; volumetric fraction of hemoglobin, and oxygen saturation. Those parameters show statistically significant differences among the different stages of the CL ulcer formation. We found that these differences are coherent with histopathological manifestations reported in the literature for the main phases of CL formation.
Assuntos
Leishmaniose Cutânea/patologia , Úlcera Cutânea/patologia , Pele/química , Espectrofotometria/métodos , Animais , Colágeno/fisiologia , Cricetinae , Modelos Animais de Doenças , Processamento Eletrônico de Dados , Feminino , Hemoglobinas/química , Leishmaniose Cutânea/metabolismo , Masculino , Mesocricetus , Oxigênio/química , Pele/patologia , Úlcera Cutânea/metabolismo , Úlcera Cutânea/parasitologiaRESUMO
Hamsters are a suitable experimental model for visceral leishmaniasis (VL) because they mimic the features of the human disease. However, the infection after inoculation can only be verified after sacrifice of the animal or several months following infection, when obvious signs of the disease appear, compromising animal welfare in both cases. Unlike other studies, the present work used an inoculum of 5â¯×â¯108 promastigotes to induce Leishmania infantum infection, which are easier to produce than amastigotes, in in vitro culture. The infection in hamsters was detected using non-invasive methods such as ultrasound imaging (USG) and blood gases, in addition to alterations in hematological parameters and weight loss. USG imaging identified changes in the size and echogenicity of the spleen, liver, and kidney as early as week 9 (W9) after experimental inoculation. However, blood gases, specially lactate, was increased in response to the infection, with statistically significant differences between W9 and W0 (before infection) (pâ¯<â¯0.0001). The conventional hematological parameters showed progressive pancytopenia and weight loss of 15% and 10% in infected males and females respectively, at W9 versus W0 (pâ¯<â¯0.0001). Histological changes in the liver, kidney, and spleen correlated with changes detected by USG imaging and the number of parasites increased proportionately to the progression of infection, being higher at W24. In conclusion, USG imaging, lactate levels, hematocrit and hemoglobin parameters, along with weight loss allowed early detection of infection, which was then confirmed by the identification and quantification of parasites in the blood, liver, and spleen by qRT-PCR. In contrast, blood chemistry was not a useful tool in the early detection of VL infection because it did not correlate with alterations evident in other techniques. The use of non-invasive tools eliminates the need for animal sacrifice to confirm infection, thus reducing the number of animals required for a given study and eliminating the need to wait until the appearance of severe signs of infection, which affect animal welfare. These tools are therefore advantageous for use in preclinical studies, for studying pathogenesis as also for vaccine and drug development.
Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Animais , Análise Química do Sangue , Gasometria , Cricetinae , Modelos Animais de Doenças , Feminino , Testes Hematológicos , Rim/diagnóstico por imagem , Rim/patologia , Leishmania infantum/classificação , Leishmaniose Visceral/sangue , Leishmaniose Visceral/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/parasitologia , Fígado/patologia , Masculino , Mesocricetus , Reação em Cadeia da Polimerase em Tempo Real , Fatores Sexuais , Baço/diagnóstico por imagem , Baço/parasitologia , Baço/patologia , Ultrassonografia , Aumento de PesoRESUMO
BACKGROUND: The rupture of the cavernous body (faux pas du coit) refers to the solution of continuity in its surrounding tunica albuginea. It occurs in one of 175,000 hospital admissions, accounting for 58% of penile lesions. When the erect penis flexes abnormally, the abrupt increase in intracavernous pressure exceeds the tensile strength of the tunica albuginea and often determines transverse laceration of the proximal body of the penis. CLINICAL CASE: A 29-year-old male patient presented to the emergency department for an 8-h course of evolution characterized by detumescence, lateral deviation, violet coloration and penile pain, following the introduction of the erect penis into his underwear. The patient was taken as soon as possible to surgical exploration and a 1 × 1 cm continuity solution was repaired in the right corpus cavernosum. CONCLUSION: The fracture of the penis is a rare disease and a urological emergency. Immediate repair of the rupture of the penis has a low complication rate, shorter hospital stay and better long-term results.
ANTECEDENTES: La rotura del cuerpo cavernoso (faux pas du coit) se refiere a la solución de continuidad en su túnica albugínea circundante. Se presenta en una de 175,000 admisiones hospitalarias, representando el 58% de las lesiones peneanas. Cuando el pene erecto se dobla anormalmente, el incremento abrupto de la presión intracavernosa excede la fuerza tensional de la túnica albugínea y determina a menudo la laceración transversal del cuerpo proximal del pene. CASO CLÍNICO: Paciente masculino de 29 años de edad que se presentó al servicio de urgencias por un padecimiento de 8 horas de evolución caracterizado por detumescencia, desviación lateral, coloración violácea y dolor peneanos, posterior a la introducción del pene erecto en su ropa interior. Se llevó al paciente lo antes posible a exploración quirúrgica y se realizó reparación de una solución de continuidad de 1 × 1 cm en el cuerpo cavernoso derecho. CONCLUSIÓN: La fractura del pene es una patología poco frecuente y una emergencia urológica. La reparación inmediata de la rotura del pene tiene una baja tasa de complicaciones, menor estancia hospitalaria y mejores resultados a largo plazo.
Assuntos
Pênis/lesões , Pênis/cirurgia , Ruptura/cirurgia , Adulto , Humanos , MasculinoRESUMO
Resumen Introducción La enfermedad litiásica renal es un padecimiento común que afecta a casi una de cada 11 personas. El tratamiento médico-quirúrgico de la enfermedad litiásica ha experimentado una dramática evolución durante las últimas 3 décadas. La laparoscopia se convirtió en una alternativa a la cirugía abierta y se ha considerado una herramienta útil para manejar muchas condiciones urológicas. Objetivo Conocer las indicaciones, diagnóstico y tratamiento actual de los litos renales piélicos. Presentación del caso Mujer de 47 años de edad con dolor lumbar izquierdo acompañado de polaquiuria, tenesmo, urgencia y hematuria. Se le efectuó una urotomografía en la que se apreció una imagen hiperdensa en la pelvis renal izquierda. Se indicó un tratamiento quirúrgico por pielolitotomía laparoscópica izquierda. Conclusiones Los procedimientos laparoscópicos se han convertido en una opción en el armamento del urólogo para el tratamiento de la litiasis del tracto urinario superior.
Abstract Introduction Renal lithiasis is a common disease, affecting almost one in 11 people. The medical-surgical treatment of stone disease has experienced a dramatic evolution during the last three decades. Laparoscopy became an alternative to open surgery and has been considered as a useful tool to handle many urological conditions. Objective To know the indications, diagnosis and current treatment of renal pelvis stones. Case report A 47-year-old female patient presented with left lower back pain accompanied by pollakiuria, tenesmus, urgency and hematuria. A urotomography was performed identifying a hyperdense image in the left renal pelvis. Surgical treatment was indicated by laparoscopic pyelolithotomy. Conclusions Laparoscopic procedures have become an option in the urological armament for the treatment of upper urinary tract lithiasis.
RESUMO
The physicochemical properties of four N-halomethylated and one non-halomethylated ammonium salts, with proven in vitro antileishmanial activity, were determined according to pharmaceutical standard procedures. The effectiveness and toxicity of these compounds were assessed in hamsters infected with Leishmania (Viannia) braziliensis and compared to that showed by meglumine antimoniate. Animals were followed during 90 days after the completion of treatment. Therapeutic response was determined according to the reduction of size of skin lesions. Toxicity was determined by the effect of compounds on body weight changes and serum levels of renal and hepatic metabolites. The effectiveness of compound 4 was similar to that showed by intralesional administration of meglumine antimoniate and better than that of the other ammonium salts. Levels of creatinine, alanine amino transferase, and blood urea nitrogen in serum were not significantly different between treatment groups, including healthy or untreated hamsters. Results imply that compound 4 has potential as a pharmaceutical active ingredient in the development of new and better formulations for the treatment of cutaneous leishmaniasis.