Effect of vitamin D3 supplementation on 25 OHD plasma levels in the presence of VDR gene polymorphisms / Efecto de la suplementación con vitamina D3 en los niveles plasmáticos de 25 OHD, en presencia de polimorfismos del gen VDR

The objective of this review was to investigate the effect of vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration in individuals with single-nucleotide polymorphisms in the vitamin D receptor gene. The research was conducted on 241 articles found in the PubMed, Scopus, Science Direct, and Cochrane Library databases between November and December 2018. After article screening, three randomized double-blind placebo-controlled clinical trials were identified as eligible for this review. Participants were Australian, Brazilian, and Chinese individuals, who ingested doses of vitamin D3 ranging from 2000 IU to a megadose of 200,000 IU. The presence of the BB/Bb genotype of the BsmI polymorphism and the FokI G allele caused an increase in the serum concentrations of vitamin D after supplementation. Nonetheless, the few studies on this subject are not unanimous in their results. It is possible that differences among populations, sample sizes, doses, and time of supplementation have an impact on data and outcomes.

El objetivo de esta revisión fue investigar el efecto de la suplementación con vitamina D3 sobre la concentración sérica de 25-hidroxivitamina D en individuos con los polimorfismos de un solo nucleótido en el gen del receptor de la vitamina D. La investigación se realizó en 241 artículos encontrados en las bases de datos PubMed, Scopus, Science Direct y Cochrane Library entre noviembre y diciembre de 2018. Después de la selección del artículo, se identificaron tres ensayos clínicos aleatorios, controlados con placebo, doble ciego, como elegibles para esta revisión. Los participantes fueron australianos, brasileños y chinos, quienes ingirieron dosis de vitamina D3 que iban desde las 2000 UI hasta una megadosis de 200,000 UI. La presencia del genotipo BB / Bb del polimorfismo BsmI y el alelo FokI G causó un aumento en las concentraciones séricas de vitamina D después de la suplementación. No obstante, los pocos estudios sobre este tema no son unánimes en sus resultados. Es posible que las diferencias entre poblaciones, tamaños de muestra, dosis y tiempo de suplementación tengan un impacto en los datos y resultados de la investigación.

Influence of Polymorphism of Vitamin D Receptor (Fok I) on Hypertension

Abstract Evidence suggests that polymorphisms in the gene encoding a vitamin D receptor might affect blood pressure. The objective of this systematic review was to investigate the association between hypertension and vitamin D receptor (Fok I) gene polymorphism. A literature search was performed according to the PRISMA guidelines using the MEDLINE®/PubMed, Scopus, Cochrane Library CENTRAL, SciELO, and LILACS databases. The quality of case-control or cohort studies and studies based on cross-sectional methodology was evaluated using the Newcastle-Ottawa Scale and the protocol of Loney and coauthors [25], respectively. In this systematic literature search, 215 publications were identified, of which 10 were analyzed, including seven case-control studies, two cross-sectional studies, and one cohort study. The association between Fok I polymorphism and hypertension was reported in 60% of the publications and the risk for hypertension was shown to be related to FF and ff genotypes. In addition, Fok I polymorphism was shown to increase plasma renin activity, which plays an important role in regulating blood pressure. However, no association was observed between Fok I polymorphism and serum vitamin D levels. In conclusion, Fok I polymorphism plays an important role in hypertension.

Use of pharmaceutical nanotechnology for the treatment of leishmaniasis

Abstract INTRODUCTION: Leishmaniasis is a global public health concern. Currently available treatments are associated with considerable side effects. The use of nanotechnology has shown promise for improving efficacy and bioavailability and minimizing side effects. METHODS: This study investigated available literature, including patents and scientific articles, to identify advances in the use of nanotechnology for the treatment of leishmaniasis. RESULTS: Our findings revealed a stable number of patents and scientific articles published over the past five years. CONCLUSIONS: There is a need to intensify research on the use of nanotechnology for the treatment of leishmaniasis.

Novos adjuvantes vacinais: importante ferramenta para imunoterapia da leishmaniose visceral / New vaccine adjuvants: an important tool for immunotherapy of visceral leishmaniasis

Atualmente, muitas das vacinas em desenvolvimento são aquelas compostas de proteínas antigênicas individuais de parasitas ou uma combinação de vários antígenos individuais que são produzidos como produtos recombinantes obtidos por técnicas de biologia molecular. Dentre elas a Leish-111f e sua variação Leish-110f tem ganhado destaque na proteção contra a LV e LC e alcançaram estudos de fase II em seres humanos. A eficácia de uma vacina é otimizada pela adição de adjuvantes imunológicos. No entanto, embora os adjuvantes tenham sido usados por mais de um século, até o momento, apenas alguns adjuvantes são aprovados para o uso em humanos, a maioria destinada a melhorar a eficácia da vacina e a produção de anticorpos protetores específicos do antígeno. os mecanismos de ação dos adjuvantes imunológicos são diversos, dependendo da sua natureza química e molecular sendo capazes de ativar células imunes especificas que conduzem a respostas imunes inatas e adaptativas melhoradas. embora o mecanismo de ação molecular detalhado de muitos adjuvantes ainda seja desconhecido, a descoberta de receptores Toll-like (TLrs) forneceu informações críticas sobre o efeito imunoestimulador de numerosos componentes bacterianos que envolvem interação com receptores TLrs, mostrando que estes ligantes melhoram tanto a qualidade como a quantidade de respostas imunes adaptativas do hospedeiro quando utilizadas em formulações de vacinais direcionadas para doenças. o potencial desses adjuvantes de TLr em melhorar o design e os resultados de várias vacinas está em constante evolução, à medida que novos agonistas são descobertos e testados em modelos experimentais e estudos clínicos de vacinação. Nesta revisão, é apresentado um resumo do progresso recente no desenvolvimento de proteínas recombinantes de segunda geração e adjuvantes de TLr, sendo o foco principal nos TLr4 e suas melhorias.

many of the vaccines in development are currently composed of individual antigenic proteins from parasites or a combination of several individual antigens that are produced as recombinant products obtained by molecular biology techniques. Among them, Leish-111f and its Leish-110f variation have gained prominence in protection against LV and LC and already have Phase II clinical trials in humans. The efficacy of a vaccine is optimized by the addition of immunological adjuvants. However, although adjuvants have been used for more than a century, until present date, only a few adjuvants are approved for use in humans, most intended to improve vaccine efficacy, the production of antigen-specific protective antibodies and an appropriate cell-immune response. The mechanisms of action of immunological adjuvants are diverse depending on their chemical and molecular nature being able to activate specific immune cells leading to improved innate and adaptive immune responses. Although the molecular mechanism of action of many adjuvants is still unknown, the discovery of Toll-like receptors (TLrs) has provided critical information on the immunostimulatory effect of numerous bacterial components involving interaction with TLr showing that these ligands improve both the quality as the amount of host adaptive immune responses when used in vaccine formulations. The potential of these TLr adjuvants in improving the design and results of many vaccines is in constantly evolution as new molecules agonists are discovered and tested in experimental models and clinical trials as well. In this review, a summary of recent progress in the development of second generation recombinant proteinsand adjuvants of TLr is presented, being the main focus in TLr4 and its improvements.

Uso e cobertura do solo e prevalência de leishmaniose visceral canina em Teresina, Piauí, Brasil: uma abordagem utilizando sensoriamento remoto orbital / Uso y cobertura del suelo y prevalencia de leishmaniosis visceral canina en Teresina, Piauí, Brasil: un enfoque utilizando teledetección / Land use, land cover, and prevalence of canine visceral leishmaniasis in Teresina, Piauí State, Brazil: an approach using orbital remote sensing

Resumo: Este estudo examina a associação entre uso e cobertura do solo e a ocorrência de leishmaniose visceral (LV) canina. Estudo caso-controle em que casos foram residências com cães soropositivos para LV canina e controles, as residências com cães soronegativos. Utilizaram-se imagens de sensoriamento remoto (CBERS: 2/CCD e 2B/HRC) para descrever o uso e cobertura do solo em quadrículas de 625m2 na região do estudo. A chance da LV canina foi duas vezes maior em domicílios localizados em quadrículas com área ≤ 25m2 coberta por estruturas residenciais com pouca vegetação em comparação com aquelas em que essa cobertura alcançou ≥ 600m2. Domicílios localizados em quadrículas com até metade da área coberta por estruturas residenciais com muita vegetação tiveram chances 65% menores de LV canina em comparação com aquelas situadas em áreas quase totalmente cobertas por essa característica. Como a infecção canina costuma preceder a ocorrência de casos humanos, a identificação de características de uso e cobertura do solo associadas à LV canina pode contribuir para a delimitação de áreas de risco para LV humana.

Resumen: Este estudio examina la asociación entre uso y cobertura del suelo y la ocurrencia de leishmaniosis visceral (LV) canina. Es un estudio de caso-control, donde los casos fueron analizados en residencias con perros seropositivos para LV canina y controles, además de residencias con perros seronegativos. Se utilizaron imágenes de teledetección (CBERS: 2/CCD e 2B/HRC) para describir el uso y cobertura del suelo en cuadrículas de 625m2 en la región del estudio. La oportunidad de la LV canina fue dos veces mayor en domicilios localizados en cuadrículas con un área ≤ 25m2, cubierta por estructuras residenciales con poca vegetación, en comparación con aquellas donde esa cobertura alcanzó ≥ 600m2. Los domicilios localizados en cuadrículas con hasta la mitad del área cubierta por estructuras residenciales con mucha vegetación tuvieron oportunidades un 65% menores de LV canina, en comparación con aquellas situadas en áreas casi totalmente cubiertas por esa característica. Como la infección canina acostumbra preceder la ocurrencia de casos humanos, la identificación de las características de uso y cobertura del suelo, asociadas a la LV canina, puede contribuir a la delimitación de áreas de riesgo para LV humana.

Abstract: This study examines the association between land use and land cover and the occurrence of canine visceral leishmaniasis (VL). This is a case-control study in which cases were households with seropositive dogs for canine VL and controls were households with seronegative dogs. We used remote sensing images (CBERS: 2/CCD and 2B/HRC) to describe land use and cover in squares of 625m2 in the study area. Odds of canine VL were twice as high in households located in squares with an area ≤ 25m2 covered by residential structures with little vegetation in comparison to those where the cover reached ≥ 600m2. Households located in squares with up to half of the area covered by residential structures with extensive vegetation showed 65% lower odds of canine VL in comparison to those situated in areas almost totally covered by this characteristic. Since canine infection usually precedes the occurrence de human cases, identification of the characteristics of land use and cover associated with canine VL can contribute to the demarcation of risk areas for human VL.

Scoring clinical signs can help diagnose canine visceral leishmaniasis in a highly endemic area in Brazil

Canine visceral leishmaniasis (CVL) diagnosis is still a challenge in endemic areas with limited diagnostic resources. This study proposes a score with the potential to distinguish positive CVL cases from negative ones. We studied 265 dogs that tested positive for CVL on ELISA and parasitological tests. A score ranging between 0 and 19 was recorded on the basis of clinical signs. Dogs with CVL had an overall higher positivity of the majority of clinical signs than did dogs without CVL or with ehrlichiosis. Clinical signs such as enlarged lymph nodes (83.93%), muzzle/ear lesions (55.36%), nutritional status (51.79%), bristle condition (57.14%), pale mucosal colour (48.21%), onychogryphosis (58.93%), skin lesion (39.28%), bleeding (12.50%), muzzle depigmentation (41.07%), alopecia (39.29%), blepharitis (21.43%), and keratoconjunctivitis (42.86%) were more frequent in dogs with CVL than in dogs with ehrlichiosis or without CVL. Moreover, the clinical score increased according to the positivity of all diagnostic tests (ELISA, p < 0.001; parasite culture, p = 0.0021; and smear, p = 0.0003). Onychogryphosis (long nails) [odds ratio (OR): 3.529; 95% confidence interval (CI): 1.832-6.796; p < 0.001], muzzle depigmentation (OR: 4.651; 95% CI: 2.218-9.750; p < 0.001), and keratoconjunctivitis (OR: 5.400; 95% CI: 2.549-11.441; p < 0.001) were highly associated with CVL. Interestingly, a score cut-off value ≥ 6 had an area under the curve of 0.717 (p < 0.0001), sensitivity of 60.71%, and specificity of 73.64% for CVL diagnosis. The clinical sign-based score for CVL diagnosis suggested herein can help veterinarians reliably identify dogs with CVL in endemic areas with limited diagnostic resources.

The performance of serological tests for Leishmania infantum infection screening in dogs depends on the prevalence of the disease

ABSTRACT Dogs are considered the main reservoir of Leishmania infantum. This protozoan causes visceral leishmaniasis (VL), an uncontrolled urban zoonosis in Brazil. Serological tests and polymerase chain reaction (PCR) on peripheral blood were performed to identify infected dogs in scenarios of higher and lower prevalence of the disease (Teresina and Vitória). One-hundred infected and 57 non-infected animals from Teresina and 100 non-infected animals from Vitória were studied. Animal selection was not dependent on previous serology. The sensitivity (Teresina) and specificity (Teresina and Vitória) were as follows: indirect antibody fluorescence (IFAT) cut-off of 1:40 (IFAT 1:40): 96%, 18%, and 76%; IFAT 1:80: 90%, 33%, and 93%; direct agglutination test (DAT): 96%, 33%, and 98%; fast agglutination screening test (FAST): 93%, 68%, and 100%; immunochromatographic assay with a recombinant rK39 antigen (rK39): 88%, 74%, and 98%; enzyme linked immunosorbent assay (ELISA): 91%, 79%, and 98%; rapid dual-path platform test (TR DPP®): 98%, 60%, and 98%; and blood PCR: 29%, 93%, and 97%, respectively. In the high transmission area, none of the tests adequately discriminated L. infantum-infected from non-infected dogs. However, in the high transmission city, the area under the receiver operating characteristic (ROC) curve of FAST, DAT, ICrK39, ELISA and TR DPP® was high.

Identification of blood meal sources of Lutzomyia longipalpis using polymerase chain reaction-restriction fragment length polymorphism analysis of the cytochrome B gene

An analysis of the dietary content of haematophagous insects can provide important information about the transmission networks of certain zoonoses. The present study evaluated the potential of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the mitochondrial cytochrome B (cytb) gene to differentiate between vertebrate species that were identified as possible sources of sandfly meals. The complete cytb gene sequences of 11 vertebrate species available in the National Center for Biotechnology Information database were digested with Aci I, Alu I, Hae III and Rsa I restriction enzymes in silico using Restriction Mapper software. The cytb gene fragment (358 bp) was amplified from tissue samples of vertebrate species and the dietary contents of sandflies and digested with restriction enzymes. Vertebrate species presented a restriction fragment profile that differed from that of other species, with the exception of Canis familiaris and Cerdocyon thous. The 358 bp fragment was identified in 76 sandflies. Of these, 10 were evaluated using the restriction enzymes and the food sources were predicted for four: Homo sapiens (1), Bos taurus (1) and Equus caballus (2). Thus, the PCR-RFLP technique could be a potential method for identifying the food sources of arthropods. However, some points must be clarified regarding the applicability of the method, such as the extent of DNA degradation through intestinal digestion, the potential for multiple sources of blood meals and the need for greater knowledge regarding intraspecific variations in mtDNA.

Factors associated with Leishmania chagasi infection in domestic dogs from Teresina, State of Piauí, Brazil / Fatores associados à infecção por Leishmania chagasi em cães domiciliados de Teresina, Estado do Piauí, Brasil

INTRODUCTION: Many studies have evaluated risk factors for human visceral leishmaniasis, but few have focused on the infection among dogs. The objective of this study was to assess the association between peridomestic socioeconomic and environmental factors and the presence of dogs seropositive for Leishmania chagasi in the City of Teresina, Brazil. METHODS: This case-control study was based on the results of a routine seroepidemiological survey among domestic dogs carried out in 2007. Serological tests were performed by means of indirect immunofluorescence antibody test. All dwellings in which at least one seropositive dog was detected were considered cases, and controls were a random sample of dwellings in which only seronegative dogs were identified. Associations between variables were expressed as odds ratios (OR) and their respective 95% confidence intervals (95%CI) estimated using multivariate logistic regression. RESULTS: Dwellings with a history of dogs removed by the visceral leishmaniasis control program in the last 12 months had five-fold higher odds of having at least one seropositive dog as compared with dwellings having no history of dog removal (OR = 5.19; 95%CI = 3.20-8.42). Dwellings with cats had 58% increased odds of dog infection as compared with those having no cats (OR = 1.58; 95%CI = 1.01-2.47). CONCLUSIONS: Identification of factors associated with canine visceral leishmaniasis might be used for the delimitation of areas of higher risk for human visceral leishmaniasis, since infection in dogs generally precedes the appearance of human cases.

INTRODUÇÃO: Diversos estudos avaliaram fatores de risco para leishmaniose visceral humana, mas poucos focalizaram a infecção canina. O objetivo deste estudo é avaliar a associação entre condições sócio-ambientais peridomiciliares e a presença de cães sorologicamente positivos para Leishmania chagasi em Teresina, Brasil. MÉTODOS: Estudo caso-controle baseado nos resultados de inquérito soroepidemiológico de rotina entre cães domésticos no ano de 2007. O exame sorológico foi realizado por meio de reação de imunofluorescência indireta. Foram consideradas como casos todas as residências que albergassem pelo menos um cão soropositivo, enquanto o grupo controle correspondeu a uma amostra aleatória das residências onde somente cães soronegativos foram registrados. Associações entre as variáveis foram expressas por meio da razão de chance ou odds ratio (OR) e respectivos intervalos de 95% de confiança (IC95%) estimados mediante regressão logística multivariada. RESULTADOS: Residências com história de pelo menos um cão recolhido pelo programa de controle da leishmaniose visceral nos últimos 12 meses apresentaram chance cerca de 5 vezes mais alta de terem cães infectados em comparação com residências sem história de cães removidos no período (OR = 5,19; IC95% = 3,20-8,42). Residências com presença de gatos apresentaram chance 58% mais alta de terem cães infectados em comparação com aquelas sem gatos (OR = 1,58; IC95% = 1,01-2,47). CONCLUSÕES: A identificação de fatores associados à leishmaniose visceral canina pode ser útil para a delimitação de áreas sob maior risco para leishmaniose visceral humana, na medida em que a infecção canina geralmente precede a ocorrência de casos humanos.

Infecção natural de Lutzomyia longipalpis por Leishmania sp. em Teresina, Piauí, Brasil / Natural infection of Lutzomyia longipalpis by Leishmania sp. in Teresina, Piauí State, Brazil

No Brasil, o controle do vetor Lutzomyia longipalpis é uma das principais estratégias utilizadas para limitar a expansão da leishmaniose visceral americana. Entretanto, poucos são os estudos sobre a infecção natural destes flebotomíneos por espécies de Leishmania. Um estudo sobre a infecção natural de Lu. longipalpis por Leishmania sp. foi realizado no bairro Bela Vista, Teresina, Piauí, um dos principais focos urbanos da leishmaniose visceral americana no Brasil. Entre fevereiro de 2004 e janeiro de 2005 realizaram-se 180 capturas usando-se armadilhas luminosas do tipo CDC. Foram dissecadas e examinadas, em média, dez fêmeas por captura para detecção de formas evolutivas de Leishmania sp., identificando-se 1.832 exemplares de Lu. longipalpis e seis de Lu. whitmani. Vinte (1,1 por cento) espécimes, todas de Lu. longipalpis, estavam infectadas com as formas procíclica e nectomonada de Leishmania sp., localizadas, principalmente, na porção posterior do trato digestivo. O maior percentual de insetos infectados foi encontrado quatro meses após o período de maior precipitação pluviométrica, sugerindo que variáveis climáticas podem contribuir para a predição não apenas da abundância destes dípteros, mas também do seu grau de infecção natural.

In Brazil, control of the vector Lutzomyia longipalpis is one of the main strategies used to limit the expansion of American visceral leishmaniasis. However, studies on the ecology of this sand fly are rare, especially regarding its natural infection with species of Leishmania. A study of the natural infection of Lu. longipalpis by Leishmania sp. was carried out in the Bela Vista neighborhood in the city of Teresina, Piauí State, Brazil, an important area of American visceral leishmaniasis transmission. From February 2004 to January 2005, sand flies were captured with CDC light traps. Approximately 10 female sand flies in each capture were dissected and examined for the presence of evolutionary forms of Leishmania sp. Two sand fly species were identified: 1,832 were Lu. longipalpis and six Lu. whitmani. Twenty female sand flies (1.1 percent), all Lu. longipalpis, were infected with procyclic and nectomonad forms of Leishmania sp., found mostly in the hindgut. Higher proportions of infected sand flies were found four months after the rainy season, suggesting that environmental factors may predict not only vector abundance (as already known) but also their level of infection.