Abstract Background Vitiligo is the most common pigmentary disorder and is considered a chronic, cumulative, multifactorial disease. The crucial role of cytotoxic CD8+ T lymphocytes and the IFNγ/CXCL10 axis has been demonstrated in its pathogenesis. Objective To evaluate the clinical profile and immuno-inflammatory markers in patients with vitiligo in a reference medical center. Methods Cross-sectional study in which all patients with vitiligo seen at the medical center the from 2019 to 2022 were evaluated, to outline the clinical profile. Moreover, cardiovascular risk biomarkers (neutrophil/lymphocyte ratio and C-reactive protein levels) were measured, as well as cytokines and chemokines (TNFα, IFNγ, IL10, IL15 and CXCL10) in the serum of a subgroup of 30 patients. Results There was a predominance of females, with a mean age of 43 years. Most were phototypes IV or V (71.3%), without comorbidities (77.55%), and without a family history of vitiligo (70.41%). Higher levels of neutrophil/lymphocyte ratio, C-reactive protein, and inflammatory cytokines/chemokines were documented in vitiligo patients when compared to the control group (non-significant). As relevant data, the highest values of CXCL10 were detected in patients with vitiligo versus controls, as well as in patients with disease of shorter duration (p < 0.05). Study limitations The number of assessed patients was small due to recruitment difficulties caused by the COVID-19 pandemic. Conclusion The present data contribute to confirming the relevant role of the IFNγ/CXCL10 axis in the pathogenesis of vitiligo, highlighting CXCL10 as a possible activity marker. chronic cumulative CD8 CD IFNγCXCL10 IFNγCXCL IFNγ CXCL IFNγ/CXCL1 immunoinflammatory immuno Crosssectional Cross sectional 201 202 evaluated Moreover neutrophillymphocyte neutrophil lymphocyte Creactive C reactive measured TNFα, TNFα (TNFα IL10 IL IL1 3 females 4 years 71.3%, 713 71.3% , 71 (71.3%) 77.55%, 7755 77.55% 77 55 (77.55%) 70.41%. 7041 70.41% . 70 41 (70.41%) cytokineschemokines nonsignificant. nonsignificant non significant (non-significant) CXCL1 controls p 0.05. 005 0.05 0 05 0.05) COVID19 COVID 19 COVID-1 pandemic marker IFNγCXCL1 IFNγ/CXCL 20 71.3 7 (71.3% 775 77.55 5 (77.55% 704 70.41 (70.41% (non-significant 00 0.0 COVID1 1 COVID- 2 71. (71.3 77.5 (77.55 70.4 (70.41 0. (71. 77. (77.5 70. (70.4 (71 (77. (70. (7 (77 (70 (

Abstract Introduction: patients with COVID-19 undergo changes in leukocyte count, respiratory disorders, and an increase in inflammatory substances. To improve the inflammatory condition, some nutrients can be used, including arginine, omega-3 fatty acids and nucleotides. This study aims to evaluate how oral immunonutrient supplements affects serum C-reactive protein (CRP) levels and lymphocyte count in patients with COVID-19. Methods: in this double-blind clinical trial, we randomized 43 adult patients with COVID-19 to receive a standard high-protein normocaloric supplement (control) or an immunonutrient-enriched supplement (experiment) for 7 days. The primary outcome was to evaluate changes in total lymphocyte count and serum level of CRP. The assessment of risk and nutritional status of these patients was also performed. Results: forty-three patients with mean age of 41.5 (± 1.8) years were followed up, 39.5 % of them women. The mean body mass index was 27.6 (± 0.8) kg/m² and 58.1 % had low nutritional risk. In the experiment group, there was a CRP reduction of 23.6 (± 7.5) mg/L, while in the control branch the decrease was 14.8 (± 12.1) mg/L (p = 0.002). There was an increase in lymphocytes in the experiment group (+367.5 ± 401.8 cells/mm³) and a reduction in the control group (-282.8 ± 327.8 cells/mm³), although there was no statistical significance (p = 0.369). Relative risk (RR) of treatment in reducing CRP by 30 % or more was 4.45 (p < 0.001; 95 % CI, 1.79-11.07). RR in increasing lymphocyte count by 30 % or more was 1.28 (p = 0.327; 95 % CI, 0.67-2.45). Conclusion: we conclude that immunonutrient supplements seem to reduce CRP levels more than standard high-protein normocaloric supplements.

Resumen Introducción: los pacientes con COVID-19 sufren cambios en el recuento de leucocitos, trastornos respiratorios y aumento de sustancias inflamatorias. Para mejorar la condición inflamatoria se pueden usar algunos nutrientes, como la arginina, los ácidos grasos omega-3 y los nucleótidos. Este estudio tiene como objetivo evaluar cómo los suplementos de inmunonutrientes orales afectan a los niveles séricos de proteína C-reactiva (PCR) y al recuento de linfocitos en pacientes con COVID-19. Métodos: en este ensayo clínico doble ciego, aleatorizamos a 43 pacientes adultos con COVID-19 para recibir un suplemento normocalórico estándar alto en proteínas (control) o un suplemento enriquecido con inmunonutrientes (experimento) durante 7 días. El resultado primario fue evaluar los cambios en el recuento total de linfocitos y el nivel sérico de PCR. También se realizó la evaluación del riesgo y el estado nutricional de estos pacientes. Resultados: cuarenta y tres pacientes con edad media de 41,5 (± 1,8) años fueron seguidos, el 39,5 % de ellos mujeres. El índice de masa corporal medio fue de 27,6 (± 0,8) kg/m² y el 58,1 % tenían bajo riesgo nutricional. En el grupo experimental hubo una reducción de la PCR de 23,6 (± 7,5) mg/L, mientras que en la rama de control la disminución fue de 14,8 (± 12,1) mg/L (p = 0,002). Hubo un aumento de linfocitos en el grupo experimental (+367,5 ± 401,8 células/mm³) y una reducción en el grupo de control (-282,8 ± 327,8 células/mm³), aunque no hubo significación estadística (p = 0,369). El riesgo relativo (RR) del tratamiento para reducir la PCR en un 30 % o más fue de 4,45 (p < 0,001; IC 95 %: 1,79-11,07). El RR en el aumento del recuento de linfocitos en un 30 % o más fue de 1,28 (p = 0,327; IC 95 %: 0,67-2,45). Conclusión: se concluye que los suplementos de inmunonutrientes parecen reducir los niveles de PCR más que los suplementos normocalóricos estándar altos en proteína.

Abstract Cutaneous leishmaniasis represents a public health problem that affects 85 countries. It is an endemic disease in Brazil, having an important socioeconomic impact. An exuberant case of cutaneous leishmaniasis is reported herein. A 28-year-old male patient with Down syndrome had had verrucous plaques on the back for over a year, with progressive growth. PCR of a lesion sample was positive for Leishmania braziliensis. The patient’s condition was classified as atypical cutaneous leishmaniasis. He was successfully treated with amphotericin B and miltefosine. The treatment remains a challenge, given the toxicity and low cure rate of the currently recommended drugs.

Abstract Cutaneous leishmaniasis is characterized by ulcers with raised edges and a granular bottom, mainly on the lower limbs. This is a case report of a male patient with an ulcer on the left plantar region. The diagnosis was confirmed by positive PCR for L. braziliensis and the presence of amastigotes of Leishmania sp. in the histopathological examination. After treatment with Glucantime, the patient showed full healing of the ulcer. The unusual location of the ulceration calls attention to atypical presentations of leishmaniasis, and the importance of histopathological examination and PCR, leading to the appropriate diagnosis and treatment.

Genes associated with wound healing have been shown to be risk factors for cutaneous leishmaniasis (CL) which is caused by Leishmania braziliensis. In this study, we examined whether the genes previously associated with CL influenced the clinical outcome. Patients were genotyped and retrospectively classified as responders, who were cured with a single course of pentavalent antimony (Sbv), or as refractories, who did not respond to Sbv. Patients characterised as responders showed a stronger response to the leishmanin skin test (LST) when compared to the refractory subjects (p = 0.0003). Furthermore, we observed an association between the FLI1 CC genotype and an increased size of ulcers (p = 0.0170). We suggest that the leishmanin skin test may be a predictive tool for therapeutic outcome and reinforce FLI1 as a potential influencer of susceptibility and lesion size in CL.

Abstract: Disseminated leishmaniasis is a severe and emerging form of American tegumentary leishmaniasis. Disseminated leishmaniasis is defined by the presence of more than 10 polymorphic cutaneous lesions, distributed over more than two noncontiguous parts of the body. Nasal mucosal involvement is observed in almost half of cases. Disseminated leishmaniasis patients present with a decreased production of Th1 cytokines in the peripheral blood due to the attraction of leishmania- activated T cells to the multiple cutaneous lesions. Disseminated leishmaniasis development is poorly understood and is related to a complex network involving environmental, host immune response, and parasite factors, in which L. braziliensis polymorphism plays an important role. Disseminated leishmaniasis is a challenging disease to cure, presenting a high failure rate of 75% to pentavalent antimony therapy. Despite its importance and severity, this form of American tegumentary leishmaniasis has been poorly studied and documented, deserving greater attention from professionals working in endemic areas.

BACKGROUND Leprosy or hansen’s disease is a spectral disease whose clinical forms mostly depends on host’s immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1β was related to TLR4 genotypes. MAIN CONCLUSIONS All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host’s production of key cytokines and chemokines involved in the pathogenesis of this disease.

Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p > 0.05) in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus.

PURPOSE:To evaluate the effect of curcumin in the acute phase of zymosan-induced arthritis.METHODS:Twenty-eight male rats were subjected to intra-articular infiltration of zymosan of both knees and, in four the infiltration was made with saline. The animals were divided into five groups second received every six hours by gavage: corn oil by (positive and negative control); curcumin (100 mg/kg); prednisone 1 mg/kg/day; prednisone 8 mg/kg. All animals were sacrificed after six, 12, 24 and 48 hours of the infiltration. The knees were removed for evaluation of neutrophil infiltration. The number of neutrophils was counted by computer-assisted analysis of the images. The neutrophil infiltrate was stratified into four grades: 0 = normal; + = mild; ++/+++ = moderate; > ++++ = severe. The results were compared using the Mann-Whitney test and the variance by Kruskal-Wallis test adopting a significance level of 5% (p<0.05).RESULTS:Curcumin reduces inflammatory activity in the first six hours after zymosan-induced arthritis when compared to saline (p<0.01). This was also observed in animals subjected to administration of prednisone (1 mg/kg) and those treated with prednisone (8 mg/kg). Curcumin was more effective than lower doses of prednisone in the first six hours after induction of the arthritis. After 12, 24 and 48 hours, curcumin does not have the same anti-inflammatory effects when compared to prednisone. After 48 hours, prednisone is more effective than curcumin in reducing the inflammatory infiltrate regardless of the dose of prednisone used.CONCLUSION:Oral administration of curcumin reduces inflammation in the first six hours after experimentally zymosan-induced arthritis.

Introduction The prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection is heterogeneous across different populations. We tested the hypothesis that HTLV-1/2 infection occurs more often in dermatological patients. Methods A total of 1,091 patients from a tropical dermatology clinic were tested for HTLV-1/2. In parallel, 6865 first-time blood donors from the same geographic area were screened for HTLV-1/2; HTLV-1/2 positive blood donors underwent dermatological examinations. Results The prevalence of HTLV-1/2 in first-time blood donors was 0.14%. No co-occurrence of HTLV-1/2 infection and dermatological conditions was observed. Conclusions Our results challenge the hypothesis that HTLV-1/2 infection occurs more often in dermatological patients.

Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.

O objetivo desta pesquisa foi avaliar a produtividade e o valor nutritivo de dois sistemas forrageiros (SF) constituídos por capim elefante (CE), azevém (AZ), trevo branco (TB) e espécies de crescimento espontâneo (ECE), como SF1; e CE + AZ + amendoim forrageiro (AF) + ECE, como SF2. O CE foi estabelecido em linhas espaçadas a cada quatro metros. Entre elas, foi estabelecido azevém, durante o período hibernal, permitindo-se o desenvolvimento de ECE no período estival. Para avaliação, foram utilizadas vacas da raça Holandesa e o método de pastejo foi o rotacionado. Avaliaram-se a massa de forragem inicial (MFI) e a composição botânica e estrutural dos pastos. Para as estimativas de valor nutritivo, foram feitas amostragens simulando o pastejo e analisados a fibra em detergente neutro (FDN), fibra em detergente ácido (FDA), proteína bruta (PB), digestibilidade in vitro da matéria seca (DIVMS) e digestibilidade in vitro da matéria orgânica (DIVMO). O delineamento experimental foi o inteiramente casualizado com dois tratamentos e duas repetições, em parcelas subdivididas no tempo. Os valores médios de massa de forragem inicial e da carga animal foram similares entre os SF. Observou-se resultado superior para o teor médio de PB da forragem do SF2. O uso do azevém, das leguminosas e das espécies de crescimento espontâneo em consórcio com o CE permite manter massa de forragem uniforme no decorrer dos pastejos.

The objective of this research was to evaluate the productivity and nutritive value of two pasture-based systems (PS) with elephant grass (EG) + ryegrass (RG) + white clover (WC) + spontaneous growing species (SGS), for PS1; and EG + RG + forage peanut (FP) + SGS, for PS2. EG was established in rows spaced by four meters. Ryegrass was seeding in the space between rows during cool-season and development of SGS was permitted in the warm-season. Holstein cows under rotational grazing were used in the evaluation. The initial forage mass (IFM), the botanical composition and the structural components were evaluated. Samples from hand-plucking method were collected to analyze neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), in vitro dry matter digestibility (IVDMD) and in vitro organic matter digestibility (IVOMD). The experimental design used was completely randomized with two treatments, two repetitions in complete split-plot time. The mean values of initial forage mass and stocking rate were similar among PS. Superior results were found for mean of CP in PS2. The use of ryegrass, legumes and spontaneous growing species mixed to EG allow the forage mass to be uniform during the grazing pastures.

Esta pesquisa foi realizada com o objetivo de avaliar a produção e o valor nutritivo da forragem de capim-elefante cultivado em sistemas convencional e agroecológico. No sistema convencional, o capim-elefante foi estabelecido em cultivo exclusivo, em linhas com espaçamento de 1,4 m e, no sistema agroecológico, em linhas afastadas 3 m. Nas entrelinhas, estabeleceu-se azevém no período hibernal para desenvolvimento de espécies de crescimento espontâneo no período estival. Avaliaram-se a massa, a produção e a composição botânica e estrutural da forragem e a carga animal. Amostras de simulação de pastejo foram coletadas para determinação dos teores de proteína bruta e fibra em detergente neutro e da digestibilidade in vitro da matéria seca e matéria orgânica. O delineamento experimental foi o inteiramente casualizado com dois tratamentos (sistemas convencional e agroecológico) e duas repetições (piquetes). Valores mais elevados para massa de forragem, produção de forragem, taxa de acúmulo diário e carga animal foram observados no sistema convencional. A relação folha: colmo foi similar entre os sistemas. Valor mais elevado de proteína bruta foi observado no sistema agroecológico. O capim-elefante sob manejo convencional apresenta maior produção de forragem, com menores teores de proteína bruta. O sistema agroecológico apresenta melhor distribuição da produção de forragem no decorrer do ano.

The objective of this research was to evaluate elephantgrass pasture on forage production and stocking rate, comparing conventional and agro-ecological production systems. In the conventional system, elephantgrass was established in a singular form, in rows spaced by 1.4 m. In the agro-ecological system, the elephantgrass was established spaced by 3 m and, in the space between lines, ryegrass in cool season was introduced, allowing the development of spontaneous growing species in the warm-season. Herbage mass, forage production, daily accumulation rate of dry matter, botanical and structural composition and stocking rate were evaluated. Hand-plucking samples were collected to determine crude protein, neutral detergent fiber, acid detergent fiber, in vitro digestibility of dry and organic matter. The experimental design was completely randomized, with two treatments (conventional and agro-ecological systems), two replications (paddocks) and repeated measures (grazing cycles). Higher values of herbage mass, forage production, daily accumulation rate of dry matter and stocking rate were observed in the conventional system. Leaf blade/steam ratio was similar between systems. Higher values of crude protein were observed in the agro-ecological system. Elephantgrass in conventional system presents higher forage production with lower values of crude protein. The agro-ecological system presents best forage distribution throughout the year.

FUNDAMENTOS: O Amazonas corresponde a aproximadamente 40% dos casos de leishmaniose do país. Nós reportamos um estudo prospectivo com 180 pacientes de uma unidade de saúde que diagnostica 10% dos casos de leishmaniose da amazônia brasileira, com combinação de métodos diagnóstico em área de alta prevalência de Leishmania guyanensis. OBJETIVOS: avaliar métodos diagnóstico da Leishmaniose em área endêmica para Leishmania Amazonensis. MÉTODOS: Todos os pacientes tiveram exame direto positivo com presença de amastigotas. Foi feita também biópsia cutânea, com realização de exame histológico, reação em cadeia da polimerase e cultura. RESULTADO: A reação em cadeia da polimerase detectou aproximadamente 90% de infecção quando foram usados duas técnicas de amplificação (mini-exon and HSP-70). A reação em cadeia da polimerase com HSP-70 foi mais sensível que a cultura associada à histopatologia. CONCLUSÃO: A melhor combinação foi a reação em cadeia da polimerase com histopatologia, com sensibilidade de 94%. A discrimanação das espécies causadoras de infecção humana nessa região mostrou Leishmania guyanensis em 94% dos casos e Leishmania brasiliensis em 6%

BACKGROUND: The Amazon region corresponds to approximately 40% of the cases of leishmaniasis in Brazil. We report a prospective study with 180 patients conducted in a health care unit that diagnoses 10% of the cases of leishmaniasis in the Brazilian Amazon. The study addresses how a combination of procedures improves diagnosis in areas with high prevalence of Leishmania guyanensis. OBJECTIVES: to evaluate diagnostic methods in areas with high prevalence of Leishmania guyanensis. METHODS: All subjects were amastigote-positive by direct microscopic examination of lesion scarifications. We conducted skin biopsy and histopathology, polymerase chain reaction and parasite cultivation. RESULTS: Polymerase chain reaction detected almost ninety percent of infections when two amplification protocols were used (mini-exon and HSP-70). HSP-70 specific polymerase chain reaction matched the sensitivity of parasite cultivation plus histopathology. CONCLUSION: The best combination was polymerase chain reaction plus histopathology, which increased diagnostic sensitivity to 94%. Species discrimination by polymerase chain reaction disclosed prevalence of human infections with Leishmania guyanensis of 94% and with Leishmania braziliensis of 6% for this region

Realizou-se o presente trabalho com o objetivo de avaliar a composição química de dois sistemas forrageiros, tendo como componentes comuns o capim-elefante, o azevém e as espécies de crescimento espontâneo, variando em um sistema o consórcio com o trevo branco, e, em outro, com o amendoim forrageiro. Para avaliação, foram usados quatro piquetes com 0,25ha cada um. Como animais experimentais, foram utilizadas vacas em lactação da raça Holandesa. O delineamento experimental utilizado foi o inteiramente casualizado, com dois tratamentos (sistemas forrageiros) e duas repetições (piquetes). Para análise de proteína bruta (PB), fibra em detergente neutro (FDN) e fibra em detergente ácido (FDA), foram retiradas amostras através de simulação de pastejo. A participação dos componentes dos sistemas forrageiros variou segundo as leguminosas componentes. O sistema composto por amendoim forrageiro permitiu suportar maior carga no período estival. Os valores médios (pré e pós-pastejo) para PB, FDN e FDA foram de 18,76; 71,46; 34,87% para o sistema forrageiro constituído com o trevo branco e de 19,31; 71,19 e 35,40%. Os resultados foram similares entre os sistemas forrageiros.

The aim of this research was to evaluate the chemical composition of two pasture-based systems having as common components the elephantgrass, ryegrass and spontaneous growth species, in one system the white clover and, in another system, the forage peanut. Four paddocks, each one with 0.25ha, were used in the evaluation. Holstein cows were used in the evaluation. The experimental design was completely randomized, with two treatments (pasture-based systems), two replications (paddocks). To analyze the crude protein (CP), neutral detergent fiber (NDF) and acid detergent fiber (ADF), hand-plucked samples were collected. Composition of forage systems changes according to its legumes compounds. Forage peanut system allowed a greater stocking rate in hot season. The mean values (pregraze and postgraze) of CP, NDF and ADF, were 18.76; 71.46 and 34.87% to the pasture-based system with white clover and 19.31; 71.19 and 35.40% to the system with forage peanut, respectively. Similar results were observed for the pasture systems.