Cornuside ameliorated experimental autoimmune encephalomyelitis by limiting the recruitment of CD4+ T lymphocytes in the spinal cord

We conducted this study to determine whether cornuside could improve the neurological deficit symptoms of experimental autoimmune encephalomyelitis (EAE) rats, as well as determine the potential involvement of CD4+ T lymphocytes, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and tumor necrosis factor-α (TNF-α). Altogether, 32 Lewis rats were randomly divided into control, EAE, EAE/prednisolone, and EAE/cornuside, wherein their neurological function was assessed every day. CD4+ T lymphocyte recruitment into the spinal cord (SC) was evaluated using immunohistochemistry. The VCAM-1, ICAM-1 and TNF-α mRNA expressions in the SC were determined by real-time quantitative PCR, and the VCAM-1 and ICAM-1 proteins were determined by western blotting. Compared to the control group, the EAE group rats with neurological deficits had enhanced CD4+ T lymphocyte infiltration and higher expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Meanwhile, compared with the EAE group, the EAE/cornuside and EAE/prednisolone groups had lower neurological scores, less CD4+ T lymphocyte infiltrations, and lower expression levels of VCAM-1, ICAM-1, and TNF-α in the SC. Thus, cornuside ameliorated EAE, which could be owed to the inhibition of CD4+ T lymphocyte recruitment and VCAM-1, ICAM-1, and TNF-α expressions in the SC

Cellular infiltrate in cutaneous leishmaniasis lesions and therapeutic outcome

Abstract Background: The treatment of cutaneous leishmaniasis is a challenge. A better understanding of the in situ mechanisms involved in the evolution and cure of the disease is essential for the development of new therapies. Objective: Correlate histopathological and immunological characteristics of cutaneous leishmaniasis lesions with clinical outcome after different treatment regimens. Methods: The authors analyzed cellular infiltration and immunohistochemistry staining for CD4, CD8 and IL-17 in biopsy samples from 33 patients with cutaneous leishmaniasis before treatment. All patients were recruited in a randomized clinical trial at Corte de Pedra (Bahia-Brazil) and assigned to receive Glucantime®, Glucantime® + Oral Tamoxifen or Glucantime® + Topical Tamoxifen. Patients were followed for 2 to 6 months to define disease outcome. Results: A similar expression of CD4, CD8 and IL-17 was observed in lesion samples regardless of clinical outcome. In general, a higher amount of CD8 cells were observed compared with CD4 cells. An important observation was that all patients whose cellular infiltrate did not contain plasma cells were cured after treatment. Study limitations: Isolated quantification of TCD8 and IL-17 using immunohistochemistry is insufficient to analyze the role of these molecules in the immunopathogenesis of cutaneous leishmaniasis. In addition, the expansion of the immunohistochemistry panel would allow a more complete analysis of the immune response in situ. Conclusions: The absence of plasma cells in cutaneous leishmaniasis lesions was related to a favorable therapeutic outcome.

AIDS in the meeting of the Tapajós and Amazon rivers: deaths in the period 2010-2018 in Santarém, Pará, Brazil / AIDS no encontro dos rios Tapajós e Amazonas: óbitos no período de 2010-2018 em Santarém, Pará, Brasil

INTRODUCTION: The city of Santarém, the regional healthcare center in the western Pará State, lacks studies on the epidemic of the human immunodeficiency virus (HIV), in particular, on the causes of death. OBJECTIVE: To characterize the sociodemographic and clinical profile related to the evolution of HIV infection to death. METHODS: The sample consisted of 94 medical records of patients from a reference center in the city of Santarém-PA, who died between 2010-2018. Data were collected on the sociodemographic profile, immunological and clinical characteristics of the patients. Data were analyzed using descriptive and inferential statistics, adopting p<0.05. RESULTS: Most deaths were male (67%), aged between 15-29 years (39%) and diagnosed between 30-44 years (41%), single (54%), mixed race (91.5%), from Santarém (77%) and with sexual intercourse being the main type of exposure (95.7%). Most patients were not being treated at the moment of death (56.4%), the main cause of death was respiratory failure (5%), in which, these individuals had, at the moment of death, TCD4+ lymphocytes <200 cell/mm3 (26%) and detectable viral load (29%). CONCLUSION: The lifetime from diagnosis to death was 48.45±50,30 months, and immunosuppression in the diagnosis was positively associated with the shortest survival time. However, sex was not associated with the immunological profile, age at the time of diagnosis, and death. There was only a tendency for women towards immunosuppression and detectable viral load.

INTRODUÇÃO: A cidade de Santarém, o polo assistencial da região oeste do Pará, carece de estudos sobre a epidemia do vírus da imunodeficiência humana (HIV), especialmente, sobre as causas de óbitos. OBJETIVO: Caracterizar o perfil sociodemográfico e clínico relacionado à evolução da infecção pelo HIV até a morte. MÉTODO: A amostra foi de 94 prontuários de pacientes de um centro de referência do município de Santarém-PA, que evoluíram a óbito entre os anos de 2010-2018. Foram levantados os dados sobre o perfil sociodemográfico, características imunológicas e clínicas dos pacientes. Os dados foram analisados por estatística descritiva e inferencial, adotando-se p<0,05. RESULTADOS: A maioria dos óbitos foi de indivíduos do sexo masculino (67%), com faixa etária do diagnóstico entre 15-29 anos (39%) e de falecimento entre 30-44 anos (41%), solteiros (54%), pardos (91,5%), procedentes de Santarém (77%) e com a relação sexual sendo o principal tipo de exposição (95,7%). A maioria dos pacientes não estava em tratamento no momento do óbito (56,4%), a principal causa de morte foi por insuficiência respiratória (5%), no qual, esses indivíduos apresentavam, no momento da morte, linfócitos TCD4+ <200 cél/mm3 (26%) e carga viral detectável (29%). CONCLUSÃO: O tempo de vida do diagnóstico ao óbito foi de 48,45±50,30 meses e a presença de imunossupressão no diagnóstico associou-se positivamente com o menor tempo de sobrevida. Contudo, o sexo não apresentou associação com o perfil imunológico, a idade no momento do diagnóstico e do óbito, apenas notou-se uma tendência das mulheres para a imunossupressão e carga viral detectável.

Association between circulating exhausted CD4+ T cells with poor meningococcal C conjugate vaccine antibody response in HIV-infected children and adolescents

OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Comparative evaluation of memory T cells in COVID-19 patients and the predictive role of CD4+CD8+ double positive T lymphocytes as a new marker

SUMMARY BACKGROUND: The COVID-19 pandemic has affected the entire world, posing a serious threat to human health. T cells play a critical role in the cellular immune response against viral infections. We aimed to reveal the relationship between T cell subsets and disease severity. METHODS: 40 COVID-19 patients were randomly recruited in this cross-sectional study. All cases were confirmed by quantitative RT-PCR. Patients were divided into two equivalent groups, one severe and one nonsevere. Clinical, laboratory and flow cytometric data were obtained from both clinical groups and compared. RESULTS: Lymphocyte subsets, CD4+ and CD8+ T cells, memory CD4+ T cells, memory CD8+ T cells, naive CD4+ T cells, effector memory CD4+ T cells, central memory CD4+ T cells, and CD3+CD4+ CD25+ T cells were significantly lower in severe patients. The naive T cell/CD4 + EM T cell ratio, which is an indicator of the differentiation from naive T cells to memory cells, was relatively reduced in severe disease. Peripheral CD4+CD8+ double-positive T cells were notably lower in severe presentations of the disease (median DP T cells 11.12 µL vs 1.95 µL; p< 0.001). CONCLUSIONS: As disease severity increases in COVID-19 infection, the number of T cell subsets decreases significantly. Suppression of differentiation from naive T cells to effector memory T cells is the result of severe impairment in adaptive immune functions. Peripheral CD4+CD8+ double-positive T cells were significantly reduced in severe disease presentations and may be a useful marker to predict disease severity.

RESUMO OBJETIVO: A pandemia de COVID-19 tem afetado o mundo todo, constituindo uma ameaça grave para a saúde humana. As células T desempenham um papel crítico na imunidade celular contra infecções virais. Procuramos desvendar a relação entre sub grupos de células T e a severidade da doença. MÉTODOS: Um total de 40 pacientes com COVID-19 foram aleatoriamente recrutados para o presente estudo transversal. Todos os casos foram confirmados por RT-PCR quantitativo. Os pacientes foram divididos em dois grupos equivalentes, um grave e um não-grave. Os dados da avaliação clínica, laboratorial e da citometria de fluxo foram obtidos para ambos os grupos e comparados. RESULTADOS: Os subconjuntos de linfócitos, células T CD4+ e CD8+, células T de memória CD4+, células T de memória CD8+, células T CD4+ virgens, células T efetoras CD4+, células T de memória central CD4+ e células T CD3+ CD4+ CD25+ estavam significativamente mais baixas nos pacientes graves. A razão células T virgens/células T efetoras TCD4+, que é um indicador da diferenciação entre células T virgens e células de memória, estava relativamente reduzida em casos graves da doença. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença (mediana das células T DP: 11,12 µL vs. 1,95 µL; p< 0,001). CONCLUSÃO: Conforme aumenta a gravidade da doença nos casos de COVID-19, o número de subconjuntos de células T diminui significativamente. A supressão da diferenciação de células T virgens para células T efetoras é o resultado do comprometimento grave das funções imunológicas adaptativas. As células T duplo-positivas CD4+CD8+ periféricas estavam notavelmente mais baixas em casos graves da doença e podem ser um marcador útil para predizer a severidade da doença.

Respuesta inmune Th1/Th2 en pacientes co-infectados con Helicobacter pylori y helmintos / Immune response Th1/Th2 to Helicobacter pylori and Helminths in co-infected patients

Resumen: Introducción: La inflamación asociada con la infección por Helicobacter pylori (H. pylori) se relaciona con la pro gresión de las lesiones precancerosas gástricas. Las infecciones por helmintos podrían modular la respuesta proinflamatoria a la infección por H. pylori desde un perfil tipo LTCD4+ Th1 hacia una respuesta menos perjudicial tipo LTCD4+ Th2. Objetivo: Caracterizar la polarización de la respuesta inmune tipo LTCD4+ Th1/Th2 de pacientes coinfectados por H. pylori y helmintiasis procedentes de áreas de bajo riego para el desarrollo de cáncer gástrico. Pacientes y Método: Se analizaron 63 pacientes, 40 adultos y 23 niños infectados con H. pylori. La determinación de los perfiles séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) se realizó con Análisis Multiplex (xMAP). La relación entre el estado de coinfección por helmintos en pacientes infectados con H. pylori y la polarización de la respuesta inmune mediada por LTCD4+ Th1 y LTCD4+ Th2, se estudió con un modelo de regresión logístico de efectos mixtos. Resultados: La frecuencia de helmintos fue similar en adultos (15%) y niños (17%). La polarización de la respuesta inmune fue más prevalente hacia el tipo LTCD4+ Th1. Los valores séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1 Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) fueron independientes del estado de infestación por helmintos. Conclusión: La prevalencia de infección por parasitismo intestinal fue alta y la polarización de la respuesta inmune fue predominantemente hacia un perfil tipo LTCD4 + Th1.

Abstract: Introduction: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer. Patients and Method: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model. Results: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status. Conclusion: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.

Epidemiological profile of HIV older adults who are patients in a reference center in Aracaju-SE / Perfil epidemiológico dos pacientes idosos com HIV em um centro de referência de Aracaju-SE / Perfil epidemiológico de pacientes ancianos con VIH en un centro de referencia en Aracaju-SE

Background and objectives: Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by HIV. 3% of the people living with HIV/AIDS in Brazil are 60 years old or over. Although older adults correspond to a small percentage, there has been a significant increase in the incidence in this group in recent years. Thus, HIV infection in older adults is a reality, however, literature hardly addresses this topic. The objective is to study the epidemiological clinical profile of older adults living with HIV monitored at a referral center. Methods:This is an observational, descriptive, cross-sectional study with data collection obtained from the medical records of the STI/AIDS outpatient clinic at a reference center. The data were sociodemographic, clinical and laboratory, collected from September 2018 to February 2019. Results:In the reference center, 309 older adults were registered, representing 6.7% of all patients registered in the service. Of these, 75.6% are men, 38% are married, 70% heterosexual and approximately 50% with low education. Comorbidities are associated, with dyslipidemia (54%) being the main one. At the time of diagnosis, 65.8% had detectable viral load and 62% had CD4 + cells <500 cls/mm³ and after therapeutic follow-up, only 20% had detectable viral load. Several therapeutic regimens are used, the main one being Tenofovir, Lamivudine and Efavirenz (35.3%). Conclusion: The epidemiological profile of the population served in the region follows national and global characteristics, with a predominance of men, heterosexuals, married and with low education.(AU)

Justificativa e Objetivos: A Síndrome da Imunodeficiência Adquirida (SIDA) é uma doença causada pelo HIV. Das pessoas vivendo com HIV(PVHIV)no Brasil, 3% apresentam 60 anos ou mais. Apesar dos idosos corresponderem a um pequeno percentual, há aumento significativo da incidência nesse grupo nos últimos anos. Dessa forma, a infecção pelo HIV em idosos é uma realidade, contudo, a literatura pouco aborda esse tema. O objetivo do trabalho é estudar o perfil clínico epidemiológico dos idosos vivendo com HIV acompanhados em um centro de referência. Métodos: Trata-se de um estudo observacional, descritivo, de corte transversal, com coleta de dados obtida através dos prontuários do ambulatório de IST/SIDA de um centro de referência. Os dados sociodemográficos, clínicos e laboratoriais, foram coletados no período setembro de 2018 a fevereiro de 2019. Resultados: No centro de referência, estão cadastrados 309 idosos, representando 6,7% de todos os pacientes matriculados no serviço. Destes, 75,6% são homens, 38% casados, 70% de orientação heterossexual e aproximadamente 50% com baixa escolaridade. Comorbidades estão associadas, sendo a dislipidemia (54%) a principal. No momento do diagnóstico, 65,8% apresentavam carga viral (CV) detectável,62% tinham células CD4+ < 500céls/mm³ e após seguimento terapêutico apenas 20% apresentavam CV detectável. Vários esquemas terapêuticos foram utilizados, sendo o principal Tenofovir, Lamivudina e Efavirenz (35,3%). Conclusão: O perfil epidemiológico da população atendida na região segue as características nacionais e mundiais, com predomínio de homens, heterossexuais, casados e de baixa escolaridade.(AU)

Justificación y Objetivos: El Síndrome de Inmunodeficiencia Adquirido(SIDA) es una enfermedad causada por el VIH. De las personas que viven con el VIH (PVVIH) en Brasil, el 3% tiene 60 años o más. Aunque los adultos mayor es corresponden a un pequeño porcentaje, en los últimos años se ha producido un aumento significativo de la incidencia en este grupo. La infección por VIH en los adultos mayores es una realidad; sin embargo, la literatura aborda poco este tema. El objetivo de este trabajo es estudiar el perfil clínico epidemiológico de adultos mayores que conviven con el VIH y se atienden en un centro de referencia. Métodos: Se trata de un estudio observacional, descriptivo, de corte transversal, con datos obtenidos de los registros de ETS/SIDA de un centro de referencia. Se recogieron datos sociodemográficos, clínicos y de laboratorio desde septiembre de 2018 hasta febrero de 2019. Resultados: En el centro de referencia están registrados309 adultos mayores, que representan el 6,7% de todos los pacientes inscriptos en el servicio. De ellos, el 75,6% es del sexo masculino, el 38%, casado, el 70% con orientación heterosexual y aproximadamente el 50% con baja escolaridad. De las comorbilidades asociadas, la dislipidemia esla principal (54%). En el momento del diagnóstico, el 65,8% tenía una carga viral detectable (CV), el 62%tenía células CD4+<500 células/mm³ y después del seguimiento terapéutico sólo el 20% tenía CV detectable. Se utilizaron varios esquemas terapéuticos, siendo los principales el Tenofovir, la Lamivudina y el Efavirenz (35,3%). Conclusión: El perfil epidemiológico de la población atendida en la región sigue las características nacionales e internacionales, con predominio de hombres heterosexuales, casados y de baja escolaridad.(AU)

Nicotinamide activates latent HIV-1 ex vivo in ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.

Consumo de álcool de pessoas vivendo com HIV e suas implicações para os desfechos clínicos / Alcohol consumption in people living with HIV and its implications for clinical outcomes

Objetivou-se analisar a prevalência do consumo de álcool em pessoas vivendo com HIV e sua associação com os desfechos clínicos. Trata-se de um estudo transversal, analítico, realizado com pessoas que vivem com HIV em tratamento ambulatorial no município de Ribeirão Preto, SP. Realizou-se entrevista com instrumento sociodemográfico e clínico e com o Cuestionario para La Evaluación de La Adhesión al Tratamiento Antirretroviral. Para análise dos dados utilizou-se os Testes Qui-quadrado, Exato de Fisher e regressão logística, adotando p<0,05. Dos 340 participantes, a prevalência do consumo de álcool foi 40,6%, dos quais 35% apresentavam consumo leve e moderado e 5,6% alto. Identificou-se que pessoas com carga viral detectável tem 1,76 vezes mais chance (p=0,04; IC95% 1,00­3,05) de consumir álcool. O estudo evidenciou uma alta prevalência de consumo de álcool entre pessoas que vivem com HIV e o desfecho clínico que apresentou associação com o alto consumo de álcool foi a carga viral.

This study aimed to analyze the prevalence of alcohol consumption among people living with HIV and its association with clinical outcomes. It is an analytical, cross-sectional study, carried out with people living with HIV in outpatient treatment in the municipality of Ribeirão Preto, SP. An interview was carried out using a sociodemographic instrument, a clinical instrument, and the Cuestionario para La Evaluación de La Adhesión alTratamiento Antiretroviral (Assessment of Adherence to Antiretroviral Therapy Questionnaire). Chi-squared test, Fisher's Exact Test, and logistical regression, adopting p<0.05, were used for data analysis. Of the 340 participants, the prevalence of alcohol consumption was 40.6%, of whom 35% presented low to moderate consumption and 5.6% high consumption. It was identified that people with detectable viral load have 1.76 times more chance of consuming alcohol (p=0.04; 95%CI 1.00­3.05). The study showed a high prevalence of alcohol consumption among people living with HIV and the clinical outcome presenting an association with high consumption was a viral load.

Caracterización de las manifestaciones otorrinolaringológicas en pacientes con infección por VIH/Sida en la ciudad de Cartagena / Characterization of the otorrinolaringological manifestations in patients with HIV/AIDS infection in the city of Cartagena

Introducción: en Colombia, la incidencia por virus de inmunodeficiencia humana (VIH) ha ido en aumento; la ciudad de Cartagena tiene una de las más altas del país. Las manifestaciones otorrinolaringológicas en personas con VIH se estiman entre un 20%-80%, lo que genera un gran impacto en la calidad de vida. Objetivo: determinar las características epidemiológicas y las manifestaciones otorrinolaringológicas en un grupo de personas con VIH/Sida de la ciudad de Cartagena. Metodología: diseño observacional descriptivo de corte transversal y prospectivo. Se recolectó información de pacientes con VIH de la ciudad de Cartagena, que asistieron a dos centros médicos. Se les aplicó un cuestionario para obtener datos epidemiológicos, signos y síntomas otorrinolaringológicos, así como un examen físico otorrinolaringológico completo. Resultados: se incluyeron 150 pacientes en el estudio, con una media de edad de 31 años, 59,3% del género masculino y 40,7% del femenino. El antecedente patológico no otorrinolaringológico más frecuente fue la coinfección por sífilis en un 10%; el otorrinolaringológico fue la sinusitis y la candidiasis oral, cada uno con un 3,3%. El 73% de los pacientes manifestó alteración otorrinolaringológica en el momento de la evaluación. Las más frecuentes fueron las otológicas, con el 39,9% de los pacientes. Además, se observó una relación estadísticamente significativa entre los conteos de CD4 y hallazgos como disfonía en laringe (p = 0,045). Conclusiones: las manifestaciones otológicas fueron las más frecuentes en nuestro medio y se encontró una relación entre el conteo de CD4 y las manifestaciones laríngeas de la enfermedad.

Introduction: In Colombia, the incidence of the disease has been increasing and Cartagena has the highest numbers of the country. Otorhinolaryngological manifestations in people with HIV/AIDS are estimated between 20%-80% generating a great impact on quality of life. Objective: To determine the epidemiological characteristics and otorhinolaryngological manifestations in a group of people with HIV / AIDS in the city of Cartagena. Methodology: Observational, descriptive, cross-sectional and prospective design. Information was collected from patients with HIV from the city of Cartagena who attended 2 medical centers, a questionnaire was applied to obtain epidemiological data, otorhinolaryngological signs and symptoms, as well as a complete otorhinolaryngological physical examination. Results: 150 patients were included in the study, with a mean age of 31 years, 59.3% male and 40.7% female. The most frequent non-otorhinolaryngological pathological antecedent was syphilis coinfection in 10% and otorhinolaryngological, sinusitis and oral candidiasis each with 3.3%. 73% of the patients at the time of the evaluation manifested otorhinolaryngological alteration, the otological ones being the most frequent with 39.9% of the patients. Furthermore, a significant relationship was observed between CD4 counts and findings such as laryngeal dysphonia (p = 0.045). Conclusions: The otological manifestations were the most frequent in our environment and a relationship was found between the CD4 count and the laryngeal manifestations of the disease.

Efectividad del tratamiento antirretroviral con el primer esquema genérico cubano en pacientes con VIH/sida / Antirretroviral treatment with the first Cuban generic pattern in patients with HIV/aids

Introducción: Uno de los progresos más significativos en el enfrentamiento a la epidemia del VIH/sida ha sido el desarrollo de la terapia antirretroviral de gran actividad. Objetivo: Estimar las variaciones en la efectividad de la terapéutica empleada (zidovudina, lamivudina y nevirapina), en lo referente a parámetros clínicos y hematológicos seleccionados. Método: Se realizó un estudio observacional y descriptivo, de series de casos, en 45 pacientes con VIH/sida, quienes egresaron del Servicio de Medicina Interna del Hospital General Docente Dr. Juan Bruno Zayas Alfonso de Santiago de Cuba, desde el 2015 hasta el 2017, para lo cual se emplearon variables clínicas y terapéuticas. Resultados: La terapia empleada modificó de manera beneficiosa los parámetros de estudio CD4 y carga viral. Asimismo, hubo una magnitud porcentual connotada en los afectados con buena evolución clínica (39 para 86,7 %) y la efectividad del esquema propuesto fue porcentualmente visible, al mostrar más de 80,0 % de los pacientes con respuesta favorable a dicha terapia. Conclusiones: El esquema terapéutico fue efectivo, pues se produjo un incremento marcado de los valores de linfocitos CD4 y la disminución relevante de la replicación viral, lo que trajo consigo un importante decremento de las enfermedades oportunistas.

Introduction: One of the most significant progresses in fighting the epidemic of HIV/aids has been the development of the antirretroviral therapy of great activity. Objective: To calculate variations in the effectiveness of the used therapeutic process (zidovudine, lamivudine y nevirapine), regarding selected clinical and hematological parameters. Method: An observational and descriptive series of cases study was carried out in 45 patients with HIV/aids who were discharged from the Internal Medicine Service in Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba, from 2015 to 2017, for which clinical and therapeutic variables were used. Results: The implemented therapy modified in a beneficial way the study parameters CD4 and viral load. Also, there was a connoted magnitude percentage in those affected patients with good clinical course (39 representing 86.7 %) and the effectiveness of the proposed pattern was visible, when showing more than 80.0 % the patients with favorable response to this therapy. Conclusions: The therapeutic pattern was effective, because a marked increment of the CD4-lymphocytes count and the marked decrease of the viral replication, what caused an important decrease of the opportunist diseases.

Relationship of T lymphocytes, cytokines, immunoglobulin E and nitric oxide with otitis media with effusion in children and their clinical significances

SUMMARY OBJECTIVE To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.

RESUMO OBJETIVO Investigar as relações entre linfócitos T, citocinas, imunoglobulina E e óxido nítrico e a otite média com efusão (OME) em crianças e sua significância clínica. MÉTODOS Cinquenta crianças com OME tratadas em nosso hospital foram incluídas no estudo (grupo de observação). Selecionamos também 50 crianças saudáveis como controle. As porcentagens de linfócitos T CD4 + e CD8 + e a razão CD4+/CD8+ no sangue periférico, além dos níveis das citocinas IL-2, IL-4, IL-6, imunoglobulina E (IgE) e óxido nítrico (NO) no sangue periférico e de efusão no ouvido médio (MEE) de ambos os grupos foram medidos. A correlação desses índices com a OME foi analisada. RESULTADOS A porcentagem dos níveis de CD4+ e CD8 +, da razão CD4+/CD8+, de IgE e NO no sangue periférico do grupo de observação foram significativamente maiores do que no grupo controle (P < 0,01). No grupo de observação, os níveis de IL-2 e IL-6, IgE e NO em MEE foram significativamente maiores do que no sangue periférico (P < 0,01). Além disso, no grupo de observação, foi encontrada uma correlação positiva entre os níveis de IL-2 e IL-6 em MEE e a razão de CD4+/CD8+no sangue periférico, respectivamente, r = 0,366, P = 0,009; r = 0,334, P = 0,018. CONCLUSÃO Os níveis de linfócitos CD4 + e CD8 + no sangue periférico e IL-2, IL-6, IgE e NO em MEE são mais altos em crianças com OME. Esses índices forneceram evidências valiosas para o diagnóstico de OME em crianças.

Manifestações oftalmológicas dos pacientes idosos com infecção pelo vírus da imunodeficiência humana / Ophthalmologic manifestations of elderly patients with human immunodeficiency virus infection

Resumo Objetivos: Identificar e descrever as alterações oculares em idosos com HIV ou aids através de exame oftalmológico. Avaliar a associação entre as alterações oculares encontradas e o nível de linfócitos T CD4, tempo da terapia antirretroviral, características demográficas e faixa etária. Métodos: Série de 40 casos de pacientes idosos com HIV examinados nos serviços de oftalmologia e imunologia do Hospital Universitário Gaffrée e Guinle (HUGG) de janeiro de 2017 a junho de 2018. Foi realizado o seguinte exame oftalmológico: anamnese, acuidade visual, motilidade ocular, reflexo pupilar, biomicroscopia, tonometria de aplanação e fundoscopia. As análises estatísticas foram realizadas pelo SPSS 20.0. Resultados: A média de idade dos 40 pacientes foi 64,7 anos (dp: 5,1) e o diagnóstico de infeção pelo HIV foi em média há 16.6 anos (dp:7). A maioria dos pacientes examinados possui visão normal (n=22; 55%) e pressão intraocular normal (entre 11 e 21 mmHg). As principais queixas dos pacientes durante a anamnese foram: embaçamento visual (50%), redução da acuidade visual (47.5%), prurido ocular (27.5%), lacrimejamento (25%) e ardência (25%). As alterações biomicroscópicas mais frequentes foram catarata (92.5%), seguida de olho seco (32.5%). Na fundoscopia encontrou-se 43,8 % de alterações da vascularização retiniana, 43.8 % de alterações relacionadas ao nervo óptico e 31,3% relacionadas ao pólo posterior da retina. Conclusão: Alterações oculares foram comuns e podem ser justificadas pela: senilidade, estado inflamatório gerado pela infecção crônica do HIV, efeitos adversos da Terapia antirretroviral prolongada e senescência biológica precoce associada a infecção do HIV.

Abstract Objectives: Identify and describe ocular changes in elderly with HIV or aids through ophthalmological examination. Evaluate the association between ocular alterations and the level of TCD4 lymphocytes, time of antiretroviral therapy, demographic characteristics and age range. Methods: Case series of 40 elderly patients with HIV infection. The study was carried out at the ophthalmology and immunology outpatient clinics of the Gaffrée and Guinle University Hospital (HUGG) from january 2017 to june 2018. The patients were attended at the ophthalmology clinic and underwent a ophthalmological exam including: anamnesis, visual acuity, ocular motility, pupillary reflex, biomicroscopy, aplanation tonometry and fundoscopy. Statistical analyses were performed using SPSS 20.0. Results: The average of the 40 patients was 64.7 years (sd: 5.1), aged between 60 and 78 years, and the average time of HIV infection was 16.6 years (sd: 7 years). Most of the patients examined had normal vision (55%) and normal intraocular pressure (between 11 and 21 mmHg). The main complaints of patients during anamnesis were visual blurring (50%), visual acuity reduction (47.5%), ocular itchiness (27.5%), tearing (25%) and burning (25%).The most frequent changes in biomicroscopy were: cataract (92.5%) and dry eye (32.5%). Funduscopy found 43.8% of retinal vascularization alterations, 43.8% of alterations related to the optic nerve and 31.3% related to retinal posterior pole. Conclusion: Ocular changes were common and can be explained by senility, inflamatory changes caused by chronic HIV infection, adverse effects of antiretroviral therapy and early biological ageing associated to HIV infection.

Subsets of T lymphocytes in the lesional skin of pityriasis rosea

Abstract: Background: Pityriasis rosea is a common papulosquamous disorder. However, its etiology and pathogenesis remain unclear. Objective: We investigate the types of inflammatory cells infiltrating the lesional skin of pityriasis rosea and demonstrate whether T-cell-mediated immunity is involved in the pathogenesis of this condition or not. Methods: The biopsies were taken from the lesional skin of 35 cases of patients diagnosed with pityriasis rosea. The specimens were prepared in paraffin sections, then submitted to routine immunohistochemistry procedures using monoclonal antibodies directed against CD3, CD4, CD8, CD20 and CD45RO and horseradish peroxidase-labeled goat anti-human antibodies. The positive sections were determined by the ratio and staining intensity of positive inflammatory cells. Results: The mean score of positive CD3, CD4, CD8, and CD45RO staining was respectively 3.74±3.88, 5.67±4.40, 2.94±3.42 and 7.68±4.33 in these pityriasis rosea patients (P<0.001). The percentage of positive staining was 54.29% (19/35), 69.7% (23/33), 40% (14/35) and 79.41% (27/34) (P<0.05). However, the staining of CD20 was negative in all samples. The mean score of CD3 staining in patients with time for remission ≤60 days (4.90±4.21) was higher than that in patients with time for remission >60 days (2.00±2.5) (P<0.05), whereas no statistical difference in the mean score of CD4, CD8 and CD45RO staining was observed. study liMitations: The sample size and the selected monoclonal antibody are limited, so the results reflect only part of the cellular immunity in the pathogenesis of pityriasis rosea. Conclusion: Our findings support a predominantly T-cell mediated immunity in the development of pityriasis rosea.

Case for diagnosis. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder

Abstract: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a rare disease, with an indolent evolution and benign course. The classic presentation is a solitary nodule on the face or trunk. The disorder's rarity and clinical and histopathological characteristics, can make the diagnosis difficult. We present the case of a 36-year-old Caucasian woman with a purplish erythematous nodule, hardened, shiny, asymptomatic, on the left nasal ala, which had grown progressively for 45 days. Histopathological examination and immunohistochemistry panel demonstrated alterations consistent with primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. There was complete remission of the condition within 60 days of treatment with potent occlusive corticosteroids.

Relationships between phenotype and function of blood cd4+ t-cells and ascending thoracic aortic aneurysm: an experimental study

Abstract Introduction: Non-familial ascending thoracic aorta dilation and aneurysms (TAAs) are silent diseases in elderly patients. Histopathology revealed that functionally polarized infiltrating CD4+ T-cells play a key role in aortic wall weakening. Objective: To evaluate the possible associations between phenotype and cytokine production of circulating CD4+ T-lymphocytes and the presence of TAA in patients with aortic valve disease (AVD). Methods: We studied blood samples from 10 patients with TAA and 10 patients with AVD. Flow cytometry was used to quantify: a) CD4+ T-lymphocytes surface expression of CD25, CD28, and chemokine receptors (CCR5, CXCR3, CX3CR1); b) fractions of in vitro stimulated CD4+ T-cells producing cytokines (interferon gamma [IFN-γ], interleukin [IL]-17A, IL-21, IL-10); c) CD4+CD25highFoxP3+ regulatory T-cells (Treg) fraction. Enzyme-linked immunosorbent assays (ELISA) were performed for cytokines (IFN-γ, IL-6, IL-10, IL-17A, IL-23, transforming growth factor beta [TGF-β]) and chemokines (RANTES, CX3CL1). Results: The total CD4+CD28±CD4+/CX3CR1+ T-cells fraction was higher (P=0.0323) in AVD (20.452±4.673) than in TAA patients (8.633±2.030). The frequency ratio of CD4+ T-lymphocytes producing IFN-γ vs. IL-17A+IL-21 cytokine-producing CD4+ T-cells was higher (P=0.0239) in AVD (2.102±0.272) than in TAA (1.365±0.123) patients. The sum of CD4+CD28±CD4+/CX3CR1+ T-cells correlated positively with values of the previous cytokine ratio (P=0.0002, R=0.732). The ratio of CD4+CD28±CD4+/CX3CR1+ T-cells vs. Treg was higher (P=0.0008) in AVD (20.859±3.393) than in TAA (6.367±1.277) patients. Conclusion: Our results show that the presence of TAA in subjects with AVD is associated with imbalance between phenotypic and cytokine-producing subsets of circulating CD4+ T-lymphocytes, prevalently oriented towards a pro-fibrotic and IFN-γ counteracting effect to functional polarization.

Low frequency of regulatory B-cells and increased CD4+ and CD8+ interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type

Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.

Artesunate promotes Th1 differentiation from CD4+ T cells to enhance cell apoptosis in ovarian cancer via miR-142

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

Β-Glucan of candida albicans cell wall extract inhibits salmonella typhimurium colonization by potentiating cellular immunity (cd8 + and cd4 + t cells)

Abstract INTRODUCTION: Antimicrobial resistance has been reported in the drugs used for the treatment of typhoid fever. The immunomodulatory substance β-glucan can be used as an alternative therapy as it potentiates host immunity. The aims of this study are to observe the effect of Candida albicans cell wall (CCW) extract towards host immunity (TCD8+ and TCD4+ cells in spleen, intestinal sIgA) and its capacity to kill Salmonella in the intestine and liver of typhoid fever mice models. METHODS: Typhoid fever mice models were created by infecting mice with S. Typhimurium orally. Mice were divided into four groups: the Non-Infected, Infected, CCW (infected mice treated with 300 µg CCW extract/mouse once a day), and Ciprofloxacin groups (infected mice treated with 15 mg/kg BW ciprofloxacin twice a day). RESULTS: Secretory IgA (sIgA) concentrations of mice in the CCW group remained unchanged. However, their TCD4+ and TCD8+ cells increased substantially compared to those in the Non-Infected group. In the Ciprofloxacin group, sIgA concentrations increased markedly compared to those in the Non-Infected and CCW groups; TCD4+ and TCD8+ cells also increased significantly compared to those in the Infected Group, but not significant compared to those in the CCW group. Colonization of S. Typhimurium in the intestine and liver decreased significantly in the CCW and Ciprofloxacin groups compared to that in the Infected group, with the lowest reduction being found in the Ciprofloxacin group. CONCLUSIONS The inhibition of S. Typhimurium colonization by CCW is associated with the increase in TCD4+ and TCD8+ cells.