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1.
Clin. transl. oncol. (Print) ; 26(4): 924-935, Abr. 2024. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-VR-55

RESUMO

Purpose: Non-small cell lung cancer (NSCLC) is a complex disease that remains a major public health concern worldwide. One promising avenue for NSCLC treatment is the targeting of transcription factors that regulate key pathways involved in cancer progression. In this study, we investigated the role of the transcription factor ZNF263 in NSCLC and its impact on the regulation of IL33, apoptosis, and autophagy. Methods: Levels of ZNF263 in tissues and cell lines were identified, after which the effects of its knockdown on cellular malignant behaviors, apoptosis and autophagy were assessed. Based on bioinformatics analysis, ZNF263 was found to bind to IL33 promoter, their mutual relationship was confirmed, as well as the role of IL33 in the regulation of ZNF263. The involvement of ZNF263 in the growth of xenograft tumors was assessed using tumor-bearing nude mouse models. Results: Experimental results revealed that ZNF263 was upregulated in NSCLC tissue samples and cell lines. Its expression level is positively correlated with cellular malignant behaviors. We further demonstrated that ZNF263 upregulated IL33 expression, which, in turn, promoted the proliferation and migration, inhibited apoptosis and autophagy in NSCLC cells. Furthermore, ZNF263 knockdown reduced the growth of xenograft tumors in nude mice. Conclusion: This finding suggests that the inhibition of ZNF263 or IL33 may represent a novel therapeutic strategy for NSCLC. Importantly, our results highlight the crucial role of transcription factors in NSCLC and their potential as therapeutic targets.(AU)


Assuntos
Humanos , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas , Autofagia , Proteínas de Ligação a DNA , Interleucina-33/metabolismo , Interleucina-33/uso terapêutico , Neoplasias Pulmonares/patologia
2.
Indian J Med Res ; 159(2): 121-129, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38577854

RESUMO

ABSTRACT: Leprosy, an ancient disease, continues to be a public health concern as it remains endemic in several countries. After reaching the elimination target (1/10,000) as a public health problem in 2005 in India, around 1.2 lakh cases have been detected every year over the last decade indicating active transmission of leprosy bacillus (Mycobacterium leprae). Single-nucleotide polymorphisms (SNPs), genomic insertions/deletions and variable-number tandem repeats (VNTRs) have been identified as genetic markers for tracking M. leprae transmission. As the leprosy bacilli cannot be cultured in vitro, molecular testing of M. leprae genotypes is done by polymerase chain reaction-based sequencing which provides a practical alternative for the identification of strains as well as drug resistance-associated mutations. Whole-genome sequencing (WGS) of M. leprae directly from clinical samples has also proven to be an effective tool for identifying genetic variations which can further help refine the molecular epidemiological schemes based on SNPs and VNTRs. However, the WGS data of M. leprae strains from India are scarce, being responsible for a gross under-representation of the genetic diversity of M. leprae strains present in India and need to be addressed suitably. Molecular studies of leprosy can provide better insight into phylogeographic markers to monitor the transmission dynamics and emergence of antimicrobial resistance. An improved understanding of M. leprae transmission is essential to guide efficient leprosy control strategies. Therefore, this review compiles and discusses the current status of molecular epidemiology, genotyping and the potential of genome-wide analysis of M. leprae strains in the Indian context.


Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , DNA Bacteriano/genética , Hanseníase/epidemiologia , Hanseníase/genética , Polimorfismo de Nucleotídeo Único/genética , Epidemiologia Molecular
3.
J Clin Invest ; 134(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618960

RESUMO

Merkel cell carcinoma (MCC) is an aggressive, fast-growing, highly metastatic neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is an oncogenic driver in the majority of MCC tumors. In this issue of the JCI, Hansen and authors report on their tracking of CD8+ T cells reactive to MCPyV T antigen (T-Ag) in the peripheral blood of 26 patients with MCC who were undergoing frontline anti-programmed cell death protein-1 (anti-PD-1) immunotherapy. They discovered unique T cell epitopes and used the power of bar-coded tetramers to portray immune checkpoint inhibitor-induced immunogenicity as a predictor of clinical response. These findings provide the foundation for therapeutic possibilities for MCC, including vaccines and adoptive T cell- and T cell receptor-driven (TCR-driven) treatments.


Assuntos
Carcinoma de Célula de Merkel , Polyomavirus , Neoplasias Cutâneas , Humanos , Carcinoma de Célula de Merkel/terapia , Polyomavirus/genética , Neoplasias Cutâneas/terapia , Linfócitos T CD8-Positivos , Epitopos de Linfócito T
4.
Cell Genom ; 4(4): 100540, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604125

RESUMO

Mechanisms underlying phenotypic divergence across species remain unresolved. In this issue of Cell Genomics, Hansen, Fong, et al.1 systematically dissect human and rhesus macaque gene expression divergence by screening tens of thousands of orthologous elements for enhancer activity in lymphoblastoid cell lines, revealing a much greater role for trans divergence at levels equal to those of cis effects, counter to the prevailing consensus in the field.


Assuntos
Evolução Molecular , Regulação da Expressão Gênica , Animais , Humanos , Macaca mulatta/genética , Sequências Reguladoras de Ácido Nucleico , Genômica
6.
Public Health ; 230: 172-182, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38560955

RESUMO

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.


Assuntos
Carga Global da Doença , Hanseníase , Humanos , Geografia , Hanseníase/epidemiologia , Exame Físico , Fatores Socioeconômicos , Saúde Global , Incidência , Anos de Vida Ajustados por Qualidade de Vida
7.
Mol Biol Rep ; 51(1): 504, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616219

RESUMO

BACKGROUND: Mycobacterium leprae causes leprosy that is highly stigmatized and chronic infectious skin disease. Only some diagnostic tools are being used for the identification M. leprae in clinical samples, such as bacillary detection, and histopathological tests. These methods are invasive and often have low sensitivity. Currently, the PCR technique has been used as an effective tool fordetecting M. leprae DNA across different clinical samples. The current study aims to detect M. leprae DNA in urine samples of untreated and treated leprosy patients using the Rlep gene (129 bp) and compared the detection among Ridley-Jopling Classification. METHODS: Clinical samples (Blood, Urine, and Slit Skin Smears (SSS)) were collected from leprosy and Non-leprosy patients. DNA extraction was performed using standard laboratory protocol and Conventional PCR was carried out for all samples using Rlep gene target and the amplicons of urine samples were sequenced by Sanger sequencing to confirm the Rlep gene target. RESULTS: The M. leprae DNA was successfully detected in all clinical samples across all types of leprosy among all the study groups using RLEP-PCR. Rlep gene target was able to detect the presence of M. leprae DNA in 79.17% of urine, 58.33% of blood, and 50% of SSS samples of untreated Smear-Negative leprosy patients. The statistical significant difference (p = 0.004) was observed between BI Negative (Slit Skin Smear test) and RLEP PCR positivity in urine samples of untreated leprosy group. CONCLUSION: The PCR positivity using Rlep gene target (129 bp) was highest in all clinical samples among the study groups, across all types of leprosy. Untreated tuberculoid and PNL leprosy patients showed the highest PCR positivity in urine samples, indicating its potential as a non-invasive diagnostic tool for leprosy and even for contact screening.


Assuntos
Bacillus , Mycobacterium leprae , Humanos , Mycobacterium leprae/genética , Pele , Firmicutes , Reação em Cadeia da Polimerase
8.
Bull World Health Organ ; 102(4): 288-295, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38562197

RESUMO

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.


L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.


La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.


Assuntos
Hanseníase , Humanos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Mycobacterium leprae/genética , Sensibilidade e Especificidade , Modelos Estatísticos , Diagnóstico Precoce
9.
PeerJ ; 12: e17170, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590701

RESUMO

Introduction: Involvement of a chemokine known as C-X-C motif chemokine ligand 10 or CXCL10 in the immunopathology of leprosy has emerged as a possible immunological marker for leprosy diagnosis and needed to be investigate further. The purpose of this systematic review is to assess CXCL10's potential utility as a leprosy diagnostic tool and evaluation of therapy. Methods: This systematic review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. A thorough search was carried out to find relevant studies only in English and limited in humans published up until September 2023 using PubMed, Scopus, Science Direct, and Wiley Online Library database with keywords based on medical subject headings (MeSH) and no exclusion criteria. The Newcastle-Ottawa Scale (NOS) was utilized for quality assessment, while the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was utilized for assessing the risk of bias. Additionally, a narrative synthesis was conducted to provide a comprehensive review of the results. Results: We collected a total of 115 studies using defined keywords and 82 studies were eliminated after titles and abstracts were screened. We assessed the eligibility of the remaining 26 reports in full text and excluded four studies due to inappropriate study design and two studies with incomplete outcome data. There were twenty included studies in total with total of 2.525 samples. The included studies received NOS quality evaluation scores ranging from 6 to 8. The majority of items in the risk bias assessment, using RoBANS, across all included studies yielded low scores. However, certain items related to the selection of participants and confounding variables showed variations. Most of studies indicate that CXCL10 may be a helpful immunological marker for leprosy diagnosis, particularly in leprosy reactions as stated in seven studies. The results are better when paired with other immunological markers. Its effectiveness in field-friendly diagnostic tools makes it one of the potential biomarkers used in diagnosing leprosy patients. Additionally, CXCL10 may be utilized to assess the efficacy of multidrug therapy (MDT) in leprosy patients as stated in three studies. Conclusion: The results presented in this systematic review supports the importance of CXCL10 in leprosy diagnosis, particularly in leprosy responses and in tracking the efficacy of MDT therapy. Using CXCL10 in clinical settings might help with leprosy early diagnosis. Yet the findings are heterogenous, thus more investigation is required to determine the roles of CXCL10 in leprosy while taking into account for additional confounding variables.


Assuntos
Quimiocinas , Hansenostáticos , Humanos , Quimioterapia Combinada , Quimiocina CXCL10
12.
Chem Biodivers ; 21(5): e202400067, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38500408

RESUMO

Tuberculosis is a communicable disease which affects humans particularly the lungs and is transmitted mainly through air. Despite two decades of intensive research aimed at understanding and combating tuberculosis, persistent biological uncertainties continue to hinder progress. Nowadays, heterocyclic compounds have proven themselves in effective treatment of tuberculosis because of their wide range of biological and pharmacological activities. Antituberculosis or antimycobacterial agents encompass a broad array of compounds utilized singly or in conjunction to combat Mycobacterium infections, spanning from tuberculosis to leprosy. Here, we summarize the synthesis of various heterocyclic compounds which includes the greener synthetic route as well as use of nano compounds as catalyst along with their anti TB activities.


Assuntos
Antituberculosos , Compostos Heterocíclicos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Antituberculosos/farmacologia , Antituberculosos/química , Antituberculosos/síntese química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Humanos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Estrutura Molecular
13.
Foot Ankle Int ; 45(5): 446-455, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38501715

RESUMO

BACKGROUND: For the temporary treatment of ankle fracture dislocations (AFDs), previous studies indicate higher rates of secondary loss of reduction (LOR) with splint immobilization, prompting consideration for expanding indications for external fixation (ExFix). However, these studies did not investigate the influence of fracture morphology to further improve patient selection. The aim of this study was to investigate the influence of Lauge-Hansen injury type on the LOR rate in bimalleolar or trimalleolar AFDs for temporary cast vs ExFix immobilization. METHODS: In this retrospective cohort study, patients with isolated AFD cases treated at our institution from 2011 to 2020 were reviewed. Inclusion criteria required radiographs depicting initial dislocation and appropriate reduction after Cast or ExFix immobilization. Exclusion criteria encompassed concomitant injuries, open fractures, conservative management as well as surgery performed within 48 hours or at a different facility. Patients were grouped by temporary treatment (Cast or ExFix). The primary endpoint was LOR prior to definitive surgery across various Lauge-Hansen types. RESULTS: The LOR rate was significantly higher in the cast group (40/152, 26.3%) compared to the ExFix group (5/191, 2.6%; P < .0001). In the cast group, LOR was associated with an increase in time to definitive surgery by a mean of 3 days (P < .002). During cast treatment, LOR was significantly more likely for pronation abduction (P = .001) and supination external rotation injuries (P < .0001), whereas no significant differences were observed for pronation external rotation (P = .006), supination adduction (P > .99), and fractures not classifiable (P > .99). CONCLUSION: In cases of AFDs resulting from supination external rotation or pronation abduction trauma according to the Lauge-Hansen classification, especially in the setting of an additional posterior malleolar fracture, primary application of external fixation should be considered to reduce the risk for secondary loss of reduction. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Assuntos
Fraturas do Tornozelo , Moldes Cirúrgicos , Fratura-Luxação , Humanos , Fraturas do Tornozelo/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fratura-Luxação/cirurgia , Fixação de Fratura/métodos , Idoso , Estudos de Coortes
14.
Ann Work Expo Health ; 68(4): 409-419, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38437526

RESUMO

Determining the vapor pressure of a substance at the relevant process temperature is a key component in conducting an exposure assessment to ascertain worker exposure. However, vapor pressure data at various temperatures relevant to the work environment is not readily available for many chemicals. The Antoine equation is a mathematical expression that relates temperature and vapor pressure. The objective of this analysis was to compare Antoine parameter data from 3 independent data sources; Hansen, Yaws, and Custom data and identify the source that generates the most accurate vapor pressure values with the least bias, relative to the referent data set from the CRC Handbook of Chemistry and Physics. Temperatures predicted from 3 different Antoine sources across a range of vapor pressures for 59 chemicals are compared to the reference source. The results show that temperatures predicted using Antoine parameters from the 3 sources are not statistically significantly different, indicating that all 3 sources could be useful. However, the Yaws dataset will be used in the SDM 2.0 because the data is readily available and robust.


Assuntos
Temperatura , Pressão de Vapor , Humanos , Exposição Ocupacional/análise , Monitoramento Ambiental/métodos , Monitoramento Ambiental/instrumentação , Modelos Teóricos
15.
BMC Infect Dis ; 24(1): 352, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532327

RESUMO

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, mainly affecting the skin and peripheral nerves, caused by the obligate intracellular bacteria Mycobacterium leprae. The disease has been discussed in several review articles in recent research, but as far as we know, only a few have addressed the effects of leprosy on nails, especially those who examine the dermoscopic features of nails in leprosy patients. PURPOSES: We aimed to document nail changes in leprosy patients and identify any particular findings through dermoscopic examination. METHOD: This was an observational study conducted in the Dermatology and Venereology Clinic of Hasan Sadikin Hospital, West Java, Indonesia, from March 2023 through May 2023. All patients have established cases of leprosy, and the diagnosis is based on clinical and bacteriological examinations. Recruitment was done through total sampling. Dermoscopic examination of all fingernails and toenails was performed at 10x magnification using a handheld dermatoscope (Heine DELTA 20 T Dermatoscope) in polarized mode without the linkage fluid to document the dermoscopic features. RESULT: Of a total of 19 patients, 15 had nail changes due to leprosy. Out of 15 patients, 13 patients were male. Patients below 25 years old had more nail changes. Most of the patients had a duration of disease greater than two years. Both fingers and toes were involved in nine patients. In this study, the most common dermoscopic feature found was the longitudinal ridge. Other dermoscopic features found in this study were transverse lines, onycholysis, longitudinal melanonychia, leukonychia, subungual hemorrhage, subungual hyperkeratosis, anonychia, and onychorrexis. CONCLUSION: Nail changes are found in leprosy patients and have a wide variety of clinical appearances. A dermoscopy should be performed to assess nail changes in leprosy.


Assuntos
Hanseníase , Doenças da Unha , Humanos , Masculino , Adulto , Feminino , Unhas , Indonésia , Centros de Atenção Terciária , Doenças da Unha/etiologia , Hanseníase/diagnóstico
16.
Artigo em Chinês | MEDLINE | ID: mdl-38538244

RESUMO

Non-tuberculosis mycobacterium (NTM) refers to a general term for a large group of mycobacteria, excluding the mycobacterium tuberculosis and mycobacterium leprae, which is an opportunistic pathogen. NTM pulmonary disease and pulmonary tuberculosis have very similar clinical and imaging manifestations. Ordinary sputum tests can not distinguish between mycobacterium tuberculosis and NTM accurately, and it needs to be differentiated through detection methods such as mycobacterium culture medium, high-performance liquid chromatography, and molecular biology. During the diagnosis of occupational pneumoconiosis, a sandblasting and polishing worker's lung CT showed dynamic changes in infiltrating shadows and cavities in the right lung. A sputum drug sensitivity test showed NTM infection, but the patient refused treatment. After 20 months, the CT examination of the lung showed further enlargement of infiltrating shadows and cavities, and NTM bacterial identification showed intracellular mycobacterial infection. Amikacin, moxifloxacin, azithromycin, and ethambutol combined antibacterial treatment were given. Currently, the patient is still under treatment.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Silicose , Tuberculose Pulmonar , Humanos , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Tuberculose Pulmonar/complicações , Micobactérias não Tuberculosas , Silicose/complicações
17.
Microb Pathog ; 190: 106610, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38484920

RESUMO

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells.


Assuntos
Antígenos CD , Molécula CD68 , Imunofenotipagem , Hanseníase Virchowiana , Macrófagos , Humanos , Macrófagos/imunologia , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/patologia , Masculino , Feminino , Citocinas/metabolismo , Antígenos de Diferenciação Mielomonocítica , Lobomicose/imunologia , Lobomicose/patologia , Pessoa de Meia-Idade , Adulto , Pele/patologia , Pele/imunologia , Idoso , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/imunologia
18.
Pulm Med ; 2024: 2182088, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487406

RESUMO

Background: Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Results: Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Conclusions: Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia.


Assuntos
Tuberculose Pulmonar , Humanos , Estudos de Casos e Controles , Tuberculose Pulmonar/diagnóstico por imagem , Resultado do Tratamento , Escarro , Instalações de Saúde
19.
Environ Sci Pollut Res Int ; 31(17): 25559-25566, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38480625

RESUMO

The objective of this study is to assess the occurrence of intestinal parasites in Mediterranean pond turtle Mauremys leprosa leprosa collected from three contrasting environments in Morocco. Stool samples from 92 turtles were examined for parasite detection and enumeration. The identified intestinal parasites belong to helminths (oxyurids and ascarid) and protozoa (Entamoebidae). A total of 25 turtles (27.17%) were found to be infected by helminths and/or protozoan parasites. No adult form of these parasites was detected. Eggs of oxyurid and ascarid were detected in individuals of populations studied from Oued Ksob (23.07% and 30.76% of n = 13 turtles) and Oued Zat (34.14% and 24.39% of n = 41 turtles), respectively. For protozoa, Entamoeba cysts were present in turtles in Oued Ksob (15.38% of n = 13 turtles), Oued Zat (12.19% of n = 41 turtles), and Oued Tensift (5.26% of n = 38 turtles) localities. Oxyurid eggs showed the highest intensity at Oued Zat reaching 29.30 ± 59.59 eggs per gram (EPG), versus 12 ± 0.38 EPG for ascaris eggs in Oued Ksob. Entamoeba cysts were detected in lower levels with a maximum of 1.66 ± 1.50 cysts per gram (CPG), in Oued Zat. The prevalence of turtles eliminating eggs was statistically significant between localities for different parasite groups. This study reports for the first time a parasitological characterization of gastrointestinal parasites in wild populations of M. leprosa leprosa from contrasting environments, suggesting a relationship between turtles' infestation and the quality of their habitat.


Assuntos
Cistos , Helmintos , Parasitos , Tartarugas , Humanos , Animais , Marrocos , Ecossistema
20.
J Infect Public Health ; 17(5): 780-788, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38518684

RESUMO

BACKGROUND: The genus Mycobacterium includes well-known bacteria such as M. tuberculosis causing tuberculosis and M. leprae causing leprosy. Additionally, various species collectively termed non-tuberculous mycobacteria (NTM) can cause infections in humans and animals, affecting individuals across all age groups and health conditions. However, information on NTM infection prevalence in Panama is limited. METHODS: This study conducted a retrospective analysis of clinical records from 2017 to 2021, specifically focusing on patients with NTM isolates. Data were categorized by variables like sex, age, HIV status, and sample source. RESULTS: Among the 4430 clinical records analyzed, 698 were linked to patients with NTM isolates. Of these patients, 397 were male, and 301 were female. Most female patients with NTM isolates (n = 190) were aged >45 to 85 years, while most male patients (n = 334) fell in the >25 to 75 years age group. A noteworthy proportion of male patients (n = 65) were aged 25-35 years. A significant age difference between male (median [min-max] = 53 years [3-90]) and female (median [61 years [6-94]) patients was observed (p < 0.001). Regarding HIV status, 77 positive individuals were male, and 19 were female (p < 0.001). Most samples (n = 566) were sputum samples, with additional pulmonary-associated samples such as broncho-alveolar lavage, tracheal secretions, and pleural fluid samples. Among extrapulmonary isolates (n = 48), sources included catheter secretions, intracellular fluids, peritoneal fluid, blood cultures, cerebrospinal fluid, bone marrow samples, and capillary transplant lesions. Specifically, the analysis identified the pathogenic microorganisms responsible for mycobacteriosis in Panama during the specific period 2017-2021, as M. fortuitum (34.4%), M. intracellulare (20.06%), and M. abscessus (13.75%), respectively. CONCLUSIONS: This study highlights the growing public health concern of NTM infections in Panama. The research provides valuable insights into the prevalence and distribution of NTM species in the country, offering a foundation for the development and implementation of effective prevention and control strategies for NTM infections in Panama.


Assuntos
Infecções por HIV , Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Tuberculose , Animais , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos , Mycobacterium leprae , Panamá/epidemiologia , Tuberculose/complicações , Infecções por HIV/complicações
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