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Disseminated leishmaniasis (DL) is an emergent severe disease manifesting with multiple lesions. To determine the relationship between immune response and clinical and therapeutic outcomes, we studied 101 DL and 101 cutaneous leishmaniasis (CL) cases and determined cytokines and chemokines in supernatants of mononuclear cells stimulated with leishmania antigen. Patients were treated with meglumine antimoniate (20 mg/kg) for 20 days (CL) or 30 days (DL); 19 DL patients were instead treated with amphotericin B, miltefosine, or miltefosine and meglumine antimoniate. High levels of chemokine ligand 9 were associated with more severe DL. The cure rate for meglumine antimoniate was low for both DL (44%) and CL (60%), but healing time was longer in DL (p = 0.003). The lowest cure rate (22%) was found in DL patients with >100 lesions. However, meglumine antimoniate/miltefosine treatment cured all DL patients who received it; therefore, that combination should be considered as first choice therapy.
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Leishmania braziliensis , Leishmania , Leishmaniasis Cutánea , Fosforilcolina/análogos & derivados , Humanos , Antimoniato de Meglumina/uso terapéutico , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológicoRESUMEN
Chimeric T. cruzi antigens have been proposed as a diagnostic tool for chronic Chagas disease (CD) in both settings where Chagas disease is endemic and those where it is not endemic. Antibody response varies in accordance to each T. cruzi strain, presenting challenges to the use of antigens lacking demonstrated cross-reactivity with Leishmania spp. Our group expressed four chimeric proteins (IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4) and previously assessed their diagnostic performance to determine cross-reactivity with Leishmania spp. Here, we validated our findings using serum samples from different Brazilian geographic areas reporting endemic Chagas disease, endemic visceral or American cutaneous leishmaniasis (ACL), or both. Overall, 829 serum samples were evaluated using commercial and IBMP enzyme-linked immunosorbent assays. Due to the absence of a reference assay to diagnosis CD, latent class analysis (LCA) was performed through the use of a statistical model. The incidence of cross-reactivity for ACL-positive samples varied from 0.35% (IBMP-8.3) to 0.70% (IBMP-8.1 and IBMP-8.2). Regarding visceral leishmaniasis (VL)-positive samples, the IBMP-8.2 and IBMP-8.3 antigens cross-reacted with six (3.49%) and with only one sample (0.58%), respectively. No cross-reactivity with either ACL or VL was observed for the IBMP-8.4 antigen. Similarly, no cross-reactions were found when VL-positive samples were assayed with IBMP-8.1. The agreement among the results obtained using IBMP antigens ranged from 97.3% for IBMP-8.2 and 99% for IBMP-8.1 and IBMP-8.3 to 100% for IBMP-8.4, demonstrating almost perfect agreement with LCA. Accordingly, in light of the negligible cross-reactivity with both ACL and VL, we suggest the use of IBMP antigens in regions where T. cruzi and Leishmania spp. are coendemic.
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Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/inmunología , Reacciones Cruzadas , Proteínas Recombinantes de Fusión/inmunología , Antígenos de Protozoos/genética , Enfermedades Endémicas/estadística & datos numéricos , Ensayo de Inmunoadsorción Enzimática , Humanos , Análisis de Clases Latentes , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Visceral/epidemiología , Proteínas Recombinantes de Fusión/genética , Sensibilidad y Especificidad , Trypanosoma cruzi/genética , Trypanosoma cruzi/inmunologíaRESUMEN
BACKGROUND: Poisoning is a worldwide public health problem that involves individuals of all ages and a wide range of chemicals. This study investigated the data from two health information systems to characterize poisoning events in the Federal District (DF), Brazil. METHODS: Data related to the period from 2009 to 2013 were obtained from the poison information center (Centro de Informação Toxicológica, CIT) and the Notifiable Diseases Information System (Sistema Nacional de Agravos de Notificação, SINAN) of the DF. RESULTS: A total of 3622 cases were reported to CIT-DF and 5702 cases to SINAN-DF. Most of the cases in CIT-DF (53%) occurred with children up to 9 years old, while this corresponded to 33.9% in SINAN-DF. Unintentional poisoning was the main circumstance involved in the cases. Pharmaceuticals were the main agent (44.3-47.1% of the cases), mainly clonazepan and paracetamol, and pesticides the most fatal (2.4% fatality rate). Out of the 47 fatal cases reported to the systems, only four were reported to both; six cases occurred with children up to 6 years. CONCLUSION: Under-reporting and missing information were identified in both systems, but the data were complementary to describe the epidemiology of poisoning cases in the DF.
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Notificación Obligatoria , Intoxicación/epidemiología , Programas Voluntarios , Adolescente , Adulto , Distribución por Edad , Anciano , Brasil/epidemiología , Niño , Preescolar , Recolección de Datos , Femenino , Sistemas de Información en Salud , Humanos , Lactante , Masculino , Persona de Mediana Edad , Centros de Control de Intoxicaciones , Intoxicación/etiología , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. Methods: A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. Results: A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. Conclusions: The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy.
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Antimonio/administración & dosificación , Antiprotozoarios/administración & dosificación , Inflamación/patología , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/patología , Adulto , Estudios Transversales , Citocinas/sangre , Femenino , Humanos , Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Cutánea/parasitología , Leucocitos Mononucleares/inmunología , Masculino , Prevención Secundaria , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
Ulcer development in patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is associated with high levels of tumor necrosis factor (TNF). We found that early after infection, before ulcer development, the frequency of CD16(+) (both intermediate [CD14(+)CD16(+)] and nonclassical [CD14(dim)CD16(+)]) monocytes was increased in the peripheral blood of patients with L. braziliensis, compared with uninfected controls. These results suggest that CD16(+) monocytes might promote disease. Also, we found that intermediate monocytes expressed CCR2 and that increased levels of CCL2 protein were present in lesions from patients, suggesting that intermediate monocytes are more likely than nonclassical monocytes to migrate to the lesion site. Finally, we found that the intermediate monocytes produced TNF. Our results show that intermediate monocytes are increased in frequency soon after infection; express CCR2, which would promote their migration into the lesions; and, owing to their production of TNF, can enhance the inflammatory response.
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Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Monocitos/inmunología , Adolescente , Adulto , Quimiocina CCL2/metabolismo , Femenino , Proteínas Ligadas a GPI/análisis , Humanos , Masculino , Persona de Mediana Edad , Monocitos/química , Receptores CCR2/análisis , Receptores de IgG/análisis , Factor de Necrosis Tumoral alfa/metabolismo , Úlcera/inmunología , Úlcera/patología , Adulto JovenRESUMEN
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.
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Vitíligo , Femenino , Humanos , Adulto , Masculino , Quimiocina CXCL10/metabolismo , Proteína C-Reactiva , Estudios Transversales , Pandemias , CitocinasRESUMEN
The CONVINCE trial demonstrates that high-dose hemodiafiltration offers a survival advantage for patients in the high-flux hemodiafiltration group compared to hemodialysis. We compared the outcomes of hemodialysis and hemodiafiltration using real-world data. We conducted an analysis on a cohort of patients who underwent hemodiafiltration therapy (HDF) at a single center, NefroStar Clinics. The results obtained were then compared with data from patients receiving hemodialysis (HD) therapy within the Brazilian Public Health System (SUS). The primary outcome was mortality from any cause. Results: A total of 85 patients undergoing hemodiafiltration were compared with 149,372 patients receiving hemodialysis through the Brazilian Public Health System (SUS). Using a 2:1 propensity score, we compared the 170 best-match HD patients with 85 HDF patients. In the Cox analysis, HDF therapy showed a reduced risk of mortality with an HR of 0.29 [0.11-0.77]. The propensity score analysis showed a HR of 0.32 [95% CI: 0.11-0.91]. This analysis was adjusted for age, type of access, KT/v, hemoglobin, and phosphorus. The Kaplan-Meier analysis showed respective survival rates for HDF and HD at the end of one year, 92.1% and 79.9%, p < 0.001. These results suggest high-flux hemodiafiltration has survival advantages over hemodialysis in a real-world scenario.
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BACKGROUND: The main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology. Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development. In the present work we investigated the immune response in CL and ML cured individuals. METHODS: Participants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy. IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA). The frequency of memory CD4+ T cell populations was determined by FACS. RESULTS: Here we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure. In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma. Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST). A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro. CONCLUSION: This study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo. These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine. Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.
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Linfocitos T CD4-Positivos/inmunología , Leishmania/inmunología , Leishmaniasis Cutánea/inmunología , Adolescente , Adulto , Antígenos de Protozoos/inmunología , Brasil/epidemiología , Niño , Femenino , Humanos , Memoria Inmunológica , Interferón gamma/sangre , Leishmaniasis Cutánea/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
INTRODUCTION: The pathogenesis of cutaneous and mucosal leishmaniasis is associated with different immune responses. Vitamin D may modulate the immune system. Here we evaluate the association of vitamin D levels with the severity of the clinical forms of cutaneous and mucosal leishmaniasis. METHODS: We conducted an observational study evaluating the association between vitamin D levels, disease severity and therapeutic response in patients with cutaneous and mucosal leishmaniasis. Additionally, we conducted a cross-sectional study to compare vitamin D levels in patients with leishmaniasis and healthy subjects. Hypovitaminosis D was defined as a serum level of 25 (OH) D < 30 ng/mL. RESULTS: In patients with leishmaniasis, vitamin D serum levels were 38.5 ± 11.54 ng/mL, and 37.5 ± 10.43 ng/mL in healthy subjects The prevalence of hypovitaminosis D was 23.3% and 20.0%, respectively (p = 0.72). There was no correlation between vitamin D serum levels, disease severity, and healing time in the mucosal leishmaniasis group. CONCLUSION: Vitamin D levels are not associated with neither susceptibility nor severity of tegumentary leishmaniasis.
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Leishmaniasis Cutánea , Deficiencia de Vitamina D , Humanos , Estados Unidos , Vitamina D , Brasil/epidemiología , Estudios Transversales , Leishmaniasis Cutánea/epidemiología , Leishmaniasis Cutánea/patología , Deficiencia de Vitamina D/epidemiología , ComunicaciónRESUMEN
BACKGROUND: Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. METHODS: Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V+normal-phosphorus diet (np)) and 'Nx+PTx': G2 (nPTH+pP), G3 (nPTH+rP), G4 (hPTH+pP) and G5 (hPTH+rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-ß) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. RESULTS: Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-ß, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. CONCLUSION: In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.
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Enfermedades Cardiovasculares/etiología , Fibrosis/etiología , Hormona Paratiroidea/metabolismo , Fósforo Dietético/metabolismo , Uremia/complicaciones , Uremia/fisiopatología , Animales , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/patología , Fibrosis/patología , Técnicas para Inmunoenzimas , Masculino , Nefrectomía/efectos adversos , Hormona Paratiroidea/administración & dosificación , Paratiroidectomía/efectos adversos , Fósforo Dietético/administración & dosificación , Ratas , Ratas WistarRESUMEN
Introduction: The high numbers of accidents involving venomous animals in tropical countries is a major public health problem and has prompted the World Health Organization to place them on its list of neglected tropical diseases. The Notifiable Diseases Information System shows that the number of notifications of accidents involving venomous animals increases every year. In Brazil, accidents involving venomous animals are the number one cause of human intoxications. The public health importance of accidents and their consequential importance for workers is clearly illustrated by the more than 100,000 accidents and almost 200 deaths that occur annually. Objectives: To observe and analyze the profile of accidents involving venomous animals in Brazil's Federal District. Methods: A retrospective descriptive case series study of data from four databases containing information on accidents involving venomous animals. In addition to analyzing each one, they were also compared to each other. Results: A total of 11,376 accidents involving venomous animals from 2009 to 2019 were registered in the Federal District. There were 363 occupational accidents and zero deaths in the period. There were discrepancies between each of the databases analyzed. Conclusions: Subnotification and discrepancies should be better evaluated and subsequently resolved by the managers of each database. Actively seeking information and better organization of the organs responsible for database management are possible solutions to the current problems.
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INTRODUCTION: The radiosynovectomy (RS) is one treatment option for recurrent hemarthrosis in patients with hemophilia (PWH). A prospective cohort study was designed to evaluate the effects of the RS on the synovial membrane volume in the ankles and knees of PWH and patient characteristics related to the RS outcome. METHODS: In a one-year follow-up, 25 joints of 22 PWH who presented 3 bleeds or more in the same joint over the last 6 months (target joints) were subjected to the RS. Two groups were compared: those who retained target joints following the RS and those who did not (less than 3 bleeds/6 months after the RS). The groups were analyzed according to age, hemophilia type/severity, joint, body mass index (BMI), inhibitor and Hemophilia Joint Health Score 2.1 (HJHS). The magnetic resonance images (MRI) of six ankles and six knees were acquired prior to, and 6 months after, the RS. The synovial membrane volume and arthropathy MRI scale were accessed and volumes were compared and correlated with the Yttrium-90 dose injected. RESULTS: Patients with a mean age of 12 years and a mean HJHS of 6.7 (pâ¯<â¯0.05) retained target joints after the RS. The inhibitor, joint, type/severity of disease and BMI showed no significant differences between groups. The synovial membrane volume had a significant reduction after the RS (pâ¯=â¯0.03), but no correlation with the Yttrium-90 dose. In proportion to the synovial membrane volume, doses injected to the ankles were larger than those injected to the knees. CONCLUSION: The synovial membrane volume is reduced after the RS, regardless of the effective 90Y dose.
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Background: Mucosal leishmaniasis (ML), the most inflammatory form of tegumentary leishmaniasis, is predominantly caused by Leishmania braziliensis. The disease is characterized by the development of lesions, mainly in the nasal mucosa. An exacerbated inflammatory response has been associated with the presence of destructive and disfiguring lesions, with stages of severity ranging from small nodulations to the complete destruction of the nasal pyramid architecture. As Leishmania is an intracellular parasite, most immunological studies have emphasized the cell-mediated immune response, while relatively few studies aimed to investigate the role antibodies in protection against, or the pathology of ML. Methods: Patients with a confirmed diagnosis of ML were classified according to clinical staging criteria. Serum levels of Leishmania-specific IgG, IgG1 and IgG2 antibodies were determined by ELISA before and after treatment with antimony or antimony plus pentoxifylline. Results: Patients in stages IV and V produced higher concentrations of IgG and IgG1 antibodies when compared to those in stage I and II. Significant reductions were seen in the concentrations of IgG and IgG2 antibodies in most patients who responded well to treatment. Conclusions: Our data demonstrate an association between IgG antibody titers and the severity of mucosal disease. The observed reduction in antibody production after successful treatment in most patients preliminarily indicates that these tests can be used to aid in the assessment of therapeutic response.
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Leishmania braziliensis , Leishmaniasis Mucocutánea , Leishmaniasis , Anticuerpos Antiprotozoarios , Humanos , Inmunoglobulina GRESUMEN
BACKGROUND: In this study, we determined the accuracy of anti-Leishmania IgG and IgG subclasses to distinguish clinical forms of American tegumentary leishmaniasis (ATL) and and determined the relationship between antibodies levels with cytokine production and severity of ATL. METHODS: Participants were 40 patients with cutaneous leishmaniasis (CL), 20 patients with mucosal leishmaniasis (ML), 20 patients with disseminated leishmaniasis (DL), and 20 individuals with subclinical Leishmania braziliensis infection (SC). Diagnosis was performed by DNA of L. braziliensis or IFN-γ production in SC. IgG and subclasses of IgG to soluble Leishmania antigen and cytokine levels in supernatants of mononuclear cells were detected by ELISA. RESULTS: IgG was detected in 95%, 95%, and 100% of patients with CL, ML, and DL, respectively. Higher levels of anti-Leishmania IgG and IgG2 were seen in DL compared to CL, ML, and SC. ROC analysis confirmed the ability of IgG to distinguish DL from the other clinical forms. A direct correlation was observed between IgG titers and levels of IFN-γ and CXCL10 in CL and DL, and IgG2 antibodies were correlated with the number of lesions in DL. CONCLUSIONS: High anti-Leishmania IgG and IgG2 levels are characteristic of DL, and while IgG was correlated with pro-inflammatory cytokines, IgG2 was direct correlated with the number of lesions.
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Inmunoglobulina G/inmunología , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Adulto , Biomarcadores/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Leishmaniasis Cutánea/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: L. braziliensis causes cutaneous (CL) and mucosal (ML) leishmaniasis. Wound healing neutrophil (PMN) and macrophage responses made following the bite of the vector sand fly contribute to disease progression in mice. To look at the interplay between PMN and macrophages in disease progression in humans we asked whether polymorphisms at genes that regulate their infiltration or function are associated with different clinical phenotypes. Specifically, CXCR1 (IL8RA) and CXCR2 (IL8RB) are receptors for chemokines that attract PMN to inflammatory sites. They lie 30-260 kb upstream of SLC11A1, a gene known primarily for its role in regulating macrophage activation, resistance to leishmaniasis, and wound healing responses in mice, but also known to be expressed in PMN, macrophages and dendritic cells. METHODS: Polymorphic variants at CXCR1, CXCR2 and SLC11A1 were analysed using Taqman or ABI fragment separation technologies in cases (60 CL; 60 ML), unrelated controls (n = 120), and multicase families (104 nuclear families; 88 ML, 250 CL cases) from Brazil. Logistic regression analysis, family-based association testing (FBAT) and haplotype analysis (TRANSMIT) were performed. RESULTS: Case-control analysis showed association between the common C allele (OR 2.38; 95% CI 1.23-4.57; P = 0.009) of CXCR1_rs2854386 and CL, supported by family-based (FBAT; Z score 2.002; P = 0.045) analysis (104 nuclear families; 88 ML, 250 CL cases). ML associated with the rarer G allele (Z score 1.999; P = 0.046). CL associated with a 3' insertion/deletion polymorphism at SLC11A1 (Z score 2.549; P = 0.011). CONCLUSIONS: The study supports roles for CXCR1 and SLC11A1 in the outcome of L. braziliensis infection in humans. Slc11a1 does not influence cutaneous lesion development following needle injection of Leishmania in mice, suggesting that its role here might relate to the action of PMN, macrophage and/or dendritic cells in the wound healing response to the sand fly bite. Together with the CXCR1 association, the data are consistent with hypotheses relating to the possible role of PMN in initiation of a lesion following the delivery of parasites via the sand fly bite. Association of ML with the rare derived G allele suggests that PMN also have an important positive role to play in preventing this form of the disease.
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Proteínas de Transporte de Catión/genética , Leishmaniasis Cutánea/genética , Leishmaniasis Cutánea/inmunología , Polimorfismo Genético , Receptores de Interleucina-8A/genética , Adulto , Alelos , Animales , Brasil , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Mutación INDEL , Leishmaniasis Cutánea/etiología , Modelos Logísticos , Macrófagos/inmunología , Masculino , Ratones , Persona de Mediana Edad , Modelos Genéticos , Neutrófilos/inmunología , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-8B/genética , Adulto JovenRESUMEN
Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.
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Huesos/efectos de los fármacos , Hormona Paratiroidea/farmacología , Animales , Enfermedades Óseas Metabólicas , Remodelación Ósea/efectos de los fármacos , Huesos/metabolismo , Humanos , Enfermedades Renales , Fallo Renal Crónico/sangre , Masculino , Glándulas Paratiroides/efectos de los fármacos , Glándulas Paratiroides/metabolismo , Hormona Paratiroidea/sangre , Paratiroidectomía , Fosfatos/sangre , Ratas , Ratas Wistar , Insuficiencia Renal/metabolismo , Uremia/metabolismoRESUMEN
Mucosal leishmaniasis (ML) affects predominantly the nose and occurs usually weeks or months after the cure of the primary cutaneous lesion. The pathology of ML is characterized by an exaggerated inflammatory reaction with infiltration of lymphocytes, macrophages, and plasma cells. There is also a paucity of parasites and a strong delayed-type hypersensitivity reaction. Herein, we report a case of a young man who had a large ulcer in his left leg and complained of dysphagia. In nasofibrolaryngoscopy, there were nodular lesions in the oropharynx and rhinopharynx. The skin lesion biopsy showed a chronic inflammation with amastigotes inside macrophages, and DNA of Leishmania braziliensis confirmed the diagnosis of ML in tissue biopsied from the pharynx. The leishmaniasis skin test was negative. Cytokine evaluation showed lack of production of interferon (IFN)-γ, interleukin (IL)-1ß, and IL-17 with enhancement of these cytokine levels after cure.
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Leishmania braziliensis/aislamiento & purificación , Leishmaniasis Mucocutánea , Antiprotozoarios/uso terapéutico , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Trastornos de Deglución/tratamiento farmacológico , Trastornos de Deglución/etiología , Humanos , Leishmania braziliensis/efectos de los fármacos , Leishmaniasis Mucocutánea/diagnóstico , Leishmaniasis Mucocutánea/tratamiento farmacológico , Leishmaniasis Mucocutánea/patología , Macrófagos/parasitología , Masculino , Antimoniato de Meglumina/uso terapéutico , Persona de Mediana Edad , Nasofaringe/parasitología , Nasofaringe/patología , Orofaringe/parasitología , Orofaringe/patología , Piel/parasitología , Piel/patologíaRESUMEN
OBJECTIVE: to describe case of occupational exposure to chemical products. METHOD: descriptive retrospective study using record data of 382 workers assisted in the Outpatient Care for Occupational Toxicology of the Reference Center of Workers' Health of the Federal District, between 2009 and 2013. RESULTS: From the total, 66.7% were men, 55.2% had up to 9 years of activity and 81% did not use personal protective equipment (PPE). Nearly 60% were farmers and environmental surveillance agents, exposed to pesticides (63%), of which 40% were organophosphorus insecticides. The majority (68%) presented butyrylcholinesterase activity decreased, mostly farmers (85.9%); 57.3% of workers were considered poisoned - 61.6% by pesticides and 37.9% by industrial chemicals -, and away from work for at least 10 days. CONCLUSION: The profile was male workers, from 30 to 39 years, which not used PPE, indicating the need for prevention together with them to prevent poisonings.
Asunto(s)
Exposición Profesional/efectos adversos , Intoxicación/etiología , Adulto , Liberación de Peligros Químicos/estadística & datos numéricos , Agricultores/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional/estadística & datos numéricos , Equipo de Protección Personal , Plaguicidas/efectos adversos , Intoxicación/complicaciones , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
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.
RESUMEN
Poisoning is a worldwide problem that involves individuals of all ages and a range of chemicals. In this study, fatal poisoning cases that occurred in the Federal District of Brazil (DF) from 2009 to 2013 were described using information from four systems, and the reasons for underreporting of each system were discussed. Data were obtained from the mortality information system (SIM), the notifiable disease information system (SINAN), the poison information center (CIT), and the forensic medicine institute (IML) of the DF. In total, 288 cases were reported to SIM, 18 to SINAN, 29 to CIT and 101 cases identified in the IML. SIM data indicated a prevalence of 2.24 cases/year/100,000 individuals in the DF, higher than the national estimation (1.36). After eliminating the 98 duplicate cases among the systems, 338 fatal unique cases were identified, from which 74.0% were reported in only one system (mainly the SIM), 23.4% in two systems, 8 cases in three systems and only 1 case was reported in the four systems. Over two thirds of the 338 fatalities involved men (67.4%), and 46.9% involved individuals aged 20-39 years. Medications were the main agent involved (49.4%), followed by pesticides (29.9%). The fatalities occurred mainly after unintentional exposure (50.8%) and suicide (47.7%, of which 53.5% involved pesticides). These results confirmed the previous hypothesis that none of the information systems could capture the whole picture of fatal poisonings in the DF. Underreporting was found in all systems, indicating the need to improve the information quality and the coordination of data reporting, so that health authorities can better understand and reduce these fatalities.