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BACKGROUND: Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is associated with an inflammatory response. Granzyme (GzmB) and IL-1ß play a key role in the pathology. Meglumine antimoniate (MA) is the first-choice drug for the treatment of CL, but therapy failure is observed in up to 50% of the cases. The protein, rSm29 of Schistosoma mansoni, down-modulates pro-inflammatory cytokine production. We evaluate if the combination of topical rSm29 plus MA increases the cure rate of CL. METHODS: In this randomized clinical trial, 91 CL patients were allocated in 3 groups. All cases received MA (20 mg/kg/weight) for 20 days. Group 1 used topical rSm29 (10 µg), group 2 a placebo topically applied, and group 3 received only MA. RESULTS: The cure rate on day 90 was 71% in subjects treated with rSm29 plus MA, and 43% in patients who received MA plus placebo or MA alone (P < 0.05). There was a decrease in GzmB and an increase in IFN-γ (P < 0.05) in supernatants of skin biopsies of the lesions obtained on D7 of therapy (P < 0.05) in patients who received rSm29. CONCLUSION: rSm29 associated with MA reduces GzmB levels, is more effective than MA alone, and decreases CL healing time. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov under NCT06000514.
Assuntos
Leishmaniose Cutânea , Viagem , Humanos , Costa Rica , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/diagnóstico , Masculino , Remissão Espontânea , Leishmania guyanensis/isolamento & purificação , Adulto , Pele/patologia , Pele/parasitologiaRESUMO
This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
Assuntos
Emulsões , Macrófagos Peritoneais , Sesquiterpenos Monocíclicos , Sesquiterpenos , Pele , Animais , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/química , Emulsões/química , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Pele/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Espectroscopia de Infravermelho com Transformada de Fourier , Absorção Cutânea/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Leishmania/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Antiprotozoários/farmacologia , Antiprotozoários/químicaRESUMO
PURPOSE: This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. METHODS: We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. RESULTS: In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. CONCLUSION: This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.
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Leishmaniose Mucocutânea , Humanos , Masculino , Leishmaniose Mucocutânea/patologia , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Adulto , Infecções por HIV/complicações , Feminino , Pessoa de Meia-Idade , Doenças da Boca/patologia , Doenças da Boca/parasitologiaRESUMO
BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.
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SUMMARY: Our team has modified Sihler's intramuscular nerve staining method to allow for calculation of nerve density. Therefore, this study aimed to show the overall distribution pattern of the thoracic cutaneous nerves to provide a morphological basis for selecting and matching sensory reconstruction during skin flap transplantation. Twelve Chinese adult cadavers were dissected; the thoracic skin was removed, and the modified Sihler's staining method was performed. Centered around the nipple, the chest skin was divided into four regions: medial-superior, lateral-superior, lateral-inferior, and medial-inferior. The thoracic skin was not only innervated by the branches of the 1st to 7th intercostal and supraclavicular nerves, but also by a small number of nerves that directly reached the skin and passed through the pectoralis major muscle. There is a phenomenon of cross overlap between the branches of adjacent intercostal nerves. The branches of the 2nd to 7th intercostal nerves were distributed in the breast, and the branches of the lateral and anterior cutaneous branches were densely distributed around the nipple, forming a grid-like anastomosis. There was no cross-overlapping innervation between the anterior cutaneous branches on both sides. The density of nerve distribution in the four regions of the chest was in the order of the medial-superior, lateral-superior, lateral-inferior and medial-inferior region, respectively. These results may be used to map sensory regions when designing thoracic skin flaps for reconstruction surgery to obtain improved sensory recovery.
Nuestro equipo ha modificado el método de tinción nerviosa intramuscular de Sihler para permitir el cálculo de la densidad nerviosa. Por lo tanto, este estudio tuvo como objetivo mostrar el patrón de distribución general de los nervios cutáneos torácicos proporcionando una base morfológica para seleccionar y combinar la reconstrucción sensorial durante el trasplante de colgajo de piel. Se diseccionaron 12 cadáveres de individuos adultos chinos. Se eliminó la piel torácica y se realizó el método de tinción de Sihler modificado, centrada alrededor del pezón, la piel del pecho se dividió en cuatro regiones: medial- superior, lateral-superior, lateral-inferior y medial-inferior. La piel torácica no solo estaba inervada por los ramos de los nervios intercostal y supraclavicular 1º a 7º, sino también por un pequeño número de nervios que llegaban directamente a la piel y pasaban a través del músculo pectoral mayor. Existe un fenómeno de superposición cruzada entre los ramos de los nervios intercostales adyacentes. Los ramos de los nervios intercostales 2º a 7º se distribuyeron en la mama, y los ramos de los ramos cutáneos lateral y anterior se distribuyeron densamente alrededor del pezón, formando una anastomosis en forma de rejilla. No hubo inervación cruzada entre los ramos cutáneos anteriores en ambos lados. La densidad de la distribución nerviosa en las cuatro regiones del tórax estaba en el orden de región medial-superior, lateral-superior, lateral-inferior y medial-inferior, respectivamente. Estos resultados pueden ser útiles para mapear regiones sensoriales al diseñar colgajos de piel torácicos para utilizarlos en cirugía de reconstrucción y obtener así una mejor recuperación sensorial.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Pele/inervação , Coloração e Rotulagem , Tórax/inervação , Retalhos Cirúrgicos/inervação , Cadáver , CorantesRESUMO
Human infections with Corynebacterium diphtheriae species complex (CdSC) bacteria were rare in French Guiana until 2016, when the number of cases diagnosed increased. We conducted an epidemiologic, multicenter, retrospective study of all human CdSC infections diagnosed in French Guiana during January 1, 2016-December 31, 2021. A total of 64 infectious episodes were observed in 60 patients; 61 infections were caused by C. diphtheriae and 3 by C. ulcerans. Estimated incidence increased from 0.7 cases/100,000 population in 2016 to 7.7 cases/100,000 population in 2021. The mean patient age was 30.4 (+23.7) years, and male-to-female ratio was 1.7:1 (38/22). Of the 61 C. diphtheriae isolates, 5 tested positive for the diphtheria toxin gene, and all results were negative by Elek test; 95% (61/64) of cases were cutaneous, including the C. ulcerans cases. The increase in reported human infections underscores the need to raise awareness among frontline healthcare practitioners to improve prevention.
Assuntos
Corynebacterium diphtheriae , Difteria , Humanos , Guiana Francesa/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Corynebacterium diphtheriae/isolamento & purificação , Corynebacterium diphtheriae/genética , Adulto , Pessoa de Meia-Idade , Adolescente , Criança , Adulto Jovem , Pré-Escolar , Difteria/epidemiologia , Difteria/microbiologia , Idoso , Incidência , Lactente , História do Século XXI , Infecções por Corynebacterium/epidemiologia , Infecções por Corynebacterium/microbiologiaRESUMO
The present study analyses the clinical characteristics of patients diagnosed with cutaneous fusarium through a systematic review of cases reported in literature. A total of 39 cases were included, of which 53% were men, 30% were women, and in 17% the sex was not specified. The age ranged from 5 to 85 years. Most cases were reported in Brazil, followed by Japan and United States of America. The most common agent was Fusarium solani, in 37.5% of the patients. Most of the affected individuals had acute myeloid leukaemia and some of the predisposing factors, which included induction chemotherapy, febrile neutropenia, and bone marrow transplantation. The clinical topography of the lesions was located in 27.5% and disseminated in 72.5%, with the most observed clinical feature outstanding the presence of papules and nodules with central necrosis in 47% of the cases. Longer survival was demonstrated in those treated with more than three antifungals. It is concluded that cutaneous fusarium is a complex and challenging clinical entity, infection in patients with leukaemias underscores the need for thorough care to decrease morbidity and mortality.
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Antifúngicos , Fusariose , Fusarium , Humanos , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Fusarium/isolamento & purificação , Idoso , Adulto , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Feminino , Masculino , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Brasil/epidemiologia , Criança , Japão/epidemiologia , Pré-Escolar , Leucemia Mieloide Aguda/complicações , Estados Unidos/epidemiologia , Leucemia/complicações , Leucemia/microbiologia , Dermatomicoses/microbiologia , Dermatomicoses/epidemiologia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologiaRESUMO
Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.