The Expression of RTN1 in Lung Adenocarcinoma and Its Effect on Immune Microenvironment / 中国肺癌杂志

BACKGROUND@#Reticulosome family gene 1 (RTN1) is a reticulosome-encoding gene associated with the endoplasmic reticulum. RTN1 plays a key role in membrane trafficking or neuroendocrine secretion of neuroendocrine cells, while RTN1 serves as a potential diagnostic/therapeutic marker for neurological diseases and cancer. However, the expression of RTN1 and its effect on the immune microenvironment in patients with lung adenocarcinoma have not been reported. In this study, we aimed to investigate the expression of RTN1 in lung adenocarcinoma and its correlation with immune infiltration and survival in lung adenocarcinoma using public databases and bioinformatics network tools.@*METHODS@#Expression levels of RTN1 mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). RTN1 protein expression was examined using the Human Protein Atlas. The clinical prognostic significance of RTN1 was analyzed using the GEPIA2 plotter database. To further confirm the potential function of RTN1, the data were analyzed using gene set enrichment analysis. In addition, We performed dimensionality-reduced clustering analysis at the single-cell sequencing level on two datasets from the Tumor Immune Single-cell Hub (TISCH) database to observe the cellular clustering of RTN1 in different types of immune cells. Using the TIMER online tool to analyze and predict the infiltration abundance of different types of immune cells in the immune microenvironment of lung adenocarcinoma patients in the TCGA cohort; TIMER and CIBERSORT were used to study the relationship between genes co-expressed with RTN1 and its associated tumor-infiltrating immune cells; finally, TIMER was used to analyze the relationship between RTN1 and immune correlations between immune checkpoints.@*RESULTS@#We found that RTN1 expression was decreased in patients with lung adenocarcinoma and was closely related to patient prognosis. RTN1 is involved in the process of phagosome formation, hematopoietic cell formation and cell adhesion, and plays an important role in T cell activation. Using cBioPortal and TCGA data to analyze, it is found that RTN1 is significantly associated with BTK, CD4, ECSF1R, MNDA, NCKAP1L and SNX20. High expression of the above genes may cause significant upregulation of CD4+ T cells, mast cells, monocytes, myeloid dendritic cells and M1 macrophages. The expression of RTN1 is closely related to the common immune checkpoints CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT and SIGLEC15 immune checkpoints.@*CONCLUSIONS@#RTN1 may act as a tumor suppressor gene and indicate better prognosis. Furthermore, RTN1 is associated with immune infiltration that may be involved in the immunotherapy response in LUAD. However, the related mechanism needs further research.

Mast cells in the kidney biopsies of pediatric patients with lupus nephritis / Mastócitos em biópsias renais de pacientes pediátricos com nefrite lúpica

ABSTRACT Introduction: Mast cells may be involved in inflammation and contribute to the onset of fibrosis in lupus nephritis (LN). Objective: This study aimed to correlate the presence of mast cells in kidney biopsy specimens of pediatric patients with LN with activity (AI) and chronicity (CI) indices and assess how effectively mast cells may be used as a prognostic factor. Method: The study included 40 patients aged 6-18 years diagnosed with LN at the Renal Disease Service of the Federal University of Triângulo Mineiro between 1996 and 2015. Workup and epidemiological data were evaluated vis-à-vis AI, CI, and mast cell counts (MCC). Results: Significant positive correlations were found between mast cell counts (MCC) and AI (p = 0.003; r: 0.66) and MCC and CI (p = 0.048; r: 0.48). The ROC curve showed that mast cells were highly sensitive and specific in the differentiation of patients with an AI > 12 from individuals with an AI ≤ 12. Serum creatinine levels were higher in individuals with class IV LN than in patients with class V disease [1.50 (0.40-20.90) vs. 0.70 (0.62-0.90), p = 0.04]. Blood urea nitrogen had a positive significant correlation with MCC (p = 0.002; r: 0.75). A trend toward a negative correlation was observed between MCC and serum albumin (p = 0.06; r: -0.5459). Kidney biopsies of patients with nephrotic syndrome had higher MCC [2.12 (0.41-5.140) vs. 0.53 (0.0-3.94), p = 0.07]. Conclusion: Inflammatory cell infiltration and morphological differences between cell types in the inflammatory infiltrate are relevant factors in the assessment of the LN. Mast cell analysis and AI/CI assessment may be relevant prognostic indicators for pediatric patients with LN.

RESUMO Introdução: Mastócitos podem participar da inflamação e contribuir para fibrose na nefrite lúpica (NL). Objetivo: Correlacionar mastócitos em biópsias renais (BR) de pacientes pediátricos com NL com índices de atividade (IA) e cronicidade (IC), avaliando sua efetividade como fator prognóstico. Metodologia: Foram estudados 40 pacientes, entre 6 e 18 anos, diagnosticados com NL pelo Serviço de Nefropatologia da UFTM entre 1996 e 2015. Dados laboratoriais e epidemiológicos foram correlacionados com IA, IC e contagem de mastócitos (CM). Resultados: Encontramos correlação positiva e significativa entre contagem de mastócitos (CM) e IA (p = 0,003; r: 0,66) e entre CM e IC (p = 0,048; r: 0,48). Conforme a curva Roc, os mastócitos têm alta sensibilidade e especificidade na diferenciação de pacientes com IA menor ou maior do que 12. A creatinina sérica foi mais elevada na classe IV em relação à classe V [1,50 (0,40 - 20,90) versus 0,70 (0,62 - 0,90), p = 0,04]. Ureia sérica apresentou correlação positiva e significativa com CM (p = 0,002; r: 0,75). Observou-se tendência à correlação negativa entre CM e albumina sérica (p = 0,06; r: -0,5459). BR de pacientes com síndrome nefrótica apresentaram maior CM [2,12 (0,41 - 5,140) versus 0,53 (0,0 - 3,94), p = 0,07]. Conclusão: Não apenas o infiltrado inflamatório como também a diferenciação morfológica dos tipos celulares que o constituem são importantes para a avaliação da NL. Isso indica que a análise dos mastócitos, juntamente com a dos IA e IC, pode ajudar os nefrologistas a definirem o prognóstico de pacientes pediátricos.

Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3 / Embora com mucosa íntegra à colonoscopia, megacólons chagásicos apresentam superexpressão de Gal-3

ABSTRACT Objective To evaluate the density of anti-galectin-3-immunostained cells, collagen percentage, mast cell density and presence of pathological processes in intestinal muscle biopsies of patients. Methods Thirty-five patients who underwent intestinal biopsy were selected from 1997 to 2015. Patients were divided into three groups: chagasic patients with mucosal lesion (n=13), chagasic patients with intact mucosa (n=12) and non-chagasic patients with no mucosal lesion (n=10). Histological processing of the biopsied fragments and immunohistochemistry for galectin-3 were performed. Additional sections were stained with hematoxylin and eosin to evaluate the general pathological processes, picrosirius for evaluation of collagen and toluidine blue to evaluate the mast cell density. Results Patients of mucosal lesion group had a significantly higher frequency of ganglionitis and myositis when compared to the chagasic patients with intact mucosa and non-chagasic group. The density of anti-galectin-3-immunostained cells was significantly higher in the chagasic patients with intact mucosa group when compared to the non-chagasic group. The group of chagasic patients with intact mucosa presented a higher percentage of collagen in relation to the patients with mucosal lesion and to the non-chagasic group, with a significant difference. There was no significant difference in mast cell density among the three groups. Conclusion The higher density of anti-galectin-3-immunostained cells in patients in the chagasic patients with intact mucosa group suggested the need for greater attention in clinical evaluation of these patients, since this protein is associated with neoplastic transformation and progression.

RESUMO Objetivo Avaliar a densidade de células imunomarcadas por anti-galectina-3, a percentagem de colágeno, a densidade de mastócitos e a presença de processos patológicos na musculatura intestinal de pacientes biopsiados. Métodos Foram selecionados 35 pacientes submetidos à biópsia de intestino entre 1997 a 2015. Os pacientes foram divididos em três grupos: chagásicos com lesão de mucosa (n=13), chagásicos com mucosa íntegra (n=12) e não chagásicos sem lesão de mucosa (n=10). Foram realizados processamento histológico dos fragmentos biopsiados e imunohistoquímica para galectina-3. Cortes adicionais foram corados por hematoxilina e eosina, para avaliar os processos patológicos gerais, pelo picrosírius, para avaliação do colágeno, e pelo azul de toluidina, para avaliar a densidade de mastócitos. Resultados Os pacientes do grupo chagásicos com lesão de mucosa apresentaram frequência significativamente maior de ganglionite e miosite quando comparados aos dos grupos chagásico com mucosa íntegra e não chagásicos. A densidade das células imunomarcadas por anti-galectina-3 foi significativamente maior no grupo chagásicos com mucosa íntegra quando comparada ao grupo não chagásico. O grupo de chagásicos com mucosa íntegra apresentou maior percentagem de colágeno em relação aos grupos chagásicos com mucosa lesada e ao grupo de não chagásicos, com diferença significativa. Não houve diferença significativa com relação à densidade de mastócitos entre os três grupos. Conclusão A maior densidade de células imunomarcadas por anti-galectina-3 nos pacientes do grupo chagásico com mucosa íntegra sugere a necessidade de maior atenção na avaliação clínica desses pacientes, uma vez que essa proteína está associada com transformação e progressão neoplásica.

Neutrophils, eosinophils, and mast cells in the intestinal wall of dogs naturally infected with Leishmania infantum / Neutrófilos, eosinófilos e mastócitos na parede intestinal de cães naturalmente infectados com Leishmania infantum

Abstract Visceral leishmaniasis (VL) is a disease caused by the protozoa Leishmania infantum and can cause an inflammatory reaction in the gastrointestinal tract, however the role of granulocytic cells (neutrophils, eosinophils, and mast cells) in the intestine of dogs infected is not fully understood. We performed a quantitative analysis these cells in the intestinal wall of dogs with canine visceral leishmaniasis (CVL). Twenty dogs were assigned to one of three groups: group 1 (G1, n=8), dogs with CVL and L. infantum amastigotes in the intestine; group 2 (G2, n=9), dogs with CVL but without intestinal amastigotes; and group 3 (G3, n=3), uninfected dogs (control group). Granulocytic cells were counted in the crypt-villus unit (mucosa), submucosa, and muscle layer of the intestinal mucosa. Cell counts were higher in the intestinal wall of dogs from G2 followed by G1 and G3 (p≤0.05). In G1, there was a low inverse correlation between parasite burden of the small intestine and granulocyte counts (r= -0.1, p≤0.01). However, in G2 dogs, mast cell and eosinophil numbers showed positive correlation (r=0.85, p≤0.01). The granulocytic cell hyperplasia observed in the intestine of L. infantum-infected dogs suggests that these cells may be involved in the cell-mediated immune response for parasite elimination.

Resumo A leishmaniose visceral (LV) é uma doença causada pelo protozoário Leishmania infantum e pode causar uma reação inflamatória no trato gastrointestinal, entretanto o papel das células granulocíticas (neutrófilos, eosinófilos e mastócitos) no intestino de cães infectados não é totalmente compreendido. Neste estudo realizamos uma análise quantitativa dessas células na parede intestinal de cães com LV. Vinte cães foram distribuídos em três grupos: grupo 1 (G1, n=8), cães com LV e amastigotas de L. infantum no intestino; grupo 2 (G2, n=9), cães com LV, mas sem amastigotas intestinais; e grupo 3 (G3, n=3), não infectados (grupo controle). Células granulocíticas foram contadas na unidade cripta-vilo (mucosa), submucosa e camada muscular da mucosa intestinal. Observamos hiperplasia dessas células na parede intestinal de cães do G2, seguidas das G1 em relação ao G3 (p≤0,05). No G1, houve uma correlação inversa baixa entre a carga parasitária do intestino delgado e a contagem de granulócitos (r= -0,1; p≤0,01). No entanto, nos cães do G2, os números de mastócitos e eosinófilos apresentaram correlação positiva (r=0,85; p≤0,01). A hiperplasia de células granulocíticas observada no intestino de cães infectados por L. infantum sugere que essas células podem estar envolvidas na resposta imune mediada por células para a eliminação do parasita.

Prevention of rocuronium induced mast cell activation with prophylactic oleuropein rich diet in anesthetized rabbits

Abstract Purpose: The effect of a prophylactic oleuropein-rich diet before anesthesia accompanied by the widely-used steroid-based neuromuscular drug rocuronium on mast cell activation was investigated in the study. Methods: 14 rabbits used in the study. The rabbits in the oleuropein group were given oleuropein-rich extract added to the animals' water at doses of 20 mg/kg oleuropein for 15 days orally. After 15 days, all rabbits in the two groups were given general anesthesia with rocuronium of 1 mg/kg. After 1 day, animals were sacrificed and the liver tissue sections stained with H&E, toluidine blue and tryptase for immunohistochemical study. Results: There was no statistically significant difference between ALT, AST and albumin averages of the oleuropein and control groups (p> 0.05). The tryptase average of the control group was higher than the tryptase average of the oleuropein group and this difference was statistically significant (p=0.003). The T. blue average in the oleuropein group was higher than the control group. However, there was no statistically significant difference between groups (p=0.482). Conclusions: Rocuronium adverse effects, like hypersensitivity and anaphylaxis, may limit routine use of this substance. The use of oleuropein reduced the number of inflammatory cells and prevented degranulation.

Density of mast cells and intensity of pruritus in psoriasis vulgaris: a cross sectional study

Abstract: BACKGROUND: Psoriasis is a chronic and prevalent disease, and the associated pruritus is a common, difficult-to-control symptom. The mediators involved in psoriatic pruritus have not been fully established. OBJECTIVE: To evaluate associations between the number of mast cells in psoriatic lesions and the intensity of pruritus. METHODS: 29 patients with plaque psoriasis were recruited. In all participants, Psoriasis Area and Severity Index and Body Surface Area were assessed. A questionnaire was administered to obtain clinical information and the Dermatology Life Quality Index. Pruritus was assessed using a visual analog scale and skin biopsies were performed for staining with Giemsa and Immunohistochemistry with C-Kit. RESULTS: Pruritus was observed in 91.3% of our patients. Median VAS was 6 (p25-75: 2-8). The immunohistochemical method revealed a mean of 11.32 mast cells/field and Giemsa staining revealed a mean of 6.72 mast cells/field. There was no correlation between the intensity of pruritus and mast cell count, neither in Immunohistochemistry (p = 0.15; rho = -0.27) nor in Giemsa (p = 0.16; rho = -0.27). Pruritus did not impact on the Dermatology Life Quality Index (p = 0.51; rho = -0.13). STUDY LIMITATIONS: The small sample size may be considered the main limitation of our study. CONCLUSIONS: Although mast cells are mediators of pruritus in many cutaneous diseases, our findings support that psoriatic pruritus is a complex disorder with multifactorial, complex pathophysiology, involving pruritogenic mediators others than mast cells.

Mastócitos discriminam esofagite eosinofílica em pacientes pediátricos / Mast cells distinguish eosinophilic esophagitis in pediatric patients

ABSTRACT BACKGROUND: Mast cells exert a substantial role in gastrointestinal allergic diseases. Therefore, it is reasonable to presume that mast cell may aid diagnosis in eosinophilic gastroenteropathy. OBJECTIVE: To evaluate whether mast cell count in the esophageal epithelium can discriminate eosinophilic esophagitis, proton-pump inhibitor (PPI)-responsive eosinophilic esophagitis and gastroesophageal reflux esophagitis. METHODS: Retrospectively we reviewed the files of 53 consecutive patients (age: 7.8 years; range: 8-14 years) with definitive diagnose established during clinical follow up in a universitary outpatient clinic as follow: eosinophilic esophagitis (N=23), PPI-responsive eosinophilic esophagitis (N=15) and gastroesophageal reflux esophagitis (N=15). Eosinophil count in the esophageal epithelium in slides stained with H-E was reviewed and immunohistochemistry for mast cell tryptase was performed. RESULTS: Count of eosinophils/high-power field (HPF) higher than 15 were found in 14 out of 15 reflux esophagitis patients. The mean count of eosinophils/HPF was similar in eosinophilic esophagitis patients and in those with PPI-responsive eosinophilic esophagitis (42 and 39 eosinophils/HPF, respectively, P=0.47). Values of mast cell tryptase (+) were higher in eosinophilic esophagitis [median: 25 mast cells/HPF; range (17-43) ] and in PPI-responsive eosinophilic esophagitis patients [25 (16-32) ], compared to reflux esophagitis [4 (2-14) ], P<0.001. There was no difference between the mean count of mast cells/HPF in the esophageal epithelium of eosinophilic esophagitis patients and PPI-responsive eosinophilic esophagitis patients, respectively, 26 and 24 mast cells/HPF, P=0.391. CONCLUSION: Tryptase staining of mast cells differentiates eosinophilic esophagitis from reflux esophagitis.

RESUMO CONTEXTO: Os mastócitos detêm papel fundamental na resposta imuno-alérgica gastrintestinal. Assim, é razoável admitir que essas células sejam úteis no diagnóstico diferencial das gastroenteropatias eosinofílicas. OBJETIVO: Determinar se a análise quantitativa de mastócitos na mucosa esofágica permite discernir esofagite eosinofílica, esofagite eosinofílica responsiva ao inibidor de bomba de prótons e esofagite péptica por doença de refluxo gastroesofágico. MÉTODOS: Revisamos retrospectivamente os prontuários 53 crianças (idade: 7,8 anos; variação: 8-14 anos), atendidas consecutivamente, num serviço terciário e cujos diagnósticos definitivos estabelecidos após seguimento clínico foram esofagite eosinofílica (N=23), esofagite eosinofílica responsiva ao inibidor de bomba de prótons (N=15) e esofagite péptica por doença de refluxo gastroesofágico (N=15). As amostras histológicas foram revisadas quanto à contagem de eosinófilos na coloração de H-E e processadas para imunoistoquímica da triptase de mastócitos. RESULTADOS: Valores de eosinófilos/campo de maior aumento (CMA; 400X) >15 foram encontrados em 14 dos 15 pacientes com refluxo gastroesofágico. A média de eosinófilos/CMA foi similar nos pacientes com esofagite eosinofílica e com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 42 e 39 eosinófilos/CMA, P=0,47). Os valores de mastócitos triptase (+) foram superiores no epitélio esofágico dos pacientes com esofagite eosinofílica [mediana: 25 mastócitos/CMA; variação (17- 43) ] e na esofagite eosinofílica responsiva ao inibidor de bomba de prótons [25 (16-32) ], comparados aos pacientes com refluxo gastroesofágico [4(2-14) ], P<0,001. Não houve diferença entre a média de mastócitos/CMA nos pacientes com esofagite eosinofílica comparados aos com esofagite eosinofílica responsiva ao inibidor de bomba de prótons, respectivamente, 26 e 24 mastócitos/CMA, P=0,391. CONCLUSÃO: A coloração para mastócitos pela imunoistoquímica da triptase diferencia as esofagites eosinofílicas da esofagite péptica.

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Psychosocial factors and mental work load: a reality perceived by nurses in intensive care units / Fatores psicossociais e carga mental de trabalho: uma realidade percebida pelos enfermeiros em Unidades de Terapia Intensiva / Factores psicosociales y Carga mental de trabajo: una realidad percibida por enfermeras/os en Unidades Críticas

OBJECTIVE: To analyse the perception of psychosocial factors and mental workload of nurses who work in intensive care units. It is hypothesised that nurses in these units could perceive psychosocial risks, manifesting in a high mental work load. The psychosocial dimension related to the position's cognitive demands is hypothesised to mostly explain mental work load. METHOD: Quantitative study, with a descriptive, cross-sectional, and comparative design. A total of 91% of the intensive care unit populations of three Chilean hospitals was surveyed, corresponding to 111 nurses. The instruments utilised included (A) a biosociodemographic history questionnaire; (b) the SUSESO-ISTAS 21 questionnaire; and (c) the Mental Work Load Subjective Scale (ESCAM, in Spanish). RESULTS: In total, 64% and 57% of participants perceived high levels of exposure to the psychosocial risks Psychosocial demands and Double shift, respectively. In addition, a medium-high level of overall mental load was observed. Positive and significant correlations between some of the SUSESO-ISTAS 21 and ESCAM dimensions were obtained. Using a regression analysis, it was determined that three dimensions of the psychosocial risk questionnaire helped to explain 38% of the overall mental load. CONCLUSION: Intensive care unit nurses felt that inadequate psychosocial factors and mental work overload existed in several of the tested dimensions. .

OBJETIVO: analisar a percepção de fatores psicossociais e a carga mental de trabalho de enfermeiros que trabalham em unidades de terapia intensiva. A hipótese é que os enfermeiros dessas unidades podem perceber os riscos psicossociais e manifestar uma alta carga mental de trabalho. Além disso, a dimensão psicossocial relacionada às demandas cognitivas do cargo explicaria a maior parte da carga mental de trabalho. MÉTODO: estudo quantitativo, com delineamento descritivo, transversal e comparativo. Foi examinada 91% da população das Unidades de Terapia Intensiva de três hospitais chilenos, correspondente a 111 enfermeiros. Os instrumentos utilizados incluíram (a) um questionário do histórico biossociodemográfico; (b) o questionário SUSESO-ISTAS 21; e (c) a Escala Subjetiva de Carga Mental de Trabalho (ESCAM). RESULTADOS: no total, 64% e 57% dos participantes perceberam um alto nível de exposição aos riscos psicossociais Demanda psicológica e Jornada dupla, respectivamente. Além disso, foi observado um nível de médio para alto de carga mental global. Foram obtidas correlações positivas e significativas entre algumas das dimensões do SUSESO-ISTAS 21 e do ESCAM. Utilizando uma análise de regressão, determinou-se que três dimensões do questionário de risco psicossocial ajudaram a explicar 38% da carga mental total. CONCLUSÃO: os enfermeiros das unidades de terapia intensiva percebem os fatores psicossociais e a sobrecarga mental de trabalho em várias de suas dimensões. .

OBJETIVO: analizar la percepción de Factores psicosociales y Carga mental de trabajo de enfermeras/os que laboran en Unidades Críticas. Se hipotetiza que los/as enfermeros/as de estas unidades pudieran percibir riesgos psicosociales; Mostrarán una Carga mental de trabajo alta; y la dimensión psicosocial relacionada con exigencias cognitivas del puesto explicará en mayor medida la Carga Mental. MÉTODO: estudio cuantitativo, de diseño descriptivo, transversal y comparativo. Se censó el 91% de la población de Unidades Críticas de tres hospitales chilenos, correspondiente a 111 enfermeras/os. Los instrumentos utilizados fueron: (a) Cuestionario de antecedentes biosociodemográficos; (b) Cuestionario SUSESO-ISTAS 21; y (c) Escala Subjetiva de Carga Mental de Trabajo (ESCAM). RESULTADOS: el 64% y el 57% de los/as participantes perciben un alto nivel de exposición a los riesgos psicosociales Demandas psicológicas y Doble presencia, respectivamente. Además, se obtiene un nivel de Carga mental global media-alta. Se obtuvo correlaciones positivas y significativas entre algunas dimensiones de SUSESO-ISTAS 21 y ESCAM, y mediante un análisis de regresión se obtuvo que tres dimensiones del cuestionario de riesgos psicosociales contribuyen a explicar un 38% de la Carga mental global. CONCLUSIÓN: las/os enfermeras/os de unidades críticas, perciben factores psicosociales inadecuados y sobrecarga mental de trabajo, en varias de sus dimensiones. .

Mast cell concentration and skin wound contraction in rats treated with Brazilian pepper essential oil (Schinus terebinthifolius Raddi)

PURPOSE: To evaluate wound contraction and the concentration of mast cells in skin wounds treated with 5% BPT essential oil-based ointment in rats. METHODS: Twenty rats, male, of adult age, were submitted to skin surgery on the right (RA) and left antimeres (LA) of the thoracic region. They were divided into two groups: control (RA - wounds receiving daily topical application of vaseline and lanolin) and treated (LA - wounds treated daily with the topical ointment). The skin region with wounds were collected at days 4, 7, 14 and 21 after surgery. Those were fixed in 10% formaldehyde and later processed for paraffin embedding. Sections were obtained and stained by H.E for histopathology analysis. The degree of epithelial contraction was measured and mast cell concentration were also evaluated. RESULTS: The treated group showed higher mast cell concentrations (p<0.05) associated with increased contraction at day 7 and 14 respectively. CONCLUSION: Ointment containing 5% Brazilian pepper tree oil increases mast cell concentration and promotes skin wound contraction in rats. .

Adult mastocytosis: a review of the Santo António Hospital 's experience and an evaluation of World Health Organization criteria for the diagnosis of systemic disease

BACKGROUND: Mastocytosis is a clonal disorder characterized by the accumulation of abnormal mast cells in the skin and/or in extracutaneous organs. OBJECTIVES: To present all cases of mastocytosis seen in the Porto Hospital Center and evaluate the performance of World Health Organization diagnostic criteria for systemic disease. METHODS: The cases of twenty-four adult patients with mastocytosis were reviewed. Their clinical and laboratorial characteristics were assessed, and the properties of the criteria used to diagnose systemic mastocytosis were evaluated. RESULTS: The age of disease onset ranged from 2 to 75 years. Twenty-three patients had cutaneous involvement and 75% were referred by dermatologists. Urticaria pigmentosa was the most common manifestation of the disease. One patient with severe systemic mast cell mediator-related symptoms showed the activating V560G KIT mutation. The bone marrow was examined in 79% of patients, and mast cell immunophenotyping was performed in 67% of the participants. Systemic disease was detected in 84% of cases, and 81% of the sample had elevated serum tryptase levels. All the diagnostic criteria for systemic mastocytosis had high specificity and positive predictive value. Bone marrow biopsy had the lowest sensitivity, negative predictive value and efficiency, while the highest such values were observed for mast cell immunophenotyping. Patients were treated with regimens including antihistamines, sodium cromoglycate, alpha-interferon, hydroxyurea and phototherapy. CONCLUSIONS: Cutaneous involvement is often seen in adult mastocytosis patients, with most individuals presenting with indolent systemic disease. Although serum tryptase levels are a good indicator of mast cell burden, bone marrow biopsy should also be performed in patients with normal serum tryptase, with flow cytometry being the most adequate method to diagnose systemic disease. .

Células cebadas en pulmón y nervio periférico en la intoxicación crónica con karwinskia humboldtiana en rata wistar: estudios histológico e histoquímico / Lung and peripheral nerve mast cells in chronic intoxication with karwinskia humboldtiana in wistar rat: histological and histochemical studies

Karwinskia humboldtiana (Kh) es un arbusto venenoso responsable de numerosos casos de intoxicación accidental en humanos. En estudios previos en nuestro laboratorio reportamos un incremento de células cebadas en nervio periférico (NP) durante la intoxicación con Kh, este hallazgo no ha sido reportado previamente en otros órganos durante esta intoxicación por lo que en el presente estudio buscamos la presencia de estas células en otros órganos, además de distinguir subpoblaciones de células cebadas mediante reacciones histoquímicas para la identificación de los gránulos de secreción. El objetivo de este estudio fue evaluar la presencia de células cebadas en órganos distintos al NP y diferenciar histoquímicamente la composición de sus gránulos. Se utilizaron 32 ratas Wistar, se dividieron en cuatro grupos (n= 8) en donde 5 ratas de cada grupo fueron intoxicadas y 3 fueron control no intoxicadas. A las ratas intoxicadas se les administraron por vía oral 3,5 g/kg del fruto seco y molido de Kh fraccionados en 5 dosis de 1,5; 0,5, 0,5; 0,5 y 0,5 g/kg los días 0, 3, 7, 10 y 14 respectivamente. Las ratas control solo recibieron agua. Cada grupo fue sacrificado a diferentes tiempos según la evolución de la parálisis. Se obtuvieron muestras de Hígado, Riñón, Pulmón y SNP, se procesaron hasta obtener bloques de parafina, se obtuvieron cortes y se tiñeron con azul de toluidina, PAS, Azul alciano/PAS y Azul alciano/Safranina. Se identificó la presencia de células cebadas en NP y pulmón con la tinción de azul de toluidina y se realizo un estudio morfométrico observando un incremento progresivo del número de células cebadas por grupo así como variaciones histoquímicas en sus gránulos en cada etapa y órgano analizado, lo que sugiere la participación de las células cebadas y sus secreciones en cada una de las etapas de la intoxicación crónica con el fruto maduro de Kh.

Karwinskia humboldtiana (Kh) is a poisonous shrub causing a number of accidental intoxications in humans. In previous studies in our laboratory, we reported an increased number of mast cells present in peripheral nerve of Kh intoxicated rats. This finding has not been reported in other organs of intoxicated animals. For this reason, in the present study we searched for mast cells in several organs, identifying mast cell subpopulations on the basis of different histochemical reactivity of their secretory granules. Thus the objective of the present study was to evaluate the presence of mast cells in organs other than peripheral nerve and, to distinguish mast cells by their granule content, applying histochemical reactions. 32 Wistar rats were divided into 4 groups (n=8). For each group, 5 rats were intoxicated with Kh and 3 received water only as a control.Intoxicated rats received 3.5 g/ Kg body weight of dry powder of Kh fruits, fractionated in 5 doses as follows 1.5, 0.5, 0.5, 0.5, 05 on days 0, 3,7,10,14 respectively. Control rats received water only. Each group was killed at different times during paralysis evolution. Samples of liver, kidney, lung and brain, were obtained and processed by routine technique until paraffin embedding. Sections were obtained and stained with toluidine blue, PAS, alcian blue/PAS and alcian blue/safranin. Mast cells infiltrates were observed in peripheral nerve and lung. Mast cells were counted. An increasing number of mast cells were recorded as well as variations in the histochemical pattern of their granules for each organ. These findings suggest a role for mast cells and their secretions in the intoxication with mature fruit of Kh.

Dermatoscopic findings of urticaria pigmentosa / Achados dermatoscopicos na urticaria pigmentosa

Mastocytosis is a rare disease characterized by proliferation and accumulation of mast cells in various organs. The maculopapular cutaneus mastocytosis is divided into three subtypes: papular/plaque variant, urticaria pigmentosa and eruptive macular telangiectasia perstans. Dermoscopic may help to better characterize the different forms of cutaneus mastocytosis. We report a 55 year-old female with urticaria pigmentosa and its dermoscopy.

Mastocitose é uma doença rara caracterizada pela proliferação e acúmulo de mastócitos em vários órgãos. A mastocitose cutanea maculopapular divide-se em três subtipos: variante máculo-papular, urticária pigmentosa e telangiectasia macular eruptiva perstans. A dermatoscopia pode ajudar a caracterizar melhor as diferentes formas de mastocitose cutânea. Relatamos um caso de paciente feminina de 55 anos com urticária pigmentosa e sua dermatoscopia.

Mast Cells in Non-neoplastic Skin Lesions.

Background: Mast cells are found in tissues throughout body, particularly in proximity to surfaces that interface with the external environment. They are found at all levels of dermis, where they are grouped around blood vessels, nerves and appendages. Increase in mast cell number have been reported in various cutaneous diseases. Aims: We aim to identify and analyse the morphological aspects of distribution of mast cells and their value in non-neoplastic skin lesions. Material and Methods: Ninety seven biopsies of various skin lesions were studied for mast cells by Toluidine Blue at pH 3.9. Result: All the skin lesions showed significant increase in mast cell number. Psoriasis showed maximum number of mast cells (127/mm2) followed by Lichen planus (108/mm2). Among the cases of cutaneous bacterial infections, mast cells were maximum in leprosy cases (99/mm2) and lowest in cutaneous tuberculosis. A comparative decrease in number of mast cells was seen from lepromatous leprosy to tuberculoid leprosy. A wide range of morphological alterations of mast cells were observed in these skin lesions. Psoriasis and bullous pemphigoid cases showed maximum spindle cell morphology. Conclusion: Tissue mast cell number, distribution and morphology vary in different skin lesions depending on the degree of mast cell activation. This may have a bearing on diagnosis and management.

Síndrome de intestino irritable, un proceso inflamatorio de bajo grado: ¿mito o realidad? / IBS, a low grade inflammatory process: myth or reality?

Irritable bowel syndrome (IBS) is one of the most prevalent functional disorders in Chile impacting on socio-economic development due to significantly impaired quality of life of the individual. It is characterised by abdominal discomfort associated with alterations in bowel habit and increased visceral hypersensitivity. One of the outstanding features of IBS is the presence of a bi-directional imbalance of gut-brain interactions, which can induce alterations in the intestinal immune response. IBS is characterised by increased intestinal mast cell activity associated with alterations of para-cellular permeability and activation of sensory nerve endings. The increased proximity of mast cell to colonic nerves is correlated with abdominal pain and increased visceral hypersensitivity of the patients. In spite of the well-described role of mast cell in the induction of mucosal inflammation, in IBS only a low-grade inflammation is observed. The present review discuses the possible immune-regulatory mechanisms that are involved in IBS pathophysiology.

El síndrome de intestino irritable (SII) es considerado uno de los trastornos funcionales más prevalente en Chile, que impacta el desarrollo socio-económico del país debido al deterioro de la calidad de vida de los individuos que lo portan. Es caracterizado por molestias abdominales asociadas a alteraciones en el hábito de defecación e hipersensibilidad visceral. Una de las características más destacadas en el SII es la presencia de un desequilibrio de las interacciones en el eje intestino-cerebro, el cual puede inducir alteraciones en la respuesta inmune intestinal. El SII es caracterizado por una aumentada actividad de los mastocitos en el intestino, asociada con alteraciones en la permeabilidad para-celular epitelial y la activación de terminaciones nerviosas en la mucosa intestinal. El aumento de la cercanía de los mastocitos a nervios colónicos está relacionado con el dolor abdominal y la hipersensibilidad visceral de los pacientes. Pese a que está muy bien descrito el papel del mastocito en la inducción de la inflamación en mucosas, en el SII se observa sólo un bajo-grado de inflamación. En la presente revisión se discute los posibles mecanismos regulatorios inmunes que están involucrados en la fisiopatología del SII.

Correlation of lifetime progress of atherosclerosis and morphologic markers of severity in humans: new tools for a more sensitive evaluation

OBJECTIVES: To describe the morphological features of atherosclerosis in the aortas of autopsied patients (ranging from young adults to the elderly), thus providing new tools for a more sensitive morphological evaluation. METHOD: We collected 141 aorta samples. We assessed the macroscopic degree of atherosclerosis, thickness of the intima and media, lipid and collagen depositions in the intima, and the infiltration of mast cells into the layers of the aorta. We correlated the findings with gender, age, race and cause of death. RESULTS: The degree of atherosclerosis was significantly higher in the elderly. The aorta was thicker in the elderly and in cases with a cardiovascular cause of death. The thickness of the intima was significantly greater in the elderly, in males and in cases with a cardiovascular cause of death. The lipid content in the intima of the aorta was significantly higher in Caucasians. Older people and men had a significantly higher number of mast cells. CONCLUSION: A macroscopic evaluation is a good indicator of the severity of atherosclerosis, but a more detailed analysis, namely evaluating the thickness of the layers of the aorta and the number of mast cells, may further elucidate the changes in the constituents of this vessel.

Evidence for eosinophil recruitment, leukotriene B4 production and mast cell hyperplasia following Toxocara canis infection in rats

It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B4 (LTB4) production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group) with 1000 embryonated eggs containing third-stage (L3) T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB4 levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB4-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

Mastocitosis cutánea: revisión de 10 años de experiencia en el Servicio de Dermatología del Hospital General de Niños Pedro de Elizalde / Cutaneous mastocytosis: 10-years experience review at the Dermatology Department, Hospital General de Niños Pedro de Elizalde

Introducción. La mastocitosis representa un espectro de trastornos clínicos con un fenotipo común correspondiente a una hiperplasia de los mastocitos tisulares. Objetivo. Presentar la experiencia del Servicio de Dermatología del Hospital General de Niños Pedro de Elizalde en mastocitosis cutánea en los últimos 10 años. Diseño. Estudio retrospectivo y descriptivo, de corte transversal. Material y método. Se revisaron los archivos histológicos correspondientes al período que va de marzo de 1999 a marzo de 2099 del Servicio de Dermatología del Hospital General de Niños Pedro de Elizalde. Se consideraron como variables de estudio la edad al momento de la consulta, sexo, presencia de antecedentes personales y familiares, tipo clínico, localización, presencia de síntomas al examen físico, así como hallazos patológicos en los estudios complementarios. Los resultados se expresaron en promedios y porcentajes. Resultados. Presentamos 49 casos con diagnóstico clínico e histológico de mastocitosis cutánea; 33 pacientes (67,3%) de sexo masculino y 16 (32,7%) de sexo femenino. En cuanto al tipo clínico de mastocitosis, se encontraron 36 casos de urticaria pigmentosa (73,4%), 6 casos de mastocitoma solitario (12,2%), 5 casos de telangiectasia macularis eruptiva perstans (10,2%) y 2 casos donde coexistía mastocitoma solitario y urticaria pigmentosa (4%). No se encontraron casos de mastocitosis cutánea difusa. Las lesiones se distribuyen en tronco 25 casos (51%), en tronco y miembros 17 casos (34,6%), en cabeza, tronco y miembros 3 casos (6,1%), en miembros 3 casos (6,1%), en cabeza y tronco un caso (2,04%). Conclusión. En nuestra casuística, la manifestación clínica más frecuente fue la urticaria pigmentosa, similar a lo señalado en la bibliografía. Encontramos, a diferencia de lo publicado en la literatura, un predominio de sexo masculino y un alto porcentaje (10,2%) de pacientes pediátricos con la forma de telangiectasia macularis eruptiva perstans.

IntroductionMastocytosis represents a spectrum of clinical disorders with a common phenotype correspondingto hyperplasia of mast cells on tissues.ObjectiveTo present the experience of the Department of Dermatology, Hospital General de Niños Pedro deElizalde in cutaneous mastocytosis during the past 10 years.DesignRetrospective and descriptive, cross sectional study.Material and methodsHistological records were reviewed for the period March 1999-March 2009 at the Department ofDermatology, Hospital General de Niños Pedro de Elizalde.The variables considered were: age at time of consultation, gender, presence of personal andfamily history, clinical type, location, presence of symptoms by physical examination andabnormal findings on complementary studies.The results were expressed as averages and percentages.ResultsForty nine patients with clinical and histological diagnosis of cutaneous mastocytosis arepresented, 33 of them were male (67.3%) and 16 were female (32.7%).As regards to the clinical type of mastocytosis, 36 patients presented urticaria pigmentosa(73.4%), 6 had solitary mastocytoma (12.2%), 5 presented telagiectasia macularis eruptivaperstans (10.2%) and 2 patients presented solitary mastocytoma combined with urticariapigmentosa (4%). Diffuse cutaneous mastocytosis was not found.Twenty five patients had lesions distributed on the trunk (51%), trunk and limbs on 17 (34.6%),head, trunk and limbs 3 patients (6.1%), on limbs only 3 patients (6.1%), while head and trunktogether were affected on 1 patient (2.04%).ConclusionIn our caseload, the most frequent clinical manifestation was urticaria pigmentosa, similar tofindings in the literature.As opposed to published data we found predominance in males, and a high incidence (10.2%)of pediatric patients with telangiectasia macularis eruptiva perstans.

Comparação entre a concentração de mastócitos em carcinomas espinocelulares da pele e da cavidade oral / A comparison between the concentration of mast cells in squamous cell carcinomas of the skin and oral cavity

FUNDAMENTOS: A letalidade dos carcinomas espinocelulares (CECs) de pele é considerada baixa. Os CECs de boca têm prognóstico ruim. Evidências atuais sugerem que os mastócitos, residentes no tecido normal, contribuem para a tumorigênese dos CECs, provavelmente por promoverem angiogênese. OBJETIVO: Comparar a concentração de mastócitos em CECs da pele e da boca e avaliar se há correlação com o grau de diferenciação desses tumores. MATERIAL E MÉTODOS: Foram analisados 30 casos de CEC de pele e 34 casos de CEC de boca. A coloração de azul de toluidina, para evidenciar os mastócitos, foi realizada nos blocos com a área central da neoplasia. RESULTADOS: Apenas um caso de CEC de pele apresentou concentração de mastócitos de 0-10 e nenhum caso de CEC de boca apresentou concentração maior que 201 mastócitos no tumor. A maioria dos CECs de boca tem concentração de mastócitos entre 0 e 10 (47 por cento - n = 16); 80 por cento dos CECs de pele têm concentração acima de 51 mastócitos. Todos os casos de CEC de boca com concentração entre 100 e 200 mastócitos e 80 por cento daqueles com concentração entre 51 e 99 eram de lábio. A concentração de mastócitos não está relacionada ao grau de diferenciação do tumor. CONCLUSÃO: A concentração de mastócitos é menor nos CECs de boca, exceto nos de lábio, podendo refletir uma menor necessidade de ativação de células do microambiente para melhorar a vascularização nos cânceres de boca.

BACKGROUND: The lethality of squamous cell carcinomas (SCC) of the skin is considered low. SCC in the mouth is usually associated with poor prognosis. Current evidence suggests that mast cells in the normal tissue contribute to the tumorigenesis of SCC, probably by promoting angiogenesis. OBJECTIVE: The aim of this study was to compare the concentration of mast cells in SCC of the mouth and skin and evaluate whether there is a correlation with the degree of differentiation of these tumors. MATERIAL AND METHODS: Thirty cases of SCC of the skin and 34 of the mouth were investigated. Toluidine blue staining was used to identify mast cells in blocks containing the central portion of the neoplasm. RESULTS: A concentration of between 0 and 10 mast cells was found in one single case of SCC of the skin and there were no cases of SCC of the mouth with concentrations of mast cells in the tumor >201. In the majority of cases of SCC of the mouth (47 percent; n=16), mast cell concentration was between 0 and 10, with a concentration >51 mast cells in 80 percent of cases of SCC of the skin. All the cases of SCC of the mouth with a concentration of mast cells between 100 and 200 and 80 percent of those with a concentration of 51-99 were located on the lip. The concentration of mast cells was unrelated to the degree of differentiation of the tumor. CONCLUSION: The concentration of mast cells is lower in SCC of the mouth except when the tumor is located on the lip. This may reflect a lower need for cell activation in the microenvironment to improve vascularization in oral cancer.