Factors associated with dermatoporosis in a sample of geriatric patients in Mexico.

INTRODUCTION: Dermatoporosis is a chronic cutaneous fragility syndrome, characterized by skin atrophy, purpura and pseudo-cicatrices. OBJECTIVE: To determine factors associated with dermatoporosis in a sample of subjects aged ≥ 60 years. METHODS: Observational, cross-sectional, descriptive, analytical study of subjects aged ≥ 60 years who underwent history taking, physical examination and application of a self-administered dermatoporosis diagnostic questionnaire. To determine the associated factors, a multivariate logistic regression analysis was used. RESULTS: In 315 evaluated subjects, the prevalence of dermatoporosis was 29%; 70% were females. Associated risk factors were age > 75 years (p = 0.001), prolonged sun exposure (p = 0.002), use of anticoagulants/antiplatelet medications (p = 0.004), oral steroids (p = 0.03) and chronic kidney disease (p = 0.03), as well as maternal age > 40 years at last pregnancy (p = 0.02), breastfeeding for > 7 months per pregnancy and > 18 cumulative months (p = 0.01). Age < 20 years at first pregnancy and menopause after 45 years were related to dermatoporosis absence. The correlation between self-assessment and clinical diagnosis was considerably high (0.95, p < 0.001). CONCLUSIONS: The risk factors associated with dermatoporosis were similar to those previously reported.

INTRODUCCIÓN: La dermatoporosis es un síndrome crónico de fragilidad cutánea, caracterizado por atrofia, púrpura y pseudocicatrices en piel. OBJETIVO: Determinar los factores asociados a dermatoporosis en una muestra de sujetos ≥ 60 años. MÉTODOS: Estudio observacional, transversal, descriptivo y analítico de sujetos ≥ 60 años a quienes se realizó historia clínica, exploración física y aplicación de un autocuestionario diagnóstico de dermatoporosis. Para determinar los factores asociados se realizó análisis de regresión logística multivariado. RESULTADOS: En 315 sujetos, la prevalencia de dermatoporosis fue de 29 %; 70 % fue del sexo femenino. Los factores asociados fueron edad > 75 años (p = 0.001), exposición solar prolongada (p = 0.002), ingesta de anticoagulantes/antiplaquetarios (p = 0.004), esteroides orales (p = 0.03) y enfermedad renal crónica (p = 0.03); así como, edad materna > 40 años en el último parto (p = 0.02), lactancia > 7 meses por embarazo y lactancia acumulada > 18 meses (p = 0.01). Se relacionaron con su ausencia, edad < 20 años en el primer embarazo y menopausia después de los 45 años. La correlación entre la autovaloración y el diagnóstico clínico fue muy alta (0.95, p < 0.001). ­. CONCLUSIONES: Los factores de riesgo asociados a dermatoporosis fueron similares a los previamente reportados.

Factores asociados a dermatoporosis en una muestra de pacientes geriátricos en México / Factors associated with dermatoporosis in a sample of geriatric patients in Mexico

Resumen Introducción: La dermatoporosis es un síndrome crónico de fragilidad cutánea, caracterizado por atrofia, púrpura y pseudocicatrices en piel. Objetivo: Determinar los factores asociados a dermatoporosis en una muestra de sujetos ≥ 60 años. Métodos: Estudio observacional, transversal, descriptivo y analítico de sujetos ≥ 60 años a quienes se realizó historia clínica, exploración física y aplicación de un autocuestionario diagnóstico de dermatoporosis. Para determinar los factores asociados se realizó análisis de regresión logística multivariado. Resultados: En 315 sujetos, la prevalencia de dermatoporosis fue de 29 %; 70 % fue del sexo femenino. Los factores asociados fueron edad > 75 años (p = 0.001), exposición solar prolongada (p = 0.002), ingesta de anticoagulantes/antiplaquetarios (p = 0.004), esteroides orales (p = 0.03) y enfermedad renal crónica (p = 0.03); así como, edad materna > 40 años en el último parto (p = 0.02), lactancia > 7 meses por embarazo y lactancia acumulada > 18 meses (p = 0.01). Se relacionaron con su ausencia, edad < 20 años en el primer embarazo y menopausia después de los 45 años. La correlación entre la autovaloración y el diagnóstico clínico fue muy alta (0.95, p < 0.001). Conclusiones: Los factores de riesgo asociados a dermatoporosis fueron similares a los previamente reportados.

Abstract Introduction: Dermatoporosis is a chronic cutaneous fragility syndrome, characterized by skin atrophy, purpura and pseudo-cicatrices. Objective: To determine factors associated with dermatoporosis in a sample of subjects aged ≥ 60 years. Methods: Observational, cross-sectional, descriptive, analytical study of subjects aged ≥ 60 years who underwent history taking, physical examination and application of a self-administered dermatoporosis diagnostic questionnaire. To determine the associated factors, a multivariate logistic regression analysis was used. Results: In 315 evaluated subjects, the prevalence of dermatoporosis was 29%; 70% were females. Associated risk factors were age > 75 years (p = 0.001), prolonged sun exposure (p = 0.002), use of anticoagulants/antiplatelet medications (p = 0.004), oral steroids (p = 0.03) and chronic kidney disease (p = 0.03); as well maternal age > 40 years at last pregnancy (p = 0.02), breastfeeding for > 7 months per pregnancy and > 18 cumulative months (p = 0.01). Age < 20 years at first pregnancy and menopause after 45 years were related to dermatoporosis absence. The correlation between self-assessment and clinical diagnosis was considerably high (0.95, p < 0.001). Conclusions: The risk factors associated with dermatoporosis were similar to those previously reported.

Atrazine modifies markers of melanocyte maturation and apoptosis in primary skin cultures.

Atrazine (ATZ) is part of a group of herbicides called triazines. ATZ is widely used in agricultural areas of Mexico, commonly used for the selective control of weeds in corn and sorghum crops. The exposure to ATZ can have serious human health effects since its use was associated with the development of cutaneous melanoma in an epidemiological study. The aim of this study was to evaluate the expression of maturation and apoptotic markers in primary skin cultures exposed to ATZ. The primary skin cultures were exposed to 0.1, and 10 µM ATZ with or without ultraviolet (UV) radiation and the expression of maturation and apoptotic markers were evaluated by RT-qPCR. We observed a significant increase in all the melanocyte maturation markers in cells exposed to ATZ with or without UV, with SOX-9 and FAK (melanoblast markers) being the highest. Also, the expression of BCL-2 (anti-apoptotic marker) was the most increased gene in cells exposed to ATZ with or without UV. Low concentrations of ATZ and UV radiation induce genetic changes associated with the development of immature melanocytes and activate mechanisms associated with the inhibition of apoptosis characteristics of malignant cell transformation, which will allow proposing new therapeutic targets and generating new restrictions or care in farmers exposed to pesticides such as the ATZ.

Study of the cytotoxic and irritant effects of skin cleansing soaps.

BACKGROUND: The use of soap for skin cleansing is common among the population. However, it is possible that it causes damage to skin cells and disrupts the skin barrier. OBJECTIVE: To determine the cytotoxic effect of soaps on in vitro-cultured keratinocytes and to correlate it with clinical irritation. METHOD: A survey was conducted to find out the most widely used commercial soaps and their number. Subsequently, their cytotoxicity was evaluated in human keratinocyte cultures using the resazurin assay. The soaps with the highest and lowest cytotoxicity were applied to the skin of healthy volunteers to assess their effect on the skin barrier using colorimetry and transepidermal water loss (TEWL) assays. RESULTS: Of the analyzed soaps, 37 % were shown to be toxic to keratinocytes in vitro. The soap with the highest toxicity induced the highest rate of erythema and TEWL, in comparison with the least toxic soap and the vehicle used as the control solution. CONCLUSION: Soaps marketed for skin cleansing can contain chemical ingredients that damage human keratinocytes and cause skin barrier subclinical irritation. Their use can worsen preexisting dermatoses, generate xerotic or irritant contact dermatitis, and cause atrophy and dermatoporosis.

INTRODUCCIÓN: El jabón para el aseo cutáneo es de empleo común entre la población, sin embargo, es posible que cause daño a las células de la piel y modifique la barrera cutánea. OBJETIVO: Determinar el efecto citotóxico de los jabones en queratinocitos cultivados in vitro y correlacionarlo con la irritación clínica. MÉTODO: Se realizó una encuesta para conocer los jabones comerciales más utilizados y su cantidad; posteriormente, se evaluó su citotoxicidad en cultivos de queratinocitos humanos mediante el método de resazurina. Los jabones con mayor y menor citotoxicidad se aplicaron en piel de voluntarios sanos para evaluar su efecto en la barrera cutánea mediante ensayos de colorimetría y pérdida transepidérmica de agua. RESULTADOS: De los jabones analizados, 37 % demostró ser tóxico para los queratinocitos in vitro. El jabón con mayor toxicidad indujo el mayor índice de eritema y pérdida transepidérmica de agua, en comparación con el jabón menos tóxico y el vehículo empleado como solución control. CONCLUSIÓN: Los jabones comercializados para el aseo cutáneo pueden incluir ingredientes químicos que dañan los queratinocitos humanos y causan irritación subclínica de la barrera cutánea. Su utilización puede agravar dermatosis preexistentes, generar dermatitis xerósica o de contacto irritativa y causar atrofia y dermatoporosis.

Estudio del efecto citotóxico e irritativo de jabones para la limpieza cutánea / Study of the cytotoxic and irritant effects of skin cleansing soaps

Resumen Introducción: El jabón para el aseo cutáneo es de empleo común entre la población, sin embargo, es posible que cause daño a las células de la piel y modifique la barrera cutánea. Objetivo: Determinar el efecto citotóxico de los jabones en queratinocitos cultivados in vitro y correlacionarlo con la irritación clínica. Método: Se realizó una encuesta para conocer los jabones comerciales más utilizados y su cantidad; posteriormente, se evaluó su citotoxicidad en cultivos de queratinocitos humanos mediante el método de resazurina. Los jabones con mayor y menor citotoxicidad se aplicaron en piel de voluntarios sanos para evaluar su efecto en la barrera cutánea mediante ensayos de colorimetría y pérdida transepidérmica de agua. Resultados: De los jabones analizados, 37 % demostró ser tóxico para los queratinocitos in vitro. El jabón con mayor toxicidad indujo el mayor índice de eritema y pérdida transepidérmica de agua, en comparación con el jabón menos tóxico y el vehículo empleado como solución control. Conclusión: Los jabones comercializados para el aseo cutáneo pueden incluir ingredientes químicos que dañan los queratinocitos humanos y causan irritación subclínica de la barrera cutánea. Su utilización puede agravar dermatosis preexistentes, generar dermatitis xerósica o de contacto irritativa y causar atrofia y dermatoporosis.

Abstract Introduction: The use of soap for skin cleansing is common among the population. However, it is possible that it causes damage to skin cells and disrupts the skin barrier. Objective: To determine the cytotoxic effect of soaps on in vitro-cultured keratinocytes and to correlate it with clinical irritation. Method: A survey was conducted to find out the most widely used commercial soaps and their number. Subsequently, their cytotoxicity was evaluated in human keratinocyte cultures using the resazurin assay. The soaps with the highest and lowest cytotoxicity were applied to the skin of healthy volunteers to assess their effect on the skin barrier using colorimetry and transepidermal water loss (TEWL) assays. Results: Of the analyzed soaps, 37 % were shown to be toxic to keratinocytes in vitro. The soap with the highest toxicity induced the highest rate of erythema and TEWL, in comparison with the least toxic soap and the vehicle used as the control solution. Conclusion: Soaps marketed for skin cleansing can contain chemical ingredients that damage human keratinocytes and cause skin barrier subclinical irritation. Their use can worsen preexisting dermatoses, generate xerotic or irritant contact dermatitis, and cause atrophy and dermatoporosis.

Decreased levels and activity of Sirt1 are modulated by increased miR-34a expression in adipose tissue mononuclear cells from subjects with overweight and obesity: A pilot study.

BACKGROUND AND AIMS: Overweight and obesity are important risk factors for chronic disorders. Fat accumulation is one of the central manifestations; it occurs via a complex mechanism where multiple metabolic signals converge. Sirtuins are an enzyme family with deacetylase functions that are implicated in the regulation of several genes. Sirt1 and its upstream regulator (miR-34a) are elements of a converging mechanism that integrates the dynamic metabolic state. In this work, we hypothesized that elevated levels of miR-34a in overweight/obese group inhibits Sirt1 activity. Therefore, we studied the miR-34a/Sirt1 axis in mononuclear cells obtained from adipose tissue. METHODS: Adipose tissue samples were collected from 36 subjects, and they were categorized according to body mass index (BMI) as overweight/obesity and normoweight. Subcutaneous adipose tissue samples were enzymatically dissociated, and mononuclear cells from adipose tissue were isolated by Ficoll Hypaque. Sirt1-positive cells and relative Sirt1 expression were determined by flow cytometry and real-time polymerase chain reaction (qPCR), respectively. Finally, Sirt1 activity was measured with a luminescence assay. RESULTS: The percentage of Sirt1-positive mononuclear cells from adipose tissue decreased along with Sirt1 enzymatic activity in overweight/obese participants. miR-34a expression increased in the overweight/obese group compared to normoweight individuals. There was a negative association between the relative miR-34a expression and Sirt1-positive cells and a synergistic effect on Sirt1-positive cells mediated by the miR-34a inhibitor and Sirt1 agonist. CONCLUSIONS: Our results describe for the first time the presence of miR-34a and Sirt1 in mononuclear cells isolated from subcutaneous adipose tissue. Additionally, these results suggest altered sirtuin function in overweight/obese patients and open the possibility for new therapies that involve these metabolic targets.

Increased levels of adipose tissue-resident Th17 cells in obesity associated with miR-326.

miRNAs are important immune regulators in the control of the CD4 + T cells phenotype. miR-326 regulates the differentiation towards Th17 cells and the inhibition of miR-155 is associated with low levels of Treg cells. However, miRNAs expression and transcription factors associated with these lymphocyte subsets in obesity-induced adipose tissue inflammation is still unknown. The aim of this work was to identify Th17 cells in subcutaneous adipose tissue (SAT), proinflammatory cytokine production and their association with the miRNAs and transcription factors involved. We collected SAT samples obtained by lipoaspiration from individuals with normal weight, overweight and obesity. We obtained the stromal vascular fractions and then a Ficoll gradient was performed to obtain adipose tissue mononuclear cells (ATMC). Th17 cells were evaluated by flow cytometry and the expression of miR-326, miR-155, RORC2 and FOXP3 by qRT-PCR. We also analyzed cytokines from the supernatants of the ATMC culture and measured the FOXP3 methylation percentage by bisulfite conversion by PCR. According to the results, the frequency of Th17 cells and RORC2 expression was higher in individuals with obesity and associated with miR-326 expression. The ATMC from this group secreted a proinflammatory cytokine profile by in vitro assay. In contrast, lower levels of mRNA FOXP3 expression was detected in ATMC from individuals with obesity that correlated with methylation percentage of FOXP3 gene but no association with miR-155 was detected. Our results suggested that miR-326 participates in the polarization towards Th17 promoting the inflammatory state in the obesity-induced adipose tissue.

Two P2X1 receptor transcripts able to form functional channels are present in most human monocytes.

To characterize the presence and general properties of P2X1 receptors in single human monocytes we used RT-PCR, flow cytometry, and the patch-clamp and the two-electrode voltage-clamp techniques. Most human monocytes expressed the canonical P2X1 (90%) and its splicing variant P2X1del (88%) mRNAs. P2X1 receptor immunoreactivity was also observed in 70% of these cells. Currents mediated by P2X1 (EC50=1.9±0.8µm) and P2X1del (EC50 >1000µm) channels, expressed in Xenopus leavis oocytes, have different ATP sensitivity and kinetics. Both currents mediated by P2X1 and P2X1del channels kept increasing during the continuous presence of high ATP concentrations. Currents mediated by the native P2X1 receptors in human monocytes showed an EC50=6.3±0.2µm. Currents have kinetics that resemble those observed for P2X1 and P2X1del receptors in oocytes. Our study is the first to demonstrate the expression of P2X1 transcript and its splicing variant P2X1del in most human monocytes. We also, for the first time, described functional homomeric P2X1del channels and demonstrated that currents mediated by P2X1 or P2X1del receptors, during heterologous expression, increased in amplitude when activated with high ATP concentrations in a similar fashion to those channels that increase their conductance under similar conditions, such as P2X7, P2X2, and P2X4 channels.

Evaluation of the expression and function of the P2X7 receptor and ART1 in human regulatory T-cell subsets.

Regulatory T cells that express CD39 (CD39+ Treg) exhibit specific immunomodulatory properties. Ectonucleotidase CD39 hydrolyses ATP and ADP. ATP is a ligand of the P2X7 receptor and induces the shedding of CD62L and apoptosis. However, the role of ATP in CD39+ Treg cells has not been defined. Furthermore, NAD can activate the P2X7 receptor via ADP-ribosyltransferase (ART) enzymes and cause cell depletion in murine models. We evaluated the expression and function of P2X7 and ART1 in CD39+ Treg and CD39- Treg cells in the presence or absence of ATP and NAD. We isolated peripheral blood mononuclear cells from healthy subjects and purified CD4+ T cells, CD4+ CD25+ T cells and CD4+ CD25+ CD39+ T cells. P2X7 and ART1 expression was assessed by flow cytometry and real-time PCR. Our results showed low P2X7 expression on CD39+ Treg cells and higher levels of ART1 expression in CD4+ CD39+ T cells than the other subtypes studied. Neither shedding of CD62L nor cell death of CD39+ Treg or CD39- Treg cells was observed by 1mM ATP or 60µM NAD. In contrast, P2Xs receptor-dependent proliferation with 300µM ATP, was inhibited by NAD in the different cell types analysed. The NAD proliferation-inhibition was increased with P2Xs and A2a agonist and was reversed with P2Xs and A2a antagonist, therefore NAD inhibits P2Xs-dependent proliferation and A2a activation. In conclusion, our results suggest that the altered function and expression of P2X7 and ART1 in the human CD39+ Treg or CD39- Treg cells could participate in the resistance against cell death induced by ATP or NAD.

Expression of CD73 and A2A receptors in cells from subjects with obesity and type 2 diabetes mellitus.

Regulatory T cells have various mechanisms to suppress the inflammatory response, among these, the modulation of the microenvironment through adenosine and with the participation of CD39, CD73 and A2A. The aim of this study was to assess the expression of CD73 and A2A in immune cells and the effect of activation of A2A by an adenosine analogue on apoptosis in patients with obesity and type 2 diabetes mellitus (T2D). CD73 and A2A expression were analyzed by flow cytometry in lymphocyte subpopulations from patients with obesity (n = 22), T2D (n = 22), and healthy subjects (n = 20). Lymphocytes were treated with the selective A2A antagonist (ZM241385) or the selective A2A agonist (CGS21680), and apoptotic cells were detected by Annexin V. We found an increased expression of CD39 coupled to a decrease in CD73 in the patient groups with obesity and T2D compared to the control group in the different studied lymphocyte subpopulations. A2A expression was found to be increased in different subpopulations of lymphocytes from T2D patients. We also detected positive correlations between CD39+ cells and age and BMI. Meanwhile, CD73+ cells showed negative correlations with age, WHR, BMI, FPG, HbAc1, triglycerides and cholesterol. Moreover, an increase in the percentage of apoptotic cells from T2D patients with regard to the groups with obesity and control was observed. In addition, the CD8+ T cells of patients with T2D exhibited decreased apoptosis when treated with the A2A agonist. In conclusion, our data suggest a possible role for CD73 and A2A in inflammation observed in patients with T2D and obesity mediated via apoptosis.