Levamisol: un peligroso adulterante de la cocaína muy presente en nuestro medio

Carta a l'editorSr. Editor: El levamisol es un antiparasitario comercializado a partir de 1966, que en la mayoría de países occidentales se prohibió su utilización en humanos a partir de los años 80 por el riesgo de agranulocitosis y de vasculitis necrotizante, aunque sigue autorizado su uso en veterinaria, fundamentalmente como nematicida1 . Es a partir del año 2008 cuando empieza a detectarse cocaína adulterada con este producto químico debido, probablemente, a que sus características organolépticas son parecidas a las de la cocaína, tiene un bajo coste y una elevada disponibilidad por su uso veterinario, además de tener propiedades psicoestimulantes. En EE.UU., hasta un 80% de los decomisos de cocaína aparecen cortados con levamisol2 . En España sólo hemos encontrado 3 casos descritos de reacción adversa al consumo de cocaína/levamisol procedentes de servicios de dermatología, nefrología y medicina interna3-5, por lo que nos ha parecido de interés presentar esta serie de pacientes visitados en urgencias

Cutaneous infection by Phaeoacremonium parasiticum

Background: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. Case report: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. Conclusions: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown

Clinical and Dermoscopic Evaluation of Melanocytic Lesions in Patients with Chronic Graft Versus Host Disease

Patients treated with haematopoietic stem cell transplantation are at increased risk of cutaneous malignant neoplasms. There are no reports on the characteristics of melanocytic lesions in patients with chronic graft versus host disease and the value of recognizing these difficult lesions in high-risk patients. The objective of this study is to describe the clinical and dermo scopic characteristics of melanocytic lesions in patients with chronic graft versus host disease in order to understand their morphology. A prospective cross-sectional study was performed; 10 melanocytic lesions on the trunk and extremities were selected from each patient. A statistically significant association was found between regression and high total dermoscopic score and 7-point checklist score. Lesions were excised or included in short-term digital follow-up. Melanocytic lesions in patients with chronic graft versus host disease developing after allogeneic-haematopoietic stem cell transplantation exhibit marked structural and colour changes similar to melanoma. This is believed to result from the inflammatory process associated with graft versus host disease

Functional characterization of a GGPPS variant indentified in atypical femoral fracture patients and delineation of the role of GGPPS in bone-relevant cell types

Atypical femoral fractures (AFFs) are a rare but potentially devastating event, often but not always linked to bisphosphonate (BP) therapy. The pathogenic mechanisms underlying AFFs remain obscure, and there are no tests available that might assist in identifying those at high risk of AFF. We previously used exome sequencing to explore the genetic background of three sisters with AFFs and three additional unrelated AFF cases, all previously treated with BPs. We detected 37 rare mutations (in 34 genes) shared by the three sisters. Notably, we found a p.Asp188Tyr mutation in the enzyme geranylgeranyl pyrophosphate synthase, a component of the mevalonate pathway, which is critical to osteoclast function and is inhibited by N-BPs. In addition, the CYP1A1 gene, responsible for the hydroxylation of 17β-estradiol, estrone, and vitamin D, was also mutated in all three sisters and one unrelated patient. Here we present a detailed list of the variants found and report functional analyses of the GGPS1 p.Asp188Tyr mutation, which showed a severe reduction in enzyme activity together with oligomerization defects. Unlike BP treatment, this genetic mutation will affect all cells in the carriers. RNAi knockdown of GGPS1 in osteoblasts produced a strong mineralization reduction and a reduced expression of osteocalcin, osterix, and RANKL, whereas in osteoclasts, it led to a lower resorption activity. Taken together, the impact of the mutated GGPPS and the relevance of the downstream effects in bone cells make it a strong candidate for AFF susceptibility. We speculate that other genes such as CYP1A1 might be involved in AFF pathogenesis, which remains to be functionally proved. The identification of the genetic background for AFFs provides new insights for future development of novel risk assessment tools. © 2018 American Society for Bone and Mineral Research

Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications

Background: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). Methods: A cross-sectional study was performed including 326 participants with MetS (55-75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT (n = 254) and TyG (n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. Results: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1-10.7) had a positive association with HOMA-IR [beta = 3.07 (95% confidence interval (CI) 2.28-3.86; p trend < 0.001)], ALT [beta = 7.43 (95% CI 2.23-12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [beta = 14.12 (95% CI 3.64-24.61; p trend = 0.008)], FGF-21 [beta = 190.69 (95% CI 93.13-288.25; p trend < 0.001)], FLI [beta = 18.65 (95% CI 14.97-22.23; p trend < 0.001)] and HSI [beta = 3.46 (95% CI, 2.23-4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62-0.79) compared with men (AUC = 0.570; 95% CI 0.48-0.66). Conclusions: A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMEDPlus study

Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Results: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). Conclusions: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health

Estudio in vivo del papel de la valencia de los autoanticuerpos del pénfigo vulgar en la patogenia de la enfermedad

[spa] Las enfermedades ampollosas autoinmunes constituyen un grupo de enfermedades cutáneas caracterizadas por la presencia de anticuerpos en el suero de los pacientes dirigidos contra antígenos propios de la piel. Por dicho motivo, estos anticuerpos se denominan "autoanticuerpos" y pueden detectarse utilizando técnicas de inmunofluorescencia, bien circulando en el suero, bien unidos "in vivo" a la piel de los pacientes. Cada enfermedad suele presentar una clínica, histopatología y patrones de inmunofluorescencia producidos por los autoanticuerpos que le son propios y permiten realizar el diagnóstico. Los conocimientos adquiridos en los últimos años han permitido demostrar que los antígenos contra los cuales van dirigidos los autoanticuerpos en las enfermedades ampollosas autoinmunes son al mismo tiempo las moléculas responsables de mantener el contacto entre los queratinocitos o entre los queratinocitos basales y la matriz extracelular en condiciones fisiológicas. Además se ha demostrado que los anticuerpos dirigidos contra estos antígenos epidérmicos son capaces de inducir enfermedad en ratones nacidos cuando se transfieren de forma pasiva; estos animales de experimentación reproducen las pérdidas de cohesión epidérmicas típicas de las enfermedades humanas cuando son inyectados con los autoanticuerpos. Por lo tanto, el estudio de estas enfermedades permite no tan sólo avanzar en el conocimiento de estas patologías concretas, sino que también amplia nuestros conocimientos en el campo de la biología cutánea. Por tanto, en este proyecto el objetivo ha sido el de investigar y reevaluar el mecanismo molecular por el cual se produce la acantolisis desde el punto de vista de la valencia de los autoanticuerpos. Para estudiar el papel de dicha valencia en la patogenia de la enfermedad, se comparó la capacidad de inducción de acantolisis de fragmentos bivalentes (IgG y F(ab')2) y monovalentes (Fab) de anticuerpos de pénfigo vulgar. El poder investigar si los autoanticuerpos de pénfigo vulgar difieren realmente de los de pénfigo violáceo en el modo en que producen la acantolisis nos proporciona una nueva visión sobre los mecanismos patógenos relevantes por los cuales estos autoanticuerpos son capaces de desencadenar acantolisis