Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells.

BACKGROUND: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). METHODS: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. RESULTS: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICD-associated DAMPs in an index (IndImunnog) that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment. CONCLUSIONS: Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapy may be a promising therapeutic strategy in NSCLC.

The role of the endocannabinoid system in tooth eruption: An ex vivo study.

The aim was to characterise the endocannabinoid system (ECS) in the dental pulp of teeth at different stages of eruption. Pulp of: erupted premolars (EPM), third molars in pre-eruptive (PThM), intraosseous (IThM) and eruptive stages (EThM) (n = 12 each group) were used. Messenger RNA expression of components of the ECS as cannabinoid receptors (CBr1 and CBr2), and anandamide synthetizing (NAPE-PLD) and degradation (FAAH) enzymes were measured by RT-PCR. Data were analysed using Student's t-test for comparisons between two groups and one-way analysis of variance and Tukey's post-test for multiple comparisons (statistical significance: p < 0.05). mRNA expression of CBr2, NAPE-PLD and FAAH was similar in the studied stages, was lower in IThM than in PThM and EThM, and the lowest in EThM (p < 0.01); of note, CBr2 mRNA expression was not detected in EThM. CBr1 mRNA did not differ significantly between IThM and PThM but was lower in EThM (p < 0.01). The absence of CBr2 and presence of CBr1 in EThM suggest the involvement of the ECS via CBr1 as a mediator of tooth and bone tissue homeostasis during tooth eruption.

[Algoritmo de tratamiento de la dermatitis atópica en Perú. Consenso de expertos].

Objective: Atopic dermatitis is a chronic, systemic, relapsing disease with dermatological manifestations, which imposes a high burden on patients, families and the health care system and has a high psychological, social, and economic impact and on the quality of life of patients. It mainly affects the pediatric population and, to a lesser extent, the adult population. The clinical presentation varies according to the age and evolution of the disease, and currently there are multiple pharmacological and non-pharmacological therapies available for the symptomatic management of patients. Methods: To present an algorithm for the management of atopic dermatitis, proposed as a series of recommendations on the management, diagnosis, education, and follow-up of these patients. Results: A consensus was reached using the nominal group technique. The methodology was developed in 7 phases, including: posing the research questions, literature search, an initial proposal of recommendations, elaboration of the final recommendations and the management algorithm with three voting cycles, consensus was established with 80% favorability. Conclusions: The result of the consensus process is a management algorithm for patients with mild, moderate/severe atopic dermatitis derived from expert recommendations. The algorithm establishes diagnostic and treatment criteria and provides updated recommendations, including all therapeutic alternatives available in Peru for the management of patients with mild, moderate, and severe atopic dermatitis.

Objetivo: La dermatitis atópica es una enfermedad crónica, sistémica, reincidente, con manifestaciones dermatológicas, que impone una alta carga a los pacientes, las familias y los sistemas de salud, y tiene repercusión psicológica, social y económica, y en la calidad de vida de los pacientes. Afecta principalmente a la población pediátrica y con menor frecuencia a la adulta. Las manifestaciones clínicas varían según la edad y evolución de la enfermedad, y en la actualidad se dispone de múltiples opciones farmacológicas y no farmacológicas para el tratamiento de los pacientes. Métodos: Presentar un algoritmo de tratamiento de la dermatitis atópica, propuesto con una serie de recomendaciones acerca del diagnóstico, tratamiento y seguimiento de los pacientes. Resultados: Se llevó a cabo un consenso de expertos, utilizando la técnica del grupo nominal. La metodología se desarrolló en 7 fases que incluyeron: planteamiento de las preguntas de investigación, búsqueda de la bibliografía, propuesta inicial de las recomendaciones, elaboración de las recomendaciones finales y del algoritmo de tratamiento con tres ciclos de votación. Se estableció el consenso con un 80% de favorabilidad. Conclusiones: El resultado del consenso fue un algoritmo de tratamiento de pacientes con dermatitis atópica leve, moderada-grave, derivado de las recomendaciones de expertos. En el algoritmo se establecen criterios diagnósticos y de tratamiento, y se aportan recomendaciones actualizadas que incluyen las alternativas disponibles en Perú.

Guía de práctica clínica: tamizaje, diagnóstico y manejo de episodios agudos y profilaxis del angioedema hereditario ­ Parte I: Enfoque diagnóstico / Clinical practice guidelines: screening, diagnosis and management of acute events and prophylaxis of hereditary angioedema ­ Part I: Diagnostic approach

El angioedema hereditario (AEH) es una enfermedad genética rara, con una prevalencia aproximada entre 1 por cada 50.000 habitantes, caracterizada por episodios de edemas a nivel subcutáneo y de mucosas (abdominal, genitourinario, respiratoria), siendo potencialmente mortal cuando hay afectación de la laringe. En Perú se estiman 600 pacientes con AEH. El AEH se puede clasificar del siguiente modo: con deficiencia del inhibidor de C1 (tipos I y II), y sin deficiencia del inhibidor de C1 (denominado anteriormente tipo III). El diagnóstico de laboratorio incluye prueba de complemento C4, prueba cuantitativa y cualitativa para inhibidor de C1 esterasa, y estudios genéticos.

Hereditary angioedema (HAE) is a genetic rare disease with a prevalence of approximately 1 per 50,000 inhabitants, characterized by episodes of edema at the subcutaneous level and mucous membranes (abdominal, genitourinary, respiratory), being potentially fatal when there is involvement of the larynx. In Peru, there are an estimated 600 patients with HAE. HAE can be classified as follows: with C1 inhibitor deficiency (types I and II), and without C1 inhibitor deficiency (previously called type III). Laboratory diagnosis includes C4 complement test, quantitative and qualitative tests for C1 inhibitor esterase, and genetic studies. In this first part of the Clinical Practice Guide, we present the recommendations for the diagnostic approach of HAE.

Guía de práctica clínica: tamizaje, diagnóstico y manejo de episodios agudos y profilaxis del angioedema hereditario ­ Parte II: Manejo y tratamiento / Clinical practice guidelines: screening, diagnosis and management of acute events and prophylaxis of hereditary angioedema ­ Part II: Management and treatment

El angioedema hereditario (AEH) es una enfermedad genética rara, con una prevalencia aproximada entre 1 por cada 50.000 habitantes, caracterizada por episodios de edemas a nivel subcutáneo y de mucosas (abdominal, genitourinario, respiratoria), siendo potencialmente mortal cuando hay afectación de la laringe. En Perú se estiman 600 pacientes con AEH. El AEH se puede clasificar del siguiente modo: con deficiencia del inhibidor de C1 (tipos I y II), y sin deficiencia del inhibidor de C1 (denominado anteriormente tipo III). El diagnóstico de laboratorio incluye prueba de complemento C4, prueba cuantitativa y cualitativa para inhibidor de C1 esterasa, y estudios genéticos. Existen tratamientos específicos a nivel mundial para crisis agudas y profilaxis en AEH. Sin embargo, en Perú el único tratamiento registrado actualmente es el ecallantide, útil en crisis agudas; además, podemos utilizar tratamientos alternativos como el ácido tranexámico y el danazol. En esta segunda parte de la Guía de Práctica Clínica, presentamos las recomendaciones para el manejo y el tratamiento del AEH.

Hereditary angioedema (HAE) is a genetic rare disease with a prevalence of approximately 1 per 50,000 inhabitants, characterized by episodes of edema at the subcutaneous level and mucous membranes (abdominal, genitourinary, respiratory), being potentially fatal when there is involvement of the larynx. In Peru, there are an estimated 600 patients with HAE. HAE can be classified as follows: with C1 inhibitor deficiency (types I and II), and without C1 inhibitor deficiency (previously called type III). Laboratory diagnosis includes C4 complement test, quantitative and qualitative test for C1 inhibitor esterase, and genetic studies. There are specific treatments worldwide for acute crises and prophylaxis in HAE; in Peru the only currently registered treatment is ecallantide, useful in acute crises; we can also use alternative treatments such as tranexamic acid and danazol. In this second part of the Clinical Practice Guide, we present the recommendations for the management and treatment of HAE.

Immunotherapy for patients with persistent allergic rhinitis unsatisfied with free chronic pharmacotherapy.

BACKGROUND: Chronic pharmacotherapy is recommended to patients with persistent moderate-severe (PM-S) allergic rhinitis (AR). The cost of pharmacotherapy is the main barrier to achieve symptoms control. AIMS OF THE STUDY: To determine the benefits of mite subcutaneous immunotherapy (SIT) in patients with PM-S AR not satisfied with chronic pharmacotherapy received free of charge. METHODS: Open study with seven (7) patients with PM-S AR not satisfied with chronic pharmacotherapy. Prior to enrollment patients had received monthly for more than five months and free of charge, optimal pharmacotherapy. We compared, off pharmacotherapy, symptoms and quality of life (QOL) before and during SIT. RESULTS: Mite SIT improved nasal symptoms, non nasal symptoms and QOL. Off pharmacotherapy patients reported adequate control of symptoms and were satisfied. CONCLUSIONS: Not all patients with PM-S AR are satisfied with chronic pharmacotherapy, even if medication is received free of charge. SIT control symptoms and satisfies patients with PM-S AR unsatisfied with free chronic pharmacotherapy.