CD39 expression by regulatory T cells participates in CD8+ T cell suppression during experimental Trypanosoma cruzi infection.

An imbalance between suppressor and effector immune responses may preclude cure in chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated the kinetics and underlying mechanisms behind the regulation of protective parasite-specific CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse model, we found that Treg cells play a role during the initial stages after T. cruzi infection, restraining the magnitude of CD8+ T cell responses and parasite control. Early Treg cell depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets, without affecting memory precursor cell formation or the expression of activation, exhaustion and functional markers. In addition, Treg cell depletion during early infection minimally affected the antigen-presenting cell response but it boosted CD4+ T cell responses before the development of anti-parasite effector CD8+ T cell immunity. Crucially, the absence of CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell responses, preventing increased parasite replication in T. cruzi infected mice adoptively transferred with Treg cells. Our work underscores the crucial role of Treg cells in regulating protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells represents a key immunomodulatory mechanism in this infection model.

ANCUT1, a novel thermoalkaline cutinase from Aspergillus nidulans and its application on hydroxycinnamic acids lipophilization.

One of the four cutinases encoded in the Aspergillus nidulans genome, ANCUT1, is described here. Culture conditions were evaluated, and it was found that this enzyme is produced only when cutin is present in the culture medium, unlike the previously described ANCUT2, with which it shares 62% amino acid identity. The differences between them include the fact that ANCUT1 is a smaller enzyme, with experimental molecular weight and pI values of 22 kDa and 6, respectively. It shows maximum activity at pH 9 and 60 °C under assayed conditions and retains more than 60% of activity after incubation for 1 h at 60 °C in a wide range of pH values (6-10) after incubations of 1 or 3 h. It has a higher activity towards medium-chain esters and can modify long-chain length hydroxylated fatty acids constituting cutin. Its substrate specificity properties allow the lipophilization of alkyl coumarates, valuable antioxidants and its thermoalkaline behavior, which competes favorably with other fungal cutinases, suggests it may be useful in many more applications.

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.

Puesta a punto de la técnica de Ussing Chamber para estudios de permeabilidad intestinal en tejido de cerdo / Optimization of the Ussing Chamber Technique for studies of intestinal permeability in pig tissue

El Sistema de Clasificación Biofarmacéutica es un marco científico para clasificar ingredientes farmacéuticos activos en base a su solubilidad acuosa y su permeabilidad intestinal, que cuando se combina con la disolución del producto toma en cuenta los tres factores principales que gobiernan la velocidad y el alcance de la absorción de un fármaco a partir de formas posológicas orales sólidas de liberación inmediata. Cuando los fármacos cumplen con determinados criterios biofarmacéuticos este sistema permite reemplazar los estudios in vivo de biodisponibilidad / bioequivalencia por estudios in vitro. La permeabilidad intestinal de los IFAs puede ser estudiada por diferentes métodos, uno de ellos es la técnica de Ussing Chamber que utiliza una porción de tejido intestinal. La ventaja de esta técnica es que permite conservar las capacidades funcionales de los tejidos. En la puesta a punto de esta nueva técnica se obtuvieron datos concordantes con bibliografía. Se evaluó la permeabilidad de ibuprofeno, metoprolol y atenolol (drogas de alta y baja permeabilidad) utilizando Ussing Chamber con intestino delgado de cerdo. Contar con esta técnica en el Departamento de Farmacología representa un valioso complemento a las metodologías ya utilizadas: estudios in vitro (células Caco-2 y MDCK) e in situ (perfusión intestinal en rata).

The Biopharmaceutical Classification System is a scientific framework for classifying Active Pharmaceutical Ingredients based on their aqueous solubility and their intestinal permeability which, when combined with the dissolution of the product takes into account the three main factors that govern the absorption speed and extent of a drug from immediate-release solid oral dosage form. When drugs meet certain biopharmaceutical criteria, this system allows in vivo bioavailability / bioequivalence studies to be replaced by in vitro studies. The intestinal permeability of APIs can be studied by different methods, one of them is the Ussing Chamber technique that uses a portion of intestinal tissue. The advantage of this technique is that it allows to conserve the functional capacities of tissues. In the development of this new technique, concordant data with bibliography was obtained. The permeability of ibuprofen, metoprolol and atenolol (high and low permeability drugs) was evaluated utilizing the Ussing Chamber Technique with pig small intestine. To have this technique in the Department of Pharmacology represents a valuable complement to the methodologies already used; both in vitro (Caco-2 and MDCK cells) and in situ (intestinal perfusion in rat) studies.

Hidroa vacciniforme / Hydroa vacciniforme

La hidroa vacciniforme (HV) es una fotodermatosis poco frecuente, que usualmente se inicia en la infancia y mejora espontáneamente en la adolescencia. Se caracteriza por la presencia de pápulas, vesículas umbilicadas y costras hemorrágicas en áreas fotoexpuestas, que curan dejando cicatrices varioliformes. La histopatología de las lesiones cutáneas, al igual que la inmunofluorescencia directa, presenta hallazgos característicos pero inespecíficos. El diagnóstico se realiza en base a la correlación clínico-patológica. Recientemente, se ha encontrado una relación entre la HV, el virus de Epstein-Barr y el desarrollo de linfoma. El tratamiento consiste en medidas de fotoprotección, aunque en algunos pacientes se requiere del uso de drogas inmunosupresoras sistémicas

Hydroa vacciniforme (HV) is a rare photodermatosis that usually begins in childhood and improves spontaneously in the adolescence. It is characterized by the presence of papules, umbilicated vesicles and hemorrhagic crusts that heal with vacciniform scarring in photoexposed areas. The histopathology of the skin lesions, as well as the direct immunofluorescence findings, is characteristic but nonspecific. The diagnosis is achieved based on clinico-pathological correlation. A relationship between the HV, Epstein-Barr virus and the development of lymphoma has been recently found. The treatment consists of photoprotective measures, but some cases require the use of systemic immunosuppressive drugs

Apoptosis de linfocitos asociada a enfermedades infecciosas. / [Lymphocyte apoptosis associated to infections]

During infections, the presence of lymphocyte apoptosis both in peripheral blood and in lymphatic organs has been described. This kind of programmed cell death can be either induced by host control mechanisms aimed at eliminating infected lymphocytes and/or retaining immune system homeostasis, or by the pathogen in order to complete its life cycle, spreading the infection and/or suppressing the immune response. Thus, apoptosis has advantages and disadvantages for the host depending on the pathogen life cycle and/or the specificity of the lymphocyte population affected. Identification of the mechanisms involved in autoreactive or pathogen-specific lymphocyte apoptosis could lead to strategies designed to interfere immunologically or pharmacologically in favor of the host.

Apoptosis de linfocitos asociada a enfermedades infecciosas / [Lymphocyte apoptosis associated to infections]

During infections, the presence of lymphocyte apoptosis both in peripheral blood and in lymphatic organs has been described. This kind of programmed cell death can be either induced by host control mechanisms aimed at eliminating infected lymphocytes and/or retaining immune system homeostasis, or by the pathogen in order to complete its life cycle, spreading the infection and/or suppressing the immune response. Thus, apoptosis has advantages and disadvantages for the host depending on the pathogen life cycle and/or the specificity of the lymphocyte population affected. Identification of the mechanisms involved in autoreactive or pathogen-specific lymphocyte apoptosis could lead to strategies designed to interfere immunologically or pharmacologically in favor of the host.