Importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, Ucayali, Perú / Cultural importance of the flora used by the Asheninka Sheremashe native community, Ucayali, Peru

The cultural significance of the flora used by the native Asheninka Sheremashe community in Ucayali, Peru was determined. To do this, a fieldwork of over 4 months was conducted, involving semi-structured interviews with 106 residents through non-probabilistic convenience sampling. The community utilizes 139 plant species in their daily lives, belonging to 120 genera and 52 families, with the most abundant being Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae, and Rutaceae. Furthermore, 25.9% of the species are of significant importance to theinhabitants according to the Cultural Index (CI), such as Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, among others. It can be concluded that the flora plays a prominent role in the life of the community, with the categories reporting the highest number of species being: food (29.35%), medicine (28.36%), culture (9.95%), construction (9.45%), lumber (6.97%), commerce (3.48%), craftsmanship (2.49%), toxic (2.49%), and other uses (7.46%)

Se determinó la importancia cultural de la flora empleada por la comunidad nativa Asheninka Sheremashe, en Ucayali, Perú. Para ello, se realizó un trabajo de campo de más de 4 meses, donde se aplicaron entrevistas semiestructuradas a 106 habitantes mediante un muestreo no probabilístico por conveniencia. La comunidad emplea 139 especies vegetales en su día a día, pertenecientes a 120 géneros y 52 familias; siendo las más abundantes las Fabaceae, Arecaceae, Malvaceae, Solanaceae, Poaceae y Rutaceae. Además, el 25.9% de las especies tiene gran importancia para los pobladores según el Índice Cultural (IC): Manihot esculenta, Theobroma cacao, Bixa orellana, Musa paradisiaca, Ficus insipida, entre otras. Se concluye que la flora tiene un rol preponderante en la vida de la comunidad, siendo las categorías que presentaron mayor reporte de especies: alimentación (29.35%), medicina (28.36%), cultura (9.95%), construcción (9.45%), aserrío (6.97%), comercio (3.48%), artesanía (2.49%), tóxico (2.49%) y otros usos (7.46%)

Clinical characteristics, laboratory findings, and tolerance acquisition in infants with cow's milk protein allergy in a private center in Lima, Peru for the period 2021-2022.

BACKGROUND: Cow's milk protein allergy (CMPA) remains relatively understudied in Latin America. METHODS: In this observational study, we enrolled 64 patients with a median age of 3 months, of whom 60% were male. Patients included had a history of IgE-mediated reactions with IgE sensitization or non-IgE-mediated reactions or symptoms following exposure to cow's milk. They underwent skin prick test, ImmunoCAP, fecal calprotectin (FC), and fecal eosinophil-derived neurotoxin (EDN), in addition to double-blinded placebo-controlled oral food challenges (DBPCFC), with clinical evolution and tolerance acquisition observed over 1 year. RESULTS: Malnutrition was present in 78.1% of patients, and 87.5% had a family history of atopy, with 51.6% receiving exclusive breastfeeding. Gastrointestinal manifestations were prevalent in 90.6% of patients, followed by dermatological manifestations (10.9%), with only 2 experiencing anaphylaxis. IgE-mediated CMPA was observed in only six patients. In those with non-IgE-mediated CMPA, FC had a median of 284 mg/dL (IQR: 138.5-415.5), while EDN had a median of 508.5 mg/dL (IQR: 160.25-868). One year after diagnosis, median FC significantly decreased (p < 0.0001), and malnutrition prevalence reduced to 17.1%. Moreover, 81% of patients acquired tolerance following DBPCFC, with 52% utilizing nutritional replacement formulas at diagnosis. Notably, 94% of those extensively hydrolyzed casein-based formulas achieved tolerance (p = 0.08). CONCLUSION: Our findings provide a foundational framework for future investigations into CMPA diagnosis, tolerance acquisition, and the utilization of hypoallergenic formulas tailored to the unique characteristics of our region.

Clinical efficacy of synbiotics in children with allergic rhinitis: An observational cohort study from a private medical center in Peru.

BACKGROUND: Probiotics in allergic rhinitis (AR) have shown improvement in clinical and quality of life scores, whereas the role of synbiotics in the treatment of AR has been poorly investigated. The purpose of this study was to evaluate the clinical efficacy of synbiotics in children with AR. METHODS: An observational, prospective cohort study of pediatric outpatients with AR from a private medical center in Peru (2021) was conducted. At baseline, patients who were prescribed synbiotics during routine and those who were not (controls) recruited and followed up on Days 30, 60, and 90 of follow-up. Clinical efficacy was assessed with differences in Visual Analogous Scale (VAS), Total Nasal Symptom Score (TNSS), Rhinitis Control Assessment Test (RCAT), and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) scores between groups at follow-up. Mean differences ± standard deviation (SD) and 95% confidence intervals (95% CI) are reported. RESULTS: Two hundred and fifteen participants were analyzed. Compared to controls (n = 115), those who used synbiotics (n = 100) had significantly lower VAS (mean difference 1.3; 95% CI: 0.8-1.8), TNSS (mean difference 1.1; 95% CI: 0.5-1.7) and higher RCAT scores and PRQLQ scores (mean difference 2.2; 95% CI: -3.3 to -1.2) and (mean difference 7.0; 95% CI: 3.1-10.9), respectively, at Day 90 of follow-up CONCLUSIONS: This paper reports significant improvement in clinical (VAS, RCAT, TNSS) and quality of life (PRQLQ) scores of small and large sizes, respectively. These preliminary findings support the need of future trials to assess the role of synbiotics in children with AR.

Contribution of minimally processed and ultra-processed foods to the cardiometabolic risk of Brazilian young adults: a cross-sectional study / Contribución de los alimentos mínimamente procesados y ultraprocesados al riesgo cardiometabólico de adultos jóvenes brasileños: un estudio transversal

INTRODUCTION: the simultaneous increase in the prevalence of cardiometabolic diseases and in the consumption of ultraprocessed foods (UPF) suggests a possible relationship between UPF and cardiometabolic risk (CMR). OBJECTIVE: to evaluate the association between food consumption, according to the degree of processing, and CMR in young adults. METHODS: this is a comparative cross-sectional study in 120 Brazilian young adults aged 18-25 years, categorized by the presence of CMR. Food consumption was investigated using a semi-quantitative food frequency questionnaire, and classified according to the extent of food processing. Food groups and tertiles in grams of unprocessed, minimally processed (MPF), processed and ultra-processed foods (UPF) were compared using the Kruskal-Wallis test. The associations of food consumption, according to level of processing (MPF and UPF), with CMR components were evaluated using logistic regression models. RESULTS: a high caloric contribution of UPF was observed in the diet of this study population. The total energy intake from lipids in all foods (p = 0.04) and in UPF (p = 0.03) was greater in the group with CMR. A greater consumption of UPF was a risk factor for abdominal obesity (OR = 1.09; 95 % CI = 1.00-1.18) while a greater consumption of MPF was protective for LDL-c alterations independently of sex, physical activity, and alcohol intake (OR = 0.70; 95 % CI = 0.50-0.98). CONCLUSIONS: UPF contributed to a greater caloric intake from fat in the CMR, and was a risk factor for abdominal obesity. MPF was an independent protective factor for LDL-c alterations

INTRODUCCIÓN: la alta prevalencia de enfermedades cardiometabólicas y el avance de los alimentos ultraprocesados en la dieta sugieren una posible relación entre ellos. OBJETIVO: valorar la asociación entre el consumo de alimentos clasificado por el grado de procesamiento y el riesgo cardiometabólico en adultos jóvenes. MÉTODOS: estudio transversal con una muestra compuesta por 120 jóvenes brasileños de 18 a 25 años, que fueron categorizados según el riesgo cardiometabólico (presencia o ausencia). El consumo de alimentos se evaluó mediante un cuestionario semicuantitativo de frecuencias a partir del que se clasificó la ingesta de acuerdo con el grado de procesamiento. Estos resultados se dividieron en terciles de gramos de alimentos (procesados y mínimamente procesados, procesados y ultraprocessados). Las diferencias de consumo diario de alimentos entre los terciles se compararon por medio del test de Kruskal-Wallis. Se realizó una regresión logística para asociar el grado de procesamiento con los componentes del riesgo cardiometabólico. RESULTADOS: se observó una alta contribución energética de los alimentos ultraprocesados en la dieta de la muestra estudiada. La ingestión de grasas totales (p = 0,04) y alimentos ultraprocesados (p = 0,03) fue mayor entre el grupo con riesgo cardiometabólico. El consumo de alimentos ultraprocesados fue un factor de riesgo de obesidad abdominal (OR = 1,09; IC 95 %: 1,00-1,18), mientras que el consumo de los mínimamente procesados fue protector frente a las alteraciones del LDL-c, independientemente del sexo, la actividad física y la ingesta de alcohol (OR = 0,70; IC 95 % = 0,50-0,98). CONCLUSIÓN: los alimentos ultraprocesados contribuyeron a aumentar la ingesta de grasas y a la obesidad abdominal; en cambio, los alimentos no procesados y mínimamente procesados redujeron los niveles de LDL-c

Contribution of minimally processed and ultra-processed foods to the cardiometabolic risk of Brazilian young adults: a cross-sectional study.

INTRODUCTION: Introduction: the simultaneous increase in the prevalence of cardiometabolic diseases and in the consumption of ultraprocessed foods (UPF) suggests a possible relationship between UPF and cardiometabolic risk (CMR). Objective: to evaluate the association between food consumption, according to the degree of processing, and CMR in young adults. Methods: this is a comparative cross-sectional study in 120 Brazilian young adults aged 18-25 years, categorized by the presence of CMR. Food consumption was investigated using a semi-quantitative food frequency questionnaire, and classified according to the extent of food processing. Food groups and tertiles in grams of unprocessed, minimally processed (MPF), processed and ultra-processed foods (UPF) were compared using the Kruskal-Wallis test. The associations of food consumption, according to level of processing (MPF and UPF), with CMR components were evaluated using logistic regression models. Results: a high caloric contribution of UPF was observed in the diet of this study population. The total energy intake from lipids in all foods (p = 0.04) and in UPF (p = 0.03) was greater in the group with CMR. A greater consumption of UPF was a risk factor for abdominal obesity (OR = 1.09; 95 % CI = 1.00-1.18) while a greater consumption of MPF was protective for LDL-c alterations independently of sex, physical activity, and alcohol intake (OR = 0.70; 95 % CI = 0.50-0.98). Conclusions: UPF contributed to a greater caloric intake from fat in the CMR, and was a risk factor for abdominal obesity. MPF was an independent protective factor for LDL-c alterations.

INTRODUCCIÓN: Introducción: la alta prevalencia de enfermedades cardiometabólicas y el avance de los alimentos ultraprocesados en la dieta sugieren una posible relación entre ellos. Objetivo: valorar la asociación entre el consumo de alimentos clasificado por el grado de procesamiento y el riesgo cardiometabólico en adultos jóvenes. Métodos: estudio transversal con una muestra compuesta por 120 jóvenes brasileños de 18 a 25 años, que fueron categorizados según el riesgo cardiometabólico (presencia o ausencia). El consumo de alimentos se evaluó mediante un cuestionario semicuantitativo de frecuencias a partir del que se clasificó la ingesta de acuerdo con el grado de procesamiento. Estos resultados se dividieron en terciles de gramos de alimentos (procesados y mínimamente procesados, procesados y ultraprocessados). Las diferencias de consumo diario de alimentos entre los terciles se compararon por medio del test de Kruskal-Wallis. Se realizó una regresión logística para asociar el grado de procesamiento con los componentes del riesgo cardiometabólico. Resultados: se observó una alta contribución energética de los alimentos ultraprocesados en la dieta de la muestra estudiada. La ingestión de grasas totales (p = 0,04) y alimentos ultraprocesados (p = 0,03) fue mayor entre el grupo con riesgo cardiometabólico. El consumo de alimentos ultraprocesados fue un factor de riesgo de obesidad abdominal (OR = 1,09; IC 95 %: 1,00-1,18), mientras que el consumo de los mínimamente procesados fue protector frente a las alteraciones del LDL-c, independientemente del sexo, la actividad física y la ingesta de alcohol (OR = 0,70; IC 95 % = 0,50-0,98). Conclusión: los alimentos ultraprocesados contribuyeron a aumentar la ingesta de grasas y a la obesidad abdominal; en cambio, los alimentos no procesados y mínimamente procesados redujeron los niveles de LDL-c.

Exploring Veterinary Medicine Students' Experiences with Team-Based Learning at the Universidad Andrés Bello.

This study explored the use of team-based learning (TBL) in a Clinical Anatomy course taken by third-year veterinary medicine undergraduate students at the Universidad Andrés Bello in Chile. While research has shown that active learning methodologies yield improved student learning outcomes compared to lecture-based teaching, the incorporation of new pedagogical strategies is complex and its success depends on a range of contextual factors. This study sought to understand the strengths and weaknesses of using TBL in a specific subject (anatomy), discipline (veterinary medicine), and country (Chile). Students in the course had not been previously exposed to TBL. At the end of the semester during which TBL was used, the research team collected student satisfaction survey data and conducted a focus group in order to understand students' experiences with TBL in the course. We found that overall, students were satisfied with TBL and appreciated that it increased the amount of feedback they received, reinforced key concepts, and helped them to build skills they would need in their future professions. There was also a certain level of dissatisfaction, which may have been caused by negative experiences with team members and difficulties reading the preparatory material, which was in English. Given our findings, we discuss modifications that could be made in order to improve veterinary medicine students' experiences with TBL.

Plasma Total Antioxidant Capacity and Cardiometabolic Risk in Non-Obese and Clinically Healthy Young Adults / Capacidade Antioxidante Total do Plasma e Risco Cardiometabólico em Adultos Jovens, Não Obesos e Clinicamente Saudáveis

Abstract Background: The oxidative biomarkers play an important role in the genesis of cardiometabolic risk-related processes. Objective: To investigate the total antioxidant capacity of plasma and its association with cardiometabolic risk in non-obese and clinically healthy young adults. Methods: University students of the state of Sergipe, Brazil, aged between 18 and 25 years, were recruited for this study from May of 2013 and October of 2014. Anthropometric, clinical and biochemical parameters were measured and analyzed using protocols which were previously standardized and described in the literature. The measurement of plasma total antioxidant capacity was based on the ability that all the antioxidants present in the sample (plasma) have to inhibit the oxidation of the oxidizable substrate ABTS (2,2`- Azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS•+ by metmyoglobin. Results: Approximately 25% of the sample presented more than one component of cardiometabolic risk. Low HDL-cholesterol was the most prevalent component. Compared to absence of components, the subjects with at least one component presented greater body weight and waist circumference, higher levels of diastolic blood pressure and fasting glucose, greater total cholesterol/HDL-c ratio, and lower levels of HDL-c (p < 0.05). Fasting glycemia was the only parameter which was associated with total antioxidant capacity (R2 = 0.10; β = 0.17; p = 0.001). Conclusions: The plasma total antioxidant capacity was not able to predict the cardiometabolic risk components due possibly to the establishment of compensatory mechanisms that become activated in physiological conditions.

Resumo Fundamentos: Os biomarcadores oxidativos exercem um importante papel na gênese dos processos relacionados ao risco cardiometabólico. Objetivo: Investigar a capacidade antioxidante total do plasma e sua associação com risco cardiometabólico em adultos jovens, não obesos e clinicamente saudáveis. Métodos: Estudantes universitários do estado de Sergipe, Brasil, com idade entre 18 e 25 anos, foram recrutados entre maio de 2013 e outubro de 2014. Parâmetros antropométricos, clínicos e bioquímicos foram medidos e analisados usando protocolos previamente padronizados e descritos na literatura. A medida da capacidade antioxidante total do plasma baseou-se na capacidade de todos os antioxidantes presentes na amostra (plasma) em inibir a oxidação do substrato oxidável ABTS (2,2-Azino-bis-(3-etilbenzotiazolina-6-sulfonato) a ABTS•+ pela metamioglobina. Resultados: Aproximadamente 25% da amostra apresentaram mais de um componente do risco cardiometabólico. Valores baixos de HDL foram o componente mais prevalente. Em comparação à ausência de componentes, os indivíduos com pelo menos um componente apresentou valores mais altos de peso corporal, circunferência da cintura, pressão sanguínea diastólica, glicemia de jejum e razão colesterol total/HDL-c, e valores mais baixos de HDL-c (p < 0,05). A glicemia de jejum foi o único parâmetro que se associou com a capacidade antioxidante total (R2 = 0,10; β = 0,17; p = 0,001). Conclusões: A capacidade antioxidante total não foi capaz de predizer os componentes do risco cardiometabólico possivelmente devido ao estabelecimento de mecanismos compensatórios que se tornam ativados em condições fisiológicas.

Plasma Total Antioxidant Capacity and Cardiometabolic Risk in Non-Obese and Clinically Healthy Young Adults.

BACKGROUND:: The oxidative biomarkers play an important role in the genesis of cardiometabolic risk-related processes. OBJECTIVE:: To investigate the total antioxidant capacity of plasma and its association with cardiometabolic risk in non-obese and clinically healthy young adults. METHODS:: University students of the state of Sergipe, Brazil, aged between 18 and 25 years, were recruited for this study from May of 2013 and October of 2014. Anthropometric, clinical and biochemical parameters were measured and analyzed using protocols which were previously standardized and described in the literature. The measurement of plasma total antioxidant capacity was based on the ability that all the antioxidants present in the sample (plasma) have to inhibit the oxidation of the oxidizable substrate ABTS (2,2`- Azino-di-[3-ethylbenzthiazoline sulphonate]) to ABTS•+ by metmyoglobin. RESULTS:: Approximately 25% of the sample presented more than one component of cardiometabolic risk. Low HDL-cholesterol was the most prevalent component. Compared to absence of components, the subjects with at least one component presented greater body weight and waist circumference, higher levels of diastolic blood pressure and fasting glucose, greater total cholesterol/HDL-c ratio, and lower levels of HDL-c (p < 0.05). Fasting glycemia was the only parameter which was associated with total antioxidant capacity (R2 = 0.10; ß = 0.17; p = 0.001). CONCLUSIONS:: The plasma total antioxidant capacity was not able to predict the cardiometabolic risk components due possibly to the establishment of compensatory mechanisms that become activated in physiological conditions. FUNDAMENTOS:: Os biomarcadores oxidativos exercem um importante papel na gênese dos processos relacionados ao risco cardiometabólico. OBJETIVO:: Investigar a capacidade antioxidante total do plasma e sua associação com risco cardiometabólico em adultos jovens, não obesos e clinicamente saudáveis. MÉTODOS:: Estudantes universitários do estado de Sergipe, Brasil, com idade entre 18 e 25 anos, foram recrutados entre maio de 2013 e outubro de 2014. Parâmetros antropométricos, clínicos e bioquímicos foram medidos e analisados usando protocolos previamente padronizados e descritos na literatura. A medida da capacidade antioxidante total do plasma baseou-se na capacidade de todos os antioxidantes presentes na amostra (plasma) em inibir a oxidação do substrato oxidável ABTS (2,2-Azino-bis-(3-etilbenzotiazolina-6-sulfonato) a ABTS•+ pela metamioglobina. RESULTADOS:: Aproximadamente 25% da amostra apresentaram mais de um componente do risco cardiometabólico. Valores baixos de HDL foram o componente mais prevalente. Em comparação à ausência de componentes, os indivíduos com pelo menos um componente apresentou valores mais altos de peso corporal, circunferência da cintura, pressão sanguínea diastólica, glicemia de jejum e razão colesterol total/HDL-c, e valores mais baixos de HDL-c (p < 0,05). A glicemia de jejum foi o único parâmetro que se associou com a capacidade antioxidante total (R2 = 0,10; ß = 0,17; p = 0,001). CONCLUSÕES:: A capacidade antioxidante total não foi capaz de predizer os componentes do risco cardiometabólico possivelmente devido ao estabelecimento de mecanismos compensatórios que se tornam ativados em condições fisiológicas.

Paquioniquia congénita tipo 1 / Pachyonycha congenita type 1

La paquioniquia cong‚nita (PC) es una rara genodermatosis de inicio en la infancia temprana caracterizada por una hiperqueratosis ungueal y frecuentes alteraciones asociadas. Se presenta el caso de una mujer de 28 a¤os con lesiones cl¡nicas compatibles con paquioniquia cong‚nita tipo 1.

The pachyonychia congenita (PC) is a rare genodermatosis of onset in early infancy characterized by hyperkeratosis nail and frequent partner changes. The case of a 28 year old woman with clinical lesions compatible with pachyonychia congenita type 1 is presented.

Síndrome de Laugier-Hunziker / Laugier-Hunziker syndrome

El síndrome de Laugier-Hunziker es un raro desorden adquirido caracterizado por una hiperpigmentación difusa de la mucosa oral y melanoniquia en adultos. Aparecen lesiones maculares menores de 5 mm de diámetro. Está considerada como una enfermedad benigna sin manifestación sistémica o con potencial maligno. Por lo tanto, es importante descartar otros trastornos pigmentarios mucocutáneos que requieran manejo médico. Se presenta el caso de una paciente de 66 años con síndrome de Laugier-Hunziker con compromiso de uñas, manos, pies y mucosa oral, es el segundo caso reportado en Perú en los dos últimos años.

Laugier-Hunriker syndrome is a rare acquired disorder characterized by diffuse hyperpigmentation of the oral mucosa and longitudinal melanonychia in adults. They appear as macular lesions less than 5 mm in diameter. It's considered to be a benign disease with no systemic manifestation or malignant potential. Therefore, it's important to rule out other mucocutaneous pigmentary disorders that do require medical management. We present one case of66 year-old woman with Laugier-Hunziker syndrome with compromise of nails, hands, feet and oral mucosa, it's a second case reported in Peru last two years.

Angiosarcoma: reporte de caso / Angiosarcoma: a case report

El angiosarcoma cutáneo es un tumor vascular maligno muy agresivo y raro. Su localización habitual es la cabeza y el cuello, y es más frecuente en personas de edad avanzada, sobretodo en el sexo masculino. Se caracteriza clínicamente por la presencia de placas induradas o nódulos eritematovioláceos. Su pronóstico es malo con tendencia a la metástasis. No existe hasta el momento un protocolo terapéutico estandarizado. Se presenta el caso de una paciente mujer de 77 años de edad con angiosarcoma cutáneo de cuero cabelludo que se intervino quirúrgicamente y recibió radioterapia, hasta el momento tres meses después no ha presentado recidivas ni metástasis.

Cutaneous angiosarcoma is a malignant, vascular tumor very aggressive and rare. The habitual locate are head and neck region, is more frequent in elderly people, with predominance in male gender. Clinically characterized by red or violet plaques or nodules. The prognosis is poor with tendency to metastasis. There isn't at present a standardized therapeutic protocol. We present one case 0177 year-old woman with cutaneous angiosarcoma of scalp, she was submitted to surgical intervention and received radiotherapy, at the moment after three months she has not been present relapse or metastasis.

Incidence of inflammatory bowel disease in five geographical areas of Uruguay in the biennial 2007-2008.

INTRODUCTION: The incidence of inflammatory bowel disease (IBD) is different according to the geographical areas. No data on the incidence of IBD in Uruguay are available. OBJECTIVE: To determine the incidence of IBD, ulcerative colitis (UC) and Crohn's disease (CD), in five areas of Uruguay and to compare the results with those from other geographical regions. MATERIAL AND METHOD: A prospective study was performed in five areas of Uruguay during 2007-2008. The study population included 645,695 inhabitants. Multiple independent sources were used for the uptake of cases. Patients older than 14 years and living in the selected areas were included only after reviewing their medical history. Confirmed IBD was defined by a standard protocol after one year of follow up. RESULTS: A total of 34 cases were diagnosed in the study period, 29 UC and 5 CD. Crude incidence rate for IBD was 2.63 per 100,000 inhabitants/year, 2.25 and 0.39 for UC and CD, respectively. Adjusted rates were 4.26 per 100,000 inhabitants/year for UC and 0.74 per 100,000 inhabitants/year for CD. The UC/CD ratio was 5.8. The average age for IBD was 40.7 years. No statistically significant differences were found between UC and CD by age (P = 0.267) or gender (P = 0.489). CONCLUSIONS: Incidence rates of IBD place Uruguay in the regions of low incidence. As it has been described in low-incidence countries, UC is more common than CD. This study establishes a precedent to follow the evolution of IBD epidemiology in Uruguay.

Heat shock protein 90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin enhances EphA2+ tumor cell recognition by specific CD8+ T cells.

EphA2, a member of the receptor tyrosine kinase family, is commonly expressed by a broad range of cancer types, where its level of (over)expression correlates with poor clinical outcome. Because tumor cell expressed EphA2 is a nonmutated "self" protein, specific CD8(+) T cells are subject to self-tolerance mechanisms and typically exhibit only moderate-to-low functional avidity, rendering them marginally competent to recognize EphA2(+) tumor cells in vitro or in vivo. We have recently reported that the ability of specific CD8(+) T cells to recognize EphA2(+) tumor cells can be augmented after the cancer cells are pretreated with EphA2 agonists that promote proteasomal degradation and up-regulated expression of EphA2/class I complexes on the tumor cell membrane. In the current study, we show that treatment of EphA2(+) tumor cells with the irreversible heat shock protein 90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), similarly enhances their recognition by EphA2-specific CD8(+) T-cell lines and clones in vitro via a mechanism that is dependent on proteasome and transporter-associated protein function as well as the retrotranslocation of EphA2 into the tumor cytoplasm. When 17-DMAG and agonist anti-EphA2 monoclonal antibodies are coapplied, T-cell recognition of tumor cells is further increased over that observed for either agent alone. These studies suggest that EphA2 represents a novel heat shock protein 90 client protein and that the treatment of cancer patients with 17-DMAG-based "pulse" therapy may improve the antitumor efficacy of CD8(+) T effector cells reactive against EphA2-derived epitopes.

Enhancement in specific CD8+ T cell recognition of EphA2+ tumors in vitro and in vivo after treatment with ligand agonists.

The EphA2 receptor tyrosine kinase is an attractive therapeutic target that is commonly overexpressed on solid tumors, with the degree of overexpression associated with disease progression, metastatic potential, and poor prognosis. Agonistic mAbs or ligand (ephrinA1)-Fc fusion protein are capable of inducing EphA2 internalization and degradation, thereby (at least transiently) eliminating the influence of this oncoprotein. We and others have also shown that EphA2 contains multiple peptide epitopes that can be recognized by effector CD4(+) and CD8(+) T cells isolated from tumor-bearing patients. Herein, we show that "agonist" reagents that trigger the proteasome-dependent degradation of tumor cell EphA2 result in the improved presentation of peptides derived from (both the extracellular and intracellular domains of) EphA2 in MHC class I complexes expressed on the tumor cell membrane for at least 48 h, as manifested by increased recognition by EphA2-specific CD8(+) T cells in vitro. We also observed that while delivery of ephrinA1-Fc fusion protein or agonist mAb into EphA2(+) tumor lesions promotes EphA2 degradation in situ, this single administration of agent does not dramatically alter tumor progression in a humanized SCID model. However, when combined with the adoptive transfer of normally nontherapeutic (human) anti-EphA2 CD8(+) CTL, this dual-agent regimen results in complete tumor eradication. These results suggest that strategies targeting the conditional proteasome-mediated destruction of tumor cell EphA2 may enable EphA2-specific CD8(+) T cells (of modest functional avidity) to realize improved therapeutic potential.

Preferential expression of very late antigen-4 on type 1 CTL cells plays a critical role in trafficking into central nervous system tumors.

We have previously shown preferential tumor-homing and therapeutic efficacy of adoptively transferred type 1 CTL (Tc1) when compared with type 2 CTL (Tc2) in mice bearing intracranial ovalbumin-transfected melanoma (M05). Further characterizing the expression of a panel of homing receptors on Tc1 and Tc2 cells, we found that very late antigen (VLA)-4 (a heterodimer of CD49d and CD29), but none of other receptors evaluated, was expressed at significantly higher levels on Tc1 cells than on Tc2 cells. Although CD49d (alpha(4) integrin) can form heterodimers with both beta(1) (CD29) and beta(7) integrins, alpha(4)beta(7) complexes were not expressed by either Tc1 or Tc2 cells, suggesting that CD49d is solely expressed in VLA-4 complexes. VLA-4 expression on Tc2 cells was down-regulated in an interleukin (IL)-4 dose-dependent manner but not by other type 2 cytokines, such as IL-10 and IL-13, suggesting that IL-4 uniquely down-regulates VLA-4 expression on these cells. In accordance with the differential expression of VLA-4 on Tc1 versus Tc2 cells, Tc1 cells alone were competent to adhere to plate-bound VCAM-1-Ig fusion protein. Finally, the efficient trafficking of Tc1 cells into intracranial M05 lesions in vivo was efficiently blocked by administration of monoclonal antibodies against CD49d or VCAM-1 or small interfering RNA-mediated silencing of CD49d on Tc1 cells. Collectively, these data support the critical role of VLA-4 in the effective intracranial tumor homing of adoptive-transferred, antigen-specific Tc1 cells and suggest that more effective vaccine and/or ex vivo T-cell activation regimens may be developed by promoting the generation of VLA-4(+) antitumor Tc1 cells.

Granuloma eosinófilo: presentación de un paciente de nueve años de edad con lesión frontal única / Eosinophilic granuloma: presentation in a 9 year old patient with a solitary frontal lesion

Presentamos un caso de granuloma eosinófilo del hueso frontal en un niño de 9 años de edad: caracterizado radiológicamente por lesión única destructiva de 3.5cm de diámetro con bordes irregulares comprometiendo ambas tablas óseas del cráneo. Esta lesión es el único signo de presentación de nuestro caso. La lesión fue confirmada por tomografía computarizada y Gammagrafía con Tc-99. La biopsia abierta de la lesión reveló histopatológicamente cuadro de granuloma eosinófilo