A synthetic peptide homologous to IL-10 functional domain induces monocyte differentiation to TGF-ß+ tolerogenic dendritic cells.

We have previously demonstrated that IT9302, a nonameric peptide homologous to the C-terminal domain of human IL-10, mimics several effects of the cytokine including down-regulation of the antigen presentation machinery and increased sensitivity of tumor cells to NK-mediated lysis. In the present report, we have explored a potential therapeutic utility for IT9302 related to the ex vivo production of tolerogenic dendritic cells (DCs). Our results indicate that IT9302 impedes human monocyte response to differentiation factors and reduces antigen presentation and co-stimulatory capacity by DCs. Additionally, peptide-treated DCs show impaired capacity to stimulate T-cell proliferation and IFN-γ production. IT9302 exerts its effect through mechanisms, in part, distinct from IL-10, involving STAT3 inactivation and NF-κB intracellular pathway. IT9302-treated DCs display increased expression of membrane-associated TGF-ß, linked to a more effective induction of foxp3+ regulatory T cells. These results illustrate for the first time that a short synthetic peptide can promote monocytes differentiation to tolerogenic DCs with therapeutic potential for the treatment of autoimmune and transplantation-related immunopathologic disease.

The effects of montelukast on tissue inflammatory and bone marrow responses in murine experimental allergic rhinitis: interaction with interleukin-5 deficiency.

The cysteinyl leukotrienes (cysLTs) are potent lipid mediators in allergic disease, acting through the receptors, cysLT1R and cysLTR2, and are produced by eosinophils derived from eosinophil/basophil (Eo/B) bone marrow (BM) progenitors. We have demonstrated the suppressive effects of either interleukin-5 (IL-5) deficiency or montelukast on eosinophil recruitment in murine allergic rhinitis, but neither of them fully abrogated the symptoms caused by residual inflammation and cytokine redundancy in eliciting BM Eo/B responses. We hypothesized that IL-5 deficiency and montelukast act synergistically to suppress tissue inflammatory and BM responses. Our objective was to investigate the effects of the cysLT1R antagonist, montelukast, on in vivo tissue inflammatory and BM responses in murine experimental allergic rhinitis with or without IL-5 deficiency. Three groups of age-matched BALB/c mice with or without IL-5 deficiency were tested: controls (ovalbumin sensitization and challenge, placebo treatment) and two montelukast-treated groups (2.5 mg/kg or 5 mg/kg). Nasal symptoms, BM and nasal mucosal eosinophils, basophils, and BM Eo/B colony-forming units (CFU) were evaluated. Montelukast decreased nasal symptoms in a dose-dependent manner, and significantly decreased the number of eosinophils in both BM and nasal tissue in IL-5-replete mice compared to controls. In IL-5-deficient mice, in which eosinophilia was absent, montelukast significantly decreased both nasal symptoms and basophils in BM and nasal mucosal tissue, and lowered IL-5-responsive Eo/B-CFU ex vivo, compared to controls. The addition of cysLT1R blockade to IL-5 deficiency more fully attenuates symptoms and upper airway inflammation than either factor alone, providing evidence of systemic, BM mechanisms in allergic rhinitis.

[Prevalence of latex hypersensitivity in operating room workers of the University of Chile Clinical Hospital]. / Prevalencia de sensibilización a látex en personal de pabellones quirúrgicos del Hospital Clínico de la Universidad de Chile.

BACKGROUND: Health care workers (HCW) are a high risk group for developing natural rubber latex (NRL) hypersensitivity and allergy. Some studies showed a correlation between time and frequency of exposure to NRL gloves and hypersensitivity, but a recent meta-analysis showed no clear evidences for such assumption. AIM: To determine the prevalence of NRL hypersensitivity and allergy in a group of HCW at the University of Chile Clinical Hospital. MATERIALS AND METHODS: Ninety five HCW (aged 37+/-10 years, 59 females) were interviewed about time of exposure, atopic diseases and latex-related allergy symptoms. Different NRL extracts and seven NRL gloves brands were tested by the prick test method. RESULTS: Twenty four workers (25%, 95% CI = 16.9%-35.2%) were sensitized. No gender differences were found. No symptomatic cases were found in the sensitized group. In the workplace, six and two non sensitized subjects had respiratory symptoms or contact urticaria, respectively. Sensitivity to bananas, avocadoes, kiwi and chestnut was not significantly more common among latex sensitive individuals. No differences between sensitized and non sensitized subjects were observed for the presence of atopic diseases or the mean number of years at the workplace. The sensitization rate to NRL increased along with years of work, from 18.6% in patients working less than 10 years, to 28.1% in the group between 10 and 20 years and to 35% in those working more than 21 years (p=0.693). Sensitization was also related to the weekly hours of exposure: 1-10 hours, 17%; 11-20 hours, 23.5%; 21-30 hours, 50% and 31-40 hours, 28.5% (p=0.036). CONCLUSIONS: Sensitization increased proportionally to the years and weekly hours wearing NLR gloves. We did not find symptomatic patients in the sensitized group.

Asertividad en el diagnóstico clínico de los tumores cutáneos / Assessment of clinical diagnostic accuracy for skin cancer

Background: There is an increase in the incidence rates of skin cancer in Chile. Aim: To study the clinical diagnostic accuracy (CDA) for skin cancer. Material y methods: CDA was defined as the percentage of agreement between clinical and pathological diagnosis. Approximately 600,000 pathological reports from five hospitals in Santiago were reviewed. A total of 2,593 skin tumours; 230 Malignant Melanoma (MM); 412 Squamous Cell Carcinoma (SCC) and 1,951 Basal Cell Carcinoma (BCC) were studied. These tumours were clinically diagnosed and surgically treated by dermatologists. The CDA was studied for each tumour, by the anatomical localization of the tumour, Breslow Index in MM, by age and sex of the patient. Results: The highest CDA was observed for BCC (76.2%); followed by MM (64.3%) and SCC (34.7%). By anatomical localization, for MM the highest CDA was observed in the soles (p <0.05); for BCC, the hightest CDA was in the face (p <0.05). No significant differences were observed in SCC. By age, for MM, the CDA was higher in patients aged less than 50 years. No differences in CDA by age were observed in the other two tumours. By sex, no differences were found. A higher CDA was found in MM with Breslow indexes III and IV than for MM with Breslow indexes I and II. Conclusions: CDA is affected by the clinical variables analyzed in this study. A more accurate clinical diagnosis of skin cancer could be obtained taking into account these variables (Rev Méd Chile 2003; 131: 1421-7).

[Assessment of clinical diagnostic accuracy for skin cancer]. / Asertividad en el diagnóstico clínico de los tumores cutáneos.

BACKGROUND: There is an increase in the incidence rates of skin cancer in Chile. AIM: To study the clinical diagnostic accuracy (CDA) for skin cancer. MATERIAL AND METHODS: CDA was defined as the percentage of agreement between clinical and pathological diagnosis. Approximately 600,000 pathological reports from five hospitals in Santiago were reviewed. A total of 2,593 skin tumours; 230 Malignant Melanoma (MM); 412 Squamous Cell Carcinoma (SCC) and 1,951 Basal Cell Carcinoma (BCC) were studied. These tumours were clinically diagnosed and surgically treated by dermatologists. The CDA was studied for each tumour, by the anatomical localization of the tumour, Breslow Index in MM, by age and sex of the patient. RESULTS: The highest CDA was observed for BCC (76.2%); followed by MM (64.3%) and SCC (34.7%). By anatomical localization, for MM the highest CDA was observed in the soles (p < 0.05); for BCC, the highest CDA was in the face (p < 0.05). No significant differences were observed in SCC. By age, for MM, the CDA was higher in patients aged less than 50 years. No differences in CDA by age were observed in the other two tumours. By sex, no differences were found. A higher CDA was found in MM with Breslow indexes III and IV than for MM with Breslow indexes I and II. CONCLUSIONS: CDA is affected by the clinical variables analyzed in this study. A more accurate clinical diagnosis of skin cancer could be obtained taking into account these variables.

Perfil epidemiológico de los tumores testiculares tratados en el Hospital Clínico de la Universidad de Chile: 1992-1999 / Epidemiological profile of testicular cancers treated in the Universidad de Chile Clinical Hospital: 1992-1999

El carcinoma testicular es la neoplasia sólida maligna más común en hombres entre 15 y 35 años. Su incidencia en Chile es desconocida. Anualmente fallecen en Chile unos 100 pacientes por esta patología, duplicándose su mortalidad en los últimos 30 años. El objetivo de este trabajo es caracterizar clínicamente a los pacientes tratados por el diagnóstico de cáncer testicular. Es un estudio descriptivo, retrospectivo, de una muestra de 244 pacientes con diagnóstico de cáncer testicular tratados en el Servicio de Urología del Hospital J.J. Aguirre, entre los años 1992 y 1999. Se analizó edad, antecedente de criptorquidia, lado afectado, presentación clínica, tiempo de latencia en consultar e histología. El promedio de edad fue de 30 años, con 84 por ciento menor de 35 años. Un 4 por ciento fue bilateral, un 50 por ciento izquierdo y 46 por ciento derecho. Un 50 por ciento se presentó con aumento de volumen indoloro, un 38 por ciento aumento de volumen doloroso, un 6 por ciento dolor sin aumento de volumen y un 6 por ciento presentó manifestaciones metastásicas. El tiempo promedio de latencia en la consulta fue de 14,5 semanas. El análisis histológico reveló 38 por ciento de seminomas, 34 por ciento de tumores no seminomas y 28 por ciento de histología mixta. Se concluye que los cánceres testiculares afectan a la población joven. Son predominantemente unilaterales. El aumento de volumen gonadal está presente en cerca de un 88 por ciento de los casos. El autoexamen podría constituir un importante método de screening. Se debe realizar una campaña de educación dirigida a promover el autoexamen y a motivar una consulta precoz, disminuyendo los tiempos de latencia y por consiguiente mejorando el pronóstico

Perfil epidemiológico del melanoma maligno en el Hospital San Juan de Dios / Epidemiologic profile of the malignan melanoma in the San Juan de Dios Hospital

Durante la última década se ha registrado un considerable incremento en la incidencia del cáncer cutáneo en el ámbito mundial. En Chile, como en el resto de Latinoamérica, existen pocos estudios respecto a la epidemiología del cáncer cutáneo. En nuestra serie se analizan retrospectivamente 64 casos de melanoma maligno, observados en el Hospital San Juan de Dios durante el período comprendido entre enero de 1992 hasta enero de 1999

Tratamiento quirúrgico del melanoma maligno: revisión de 44 casos / Surgical treatment of malignant melanoma: review of 44 cases

La incidencia del melanoma maligno cutáneo está en incremento sostenido en todo el mundo como consecuencia de varios factores demográficos: exposición a la luz solar, disminución de la capa de ozono, mayor tendencia a deportes al aire libre y prolongación del promedio de vida de la población entre otros. Los factores más significativos en el pronóstico son: etapa de la enfermedad, espesor de la lesión grado de crecimiento vertical, sitio anatómico, ulceración y hemorragia, edad, sexo, forma de tratamiento. Se presenta un estudio descriptivo en relación con el tratamiento en un período de 8 años (1992-1999) de 44 pacientes. En ellos se estudiaron variables de edad, sexo, grado, grado de exposición solar, antecedentes familiares correlacionados, características clínicas de la lesión, tratamiento y recidiva. Los resultados se exponen en relación a las características señaladas. Se destaca la necesidad de hacer un registro minuciso de las características demográficas, epidemiológicas y clínicas así como un seguimiento controlado de los pacientes. Se señala las características del tratamiento quirúrgico y la necesidad de implementar el estudio del linfonodo centinela y linfocintigrafía

Hipocratismo digital: un indicador de enfermedad subyacente / Digital hippocratism: indicator of an underlying disease

El hipocratismo digital es un signo semiológico relativamente frecuente, pero que suele pasar inadvertido en sus formas leves o incipientes. Su aparición es un indicador de patologías orgánicas subyacentes especialmente pleuropulmonares, cardíacas e intestinales. Se describen las características semiológicas del hipocratismo y sus principales posibles causas y mecanismos etiopatogénicos