Deroofing: A safe, effective and well-tolerated procedure in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a recurrent, debilitating, chronic disorder of the pilosebaceous unit. Although advances in HS treatment have been made, more than 45% of patients remain dissatisfied with systemic treatment, and more than one-third are dissatisfied with surgical procedures. OBJECTIVES: A prospective, observational study on the deroofing procedures in HS with special attention paid to patient satisfaction and complications. METHODS: HS lesions were assessed clinically and by the use of ultrasound. Patients reported outcomes, including pain, itch and satisfaction, were measured at 24 h post-surgery by a numeric rating scale (NRS) ranging from 0 to 10. Additionally, the timeline of objective wound closure reported by patients in (weeks), in addition to the need for any analgesics use, were both evaluated. RESULTS: The mean closure time of the post-deroofing wound was assessed as 4.4 ± 1.9 weeks. A statistically longer time was necessary for complete closure in males than in females (4.9 ± 2.2 weeks and 3.9 ± 1.6 weeks, respectively; p = 0.046). The closure time correlated positively yet weakly with the HS tunnel's width (r = 0.27, p = 0.016) and length (r = 0.228, p = 0.044). Patients assessed mean pain at 24 h post-op as mild with 0.7 ± 1.2 points according to NRS, with no differences between sexes. Similarly, itch in the first 24 h was assessed as mild with 1.8 ± 1.1 points, without differences between sexes. No pain, itch or adverse events were reported after 1 week following deroofing. Moreover, no cases of wound infection were reported. An overall patient satisfaction was assessed as 9.9 ± 0.4 points (range 9-10 points). CONCLUSION: Deroofing is an easy, effective and safe dermatosurgical procedure that does not require surgical experience or operating theatre. It is associated with no complications and very low post-op pain and should be part of holistic HS management.

Defining hidradenitis suppurativa phenotypes based on the elementary lesion pattern: results of a prospective study.

BACKGROUND: It has been proposed that two main phenotypes of hidradenitis suppurativa (HS) exist. This proposal is based upon different elementary structures detected in the skin, namely follicular subtypes and inflammatory subtypes. Having an accurate definition of these two variants could help us to better identify patients who may require an early intervention with currently approved targeted immunomodulatory therapies. OBJECTIVE: To define and distinguish between the epidemiological, clinical and analytic characteristics of these two HS phenotypes. METHODS: An observational, descriptive, non-randomized and prospective study was conducted. Patients diagnosed with HS between May 2012 and April 2017 by a specialized unit were included. Ultrasound evaluation was performed in all cases. RESULTS: About 197 patients were included, 100 women and 97 men, aged between 25 and 47 years. The mean age of onset was significantly different between phenotypes, ranging between 26.69 ± 9.05 in the inflammatory subtype and 17.62 ± 6.42 in the follicular subtype. Follicular subtype patients exhibited a significantly higher number of nodules combined with the presence of multiple commedons (5.65 ± 3.38 versus 0.89 ± 2.72). This contrasted with the higher count of abscesses and fistulas detected in the inflammatory subtype (respectively, 4 ± 2.74 and 3.11 ± 2.56 versus 0.56 ± 1.02 and 0.26 ± 0.56). IgA levels were significantly higher in the inflammatory subtype (497.71 ± 262.26 versus 232.38 ± 84.06). Mean IHS4 score evaluation was higher in the inflammatory subtype (21.04 ± 11.9) compared with the follicular phenotype (7.54 ± 4.66). The inflammatory subtype was found to be an independent risk factor for disease aggressiveness in the multivariate analysis (OR 0.034 [95% CI 0.015-0.072]). LIMITATIONS: Small sample size. CONCLUSION: Preliminary data suggest the existence of an inflammatory HS phenotype that is associated with higher aggressiveness and major risk of progression during natural history of the disease.

Lesiones eccematosas y cuadro ictiosiforme adquirido como forma de presentación de un linfoma anaplásico de células grandes CD30+ / Eczematous lesions and acquired ichthyosis as a presenting finding of CD30+ anaplastic large cell lymphoma

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La utilidad de la nitroglicerina tópica al 0, 2% en la condrodermatitis nodular del hélix / The Usefulness of 0. 2% Topical Nitroglycerin for Chondrodermatitis Nodularis Helicis

INTRODUCCIÓN: La condrodermatitis nodular del hélix (CNH) es un proceso idiopático, degenerativo y doloroso que afecta a la piel y al cartílago del hélix o del antéhelix. Recientemente se ha descrito la utilidad de la nitroglicerina (NTG) tópica a 2% en el tratamiento de la CNH con buenos resultados, aunque con una tasa de efectos secundarios en el 17% de los casos. Es probable que a una concentración menor se pueda mantener el mismo efecto mejorando la tolerancia. Nuestra finalidad fue evaluar la efectividad y seguridad de la NTG tópica al 0,2% para el tratamiento de la CNH. MATERIAL Y MÉTODOS: Se llevó a cabo un estudio observacional retrospectivo entre los años 2012 y 2014 en 2 centros hospitalarios españoles. La efectividad se determinó a través de la evaluación clínica, realizada mediante seguimiento fotográfico, y de los síntomas de la lesión, medido mediante una escala numérica verbal. RESULTADOS: Veintinueve pacientes recibieron el tratamiento, de los cuales el 93% manifestaron una mejoría clínica con una duración media del tratamiento de 1,8 meses y un tiempo de seguimiento medio en los pacientes respondedores de 5,9 meses. La tolerancia fue buena en general en todos los casos. CONCLUSIÓN: La NTG tópica al 0,2% se plantea como una opción conservadora, efectiva y bien tolerada para el tratamiento de la condrodermatitis nodular del hélix que mejora tanto la apariencia clínica como la sintomatología en la mayoría de los pacientes

BACKGROUND AND OBJECTIVE: Chondrodermatitis nodularis helicis (CNH) is a painful idiopathic degenerative condition involving the skin and cartilage of the helix or antihelix of the ear. Topical nitroglycerin 2% is a relatively recent treatment option for CNH that has produced good results, although with adverse effects (17% of cases). The use of a lower concentration would probably achieve similar results with fewer adverse effects. The aim of this study was to evaluate the effectiveness and safety of topical nitroglycerin 0.2% in the treatment of CNH. MATERIAL AND METHODS: We performed a retrospective observational study of patients treated in 2 Spanish hospitals between 2012 and 2014. The effectiveness of treatment was determined by clinical photography and assessment of symptoms using a verbal numerical rating scale. RESULTS: Of the 29 patients treated, 93% showed clinical improvement. In the group of responders, mean treatment duration was 1.8 months and mean follow-up was 5.9 months. Overall tolerance was good in all cases. CONCLUSION: Topical nitroglycerin 0.2% is an effective and well-tolerated conservative treatment option that improves the appearance of lesions and provides symptomatic relief in the majority of patients with CNH

The Usefulness of 0.2% Topical Nitroglycerin for Chondrodermatitis Nodularis Helicis.

BACKGROUND AND OBJECTIVE: Chondrodermatitis nodularis helicis (CNH) is a painful idiopathic degenerative condition involving the skin and cartilage of the helix or antihelix of the ear. Topical nitroglycerin 2% is a relatively recent treatment option for CNH that has produced good results, although with adverse effects (17% of cases). The use of a lower concentration would probably achieve similar results with fewer adverse effects. The aim of this study was to evaluate the effectiveness and safety of topical nitroglycerin 0.2% in the treatment of CNH. MATERIAL AND METHODS: We performed a retrospective observational study of patients treated in 2 Spanish hospitals between 2012 and 2014. The effectiveness of treatment was determined by clinical photography and assessment of symptoms using a verbal numerical rating scale. RESULTS: Of the 29 patients treated, 93% showed clinical improvement. In the group of responders, mean treatment duration was 1.8 months and mean follow-up was 5.9 months. Overall tolerance was good in all cases. CONCLUSION: Topical nitroglycerin 0.2% is an effective and well-tolerated conservative treatment option that improves the appearance of lesions and provides symptomatic relief in the majority of patients with CNH.

Parche biosintético de colágeno porcino como herramienta coadyuvante o definitiva en el cierre de defectos del cuero cabelludo sin periostio / Biosynthetic Porcine Collagen Dressings as an Adjunct or Definitive Tool for the Closure of Scalp Defects Without Periosteum

Introducción: Los carcinomas cutáneos agresivos que aparecen en el cuero cabelludo se desarrollan habitualmente en pacientes de edad avanzada que presentan múltiples comorbilidades. La exéresis completa de estos tumores incluye en muchos casos el periostio, lo que conlleva que la reconstrucción de este tipo de defectos se convierta en un reto. Objetivo: Se evalúa la utilidad de un parche de colágeno porcino tipo I como tratamiento coadyuvante o definitivo en el cierre quirúrgico de este tipo de defectos cutáneos. Material y métodos: Se realizó un estudio prospectivo en el que se incluyeron aquellos pacientes que presentaron defectos de más de 5 cm en el cuero cabelludo, en los que el periostio tuvo que ser extirpado para alcanzar márgenes libres de enfermedad entre enero de 2009 y noviembre de 2011. Resultados: La tumoración más prevalente fue el carcinoma epidermoide cutáneo recurrente. El defecto posquirúrgico osciló entre 5 y 7cm de diámetro. En el grupo de casos en los que se colocó un injerto posparche (n=4), en el 100% de los casos el tejido prendió completamente. En el caso de aquellos pacientes en los que el parche fue el recurso definitivo (n=6) el tejido de granulación generado por el material biosintético de colágeno porcino ocupó el defecto quirúrgico, dejándolo completamente restituido en aproximadamente 3,5 meses. Conclusiones: El parche de colágeno porcino tipo i es una herramienta sencilla, barata y eficaz en el tratamiento coadyuvante o definitivo del cierre de defectos quirúrgicos del cuero cabelludo de más de 5cm que carecen de periostio (AU)

Background: Aggressive carcinomas of the scalp usually occur in elderly patients with multiple comorbidities. Complete excision of this type of tumor often involves the removal of periosteum, and the resulting defects can be difficult to reconstruct. Objective: To evaluate the usefulness of porcine type I collagen dressings as adjunct or definitive treatment in the surgical closure of scalp defects without periosteum. Materials and methods: We performed a prospective study between January 2009 and November 2011 of patients with scalp defects larger than 5 cm resulting from surgery that required the removal of periosteum to obtain tumor-free margins. Results: The most prevalent type of tumor was recurrent cutaneous squamous cell carcinoma. The surgical defects ranged in diameter from 5 to 7 cm. In 100% of the patients who received a graft after dressing removal (n = 4), the graft took well. In the patients in whom the biosynthetic dressing was definitive (n = 6), granulation tissue filled the defect and complete closure was achieved in approximately 3.5 months. Conclusions: The use of porcine type I collagen dressings as an adjunct or definitive tool for the closure of surgical defects on the scalp measuring more than 5 cm in which periosteum has been removed proved to be simple, inexpensive, and effective (AU)

Biosynthetic porcine collagen dressings as an adjunct or definitive tool for the closure of scalp defects without periosteum.

BACKGROUND: Aggressive carcinomas of the scalp usually occur in elderly patients with multiple comorbidities. Complete excision of this type of tumor often involves the removal of periosteum, and the resulting defects can be difficult to reconstruct. OBJECTIVE: To evaluate the usefulness of porcine type I collagen dressings as adjunct or definitive treatment in the surgical closure of scalp defects without periosteum. MATERIALS AND METHODS: We performed a prospective study between January 2009 and November 2011 of patients with scalp defects larger than 5cm resulting from surgery that required the removal of periosteum to obtain tumor-free margins. RESULTS: The most prevalent type of tumor was recurrent cutaneous squamous cell carcinoma. The surgical defects ranged in diameter from 5 to 7cm. In 100% of the patients who received a graft after dressing removal (n=4), the graft took well. In the patients in whom the biosynthetic dressing was definitive (n=6), granulation tissue filled the defect and complete closure was achieved in approximately 3.5 months. CONCLUSIONS: The use of porcine type I collagen dressings as an adjunct or definitive tool for the closure of surgical defects on the scalp measuring more than 5cm in which periosteum has been removed proved to be simple, inexpensive, and effective.

Biosynthetic Porcine Collagen Dressings as an Adjunct or Definitive Tool for the Closure of Scalp Defects Without Periosteum. / Parche biosintético de colágeno porcino como herramienta coadyuvante o definitiva en el cierre de defectos del cuero cabelludo sin periostio.

BACKGROUND: Aggressive carcinomas of the scalp usually occur in elderly patients with multiple comorbidities. Complete excision of this type of tumor often involves the removal of periosteum, and the resulting defects can be difficult to reconstruct. OBJECTIVE: To evaluate the usefulness of porcine type I collagen dressings as adjunct or definitive treatment in the surgical closure of scalp defects without periosteum. MATERIALS AND METHODS: We performed a prospective study between January 2009 and November 2011 of patients with scalp defects larger than 5cm resulting from surgery that required the removal of periosteum to obtain tumor-free margins. RESULTS: The most prevalent type of tumor was recurrent cutaneous squamous cell carcinoma. The surgical defects ranged in diameter from 5 to 7cm. In 100% of the patients who received a graft after dressing removal (n=4), the graft took well. In the patients in whom the biosynthetic dressing was definitive (n=6), granulation tissue filled the defect and complete closure was achieved in approximately 3.5 months. CONCLUSIONS: The use of porcine type I collagen dressings as an adjunct or definitive tool for the closure of surgical defects on the scalp measuring more than 5cm in which periosteum has been removed proved to be simple, inexpensive, and effective.

Lesión quística peneana tras administración intramuscular de testosterona / Penile cystic lesion after intramuscular testosterone injection

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Ensayo clínico: la infiltración intralesional con metotrexato de forma neoadyuvante en la cirugía del queratoacantoma permite obtener mejores resultados estéticos y funcionales / Intralesional Infusion of Methotrexate as Neoadjuvant Therapy Improves the Cosmetic and Functional Results of Surgery to Treat Keratoacanthoma: Results of a Randomized Trial

Introducción: El queratoacantoma es considerado hoy día un carcinoma epidermoide in situ que aparece principalmente en pacientes mayores de 70 años. Se trata de un tumor de buen pronóstico que, en algunos casos, muestra resolución espontánea.El tratamiento de este tipo de tumoración es la exéresis simple. Sin embargo, la localización preferente en las regiones facial y acral, el tamaño y su rápido crecimiento son factores que hacen que la cirugía sea en algunos casos agresiva y antiestética. Objetivo: El objetivo principal del estudio es evaluar la eficacia de la infiltración intralesional de metotrexato en la reducción del tamaño prequirúrgico de la lesión y del correspondiente defecto quirúrgico resultante de la intervención. Material y métodos: Se realizó un estudio prospectivo aleatorizado en el que se incluyeron todos aquellos pacientes atendidos en nuestro Servicio diagnosticados de queratoacantoma de al menos 1,5cm de tamaño entre enero de 2009 y enero de 2010. Se establecieron dos grupos, uno en el que los pacientes recibieron una infiltración de metotrexato previamente al acto quirúrgico y otro en el que se realizó directamente la cirugía. Resultados: De los 25 pacientes incluidos en el estudio, 10 casos recibieron neoadyuvancia con metotrexato intralesional (grupo A) y 15 casos fueron intervenidos mediante cirugía aislada (grupo B).Los pacientes del grupo A mostraron una reducción en el tamaño tumoral en el momento de la cirugía que osciló entre un 50 y un 80%. Ninguno de los pacientes presentó complicaciones relacionadas con la inoculación del metotrexato ni con la intervención quirúrgica. En el grupo B sólo uno de los casos mostró una discreta disminución de sus dimensiones en el momento del acto quirúrgico. El resto de las lesiones mostraron una estabilidad (4 casos; 26%) e incluso un aumento de las dimensiones del tumor (10 casos; 66%) en el momento de la intervención. Cinco de los casos incluidos en este último grupo requirieron ingreso hospitalario en relación con la intervención quirúrgica. Conclusiones: El metotrexato intralesional como terapia neoadyuvante es una medida bien tolerada, que permite evitar cirugías agresivas en pacientes de edades avanzadas que presentan un queratoacantoma de diámetro superior a 1,5cm localizado en la región facial y acral (AU)

Background: Keratoacanthoma is currently considered to be an in situ squamous cell carcinoma that mainly affects patients over 70 years of age. The tumor has a good prognosis and, in some cases, can resolve spontaneously. Treatment involves simple excision. However, since the tumors generally occur on the face or extremities and display rapid growth, aggressive surgery may be required and the cosmetic results may be poor. Objective: The primary study objective was assessment of the efficacy of presurgical intralesional methotrexate infiltration to reduce the size of the tumor and the corresponding surgical defect. Material and methods: A prospective, randomized study was undertaken in patients with a diagnosis of keratoacanthoma of at least 1.5cm who were seen in our service between January 2009 and January 2010. Two groups were established: one receiving a single infiltration of methotrexate prior to surgery and another that did not receive methotrexate. Results: Of the 25 patients included in the study, 10 received neoadjuvant intralesional methotrexate (group A) and 15 underwent surgery without prior infiltration of methotrexate (group B). The patients in group A displayed a reduction of between 50% and 80% in the size of the lesion prior to surgery. No complications were observed either in relation to methotrexate infusion or surgery. In group B, only 1 patient had a slight reduction in the dimensions of the lesion prior to surgery. In the remaining cases, the lesions remained similar (4 cases, 26%) or had increased in size (10 cases, 66%) at the time of surgery. Five patients in this group required hospital admission following surgery. Conclusions: Neoadjuvant intralesional methotrexate is well tolerated and reduces the need for aggressive surgery in elderly patients with keratoacanthoma measuring more than 1.5cm on the face or extremities (AU)

[Intralesional infusion of methotrexate as neoadjuvant therapy improves the cosmetic and functional results of surgery to treat keratoacanthoma: results of a randomized trial]. / Ensayo clínico: la infiltración intralesional con metotrexato de forma neoadyuvante en la cirugía del queratoacantoma permite obtener mejores resultados estéticos y funcionales.

BACKGROUND: Keratoacanthoma is currently considered to be an in situ squamous cell carcinoma that mainly affects patients over 70 years of age. The tumor has a good prognosis and, in some cases, can resolve spontaneously. Treatment involves simple excision. However, since the tumors generally occur on the face or extremities and display rapid growth, aggressive surgery may be required and the cosmetic results may be poor. OBJECTIVE: The primary study objective was assessment of the efficacy of presurgical intralesional methotrexate infiltration to reduce the size of the tumor and the corresponding surgical defect. MATERIAL AND METHODS: A prospective, randomized study was undertaken in patients with a diagnosis of keratoacanthoma of at least 1.5 cm who were seen in our service between January 2009 and January 2010. Two groups were established: one receiving a single infiltration of methotrexate prior to surgery and another that did not receive methotrexate. RESULTS: Of the 25 patients included in the study, 10 received neoadjuvant intralesional methotrexate (group A) and 15 underwent surgery without prior infiltration of methotrexate (group B). The patients in group A displayed a reduction of between 50% and 80% in the size of the lesion prior to surgery. No complications were observed either in relation to methotrexate infusion or surgery. In group B, only 1 patient had a slight reduction in the dimensions of the lesion prior to surgery. In the remaining cases, the lesions remained similar (4 cases, 26%) or had increased in size (10 cases, 66%) at the time of surgery. Five patients in this group required hospital admission following surgery. CONCLUSIONS: Neoadjuvant intralesional methotrexate is well tolerated and reduces the need for aggressive surgery in elderly patients with keratoacanthoma measuring more than 1.5 cm on the face or extremities.

[Metastatic Basal cell carcinoma in the axilla: reconstruction with a lateral pectoral island flap]. / Carcinoma basocelular metastásico en la axila: reconstrucción mediante un colgajo en isla pectoral lateral.

Although basal cell carcinoma (BCC) is one of the most common forms of cancer worldwide, it rarely occurs in the axilla. Only 31 cases have been reported in the literature. The incidence of metastatic BCC, particularly in areas not exposed to the sun, is very low. We present a new case of axillary BCC with lymph node metastases and the results of an extensive review of cases previously reported in the literature. BCC in the axilla is rare and metastasis is exceptional. Factors other than UV radiation probably contribute to its development. The lateral pectoral island flap was used for surgical closure. This method is useful for the reconstruction of axillary defects, obtaining excellent cosmetic and functional results. This flap should therefore be considered for the repair of large surgical defects in the axilla.

Carcinoma basocelular metastásico en la axila: reconstrucción mediante un colgajo en isla pectoral lateral / Metastatic Basal Cell Carcinoma in the Axilla: Reconstruction with a Lateral Pectoral Island Flap

A pesar de que el carcinoma basocelular (CBC) es una de las formas más comunes de cáncer, esta neoplasia cutánea raramente ocurre en la axila, con sólo 31 casos recogidos en la literatura. La incidencia del CBC metastásico es excepcional, siendo aún más infrecuente en áreas no fotoexpuestas. Se presenta un nuevo caso de CBC axilar con metástasis nodal y se realiza una revisión extensa de la literatura de aquellos casos publicados previamente. El CBC localizado en la axila es un raro evento, pero el desarrollo de metástasis es excepcional. Otros factores diferentes a la radiación ultravioleta probablemente contribuyan a su desarrollo. El colgajo en la isla pectoral lateral fue la técnica aplicada en el cierre quirúrgico. Este resulta útil en la reconstrucción de defectos quirúrgicos axilares y obtiene excelentes resultados tanto estéticos como funcionales. Por estas razones, la realización de este colgajo debería considerarse ante importantes defectos quirúrgicos en la región axilar (AU)

Although basal cell carcinoma (BCC) is one of the most common forms of cancer worldwide, it rarely occurs in the axilla. Only 31 cases have been reported in the literature. The incidence of metastatic BCC, particularly in areas not exposed to the sun, is very low. We present a new case of axillary BCC with lymph node metastases and the results of an extensive review of cases previously reported in the literature.BCC in the axilla is rare and metastasis is exceptional. Factors other than UV radiation probably contribute to its development. The lateral pectoral island flap was used for surgical closure. This method is useful for the reconstruction of axillary defects, obtaining excellent cosmetic and functional results. This flap should therefore be considered for the repair of large surgical defects in the axilla (AU)

Role of different inflammatory and tumor biomarkers in the development of ulcerative colitis-associated carcinogenesis.

BACKGROUND: Colorectal cancer (CRC) is the most severe complication in inflammatory bowel disease (IBD). In the present study we investigated different mechanistic links between chronic colonic inflammation and its progression to adenocarcinoma. Along these lines, given that adrenomedullin (AM) has been implicated in carcinogenesis, we also analyzed changes in its colonic expression. METHODS: Mice were exposed to 5, 10, and 15 cycles of dextran sulfate sodium (DSS); each cycle consisted of 0.7% DSS for 1 week followed by distilled water for 10 days. After each period, macroscopic and histological studies, as well as characterization of inflammatory and tumor biomarkers, were carried out. RESULTS: The disease activity index (DAI) showed that the disease was present from the third cycle and it gradually increased during the course of DSS treatment. Macroscopic tumors were only seen after 15 cycles, and microscopic study showed that inflammation, dysplasia, and adenocarcinomas correlated with DSS cycles. ß-Catenin and proliferating cell nuclear antigen expressions progressively increased in animals treated with the different cycles of DSS. TNF-α and IFN-γ showed the highest production at the tenth cycle. COX-2, mPGES-1, and iNOS levels were also appreciably higher at the fifth and tenth cycles. Moreover, we observed a progressive enhancement in AM expression and changes in its intracellular location during the progression of the disease. CONCLUSIONS: Our results show an early induction of proinflammatory factors, which may contribute to the development of colon cancer, as well as demonstrate, for the first time, the expression of AM in IBD-derived CRC.

Extra-virgin olive oil-enriched diet modulates DSS-colitis-associated colon carcinogenesis in mice.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk for developing ulcerative colitis (UC)-associated colorectal cancer (CRC). Several studies have shown that extra virgin olive oil (EVOO) might possess anti-inflammatory, antiproliferative and antiapoptotic effects. We have evaluated EVOO diet effects on the severity of repeated colitis-associated CRC. METHODS: Six-week-old C57BL/6 mice were randomized into two dietary groups: sunflower oil (SFO) and EVOO diets, both at 10%. Mice were exposed to 15 cycles of 0.7% dextran sodium sulphate (DSS) for 1 week followed by distilled water for 10 days. After, the rats were sacrificed and colonic damage was both histologically and biochemically assessed. RESULTS: Disease activity index (DAI) was significantly higher on SFO vs. EVOO diet at the end of the experimental period. EVOO-fed mice showed less incidence and multiplicity of tumors than in those SFO-fed mice. ß-catenin immunostaining was limited to cell membranes in control groups, whereas translocation from the cell membrane to the cytoplasm and/or nucleus was showed in DSS-treated groups and its expression was higher in SFO-fed animals. Cytokine production was significantly enhanced in SFO-fed mice, while this increase was not significant in EVOO-fed mice. Conversely, cyclooxygenase-2 (COX-2) and inducible nitric oxidase synthase (iNOS) expression were significantly lower in the animal group fed with EVOO than in the SFO group. CONCLUSIONS: These results confirm that EVOO diet has protective/preventive effect in the UC-associated CRC. This beneficial effect was correlated with a better DAI, a minor number of dysplastic lesions, a lower ß-catenin immunoreactivity, a proinflammatory cytokine levels reduction, a non modification of p53 expression and, COX-2 and iNOS reduction in the colonic tissue.

Acute and chronic responses associated with adrenomedullin administration in experimental colitis.

Adrenomedullin (AM) is a 52 amino acid peptide and member of the calcitonin gene-related peptide (CGRP) super family. Given that AM has emerged as a potential immuno-regulatory and anti-inflammatory agent in various experimental models, this study has deepened into its possible therapeutic effect in intestinal inflammation analyzing the responses in both acute and chronic (14 and 21 days) phases of TNBS-induced colitis in rats. In the acute model, AM treatment reduced the incidence of diarrhea and the severity of colonic damage, and improved the survival rate at the three doses assayed (50, 100, and 200ng/kg animal). AM administration was able to reduce the early production of TNF-alpha and collaborated to maintaining basal levels of IFN-gamma and IL-10. In the chronic studies the peptide attenuated the extent of the damage with lesser incidence of weight loss and diarrhea (50 and 100ng/kg animal). Cellular neutrophil infiltration, with the subsequent increase in myeloperoxidase (MPO) levels caused by TNBS, was reduced after chronic AM administration. The peptide played a role in the evolution of Th1/Th2 cytokines balance and chronic disease recuperation: levels of proinflammatory TNF-alpha and IFN-gamma decreased and anti-inflammatory IL-10 increased significantly. Cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) protein expression were not modified by AM administration, although a reduction of nitric oxide (NO) production could be detected in the chronic model. These results support a role of AM as an anti-inflammatory factor with beneficial effects in intestinal inflammatory colitis.

Intestinal immunomodulation. Role of regulative peptides and promising pharmacological activities.

About 50 peptides, and a similar number of peptide receptors, are known to be present in the gut and this amount is likely to rise significantly over the next few years. While there has been a massive research effort to define their functions and their anatomical distribution in the central nervous system (CNS), the understanding of their roles in the gut is far more limited. Classically, the physiological functions include the control of motility, fluids, electrolytes, and digestive enzymes secretion, or vascular and visceral pain function, and more recently, the role-played in cell proliferation and survival, and in immune-inflammatory responses. The term inflammatory bowel disease (IBD) that encompasses Crohn's disease and ulcerative colitis, is clearly an inflammatory disease where several mediators such as cytokines, chemokines, prostanoids, nitric oxide or free radicals, produced by infiltrating cells, play a critical role in intestine tissue alteration. Some peptides, initially known for their neuroregulative properties, have been suggested to act as endogenous immune factors, with predominant antiinflammatory effects. Based on these actions, these molecules are proposed as potential agents for the treatment of IBD and selective peptide analogs are being developed as novel therapeutic strategies for IBD patients. Patients with IBD have an increased risk for developing colorectal cancer (CRC). Up to the present time, no known genetic basis has been identified to explain CRC predisposition in these IBD. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations, and the fact that certain drugs used to treat inflammation, may prevent the development of CRC. However, though different regulative peptides play a beneficial role in experimental IBD, an increasing number of articles about cancer pathology are starting to implicate different peptides in tumor initiation and progression. The complexities of cancer could be described in terms of a small number of underlying principles and the malignant growth is dependent upon a multi-step process including different basic essential alterations. The activities of many peptides that are overexpressed in cancer cells help them to develop several of the molecular and physiological features that are now considered the basis of malignant growth. These collective findings implicate regulative peptides, receptors, or peptide-levels modulators, as important biological targets for developing intervention strategies against intestinal immunological disorders and cancers.