Interobserver variability in the histopathological evaluation of melanoma: analysis of 60 case reports.

INTRODUCTION: Since the field of dermatopathology is not an exact science, it is prone to personal subjectivity, which sometimes causes disagreements on the diagnosis and assessment of some histological features. In the case of melanoma, some variables such as regression are associated with low interobserver agreement. On the contrary, other variables such as the measurement of Breslow thickness show high reproducibility. OBJECTIVE: The main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility. METHODS AND MAIN RESULTS: We conducted an observational and descriptive study at Hospital de Manises, Valencia, Spain, IVO Foundation, Valencia, Spain, and Hospital 12 de Octubre, Madrid, Spain. The mean level of agreement of all study variables was moderate (Cohen's kappa coefficient statistic = 0.5). The highest agreement corresponded to polypoid morphology, pigmentation, ulceration, and solar elastosis. On the other hand, the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis. CONCLUSIONS: Our mean level of agreement was moderate, which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility, reestablished. When conducting a research study, it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature. It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice.

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.

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.

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.

[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.

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.

Chronic administration of galanin attenuates the TNBS-induced colitis in rats.

Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder considered as a consequence of an aberrant response of the immune system to luminal antigens. Numerous groups of agents are being evaluated as novel therapeutic approaches for its treatment; in this way, different peptides have emerged as potential candidates. Galanin is an active neuropeptide distributed in the central and periphery nervous systems although it has been also described having important autocrine and paracrine regulatory capacities with interesting inflammatory and immune properties. In this line, we have observed that galanin treatment has a significant preventive effect in the experimental trinitrobenzensulfonic acid (TNBS) acute model of inflammatory colitis. The aim of the present study was to investigate intensively the role played by the peptide in the evolution of the inflammatory pathology associated to IBD. Galanin (5 and 10 microg/kg/day) was administered i.p., daily, starting 24 h after TNBS instillation, and continuing for 14 and 21 days. The lesions were blindly scored according to macroscopic and histological analyses and quantified as ulcer index. The results demonstrated that chronic administration of galanin improved the colon injury than the TNBS induced. The study by Western-blotting of the expression of nitric oxide inducible enzyme (iNOS), as well as the total nitrite production (NO) assayed by Griess-reaction, showed significant reduction associated with peptide administration. The number of mast cells was also identified in histological preparations stained with toluidine blue and the results showed that samples from galanin treatment, mostly at 21 days, had increased the number of these cells and many of them had a degranulated feature. In conclusion, chronic administration of galanin is able to exert a beneficial effect in the animal model of IBD assayed improving the reparative process. Participation of nitric oxide pathways and mucosal mast cells can not be discarded.

Administration of L-arginine reduces the delay of the healing process caused by ibuprofen. Implication of COX and growth factors expression.

The objective of the present study has been to advance knowledge of the gastric role played by the amino acid L-Arginine (L-Arg) in the evolution of a chronic gastric ulcer. In order to clarify it, L-Arg alone or together with Ibuprofen have been administrated in an experimental acetic acid chronic ulcer, analysing characteristic parameters of an active curative process, such as PGE2 production, COX expression, and also angiogenesis, proliferation/apoptosis and growth factors expression. Our results reveal that L-Arg is favourable in the healing process improving the curative course. Ibuprofen caused a delay in ulcer healing, more evident 14 days after ulcer induction; COX-2 expression was increased at the 7th day although no signal of protein could be detected after 14 days; PGE2 production was inhibited in intact and ulcerated areas at both times assayed. In contrast, treatment with L-Arg reduced the delay of the lesion, the increment in COX-2 expression induced by Ibuprofen, and was able to maintain PGE2 levels similar to the control group after 14 days. Additionally, the histological study showed that the healing effects of L-Arg might be associated with an increased angiogenesis and FGF-2 expression. These actions could be considered key factors in the healing response associated with L-Arg administration. However, the proliferation study assayed with the PCNA-immunostaining method did not reveal significant differences, as the same as the apoptosis analysis. In conclusion, the coupling of L-Arg to Ibuprofen is an attractive alternative to Ibuprofen administration alone because it not only attenuates but also improves the evolution of chronic lesions through mechanisms that implicate endogenous PG and FGF-2-associated pathways, which allow an increase of angiogenesis process.

New pharmacological perspectives and therapeutic potential of PPAR-gamma agonists.

The peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily has classically been characterized for its implications in adipocyte differentiation and fat metabolism. Recently, PPARgamma has been implicated in the pathophysiology of inflammatory and immune responses possibly through inhibition of the mitogen-activated protein kinase (MAPK) pathways or the activation of the transcription nuclear factor kappa B (NF-kappaB). Thus, these agents might also have therapeutic potential in the treatment of gastrointestinal inflammatory disorders, such as ulcerative colitis and Crohn's disease. The synthetic thiazolidinediones (TZDs), a novel class of insulin-sensitizing drugs, were the first class of compounds identified as PPARgamma ligands, and represent a significant advance in anti-diabetic therapy. However, there is less information about endogenous ligands, although the prostaglandin (PG)J(2) and the oxidized phosphatidylcholine have been suggested. Furthermore, PPARgamma ligands have been shown to be potent inhibitors of angiogenesis, a process necessary for tumor growth and metastasis, and protect against cellular transformation. Further work is needed to establish in detail the anti-proliferative and pro-differentiation mechanisms of PPARgamma activators and their efficacy in certain cancers.

Role of L-arginine in ibuprofen-induced oxidative stress and neutrophil infiltration in gastric mucosa.

It has been proposed that neutrophil and oxygen dependent microvascular injuries may be important prime events in gastrointestinal (GI) toxicity of non-steroidal antiinflammatory drugs (NSAIDs). L-arginine (L-ARG) is an essential amino acid which participates in many important biochemical reactions associated to the normal physiology of the organism. In these experimentations, we studied the role of L-ARG, aminoacid precursor of NO synthesis, on ibuprofen (IB) induced gastric lesions, and also on the inflammatory and oxidative mechanisms related to mucosal damage. Oral administration of IB (100 mg kg(-1)), produced severe damage on gastric mucosa, which was more important after 6 h test-period, and was accompanied by a significant increment in myeloperoxidase (MPO) activity, as index of neutrophil activation, as well as lipid peroxidation (LP) levels and xanthine oxidase (XO) activity. However, no changes were observed in total mucosal glutathione (tGSH), nor glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. Simultaneous treatment with equimolar doses of L-ARG (oral and i.p.), considerably reduced the number and intensity of lesions, and at the same time (6 h) the maximum protection was also observed. In addition, L-ARG inhibited the IB-induced LP and XO enhancement, but did not produce changes in leukocyte infiltration, tGSH, GSH-Px and SOD activity. These findings suggest that (1) L-ARG protective effect on gastric mucosa against IB-induced mucosal lesions could be explained by a local effect and also might be due to the systemic action of the aminoacid; (2) the active oxygen species, derived both from XO and activated neutrophils, could play a role in the pathogenesis of gastric injury induced by IB, (3) L-ARG exhibit a protective effect against IB-induced mucosal damage, probably through the inhibition of oxidative stress derived via xanthine-XO, but it does not block the oxygen free radical production through polymorphe nuclear leukocytes.

Extra-virgin olive oil-enriched diets reduce indomethacin-induced gastric oxidative damage in rats.

Olive oil, the main fat component of the Mediterranean diet, has been found to be protective against oxidative stress and could be beneficial in inflammatory and gastrointestinal disorders. First-pressed, extra-virgin olive oil (EVOO) has appreciable amounts of powerful antioxidants such as polyphenolic compounds that prevent its autoxidation and are responsible for its high stability. The aim of the present study was to determine whether diets supplemented with EVOO could reduce the severity of indomethacin-induced gastric oxidative damage and also to study changes in the activities of certain oxidative stress-related enzymes such as xanthine oxidase, myeloperoxidase as a marker of neutrophil infiltration, and the antioxidant enzyme superoxide dismutase. Lipid peroxidation and possible modifications in gluthatione metabolism were also studied. Weanling rats were maintained on semisynthetic diet for 6 weeks; a standard diet containing 5% (w/w) of fat as control or EVOO supplemented diets (5% and 20% w/w). Gastric lesions were induced on the last day by oral administration of indomethacin (60 mg/kg body wt). In animals fed EVOO diets, gastric lesions were decreased significantly and in parallel with dietary fat, when compared to animals consuming a standard diet. These protective effects were related to a reduction of lipid peroxides generation, neutrophil infiltration, and xanthine oxidase activity. Superoxide dismutase, an important enzyme to scavenger of lipid peroxides, was unaffected by feeding conditions. On the other hand, dietary supplementation with EVOO significantly increased both glutathione peroxidase activity and total glutathione content. In conclusion, this study provides evidence that fat diets containing EVOO reduces indomethacin-induced gastric damage in rats. This effect may be partly due not only to reducing oxidative stress and neutrophil-induced toxicity but also to enhancing the glutathione antioxidant defense system.