Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

BACKGROUND: Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO2 -FAs), such as nitro oleic acid (OA-NO2 ) and nitro linoleic acid (LNO2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. METHODS: We evaluated the effect of OA-NO2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. RESULTS: We found that subcutaneous (SC) OA-NO2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. CONCLUSION: Overall, these results support the development of OA-NO2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases.

Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE).

BACKGROUND: Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of gastroenteropancreatic neuroendocrine tumors from a Southern European country. PATIENTS AND METHODS: Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. RESULTS: The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival. CONCLUSION: This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.

[Malignant peripheric nerve sheath tumor of the orbit: first description of orbital location in a patient with NF1]. / Tumor maligno de la vaina del nervio periférico (MPNST) glandular de la órbita: primera descripción de la literatura de localización orbitaria en un paciente con neurofibromatosis tipo 1.

INTRODUCTION: The malignant peripheric nerve sheath tumor (MPNST), is a malignant neoplastic lesion originated in Schwann cells of the lining sheath of peripheral nerves. This neoplasia may appear with benign or malignant heterologous components, with divergent differentiation, as the glandular one. AIM: To describe for the first time in the literature, a case of a glandular MPNST, located at the orbit and to revise the literature on this tumoral lesion. CLINICAL CASE: Nine year old male, with a base diagnosis of NF1, who had exophthalmos, retro-ocular pain, headache, facial asymmetry and descent of the right eyeball, that started 1 year earlier. This patient showed in the Computed Tomography an Magnetic Resonance, a well delimited, lobulated, solid mass at the eyeball, which extended to the fontal and temporal brain parenchyma. A right Fronto-temporal craniotomy was made with fronto -orbital- zygomatic resection of the tumoral lesion. Later, a dural plasty and reconstruction with titanium mesh was made at the skull base. At present, the patient is asymptomatic after 4 months of follow up. A malignant biphasic neoplastic lesion was observed, reactive in the mesenchymal elements S100, PGP 9.5, neurofilaments and vimentin. The glandular component was positive for AE1/AE3, EMA, CEA and focally for CD57. There was also reactivity to cromogranin, synaptophysin, serotonin and somatostatin. The diagnosis of Glandular MPNST was made. CONCLUSION: For the first time in the literature a case of Glandular MPNST located at the orbit, which occurred in child with NF1, is described. This extremely uncommon neoplasia must be taken into account, in the study of biphasic malignant lesions, as its diagnosis is of great importance because of the bad prognosis of the affected patients.

[Cryptococcoma in the central nervous system of a non-immunocompromised patient]. / Criptococoma en el sistema nervioso central de un paciente no inmunoafectado.

INTRODUCTION: Central nervous system cryptococcosis is an important cause of morbidity and mortality in immunocompromised patients; nevertheless, its presentation in immuno-spared patients is extremely rare, giving rise to a hole different spectrum, since it is manifested like granulomatous masses named cryptococomas. AIM. To describe an intracerebral case of cryptococcoma in an immuno-spared woman in the Hospital Universitario de Santander and to discuss the most relevant topics of this pathology. CASE REPORT: A 24 years-old woman, coming to the service presenting generalized tonic-clonic seizure, fixed upward gaze, sialorrhea and lost, without any data suggesting immunosupression. The computarized tomography of skull demonstrates a mass of possible inflammatory vs. noeplasmic origin. After performing imaging the patient is taken to surgery for craniotomy with excisional biopsy. By means of hystological analysis the diagnosis of cerebral criptococcoma is made, and antimycotic therapy is started, with favorable response. Actually the patient evidences good health, and no evidence of active disease. CONCLUSIONS: The presence of masses of criptococcal origin located at the central nervous system, which origin is due to a chronic granulomatous reaction, is rarely reported; these appear in almost all cases in immunocompetent patients, in which there is of primary importance to discard all causes of cellular immune deficit. Also, the diagnosis of these injuries must be considered before the presence of intracerebral masses that show inflammatory characteristics.

[Rhabdomyomatous mesenchymal hamartoma]. / Hamartoma mesenquimal rabdomiomatoso.

Rhabdomyomatous mesenchymal hamartoma is an extremely rare congenital lesion, and very few cases have been reported even though its macroscopic and microscopic features make diagnosis easy. An 18-year-old woman consulted with a pedunculated mass in the medial region of her neck. The mass was surgically removed, and rhabdomyomatous mesenchymal hamartoma was diagnosed. The clinical, macroscopic, histologic, and immunochemical characteristics that allow diagnosis of this entity are discussed. Although association with congenital abnormalities is uncommon, this possibility should be assessed by the clinician.