PROTECTIVE EFFECTS OF ANTHOCYANINS FROM BLACKBERRY IN A RAT MODEL OF ACUTE LUNG INFLAMMATION.

Anthocyanins are a group of naturally occuring phenolic compounds related to the coloring of plants, flowers and fruits. These pigments are important as quality indicators, as chemotaxonomic markers and for their antioxidant activities. Here, we have investigated the therapeutic efficacy of anthocyanins contained in blackberry extract (cyanidin-3-O-glucoside represents about 80% of the total anthocyanin contents) in an experimental model of lung inflammation induced by carrageenan in rats. Injection of carrageenan into the pleural cavity elicited an acute inflammatory response characterized by fluid accumulation which contained a large number of neutrophils as well as an infiltration of polymorphonuclear leukocytes in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx) and prostaglandin E2 (PGE2). All parameters of inflammation were attenuated in a dose-dependent manner by anthocyanins (10, 30 mg kg-1 30 min before carrageenan). Furthermore, carrageenan induced an upregulation of the adhesion molecule ICAM-1, nitrotyrosine and poly (ADP-ribose) synthetase (PARS) as determined by immunohistochemical analysis of lung tissues. The degree of staining was lowered by anthocyanins treatment. Thus, the anthocyanins contained in the blackberry extract exert multiple protective effects in carrageenan-induced pleurisy

ROLE OF 5-LIPOXYGENASE IN THE MULTIPLE ORGAN FAILURE INDUCED BY ZYMOSAN.

Objective: This study investigated the role of 5-lipoxygenase in the pathogenesis of multiple organ failure (MOF) induced by zymosan. Design: Male mice with a targeted disruption of the 5-lipoxygenase gene (5-LOKO) and littermate wild-type (WT) controls (5-LOWT) were used to evaluate the role of 5-lipoxygenase (5-LO) in the pathogenesis of MOF. Setting: University research laboratory. Interventions and measurements: MOF was induced by peritoneal injection of zymosan (500 mg/kg i.p. as a suspension in saline) in 5-LOWT and in 5-LOKO mice. MOF was assessed 18 h after administration of zymosan and monitored for 12 days (for loss of body weight and mortality). Results: A severe inflammatory process induced by zymosan administration in WT mice coincided with the damage of lung and small intestine, as assessed by histological examination. Myeloperoxidase activity indicative of neutrophil infiltration and lipid peroxidation were significantly increased in zymosan-treated WT mice. Zymosan in the WT mice also induced a significant increase in the plasma level of nitrite/nitrate. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to ICAM-1 and P-selectin in the lung and intestine of zymosan-treated WT mice. In contrast, the degree of (a) peritoneal inflammation and tissue injury, (b) upregulation/expression of P-selectin and ICAM-1, and (c) neutrophil infiltration were markedly reduced in intestine and lung tissue obtained from zymosan-treated 5-LO deficient mice. Zymosan-treated 5-LOKO showed also a significantly decreased mortality. Conclusions: These findings clearly demonstrate that 5-LO exerts a role in zymosan-induced nonseptic shock

Immune activation, immune senescence and levels of Epstein Barr Virus in kidney transplant patients: Impact of mTOR inhibitors

Abstract Post-transplant lymphoproliferative disorders (PTLD) represent a severe complication in transplanted patients and Epstein-Barr Virus (EBV) is the main driver. Besides immunodepression, immune activation/chronic inflammation play an important role in both virus reactivation and expansion of EBV-positive B cells. The aim of this study was to assess the impact of immunosuppressive strategies on factors involved in the PTLD's pathogenesis. 124 kidney transplanted patients were enrolled in this study: 71 were treated with mycophenolic acid (MPA) and 53 treated with mTOR inhibitor (mTORi), both in combination with different doses of calcineurin inhibitor. At the time of the transplant (T0), profile of inflammation/immune activation and immune senescence didn't differ between the two groups, but after one year of treatment (T1) markers were significantly higher in MPA-treated patients; their immunosenescence process was supported by the greater erosion of telomeres despite their younger age. Percentages of activated B cells and levels of EBV-DNA significantly increased in MPA-treated patients, and at T1 were significantly higher in MPA- than in mTORi-treated patients. Overall, these findings indicate that mTOR inhibitors constrain the inflammation/immune activation and senescence status, thus reducing the expansion of EBV-infected B cells and the risk of virus-associated PTLD in kidney transplant recipients

High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

BACKGROUND: Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. RESULTS: At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L(+ )lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. CONCLUSION: sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation

Incidence of Second Primary Cancer in Transplanted Patients

Background. Solid organ transplanted patients have a three-to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model. Methods. We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years. Results. During the follow-up, 499 subjects developed a first cancer (annual incidence: 98.6ϫ10,000 PY), and 22 of them developed a SPC (annual incidence: 3.9ϫ10,000 PY). The annual incidence of a SPC in the transplanted patients who developed a first cancer was 107.8ϫ10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41). Conclusions. This result shows that the incidence of the SPC was the same as the incidence of a first cancer. Our study does not indicate an increased risk of SPC in transplanted subjects who already suffered a first malignancy

Clinicopathological predictors of recurrence in nodular and superficial spreading cutaneous melanoma: A multivariate analysis of 214 cases

Abstract Background Nodular melanoma (NM) accounts for most thick melanomas and because of their frequent association with ulceration, fast growth rate and high mitotic rate, contribute substantially to melanoma-related mortality. In a multicentric series of 214 primary melanomas including 96 NM and 118 superficial spreading melanoma (SSM), histopathological features were examined with the aim to identify clinicopathological predictors of recurrence. Methods All consecutive cases of histopathologically diagnosed primary invasive SSM and NM during the period 2005–2010, were retrieved from the 12 participating Italian Melanoma Intergroup (IMI) centers. Each center provided clinico-pathological data such as gender, age at diagnosis, anatomical site, histopathological conventional parameters, date of excision and first melanoma recurrence. Results Results showed that NM subtype was significantly associated with Breslow thickness (BT) at multivariate analysis: [BT 1.01–2 mm (OR 7.22; 95% CI 2.73–19.05), BT 2.01–4 mm (OR 7.04; 95% CI 2.54–19.56), and BT > 4 mm (OR 51.78; 95% CI 5.65–474.86) (p  5 mitoses/mm2 (OR 4.87; 95% CI 1.77–13.40) (p = 0.002)]. The risk of recurrence was not significantly associated with NM histotype while BT [BT 1.01–2.00 mm (HR 1.55; 95% CI 0.51–4.71), BT 2.01–4.00 mm (HR 2.42; 95% CI 0.89–6.54), BT > 4.00 mm. (HR 3.13; 95% CI 0.95–10.28) (p = 0.05)], mitotic rate [MR > 2 mitoses/mm2 (HR 2.34; 95% CI, 1.11–4.97) (p = 0.03)] and the positivity of lymph node sentinel biopsy (SNLB) (HR 2.60; 95% CI 1.19–5.68) (p = 0.007) were significantly associated with an increased risk of recurrence at multivariate analysis. Conclusions We found that NM subtype was significantly associated with higher BT and MR but it was not a prognostic factor since it did not significantly correlate with melanoma recurrence rate. Conversely, increased BT and MR as well as SNLB positivity were significantly associated with a higher risk of melanoma recurrence

Valutazione degli effetti dell'acqua elettrolizzata come agente per ridurre la contaminazione fungina sulle granaglie

Obiettivi: L’acqua elettrolizzata acida (EO-A), che è un prodotto della reazione data dal passaggio di corrente elettrica attraverso una soluzione salina, Contiene acido ipocloroso (HOCl) e rilascia cloro libero che ha un alto potenziale ossidoriduttivo, simile a quello dell’ozono. Diversi studi hanno evidenziato come questa soluzione sia in grado di abbattere la carica microbica superficiale in alimenti di origine animale e vegetale (Kim et al., 2005 Poultry Science 84, 1778-1784., Lin et al, 2005, Int J Food Sci Techn, 40, 495-500) e il suo utilizzo è stato approvato negli USA nei sistemi di processazione degli alimenti. In questo lavoro è stata saggiata l’ attività di un prodotto commerciale denominato “Soluzione 259” nell’abbattere la carica micotica su mais ammuffito. Materiali e Metodi: Per la prova sono stati utilizzati 8 campioni di mais fortemente ammuffiti. E’ stata effettuata la conta totale dei miceti sul prodotto tal quale, dopo immersione per 30'' e 60” in EO-A e per 60''in acqua deionizzata sterile (AD); su due campioni i controlli sono stati effettuati anche dopo immersione per 5 minuti in EO-A e in AD. Un ulteriore campione di mais è stato analizzato tal quale, dopo aspersione a spruzzo con EO-A e dopo aspersione a spruzzo con AD. La determinazione della carica fungina totale, espressa in Unità Formanti Colonia (UFC)/g, è stata effettuata in accordo con la normativa ISO/DIS 7954. Una sospensione di spore di A. flavus, il micete maggiormente contaminante il mais esaminato, è stata posta a contatto con EO-A per un minuto e quindi insemenzata in diluizioni scalari per inglobamento in Cloramphenicol Glucose yeast estract agar È stata inoltre effettuata la titolazione iodometrica del cloro (Christian 1994. Chimica analitica Edizioni Piccin, Padova), indicativa della presenza di sostanze ossidanti disponibili nell’EO, prima e dopo l’utilizzo per il trattamento del mais. Risultati e Conclusioni – Di seguito è riportata la carica fungina media riscontrata nei campioni prima e dopo i diversi trattamenti No trattamento 5 x 106 UFC/g EO-A per 30 '' 2 x 106 UFC/g AD per 60” 1,8 x 106 UFC/g, EO-A per 60” 2,5 x 106 UFC/g AD per 5 minuti 2.2 x 106 UFC/g EO-A per 5 minuti, 1,8 x 106 UFC/g Aspers. con AD 5,1 x 106 UFC/g Aspers. con EO-A 8,5 x 106 UFC/g Il prodotto saggiato con diversi modi e tempi di contatto, non sembra quindi incidere significativamente sulla carica micotica del campione. Viceversa il contatto per un minuto con EO-A delle le sole spore in sospensione ha determinato un evidente effetto fungicida. La titolazione idrometrica ha mostrato un drastico abbattimento delle sostanze ossidanti nell’EO dopo contatto con il mais ammuffito. Con ogni probabilità l’elevato presenza di sostanza organica nel prodotto esaminato determina una drastica riduzione del potere fungicida della soluzione esaminat

Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset