Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial.

BACKGROUND: The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer. METHODS: We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174. FINDINGS: 124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group. INTERPRETATION: Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone

Soil functionality assessment in degraded plots of vineyards

Land transformation to adapt fields to mechanization in perennial crop farming is a common practice which includes land levelling, deep ploughing, stone-breakage and clearing, application of fertilizers and amendments. Manipulation of the natural soil profile along its entire depth can severely disturb the naturally existing chemical physical,biological and hydrological equilibrium (Costantini and Barbetti, 2008; Costantini et al., 2013). The most common effects of the land transformation are mixing of soil horizons and soil truncation, which result in reduction of soil depth and available water, organic matter depletion, enrichment of calcium carbonate content in the topsoil,imbalance of some element ratio, and decline in the activity and diversity of soil biological communities involved in nutrient cycles. A decline in the capacity of soil to accommodate the soil-dwelling organisms causes a strong impact on several ecosystem services, in particular, the growth of the vine, the quality and quantity of the grapes,the production costs and the risk of erosion. These negative effects of a pre-planting mismanagement can occur simultaneously and interact to decrease soil fertility and grapevine performance (Lanyon et al., 2004; Tagliavini and Rombolà, 2001; Martínez-Casasnovas and Ramos, 2009).Since soil spatial variability is usually high, soil manipulations frequently result into reduced soil functionality and decline of soil ecosystem services in defined plots of the vineyards. Sometimes soil degradation in these areas is very high and compromises not only vine performance and crop yield, but also disease resistance of plants to diseases and their survival. The impact of improper soil manipulations in vineyards may be of particular concern, because vineyards are frequently located on marginal hillsides, which are sensitive to soil erosion and characterized by shallow soil depth (Ramos, 2006). This paper wants to show the assessment of soil functionality in degraded areas within two farms in Tuscany. This work reports the results of the first activities in Italian sites of the ReSolVe Core-organic+ project, aimed at restoring optimal Soil functionality in degraded areas within organic European vineyards

Assessment and restoring soil functionality in degraded areas of organic vineyards. The preliminary results of the ReSolVe project in Italy

In both conventional and organic Italian vineyards, it is quite common to have areas characterized by problems in vine health, grape production and quality, often caused by improper land preparation before vine plantation and/or management. Causes for soil malfunctioning can include: reduced contribution of the soil fauna to the ecosystem services (i.e. nutrient cycles), poor organic matter content, imbalance of some element ratio, altered pH, water deficiency, soil compaction and/or scarce oxygenation. ReSolVe is a transnational and interdisciplinary 3-years research project aimed at testing the effects of selected organic strategies for restoring optimal soil functionality in degraded areas within vineyard. The different restoring strategies implemented in each plot will be: i) compost produced on farm by manure + pruning residue + grass, ii) faba bean and barley green manure, iii) sowing and dry mulching with Trifolium squarrosum L. During two years of such treatments, the trend of the soil features and the grapevine status will be monitored in detail, to reveal the positive and negative effects of such treatments. The project involves 8 research groups in 6 different EU countries (Italy, France, Spain, Sweden, Slovenia, and Turkey), with experts from several disciplines, including soil science, ecology, microbiology, grapevine physiology, viticulture, and biometry. The experimental vineyards are situated in Italy (Chianti hills and Maremma plain, Tuscany), France (Bordeaux and Languedoc), Spain (La Rioja) and Slovenia (Primorska) for winegrape, and in Turkey (Adana and Mersin) for table grape. Soil features before implementing restoring strategies showed lower content of soil organic matter and enzyme activities, and higher carbonates in degraded areas than in the non-degraded areas. The Biological Soil Quality values of microarthropods were always high, in comparison with data registered in similarly managed vineyards or stable ecosystems, and the data showed homogeneous patterns within the experimental plots. Nematode abundance, taxa richness and maturity (MI) and plant parasitic (PPI) indices were higher in nondegraded than degraded areas, but differences were not significant. Grapevines in degraded areas of both farms showed less vegetative vigour and significantly lower values in the SPAD colour index. The yield and the weight of the grape bunches and berries were greater in the not degraded. The grapes of degraded areas at harvest had instead a sugar content significantly higher (on average +2.5�Brix). The restoration techniques and the monitoring methodologies developed and tested during the ReSolVe project will be described in specific final guidelines. The restoration techniques will be accessible for all the European farmers and will be low cost and environmental-friendly. A protocol of analyses and measurements between the all partners will allow an effective and comparable monitoring of vineyard ecosystemic functioning in European countries

Human tenascin: primary structure, pre-mRNA splicing patterns and localization of the epitopes recognized by two monoclonal antibodies.

By sequencing cDNA clones which cover the complete coding region of human tenascin (TN), we have established its primary structure. This confirms that, as in the case of chicken, TN is mainly made up of three groups of sequences with a high homology to Epidermal Growth Factor (EGF) fibronectin (FN) type III repeat and fibrinogen. Furthermore, we have determined the amino-terminal sequence of the mature peptide directly on purified TN. The main differences with respect to the chicken TN molecule are that in the human there are 14 and half EGF-like repeats compared to 13 and half in the chicken and that, as previously reported, there are 15 FN-like repeats compared to 11 in the chicken. By Polymerase Chain Reaction (PCR) amplification we have also studied the different splicing patterns of the TN pre-mRNA in cultured cells. The results show the presence of at least four different isoforms containing different numbers of FN-like type III repeats. Using purified human TN as immunogen, we have obtained numerous monoclonal antibodies (Mabs) to TN. By screening a human melanoma cDNA library in the expression vector lambda gt11 with these Mabs and subsequently sequencing the insert of the positive clones, we have been able to localize, within the TN molecule, the epitopes recognized by two of these Mabs: BC-4, which recognizes an epitope within the EGF-like sequence and BC-2 which recognizes an epitope within the FN like type III repeats whose expression is regulated by alternative splicing of the TN pre-mRNA. Thus, while the Mab BC-4 may be useful in studies on TN distribution (since it recognizes all different TN isoforms) BC-2 may be useful in the study of the expression of particular TN isoforms generated by the alternative splicing of the TN primary transcript

[Modulation of the expression of histocompatibility antigens class I (HLA-A,B,C) in the human pancreas].

In this study the expression of HLA class I molecules was analysed on caudal portions of ten pancreata from cadaver donors by means of indirect immunoperoxidase and immunophosphatase techniques. In 7 out of ten pancreata the results showed that islets tissue was almost negative for the expression of HLA Class I antigens as opposed to exocrine tissue that appeared positive. Within exocrine tissue and large sized islets strongly positive interstitial cells were also detected. Double stainings showed that the strongly positive interstitial cells expressed also Leu M1 antigens. Preliminary studies on the remaining three pancreata demonstrate an increase of hematic interstitial cells together with a parallel increase of HLA class I antigens by endocrine parenchyma. The above data suggest that an increase of interstitial cells within pancreas may influence islets antigenicity