Guided folding takes a start from the molecular imprinting of structured epitopes.

A biomimetic route towards assisted folding was explored. Molecularly imprinted polymeric nanoparticles (MIP NPs), i.e. biomimetics with entailed molecular recognition properties made by a template assisted synthesis, were prepared to target a structured epitope: the cystine containing peptide CC9ox, which corresponds to the apical portion of the ß-hairpin hormone Hepcidin-25. The structural selection was achieved by the MIP NPs; moreover, the MIP NPs demonstrated favouring the folding of the linear random peptide (CC9red) into the structured one (CC9ox), anticipating the future role of the MIP NPs as in situ nanomachines to counteract folding defects.

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.

The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases.

Myotonic dystrophy type-1 (DM1) is the most prevalent form of muscular dystrophy in adults. This disorder is an RNA-dominant disease, caused by expansion of a CTG repeat in the DMPK gene that leads to a misregulation in the alternative splicing of pre-mRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5 and the respective protein isoforms (MBNL142-43) were found to be overexpressed in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed that MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via their proline-rich motifs, enhancing the SFK activity. Notably, this association was also confirmed in DM1 muscle and myotubes. The recovery, mediated by an siRNA target to Ex5-MBNL142-43, succeeded in reducing the nuclear localization of both Lyn and MBNL142-43 proteins and in decreasing the level of tyrosine phosphorylated proteins. Our results suggest an additional molecular mechanism in the DM1 pathogenesis, based on an altered phosphotyrosine signalling pathway.

Bloodless hepatic resection with automatic bipolar radiofrequency generator and multielectrode device.

Liver resection is a standard treatment for liver tumours. Intra-operative blood loss remains a major concern during liver resection due to its association with higher postoperative complications and shorter long-term survival. To perform bloodless hepatic resection we realized an apparatus consisting of an incremental, bipolar radiofrequency generator and a probe with six in-line needles (SURTRON SB). Several ex-vivo and in-vivo pig liver experiments and a first-phase clinical study allowed the realization of a prototype radiofrequency (RF) generator that works at 470 kHz, 150 watts maximum power delivered. The probe consists of six needle electrodes of 1.5 mm diameter, with 4.5 mm free space, 6.0 mm centre to centre, between each. We obtained a coagulation of 35 mm length and 12 mm width. The transection was performed with a common scalpel after coagulation of liver parenchyma. We observed good healing of the liver edge both in animal model and in ongoing pilot clinical study. Coagulation with SURTRON SB allows a feasible, easy and safe bloodless liver resection. This method is tolerated with no systemic complication or adverse reaction. This technique offers a method for a bloodless hepatic transection without the need for sutures, ties, staples or tissue glue.

Evaluating the environmental impact of various dietary patterns combined with different food production systems.

OBJECTIVE: Recent studies support the hypothesis that plant-based diets are environmentally better than meat-based diets. This study aims to further explore this topic and to compare different environmental impacts resulting from different dietary patterns (omnivorous, vegetarian, vegan) and methods of production (conventional farming and organic agriculture). DESIGN: Three weekly balanced diets, equivalent to one another for energetic and nutrient content, have been planned: an omnivorous one, a vegetarian one and a vegan one. For each one, the Life Cycle Assessment (LCA) method has been applied in order to calculate the environmental impact, expressed in 'points'. INTERVENTIONS: The software we selected to carry out the Inventory Analysis and the Impact Assessment is SimaPro5. The Assessment phase has been conducted using Ecoindicator 99, a damage-oriented method, which analyses the impact according to three large damage categories, each of them subsuming various impact categories.

Retrospective study of adverse reactions to non steroid anti-inflammatory drugs (NSAIDs): predictive value of controlled challenge with alternative drugs.

Acetylsalicylic acid (ASA) and NSAIDs, which inhibit the cyclo-oxygenase enzyme (C-O), are responsible, when administered at therapeutic doses, for adverse reactions mainly involving the skin and respiratory tract. The prevalence of intolerance to ASA and NSAIDs, assessed by the Section of Allergic and Immunological Diseases at the University of Bari on a population of 15,800 patients referred for allergic diseases over a period of 7 years, was found to be 11.4%. The adverse reactions to NSAIDs observed were in most cases skin complaints (88.9%), followed by respiratory symptoms (asthma +/- rhinitis, rhinitis) and general symptoms (shock, hypotension, lipothymia). The most common types of NSAIDs taken were pyrazolones, salicylics, arylpropionics, paracetamol. Controlled oral challenges with alternative NSAIDs (especially nimesulide) confirm the predictive power of this test: in fact, among patients who showed tolerance to the challenge drug, only 10.6% manifested unexpected reactions during the course of one year's follow-up.

[Rokitamycin tolerance in patients with adverse reactions to chemotherapeutic agents]. / Tolleranza alla rokitamicina in pazienti con reazioni avverse a chemioterapici.

The main task in the drug intolerance reactions is the choice of "alternative" drug by oral challenge. The tolerance of rokitamycine (RKM), a new macrolide with a wide activity spectrum in 133 antibiotic-intolerant patients has been studied by open oral challenge with incremental dosage until a cumulative dose of 406 mg. The RKM in 96.2% of cases has been well tolerated. Only 5 patients (3.8%) have had reactions, mainly "atypical" and of minor clinical importance, at cumulative doses ranging from 31.25 to 250 mg. The RKM has been well tolerated also by 6 patients who have had reactions to macrolides belonging to the same group (16 membered). Finally, the use of RKM as alternative drug in chemotherapeutics-intolerant patients has been proposed.

Allergic bronchial asthma: eosinophil chemotaxis and antihistaminic drug modulation.

This paper investigated the chemotactic capacity of blood eosinophils (EOS) in response to C5a and formyl-leucyl-phenylalanine (FMLP) in 15 Parietaria-pollen-allergic patients with mild asthma during the Parietaria pollen season. Data showed that EOS chemotaxis toward C5a was significantly reduced during the peak pollen count, compared with the values obtained in normal subjects. On the other hand, FMLP could induce EOS chemotactic activity only in Parietaria-allergic patients, the highest value being registered during the height of the Parietaria season. In vitro cimetidine modulation of chemotactic function in comparison with C5a led to a recovery of the impaired results obtained in the presence of high histamine levels. Moreover, diphenhydramine preincubation of EOS induced a reduction of the enhanced chemotactic activity obtained with low concentrations. The data suggest that different serum histamine levels give rise to an impaired immune-phlogistic response in allergic patients and that histamine-receptor antagonists may modulate this effect.