Le proteine leganti gli odori negli afidi

Questo lavoro di tesi presenta una ricerca effettuata con tecniche di biochimica e di biologia molecolare su proteine solubili coinvolte nella chemorecezione negli insetti. Lo studio della percezione olfattiva e gustativa negli insetti è stato affrontato solo recentemente, grazie alla identificazione dei recettori olfattivi in Drosophila melanogaster, reso possibile dal genoma completo del moscerino. Ma già 20 anni prima erano note proteine solubili capaci di legare reversibilmete odori e feromoni, le odorant-binding protein (OBP). Si tratta di polipeptidi di basso peso molecolare, presenti in alte concentrazioni nella linfa sensillare degli insetti, dove sono immerse le terminazioni dendritiche dei neuroni olfattivi. Per le OBP è stato inizialmente suggerito un ruolo di trasportatori di molecole odorose idrofobiche, ma le ultime ricerche dimostrano l’importanza della loro presenza per una corretta percezione degli stimoli olfattivi. Il lavoro sperimentale, descritto in questa tesi, riguarda la caratterizzazione delle OBP negli afidi, per la prima volta identificate in questi insetti fitofagi, estremamente dannosi in agricoltura. Sono state identificate nove OBP in Acyrthosiphon pisum, il cui genoma è in corso di sequenziamento, e la presenza di alcune di esse è stata saggiata in altre otto specie di afidi, mediante esperimenti di PCR. Due OBP risultano altamente conservate, un fenomeno abbastanza insolito per queste proteine. Il motivo di questo fatto probabilmente va collegato con la presenza di feromoni sessuali (nepetalattone e nepetalattolo) e di allarme (beta-farnesene) utilizzati da molte specie di afidi. Tre OBP sono state espresse per via eterologa in sistema batterico, ottenendo ottime rese, e sono state purificate mediante cromatografia a scambio ionico e gel filtrazione. Le proteine purificate sono state utilizzate in esperimenti di binding con diversi composti organici. Il dato piu’ interessante è rappresentao dal fatto che il farnesolo, una molecola simile al feromone di allarme beta- farnesene, viene legato solo da una delle tre OBP. Lo studio delle OBP negli afidi potrebbe fornire informazioni utili per adottare strategie alternative, mirate alla inibizione di queste proteine, nel controllo di popolazione di questi insetti in agricoltura

VALUTAZIONE DEL RISCHIO DI LEUCOENCEFALOPATIA MULTIFOCALE PROGRESSIVA IN PAZIENTI CON LINFOMA NON-HODGKIN ESPOSTI A RITUXIMAB

Riassunto Introduzione e razionale: Rituximab è un anticorpo monoclonale che ha migliorato gli esiti di trattamento in pazienti con linfoma non-Hodgkin (NHL). Serie di casi di leucoencefalopatia multifocale progressiva (PML) in pazienti trattati con rituximab nel contesto di protocolli che prevedono polichemioterapia hanno determinato l’introduzione di black box warning, tuttavia non è stato possibile stimare il rischio associato al trattamento. Metodi: Questa tesi descrive uno studio retrospettivo, monocentrico di coorte condotto su 976 pazienti affetti da NHL diagnosticata tra il 1994 e il 2008, compresi 517 pazienti trattati con almeno una dose di rituximab. L’obiettivo è quello di stimare il rischio di PML in pazienti esposti a rituximab rispetto ai non esposti nella coorte selezionata. Risultati: L’ìnclusione di rituximab nei protocolli chemioterapici standard per il NHL ha causato un aumento statisticamente dell’incidenza dei casi PML (rate difference, 2,2 per 1000 anni paziente; intervallo di confidenza al 95%CI: 0.1-4.3). Conclusione: sulla base di questi risultati. La sorveglianza clinica dei sintomi correlati alla PML è raccomdata in pazienti con NHL esposti a rituximab. Summary Background e rationale: Rituximab is an anti-CD20 monoclonal antibody that promotes better treatment outcomes in patients with non-Hodgkin's lymphoma (NHL). Case series of progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab within polychemotherapy regimens have led to the introduction of a black box warning, but no risk estimation has ever been provided. Methods: The present thesis describes a retrospective, monocentric cohort study on 976 NHL patients diagnosed in 1994-2008, including 517 patients who received at least one dose of rituximab. The main endpoint of the study is represented by the estimation of the risk of PML in rituximab-exposed patients as compared to non-exposed. Results: Inclusion of rituximab into standard chemotherapy regimens for NHL caused a significantly higher incidence of PML cases (rate difference, 2.2 every 1,000 patient-years; 95% confidence interval, 0.1-4.3). Conclusion. Based on this finding, clinical surveillance of PML-related symptoms is recommended in NHL patients exposed to rituximab

Pathophysiology of Gastric Ulcer Development and Healing: Molecular Mechanisms and Novel Therapeutic Options

Peptic ulcer disease is one of the most common chronic infections in human population. Despite centuries of study, it still troubles a lot of people, especially in the third world countries, and it can lead to other more serious complications such as cancers or even to death sometimes. This book is a snapshot of the current view of peptic ulcer disease. It includes 5 sections and 25 chapters contributed by researchers from 15 countries spread out in Africa, Asia, Europe, North America and South America. It covers the causes of the disease, epidemiology, pathophysiology, molecular-cellular mechanisms, clinical care, and alternative medicine. Each chapter provides a unique view. The book is not only for professionals, but also suitable for regular readers at all levels

Is There a Risk of Lymphoma Associated With Anti-tumor Necrosis Factor Drugs in Patients With Inflammatory Bowel Disease? A Systematic Review of Observational Studies

Background: Inflammatory bowel diseases (IBDs) are generally not considered a risk factor for the development of lymphoma. When considering IBD treatments, there is good evidence supporting thiopurines (azathioprine, 6-mercaptopurine) as a risk factor for lymphoma. Conversely, the association between the use of anti-TNF agents and the development of lymphoma remains undetermined. In this systematic review, we analyzed the evidence coming from observational studies supporting an association between the use of anti-TNF drugs and lymphoma in patients with IBDs.Methods: This systematic review was performed according with MOOSE and PRISMA statements. We searched observational studies conducted on IBD patients, using MEDLINE, EMBASE, and Google Scholar, published in English language, within the period ranging from January 1st, 1999 to June 30th, 2018. An assessment of the methodologic shortcomings of selected studies was performed as well.Results: Fourteen studies met the eligibility criteria and were included in the review. Only four studies found a significant association of anti-TNF drug with lymphoma or groups of cancers including lymphoma. However, the methodologic shortcomings of all the included studies made their results unreliable, irrespectively of whether their findings supported an association or not.Conclusions: Current evidence from observational studies does not allow excluding or confirming an association of the exposure to anti-TNF treatments with lymphoma in IBD patients

Adverse reactions to oncologic drugs: spontaneous reporting and signal detection

Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting

Performance comparison between signal digitizers and low-cost digital oscilloscopes: spectroscopic, pulse shape discrimination and timing capabilities for nuclear detectors

Signal digitizers revolutionized the approach to the electronics readout of radiation detectors in Nuclear Physics. These highly specialized pieces of equipment are designed to acquire the signals that are characteristic of the detectors in nuclear physics experiments. The functions of the several modules that were once needed for signal acquisition, can now be substituted by a single digitizer. As suggested by the name, with such readout modules, signals are first digitized (i.e. the signal waveform is sampled and converted to a digital representation) and then either stored or analyzed on-the-fly. The performances can be comparable or better than the traditional analog counterparts, in terms of energy, time resolution, and acquisition rate. In this work, we investigate the use of general-purpose digital oscilloscopes as signal digitizers for nuclear detectors. In order to have a proper comparison, we employ a distributed data acquisition system (DAQ), that standardizes the interface between the hardware and the on-line data analysis. The signals, from a set of typical radiation detectors, are digitized and analyzed with the very same algorithms in order to avoid biases due to different software analysis. We compare two traditional signal digitizers (CAEN DT5725 and CAEN DT5751) to two low-cost digital oscilloscopes (Digilent Analog Discovery 2, and Red Pitaya STEMLab 125-14), in terms of their capabilities for spectroscopy (energy resolution), time resolution, pulse shape discrimination, and maximum acquisition rate.Comment: 17 pages, 8 figures, 4 tables, Prepared for submission to JINS

Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive elderly patient

BACKGROUND: An increased risk of venous thromboembolism has been reported in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)-positive elderly patient following administration of indomethacin. CASE PRESENTATION: A 79-year-old HCV-positive man was hospitalized for severe abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back pain. Clinical signs and imaging evaluations disclosed a picture of PVT. Indomethacin was discontinued, and the patient was started on fondaparinux and antithrombin. He was discharged 15 days later due to improvement of his clinical conditions. Thirty days later, a follow-up ultrasound did not show appreciable signs of PVT. The time elapsing between the start of analgesic therapy and PVT onset suggests a role of indomethacin as the triggering agent. Indomethacin could have precipitated PVT by a combination of at least two detrimental mechanisms: 1) direct action on liver vascular endothelium by inhibition of prostacyclin biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and pro-coagulant activation of portal endothelium upon exposure to bacterial endotoxins. CONCLUSIONS: This case can be of interest to physicians, who should exert caution when prescribing NSAIDs for inflammatory pain in patients with background inflammatory dysfunctions of the portal vein endothelium

Acute myocardial infarction following off label retrobulbar injection of desmopressin for non-arteritic anterior ischemic optic neuropathy (NAION). Causal correlation or coincidence?

A 60-year-old man, apparently healthy with negative history for cardiovascular diseases, was hospitalized because of an unilateral sudden and painless severe visual loss. Diagnosis of NAION was made. Two separate and immediately consecutive injections of betamethasone (2 mg/0.5 mL) and desmopressin (2 mcg/0.5 mL) were performed in the retrobulbar space. Fifteen minutes later, the patient suddenly developed cold sweat, dyspnoea, thoracic pain and severe hypotension. Acute myocardial infarction was diagnosed by ECG. Desmopressin was the probable causative agent. Thrombotic events following intravenous or oral administration of desmopressin have been documented in the medical literature. To the best of our knowledge this is the first case in which a thrombotic event was associated with the retrobulbar route. Retrobulbar desmopressin administration in patients with NAION can be probably associated with AMI. Considering its invasiveness and the unproven benefit in the treatment of NAION, this therapeutic approach can not be currently recommende