Cell-cycle Alterations in Post-mitotic Cells and Cell Death by Mitotic Catastrophe

Mitotic catastrophe (MC) has long been accounted as a cell death path activated by premature or inappropriate entry of cells into mitosis following chemical or physical stresses. Although various possible explanations related to MC have been formulated, no general accepted definition of this phenomenon has been found yet. Recent evidences, however, demonstrate that MC is not a distinguished way of cell death, rather a “prestage” anticipating cell death, taking place in mitotically disrupted cells, which later occurs via necrosis or apoptosis. Moreover, even though it is widely accepted that MC is the main outcome after ionizing radiation treatment or treatment with drugs that influence microtubule assembly/stability inducing mitotic failure, the final cell death pathway and the final outcome of MC, which strongly depend on the cell type and its related molecular profile, still need to be fully elucidated. Post-mitotic cells, like neurons in the central nervous system, and podocytes or tubular cells in the kidney, are particularly susceptible to MC. In the central nervous system, MC has been claimed as the cause of neuronal death in many neurologic disorders, while MC in podocytes and tubular death is connected with the development of progressive glomerulosclerosis

Genome comparison and physiological characterization of eight Streptococcus thermophilus strains isolated from Italian dairy products

Eight Streptococcus thermophilus strains of dairy origin isolated in Italy were chosen to investigate autochthonous bacterial diversity in this important technological species. In the present study a comparative analysis of all the 17 S. thermophilus genomes publicly available was performed to identify the core and the variable genes, which vary among strains from 196 to 265. Additionally, correlation between the isolation site and the genetic distance was investigated at genomic level. Results highlight that the phylogenetic reconstruction differs from the geographical strain distribution. Moreover, strain M17PTZA496 has a genome of 2.15 Mbp, notably larger than that of the others, determined by lateral gene transfer (including phage-mediated incorporation) and duplication events. Important technological characters, such as growth kinetics, bacteriocin production, acidification kinetics and surface adhesion capability were studied in all the Italian strains. Results indicate a wide range of variability in adhesion properties that significantly clustered strains into four groups. Genomic differences among strains in relation to these characters were identified but a clear correlation between genotype and phenotype was not always found since most of the genomic modifications arise from single nucleotide polymorphisms. This research represents a step forward in the identification of strains-specific functions in Streptococcus thermophilus and it has also the potential to provide valuable information to predict strain specific behaviors in industrial processes

An Attempted Suicide with Copper Sulphate injected intravenously:Pathopsysiology and Therapy about a case report

Acute copper sulphate poisoning is an unusual event, rarely following parenteral exposure, complicated by toxicological effects as haemolytic anaemia, methaemoglobinaemia , hepato-renal damage and acute rhabdomyolysis. Currently, the therapeutic management ignores unique classes of evidence and is mainly based on supportive and chelation therapies. Case details. This case report describes acute copper sulphate poisoning in a 37-year-old man who attempted suicide by self-injecting an unknown amount of copper sulphate. Within three days the patient developed severe intravascular haemolysis and rhabdomyolysis. Initial therapy relied on intensive supportive care with fluids administration, electrolyte correction and packed red blood cells transfusion. The D-penicillamine (30 mg/Kg/day per os) was prescribed as chelation therapy by the poison control centre. The N-acetilcysteine and ascorbic acid were administered to prevent further oxidative stress. Later on, two sessions of therapeutic plasma exchange were performed in order to support the drug therapy. Haemolysis and rhabdomyolysis reversed throughout the hospital stay. Discussion. In this case the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage. Moreover, this case underlies that therapeutic plasma exchange should be considered as an additive measure to undertake since the earlier stages of the emergency intervention. Acute copper sulphate poisoning is an event complicated by toxicological effects: haemolytic anaemia, methaemoglobinaemia, hepato-renal damage, acute rhabdomyolysis. The therapeutic management ignores unique classes of evidence and is based on supportive and chelation therapies. In this case: i) the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage, ii) therapeutic plasma exchange should be considered as an additive measure to undertake

Importance of perforating vessels in nipple-sparing mastectomy. an anatomical description

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex

Effetti del PACAP-38 in forme di plasticità sinaptica nella sanguisuga Hirudo medicinalis

PACAP-38 è un peptide di 38 amminoacidi la cui sequenza è ben conservata in molte specie animali. Agisce da neuromodulatore e da neurotrasmettitore nel sistema nervoso centrale e periferico (Arimura, 1998; Vaudry et al., 2000) ed inoltre è presente in diversi tessuti periferici. Ciò suggerisce un suo ruolo regolatorio in molte funzioni fisiologiche. Alcuni studi hanno evidenziato un suo ruolo nel migliorare l’apprendimento e la memoria sia nei Vertebrati che negli Invertebrati (Arimura, 1992; Masuo et al., 1993). Ad esempio, nei ratti è stato dimostrato che PACAP-38, a bassi dosaggi, migliora significativamente l’acquisizione del paradigma di passive avoidance response (Sacchetti et al., 2001). A livello dell’ippocampo, struttura coinvolta nei fenomeni di apprendimento e memoria, è stato evidenziato un aumento dei fEPSPs nella regione CA1 durante la trasmissione sinaptica basale (Roberto e Brunelli, 2000; Roberto et al., 2001). In alcuni Invertebrati la mancanza di un peptide omologo al PACAP dei Mammiferi, determina deficit nell’apprendimento (Kandel and Abel, 1995). In Drosophila, per esempio, i mutanti per il gene che codifica per il neuropeptide PACAP-simile amnesiac (Feany and Quinn, 1995), hanno disturbi nel consolidamento mnemonico (Davis, 1996). Allo scopo di indagare i meccanismi d’azione di PACAP-38 sono stati analizzati gli effetti del neuropeptide nell’induzione al nuoto nella sanguisuga H. medicinalis, dove è possibile correlare cambiamenti del comportamento con modificazioni dell’attività cellulare e dei circuiti neurali. L’analisi è stata condotta sia a livello comportamentale sia a livello cellulare. In animali aventi il ganglio cefalico disconnesso dal primo segmentale sono stati indotti cicli di nuoto applicando sulla cute in posizione caudale lievi stimoli elettrici (stimolo test) costituiti da treni della durata di 1,6 s di impulsi quadri (5 ms, 8,3 Hz). Mediante un opportuno software collegato ad un dispositivo on/off è stato misurato l’intervallo di tempo che intercorre tra l’applicazione dello stimolo test e l'inizio del nuoto (latenza), prima e dopo iniezione di una soluzione contenente PACAP-38 a varie concentrazioni(0,01 nM - 1 nM). La valutazione delle variazioni di latenza indotte dall’iniezione di PACAP-38 ha dimostrato che alla concentrazione di 0,1 nM il neuropeptide produce effetto sensitizzante. Lo stimolo test da noi utilizzato nel paradigma dell’induzione al nuoto attiva selettivamente le cellule sensoriali T. la riduzione della latenza riscontrata in seguito all’applicazione di PACAP-38 indica una maggiore responsività dell’animale allo stimolo test, suggerendo che PACAP-38 possa modificare le caratteristiche elettrofisiologiche esibite dai neuroni T. Sono state quindi condotte registrazioni intracellulari da neuroni T appartenenti a gangli segmentali estratti da animali naive, e perfusi per 5 minuti con PACAP-38 5•10-3 nM. Sono stati valutati i seguenti parametri elettrofisiologici: voltaggio a riposo (Vm), resistenza di ingresso (Rm) misurata su impulsi iperpolarizzanti di 200 msec, 0,5 nA e ampiezza dell’iperpolarizzazione postuma (AHP). Quest’ultima caratterizza il “firing” dei neuroni T ed è responsabile di variazioni dell’efficacia sinaptica (Scuri et al., 2002; Scuri et al., 2007). I nostri dati hanno evidenziato che PACAP-38 determina una riduzione significativa dell'ampiezza della AHP che si osserva a 20' di lavaggio senza indurre cambiamenti di Vm e Rm. L’AHP, nei neuroni T, è determinata principalmente da un incremento dell’attività della pompa Na+ /K+-ATPasi e solo parzialmente dall’attivazione di una conduttanza K+/Ca2+-dipendente apamina-sensibile. In presenza dell’inibitore apamina 1 nM PACAP-38 5•10-3 nM si è dimostrato in grado di ridurre l’ampiezza dell’AHP, indicando che l’azione del neuropeptide coinvolge una modulazione della pompa Na+ /K+-ATPasi. Il fatto che gli effetti di PACAP-38 si manifestano dopo 20 minuti dall’applicazione suggerisce che il neuropeptide attivi una cascata di trasduzione del segnale intracellulare. Allo scopo di comprendere i meccanismi intracellulari attivati da PACAP-38, sono stati condotti esperimenti per valutare la via dei secondi messaggeri attivata dal neuropeptide: l’utilizzo di LY 83583 0,1 microM, un bloccante delle guanilato ciclasi, ha dimostrato che non è coinvolta la via del guanosin monofosfato ciclico; mentre esperimenti in cui è stato utilizzato il bloccante dell’adenilato ciclasi MDL12330A 1 microM hanno messo in evidenza un probabile coinvolgimento della via dell’cAMP. Dai nostri risultati emerge che PACAP-38 attraverso la via del cAMP modifica l’integrazione sensoriale operata dai neuroni T producendo un effetto sensitizzante in risposta alle lievi stimolazioni tattili che inducono il nuoto nella sanguisuga

Il paradigma della programmazione logica per supportare lo sviluppo di abilità deduttive attraverso l’uso di un artefatto

2014 - 2015The aim of this work is to explore the relationship between the manipulation of linguistic objects and the development of logical-deductive abilities, through teaching experiments in primary and secondary schools. Our theoretical framework is within the wide area of Mathematical Education about the use of artefacts in the teaching and learning processes. The elaborated activities are inspired to Logic Programming, which is a part of Mathematical Logic well suited to didactical purposes. The artefact of choice is the language, that we regard not only as a communication tool but as a “concrete object” to be manipulated according with assigned rules. In our experiments pupils manipulated magnetic cards, which were our artifact purposefully planned and constructed. In accordance with the theoretical framework, the obtained results show that even pupils from primary school can be involved in appropriate logical-deductive activities. [edited by author]XIV n.s

INTRODUCING CORE-SHELL TECHNOLOGY FOR CONFORMANCE CONTROL

Reservoir heterogeneities can severely affect the effectiveness of waterflooding because displacing fluids tend to flow along high-permeability paths and prematurely breakthrough at producing wells. A Proof-of-Concept (PoC) study is presented while discussing the experimental results of a research on "core-shell" technology to improve waterflooding in heterogeneous oil reservoirs. The proposed methodology consists in injecting a water dispersion of nanocapsules after the reservoir has been extensively flushed with water. The nanocapsules are made of a "core" (either polymeric or siliceous materials), protected by a "shell" that can release its content at an appropriate time, which activates through gelation or aggregation thus plugging the high permeability paths. Additional flooding with water provides recovery of bypassed oil. The initial conceptual screening of possible materials was followed by extensive batch and column lab tests. Then, 3D dynamic simulations at reservoir scale were performed to compensate for the temporary lack of pilot tests and/or field applications

A New Mutation (Arg251 Trp) in the Ca2+ Binding Site of Factor X Protease Domain Appears to be Responsible for the Defect in the Extrinsic Pathway Activation of Factor X Padua

Factor X Padua, first described a few years ago, is characterized by a defect only in the extrinsic system. In this present paper, the molecular basis for this peculiar defect is investigated. Polymerase chain reaction amplification and direct sequencing of the entire FX coding sequence and of exon-intron junctions detected in the proposita a C-to-T translocation in exon 8 of nucleotide 875 at the homozygous level. This resulted in the substitution of tryptophan for arginine 251. A niece of the proposita was shown to be heterozygous for the abnormality. Molecular modeling suggested that the mutation does not alter significantly folding and stability of the protein but may be involved in the Ca2+ binding site