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Effect of hyperbaric oxygenation and gemcitabine on apoptosis of pancreatic ductal tumor cells in vitro
Full text linkBackground: la gemcitabina rappresenta una terapia di prima linea nel trattamento dell’adenocarcinoma pancreatico (PDAC), neoplasia ancora caratterizzata da una sopravvivenza scarsa e da una bassa risposta chemioterapica. La terapia iperbarica (HBO) aumenta la quantità di ossigeno nelle cellule ed aumenta la risposta citotossica indotta dalla chemioterapia. Abbiamo pensato come l’attività chemioterapica della gemcitabina (GEM) possa aumentare in ambiente ricco di ossigeno. In questo studio, infatti, è stata valutata l’effetto della gemcitabina, della terapia iperbarica e della loro associazione nel processo apoptotico delle cellule neoplastiche di adenocarcinoma pancreatico.
Materiale e metodi: Nello studio sono state utilizzate due tipi di cellule di adenocarcinoma pancreatico: PANC-1 e AsPc-1. Le cellule sono state trattate con la quantità di GEM pari alla concentrazione inibente del 50% delle cellule neoplastiche (IC50), con HBP a 2.5 ATA per 90 minuti, con la combinazione di entrambi (HBO prima di GEM [HBO-GEM] e GEM prima di HBO [GEM-HBO]) e con la somministrazione contemporanea di GEM e HBO (GEM+HBO). Nel gruppo controllo (Ctrl) le cellule neoplastiche sono state trattate con PBS alla concentrazione usata per disciogliere la gemcitabina usata negli altri campioni sperimentali. Ventiquattro ore dopo, è stato valutato l’indice apoptotico (AI) in ogni gruppo.
Risultati: PANC-1: HBO da sola non presenta alcun effetto sull’indice apoptotico rispetto al gruppo Ctrl AI: 6.5±0.1 vs. 5.9±0.1. HBO prima e dopo GEM non aumenta l’indice apoptotico AI: 8.2±0.1 (HBO-GEM), 8.5±0.1 (GEM-HBO) vs. 8.1±0.1 (GEM). La combinazione di HBO e GEM aumenta significativamente AI: 10.7±0.02 (p<0.001 vs .tutti gli altri trattamenti).
AsPc-1: HBO da sola non presenta alcun effetto sull’indice apoptotico rispetto al gruppo Ctrl AI: 5.9±0.1 vs. 5.9±0.1. HBO prima e dopo GEM non aumenta AI: 8.2±0.1 (HBO-GEM), 8.4±0.1 (GEM-HBO) vs. 8.0±0.1 (GEM). La combinazione di HBO e GEM aumenta significativamente AI: 9.7±0.1 (p<0.001 vs. tutti gli altri trattamenti).
Conclusione: HBO da sola o quando viene somministrata prima o dopo GEM non presenta alcun effetto nell’indice apoptotico in cellule di PDAC. HBO aumenta significativamente l’indice apoptotico quando somministrata contemporaneamente alla GEM. I nostri risultati suggeriscono come la finestra temporale sarebbe fondamentale per l'utilizzo di HBO come coadiuvante alla chemioterapia .Background: Gemcitabine is first-line therapy for advanced pancreatic ductal adenocarcinoma (PDAC) with a poor survival and response rate. Hyperbaric oxygenation (HBO) enhances delivery of oxygen to hypoxic tumor cells and increases their susceptibility to cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine (GEM) may be enhanced if tumor cells are placed in an oxygen-rich environment. The present study evaluated the effects of gemcitabine, HBO and their combination on apoptosis of tumor cells.
Materials and Methods: PANC-1 and AsPc-1 PDAC tumor cell lines were used. Cultured tumor cells were treated with GEM at its growth-inhibitory concentration (IC50) , HBO at 2.5 ATA for 90 min, a combination of both (HBO before GEM [HBO-GEM] and GEM before HBO [GEM-HBO]) and with the administration at the same time of GEM and HBO (GEM+HBO). In the control group (Ctrl) the tumor cells were treated with PBS (as placebo) equal in quantity to that used to dissolve gemcitabine for administering to the experimental samples. Twenty-four hours later, apoptotic cells in each group were analyzed and the apoptotic index (AI) was calculated.
Results: PANC-1 cell line: HBO alone had no effect on AI: 6.5±0.1 vs. 5.9±0.1. HBO before and after gemcitabine did not further increase AI: 8.2±0.1 (HBO-GEM), 8.5±0.1 (GEM-HBO) vs. 8.1±0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 10.7±0.02 (p<0.001 vs. all groups).
AsPc-1 cell line:HBO-alone had no effect on AI: 5.9±0.1 vs. 5.9±0.1. HBO before and after gemcitabine did not further increase AI: 8.2±0.1 (HBO-GEM), 8.4±0.1 (GEM-HBO) vs. 8.0±0.1 (GEM). The combination of HBO and gemcitabine significantly increased AI: 9.7±0.1 (p<0.001 vs. all groups).
Conclusion: HBO-alone, whether administered before and after gemcitabine has no effect on apoptosis of PDAC cells in vitro. HBO significantly enhanced gemcitabine-induced apoptosis when administered during gemcitabine. Our findings suggest that the time window would be critical for using HBO as adjuvant to chemotherapy
Hebbian-like plasticity induction in ventral premotor–primary motor network reveals its dynamics during different prehension actions
No full textOgni funzione espressa dal cervello si basa su una rete complessa e, nessuna funzione integrativa può emergere dal contributo di una singola area. Su questa base e al fine di indagare tale complessità in un'ipotesi direttamente testabile, abbiamo focalizzato la nostra attenzione su un preciso segmento della rete che sottende le azioni volte ad uno scopo. Sono stati condotti diversi esperimenti sulla connettività tra la corteccia premotoria ventrale (PMv) e la corteccia motoria primaria (M1) attraverso la stimolazione magnetica transcranica (TMS), l'elettromiografia (EMG) e la registrazione del movimento (Motion Capture - MoCap). In tutti gli studi sono stati impiegati protocolli di cortico-cortical paired associative stimulation (cc-PAS) volti a indurre plasticità nel network PMv-M1. L'obiettivo finale della tesi era infatti quello di capire se fosse possibile modulare l'attività della rete PMv-M1 al fine di ottenere cambiamenti neurofisiologici e comportamentali, rilevanti dal punto di vista funzionale, durante l’esecuzione di azioni di raggiungimento e presa. Il primo capitolo contiene un’introduzione degli aspetti alla base degli esperimenti poi presentati. L'introduzione delinea l'organizzazione della rete PMv-M1 e il modo in cui può essere studiata nell'uomo attraverso la TMS. In seguito, ci si concentra sulla descrizione della plasticità di tipo Hebbiano e su come sia possibile promuoverla attraverso la TMS. Riassumendo, il protocollo di cc-PAS potrebbe essere un utile strumento per lo studio della connettività PMv-M1 e delle sue proprietà plastiche. Il primo studio è specificamente diretto alla comprensione di come questo protocollo impatti sulla neurofisiologia della rete PMv-M1. In cinque esperimenti abbiamo testato diversi protocolli di cc-PAS con diversi orientamenti del coil. Abbiamo analizzato i loro effetti sulla connettività tra PMv e M1 e sui circuiti intracorticali eccitatori e inibitori di M1. Il risultato principale è stato che i diversi orientamenti del coil reclutano preferenzialmente diverse popolazioni di M1, le quali forniscono potenzialmente contributi diversi nei diversi compiti motori. Di conseguenza, la seconda serie di esperimenti ha verificato se fosse possibile modulare l'output motorio durante diverse azioni di presa. Abbiamo testato l'effetto di due diversi protocolli di cc-PAS, uno somministrato con orientamento del coil postero-anteriore (PA) e uno con orientamento del coil antero-posteriore (AP), sull’output motorio durante l'esecuzione isometrica di una presa di precisione e di una presa più grossolana effettuata con tutta la mano. Questo studio ha aggiunto un'informazione fondamentale: l'orientamento AP della bobina modula preferenzialmente l'output motorio di M1 durante l'azione di presa di precisione e, di conseguenza, abbiamo ora accesso alle popolazioni neurali preferenzialmente coinvolte nell'esecuzione di questa azione. Abbiamo quindi deciso di esplorare l'impatto del protocollo di cc-PAS sulla rete PMv-M1 durante l’esecuzione di azioni naturalistiche. Infatti, uno degli obiettivi principali di questo progetto era capire se fosse possibile modulare lo svolgimento di azioni naturalistiche di presa di precisione. L'ultimo esperimento è stato progettato con questo obiettivo. Questo studio ha utilizzato i protocolli di cc-PAS, perfezionati nei nostri studi precedenti, e le registrazioni MoCap per quantificare i cambiamenti nella cinematica delle azioni eseguite in modo ecologico. I nostri dati mostrano come l’induzione di plasticità nel network PMv-M1 influenzi l'equilibrio tra i processi di controllo a feedforward e feedback durante la fase di raggiungimento delle azioni di presa di precisione. Questo è probabilmente uno dei risultati più rilevanti ottenuti finora, in quanto colma il divario tra le modulazioni fisiologiche e le espressioni comportamentali misurabili dei principi fondamentali di come le azioni vengono pianificate, eseguite e corrette.The theoretical rationale stems from the assumption that every function expressed by the brain must be based on a complex network and that no integrative function can emerge from the contribution of a single area. Along these lines and, for the sake of operationalizing such a complexity into directly testable hypothesis, we focused our attention towards one particular segment of the network responsible for goal-directed actions. We conducted several experiments on the ventral premotor cortex (PMv)-primary motor cortex (M1) connectivity by means of Transcranial Magnetic Stimulation (TMS), electromyography (EMG) and motion capture (MoCap). All studies employed the administration of protocols aimed at inducing plasticity between two anatomically connected brain areas – cortico-cortical Paired Associative Stimulation (cc-PAS). In fact, the ultimate goal of my thesis was to discern whether it was possible to modulate the activity of the PMv-M1 network to obtain functionally-relevant neurophysiological and behavioural change in reaching and grasping actions. The first chapter contains a brief introduction to the fundamental aspects of the experiments presented. The introduction will sketch the organisation of the brain network that supports grasping actions. In particular, I focused on the PMv-M1 network and how it can be studied in humans through TMS. Then, I moved to the description of Hebbian-like plasticity and how it can be promoted via TMS. The overall message is that the cc-PAS might be a useful tool to investigate the PMv-M1 connectivity and its plastic properties. However, we lack fundamental information to fine-tune its properties and to understand why and how it works. The first study is specifically motivated by this lack neurophysiological understanding of how the cc-PAS impacts on PM-M1 connectivity. In five experiments, we tested different cc-PAS protocols with different coil orientations. We analysed their effects on the connectivity between PMv and M1 and on M1 excitatory and inhibitory intracortical circuits. The key result was that different coil orientations preferentially recruit different M1 populations, potentially providing different contributions to different motor task. Consequently, the second set of experiments was aimed at testing whether we could modulate the descending motor output during different grasping actions. Here we tested the effect of two different cc-PAS protocols, one administered with a posterior-anterior (PA) and one with an anterior-posterior (AP) coil orientation, on the motor drive during the isometric execution of a precision and power grip. This study adds one fundamental pieces of information: AP coil orientation preferentially modulates the M1 motor output during the precision grip action and, consequently, we have now access to the neural populations preferentially involved in the execution of this action. This fact opens to several possible expansions of our work. However, first we had to explore the impact of PMv-M1 cc-PAS on real goal directed actions. Indeed, one of the main goals of my project was to understand whether we could non-invasively manipulate ecological reach to grasp actions. The last experiment was designed with this goal in mind. This study used cc-PAS protocols, refined in our previous studies, and MoCap recordings to accurately quantify motor performance changes after brain stimulation. Differently from the few studies investigating the impact of PMv-M1 cc-PAS on motor performance, we set to understand how naturalistic motor performance was affected. Our data shows that PMv-M1 cc-PAS affect the relative balance between feedforward and feed-back control processes during the reaching phase of precision grip actions. This is probably one of the most relevant results obtained so far, as it bridges the gap between physiological modulations and measurable behavioural proxies of fundamental principles of how actions are planned, executed, and eventually corrected
Appendectomy in women. Is the laparoscopic approach always better than the "open" approach in uncomplicated appendicitis?
No full textBACKGROUND:Acute appendicitis is the most common emergency in abdominal surgery, but remains a continuing controversy regarding the most appropriate method of removing the inflamed appendix.
MATERIALS AND METHODS: From January 2002 to December 2012, 1037 women underwent appendectomy (average age: 25±15.7 y; range: 6 to 91 y). Of these, 519 underwent open appendectomy (OA) and 518 underwent laparoscopic appendectomy (LA). For all the patients we determined the postoperative hospital stay, the eventual readmissions within 30 days after discharge, the length of surgical procedures (data were available only for the period from January 2008 to December 2012), the costs for the OA and LA, and the rate of negative appendicitis.
RESULTS:
In our cohort of patients, 189 women (18.2%) had a negative appendectomy. Considering the postoperative hospital stay (average: 4.2±3.6 d; range: 1 to 32 d in OA group and average: 3.9±3.1 d; range: 1 to 21 d in LA group; P=0.15) there were no statistical differences between 2 groups. The average length of surgical procedures in LA group was 42.3±18.4 minutes (range: 8 to 135 min) and 43.2±19 minutes in the OA group (range: 10 to 135 min) (P=0.63). The average net cost of LA was 1203.61 euros, whereas for OA it was 95.18 euros. In this study, we considered only the surgical materials.
CONCLUSIONS: LAs are not associated with a lower complication rate than the OAs and, above all, LAs are more expensive than OAs. Also we believe that laparoscopic approach should be used only in case of unclear abdominal pain and not for the treatment of clear acute and uncomplicated appendicitis
Pneumatosis cystoides intestinalis of the ascending colon.
No full textPneumatosis cystoides intestinalis (PCI) is
a rare condition in which multiple submucosal
or subserosal air-filled cysts develop
in the submucosa or in subserosa of
the colon. The etiological mechanisms
are not clear
Hernioplasty in elderly high-risk adults: efficacy of fibrin glue.
No full textGroin hernia surgery is common; the
lifetime risk of undergoing surgery for groin hernia is 27%
in men and 3% in women. Elective groin hernia repair is
considered a low-risk procedure, with fewer than one
death per 10,000 operations. By contrast, emergency
repair of hernia is associated with significant morbidity
and mortality; in elderly adults with groin hernias, early
elective surgery is preferre
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Cortico‐cortical paired associative stimulation conditioning superficial ventral premotor cortex–primary motor cortex connectivity influences motor cortical activity during precision grip
No full textThe ventral premotor cortex (PMv) and primary motor cortex (M1) represent critical nodes of a parietofrontal network involved in grasping actions, such as power and precision grip. Here, we investigated how the functional PMv-M1 connectivity drives the dissociation between these two actions. We applied a PMv-M1 cortico-cortical paired associative stimulation (cc-PAS) protocol, stimulating M1 in both postero-anterior (PA) and antero-posterior (AP) directions, in order to induce long-term changes in the activity of different neuronal populations within M1. We evaluated the motor-evoked potential (MEP) amplitude, MEP latency and cortical silent period, in both PA and AP, during the isometric execution of precision and power grip, before and after the PMv-M1 cc-PAS. The repeated activation of the PMv-M1 cortico-cortical network with PA orientation over M1 did not change MEP amplitude or cortical silent period duration during both actions. In contrast, the PMv-M1 cc-PAS stimulation of M1 with an AP direction led to a specific modulation of precision grip motor drive. In particular, MEPs tested with AP stimulation showed a selective increase of corticospinal excitability during precision grip. These findings suggest that the more superficial M1 neuronal populations recruited by the PMv input are involved preferentially in the execution of precision grip action
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