PAC1 Deficiency in a Murine Model Induces Gastric Mucosa Hypertrophy and Higher Basal Gastric Acid Output

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion

Preparation and Characterization of a Novel Skin Substitute

Autologous epidermal cell cultures (CEA) represent a possibility to treat extensive burn lesions, since they allow a significative surface expansion which cannot be achieved with other surgical techniques based on autologous grafting. Moreover currently available CEA preparations are difficult to handle and their take rate is unpredictable. This study aimed at producing and evaluating a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis (AAGD) and CEA to overcome these difficulties. A procedure that maintained an intact basement membrane was developed, so as to promote adhesion and growth of CEA on AAGD. Keratinocytes were seeded onto AAGD and cultured up to 21 days. Viability tests and immunohistochemical analysis with specific markers were carried out at 7, 14, and 21 days, to evaluate keratinocyte adhesion, growth, and maturation. Our results support the hypothesis that this newly formed skin substitute could allow its permanent engraftment in clinical application

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-na\uc3\uafve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-na\uc3\uafve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-na\uc3\uafve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p < 0.0001), while overall survival was positively affected by lower ECOG PS (p < 0.0001), absence of brain metastases (p 0.05), and clinical benefit (p < 0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order

An X-ray burst from a magnetar enlightening the mechanism of fast radio bursts

Fast radio bursts (FRBs) are millisecond radio pulses originating from powerful enigmatic sources at extragalactic distances. Neutron stars with large magnetic fields (magnetars) have been considered as the sources powering the FRBs, but the connection requires further substantiation. Here we report the detection by the AGILE satellite on 28 April 2020 of an X-ray burst in temporal coincidence with a bright FRB-like radio burst from the Galactic magnetar SGR 1935+2154. The burst observed in the hard X-ray band (18-60 keV) lasted about 0.5 s, it is spectrally cut off above 80 keV and implies an isotropically emitted energy of about 1040 erg. This event demonstrates that a magnetar can produce X-ray bursts in coincidence with FRB-like radio bursts. It also suggests that FRBs associated with magnetars can emit X-ray bursts. We discuss SGR 1935+2154 in the context of FRBs with low-intermediate radio energies in the range 1038-1040 erg. Magnetars with magnetic fields B ≈ 1015 G may power these FRBs, and new data on the search for X-ray emission from FRBs are presented. We constrain the bursting X-ray energy of the nearby FRB 180916 to be less than 1046 erg, smaller than that observed in giant flares from Galactic magnetars

Diagnosi di Laboratorio per Infezione nel Distretto Parodontale, dalla PCR al “Molecular Beacon Array”

I dati forniti dall’ Organizzazione Mondiale della Sanità (OMS) riportano che a fronte del 30% della popolazione italiana che presenta salute parodontale, il restante 70 % è affetta da una forma di patologia che può essere lieve (80%) e grave (5-20%). Si tratta dunque di una patologia che ha un forte impatto sociale, e quindi una notevole incidenza nei costi della spesa sanitaria. Si impone pertanto un corretto approccio in termini di: prevenzione della diagnosi clinica e di laboratorio, delle strategie terapeutiche. L ‘eziologia della malattia parodontale e di tipo infettivo ma rispetto ad altre patologie causate da microorganismi la parodontite presenta notevoli peculiarità, peculiarità che vanno ricercate nelle caratteristiche dei patogeni parodontali, in particolare : (a) sono descritte almeno 300 specie differenti ( la maggior parte non ancora identificate), (b) La maggior parte sono anaerobi, (c) difficoltà nella coltura, (d) crescita molto lenta ( anche 2 settimane), (e) presentano un' organizzazione a ” biofim complesso”. Attualmente, un aiuto importante alla diagnostica di laboratorio in parodontologia, viene dalla biologia molecolare. Le tecniche più efficaci e moderne attualmente in uso sono la Polymerase Chain Reaction (PCR), e la sua versione quantitativa : la PCR real-Time. Queste metodiche hanno come principio lo specifico riconoscimento di una sequenza di DNA/RNA appartenente al microorganismo patogeno. I vantaggi principali vengono rilevati nella sensibilita’ ( un incremento di 10-100 volte) e nel tempo del risultato (1- 6 ore ). Nonostante questi vantaggi notevoli , i metodi citati possono presentare una bassa specificità , dovuta a sequenze di DNA molto simili appartenenti a specie microbiche affini. 2 Recentemente un ulteriore passo nella diagnostica microbiologica molecolare e’ stato raggiunto con i “Molecular Beacon”MB, (Tyagi et al., 1996). I MB, ,rappresentano sonde fluorescenti a DNA con struttura circolare (Fig.1). La sonda presenta una sequenza nucleotidica che si apre (ed emette fluorescenza),solo se trova una regione complementare perfettamente identica nel DNA bersaglio del patogeno parodontale, questo determina il massimo grado di specificità possibile nella diagnostica molecolare, di conseguenza vengono ridotti i possibili falsi positivi della PCR tradizionale. L’utilizzo dei MB in un pannello analitico contenente tutte le specie rappresentative della malattia parodontale “molecular beacon array”, dispone per il clinico elementi più oggettivi e, soprattutto scientificamente/tecnologicamente più significativi, su cui basare la diagnosi di infezione per malattia parodontale

Ruthenium Oxide Nanotubes Via Template Electrosynthesis

Ruthenium oxide nanotubes were fabricated by a single-step galvanostatic deposition using porous anodic alumina membrane as template. For the electrodeposition process, we used a electrochemical cell specifically designed in order to employ only 0.5 ml of 0.02 M RuCl3•xH2O solution. The deposition from a very small volume was specifically addressed owing to the high cost of ruthenium compounds, which could be of some relevance from an applicative point of view. Several techniques were used to characterize the samples prior to and after thermal treatment, which was carried out at different temperatures in order to study the crystallization process of the deposit. Raman spectroscopy of as-deposited nanotubes revealed the presence of RuO2 vibrating modes, while XRD patterns did not show RuO2 peaks, consequently the formation of a subnano-crystalline structure was proposed. After thermal treatment at different temperature above 600°C, they crystallized in the tetragonal form of RuO2. Both XRD analysis and Raman spectroscopy revealed that crystal size of the deposit grew with temperature up to 1000°C. SEM investigations showed the formation of nanotubes having an uniform average external diameter, while wall thickness changed throughout the height

The Role of Neuropeptides in Mouse Models of Colitis.

Inflammatory bowel disease (IBD) constitutes an important clinically significant condition that results in morbidity and mortality. IBD can be generally classified into either ulcerative colitis (UC) or Crohn's disease (CD) that differs in the clinical and histopathology. The role of neuropeptides in the pathogenesis of these conditions is becoming increasingly recognized for their importance in modulating the inflammatory state. Animal models provide the greatest insight to better understand the pathophysiology of both disorders which will hopefully allow for improved treatment strategies. This review will provide a better understanding of the role of murine models for studying colitis

MUCA MUTATIONS IN CLINICAL ISOLATES OF PSEUDOMONAS AERUGINOSA

INTRODUZIONE Il genere Pseudomonas aeruginosa rappresenta un’importante patogeno isolato nelle infezioni ospedaliere, è all’attenzione in campo sanitario per la sua multiresistenza ai farmaci antimicrobici, infatti è in grado di esprimere resistenza verso una lunga serie di antibiotici come amminoglicosidi, fluorochinoloni e cefalosporine. In campo umano questa specie è coinvolta in diverse malattie infettive a decorso cronico come la fibrosi cistica. Le resistenze agli antimicrobici in questo microorganismo sono dovute a diversi meccanismi genetici come mutazioni lungo il cromosoma batterico. Lo scopo del presente lavoro è stato quello di verificare, in isolati nosocomiali di P. aeruginosa, le mutazioni lungo il gene mucA, un fattore sigma responsabile nella produzione di alginato e correlato alle resistenze ai farmaci