Vegetal diamine oxidase alleviates histamine-induced contraction of colonic muscles

Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5′-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions

Integrated SEED data archive for temporary seismic experiments

One of the most valuable results achieved during the work on S5 project is the implementation of a new temporary network data management that allows the integration in the National Data Center together with all other seismological data produced by INGV. This makes all data gathered during temporary experiments immediately available from the same source and in the same data format (SEED) increasing the availability for processing and analysis. Moreover the data are distributed to the scientific community using the EIDA (European Integrated Data Archive http://eida.rm.ingv.it/). The first application has been carried out for the Messina 1908-2008 experiment (WP2.2) http://dpc-s5.rm.ingv.it/en/Database-MessinaFault.html where has been achieved the complete integration of permanent networks (National Seismic Network, MedNet and Peloritani Local Network), temporary deployments (INGV-CNT and INGVCT mobile networks) and OBS data. All the procedures were used and further improved during the L'Aquila sequence (Task 4) where data was available for processing together with permanent network data as soon as it was gathered from the field giving to the scientific community the opportunity to study the evolution of the seismic sequence with higher density of stations (WP4.2) ( h t t p : / / d p c - s 5 . r m . i n g v . i t / e n / D a t a b a s e - AquilaFaultSystem.html).UnpublishedSede Ispra | Via Curtatone 7, Roma1.1. TTC - Monitoraggio sismico del territorio nazionaleope

Tuning an Earthworm phase picker: some considerations on the pick_ew parameters

Although the Earthworm project started with the initial mission of replacing the old real time picker by Rex Allen, as developed by Jim Ellis [Allen, 1978; Allen, 1982; USGS et al., 2010], that picker is still in use in many networks. The name of the procedure that implements the Allen’s algorithm is pick_ew. Despite its long-lived use, configuring this picker still seems not so immediate and easy. We discuss here a few simple rules to define some of the numerous (18) parameters of pick_ew, interpreting their physical meaning

Experimental data based machine learning classification models with predictive ability to select in vitro active antiviral and non-toxic essential oils

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies. In line with the authors previous reports the investigation of an in-house library of extracted essential oils as a potential blocker of HSV-1 infection is reported herein. A subset of essential oils was experimentally tested in an in vitro model of HSV-1 infection and the determined IC50s and CC50s values were used in conjunction with the results obtained by gas-chromatography/mass spectrometry chemical analysis to derive machine learning based classification models trained with the partial least square discriminant analysis algorithm. The internally validated models were thus applied on untested essential oils to assess their effective predictive ability in selecting both active and low toxic samples. Five essential oils were selected among a list of 52 and readily assayed for IC50 and CC50 determination. Interestingly, four out of the five selected samples, compared with the potencies of the training set, returned to be highly active and endowed with low toxicity. In particular, sample CJM1 from Calaminta nepeta was the most potent tested essential oil with the highest selectivity index (IC50 = 0.063 mg/mL, SI > 47.5). In conclusion, it was herein demonstrated how multidisciplinary applications involving machine learning could represent a valuable tool in predicting the bioactivity of complex mixtures and in the near future to enable the design of blended essential oil possibly endowed with higher potency and lower toxicity

Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation

Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson's 'two hit' concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting

Task 1 - Deliverable 1: Database structure

The Italian strong motion data base (Italian Strong Motion Data Base) is a joint product of the agreement between the Dipartimento della Protezione Civile – Ufficio Valutazione Prevenzione e Mitigazione del Rischio Sismico ed Attività ed Opere Post-Emergenza (Department of Civil Protection – Evaluation, Prevention and Mitigation of Seismic Risck and Post-Emergency Works) and the Istituto Nazionale di Geofisica e Vulcanologia (National Institute of Geophysics and Volcanology). The data base is handled through two different relational data base management system: Ms Access® 2003, of major use among research institutions and public administrations, for CD-ROM release, and MySQL for the web distribution. The selection of the former product is driven by the simplicity of the software, the worldwide diffusion and the possibility of being linked to software’s for the management of spatial data, such as ESRI ArcGis® and Arcview®, and software for the scientific calculation such as Matlab ®. The data base will store the information regarding the seismic events, the recording stations, the installed instruments, the main features of the recordings and the engineering parameters. The structure is based on a previous version of the Italian strong-motion data base created by ENEA in collaboration with Department of Civil Protection, which stores the information regarding the accelerometric recordings in the time span 1972-1993. This manuscript will explain the structure of the tables containing the information, the data base architecture, the relationships existing among tables and the technical features for data input.Progetto DPC-INGV S6 “Data base dei dati accelerometrici Italiani relativi al periodo 1972-2004"Published5.2. TTC - Banche dati di sismologia strumentaleope

Task 1 - Deliverable 1: Database structure

The Italian strong motion data base (Italian Strong Motion Data Base) is a joint product of the agreement between the Dipartimento della Protezione Civile – Ufficio Valutazione Prevenzione e Mitigazione del Rischio Sismico ed Attività ed Opere Post-Emergenza (Department of Civil Protection – Evaluation, Prevention and Mitigation of Seismic Risck and Post-Emergency Works) and the Istituto Nazionale di Geofisica e Vulcanologia (National Institute of Geophysics and Volcanology). The data base is handled through two different relational data base management system: Ms Access® 2003, of major use among research institutions and public administrations, for CD-ROM release, and MySQL for the web distribution. The selection of the former product is driven by the simplicity of the software, the worldwide diffusion and the possibility of being linked to software’s for the management of spatial data, such as ESRI ArcGis® and Arcview®, and software for the scientific calculation such as Matlab ®. The data base will store the information regarding the seismic events, the recording stations, the installed instruments, the main features of the recordings and the engineering parameters. The structure is based on a previous version of the Italian strong-motion data base created by ENEA in collaboration with Department of Civil Protection, which stores the information regarding the accelerometric recordings in the time span 1972-1993. This manuscript will explain the structure of the tables containing the information, the data base architecture, the relationships existing among tables and the technical features for data input

Vasa vasorum lumen narrowing in brain vascular hyalinosis in systemic hypertension patients who died of ischemic stroke

Ischemic stroke is a major cause of death among patients with systemic hypertension. The narrowing of the lumen of the brain vasculature contributes to the increased incidence of stroke. While hyalinosis represents the major pathological lesions contributing to vascular lumen narrowing and stroke, the pathogenic mechanism of brain vascular hyalinosis has not been well characterized. Thus, the present study examined the postmortem brain vasculature of human patients who died of ischemic stroke due to systemic hypertension. Hematoxylin and eosin staining and immunohistochemistry showed the occurrence of brain vascular hyalinosis with infiltrated plasma proteins along with the narrowing of the vasa vasorum and oxidative stress. Transmission electron microscopy revealed endothelial cell bulge protrusion into the vasa vasorum lumen and the occurrence of endocytosis in the vasa vasorum endothelium. The treatment of cultured microvascular endothelial cells with adrenaline also promoted the formation of the bulge as well as endocytic vesicles. The siRNA knockdown of sortin nexin-9 (a mediator of clathrin-mediated endocytosis) inhibited adrenaline-induced endothelial cell bulge formation. Adrenaline promoted protein-protein interactions between sortin nexin-9 and neural Wiskott–Aldrich syndrome protein (a regulator of actin polymerization). Spontaneously hypertensive stroke-prone rats also exhibited lesions indicative of brain vascular hyalinosis, the endothelial cell protrusion into the lumen of the vasa vasorum, and endocytosis in vasa vasorum endothelial cells. We propose that endocytosis-dependent endothelial cell bulge protrusion narrows the vasa vasorum, resulting in ischemic oxidative damage to cerebral vessels, the formation of hyalinosis, the occurrence of ischemic stroke, and death in systemic hypertension patients

MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation

Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication. Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy