Value of polymorphisms and DNA methylation for the expression of CYP2E1 enzyme: implications in pharmacogenomics

Different individuals possess slightly different genetic information and show genetically-determined differences in several enzyme activities due to genetic variability. Following an integrated approach, we studied the polymorphisms and DNA methylation of the 5′ flanking region of the metabolizing enzyme CYP2E1 in correlation to its expression in both tumor and non-neoplastic liver cell lines, since to date little is known about the influence of these (epi)genetic elements in basal conditions and under induction by the specific inductor and a demethylating agent. In treated cells, reduced DNA methylation, assessed both at genomic and gene level, was not consistently associated with the increase of enzyme expression. Interestingly, the Rsa/Pst haplotype differentially influenced CYP2E1 enzyme expression. In addition, regarding the Variable Number of Tandem Repeats polymorphism, cells with A4/A4 genotype showed a greater expression inhibition (ranging from 20% to 30%) compared with others carrying the A2/A2 one, while those cells bringing A2/A3 genotype showed an increase of expression (of 25%, about). Finally, we demonstrated for the first time that the A2 and A3 CYP2E1 alleles play a more important role in the expression of the enzyme, compared with other (epi)genetic factors, since they are binding sites for trans-acting proteins. In conclusion our data contributes to define a hypothetical model of regulation of the expression of this enzyme. Clarifying the complex regulation of CYP2E1 enzyme expression, either by genetic or epigenetic elements, will give useful topics in pharmacogenomics, for typing people regarding its metabolizing capability and therapy response

An experimental investigation of the parallel blade-vortex interaction

A scheme for investigating the parallel blade vortex interaction (BVI) has been designed and tested. The scheme involves setting a vortex generator upstream of a nonlifting rotor so that the vortex interacts with the blade at the forward azimuth. The method has revealed two propagation mechanisms: a type C shock propagation from the leading edge induced by the vortex at high tip speeds, and a rapid but continuous pressure pulse associated with the proximity of the vortex to the leading edge. The latter is thought to be the more important source. The effects of Mach number and vortex proximity are discussed

The arterial blood supply of the temporomandibular joint: an anatomical study and clinical implications.

Purpose: The aim of this study was to analyze three-dimensional images of the arterial supply to the temporomandibular joint. Materials and Methods: Ten patients (five men and five women, mean age 36 years) without signs or symptoms of temporomandibular disorders, who underwent contrast-enhanced computed tomographic (CT) scanning with intravenous contrast, were studied. The direct volume rendering technique of CT images was used, and a data set of images to visualize the vasculature of the human temporomandibular joint in three dimensions was created. After elaboration of the data through post-processing, the arterial supply of the temporomandibular joint was studied. Results: The analysis revealed the superficial temporal artery, the anterior tympanic artery, the deep temporal artery, the auricular posterior artery, the transverse facial artery, the middle meningeal artery, and the maxillary artery with their branches as the main arterial sources for the lateral and medial temporomandibular joint. Conclusion: The direct volume rendering technique was found to be successful in the assessment of the arterial supply to the temporomandibular joint. The superficial temporal artery and maxillary artery ran along the lateral and medial sides of the condylar neck, suggesting that these arteries are at increased risk during soft-tissue procedures such as an elective arthroplasty of the temporomandibular joint

CYP2E1 VNTR genotyping associated to anti\u2013tuberculosis drug-induced hepatotoxicity

Tuberculosis (TB) remains a major worldwide health problem with an estimated of 9.0 million of new cases and 1.5 million of deaths in 2013. Anti\u2013TB drug-induced hepatotoxicity (ATDH) is considered the most serious and prevalent adverse drug reaction in TB treatment. Isoniazid (INH), one of the first-line drugs against TB, is more commonly associated to ATDH and, it is well known that the enzyme Citochrome P450 2E1 (CYP2E1) is involved in INH metabolism. It has been found that variable number tandem repeat (VNTR) polymorphic sequences in the promoter region regulate negatively CYP2E1 gene transcription: consequently, it could be put in relationship with adverse TB-drugs reactions. In this report we for the first time show advanced investigations regarding the association between CYP2E1- VNTR and ATDH; the study started last year also thank to a small grant by CUIA but was widely extended with other funds. We studied genotypic frequency distributions of the CYP2E1-VNTR (using PCR-RFLP methodology) in a cohort 294 TB patients treated with anti-TB drugs: 167 were Argentines (130 controls without ATDH and 37 cases with ATDH) and 127 were Bolivians (83 controls without ATDH and 44 cases with ATDH). Chi-squared test was used to compare proportions: a value of P<0.05 was considered to be statistically significant. In the Argentine population, we observed that the A2/A4 genotype frequency was significantly higher in cases than in controls (P=0.048). In contrast, no significant differences were observed in Bolivian population between controls and cases regarding to distribution of VNTR genotypes. Our preliminary results showed that the presence of A4 allele of CYP2E1-VNTR could be associated to ATDH, at least in the Argentine population. These results are in agreement with previously reported data which proposed that the transcriptional activity of A4 allele was higher than that of A2 allele since the transcriptional suppression of A4 was weaker than that of A2. It will be necessary to increase the number of cases in both populations to confirm this possible and interesting association. The CYP2E1 VNTR genotype, in fact, promises to be an attractive marker that could be used to predict or prevent ATDH like the acetylator profile

ANTERIOR OPEN BITE TREATED WITH E F APPLIANCE: A CASE REPORT

Aim. Current trends in pediatric orthodontics aim to identify incorrect development of occlusion and medium/lower facial third as early as possible. Functional appliances are a popular type of device used for treating malocclusion in patients who are growing. Among the functional orthodontic devices intended for this purpose, \u201cEducation Functional\u201d is highlighted. It was developed by Dr. Daniel Rollet. In fact, in the occlusal alterations, early preventive treatment with elastodontic devices resulted in avoiding dysfunctional forces from acting on the skeletal pattern, thus reaching a balance between bone basis and muscular components. This report describes a clinical case of a patient (9-year-old female) with anterior open bite associated to oral dysfunction, treated, in the mixed dentition, with EF-line appliance. Our purpose is to evaluate the effectiveness of this device for the correction of the dysmorphoses

Platform optimization and cost analysis in a floating offshore wind farm

Floating offshore wind represents a new frontier of renewable energies. The absence of a fixed structure allows exploiting wind potential in deep seas, like the Atlantic Ocean and Mediterranean Sea, characterized by high availability and wind potential. However, a floating offshore wind system, which includes an offshore turbine, floating platform, moorings, anchors, and electrical system, requires very high capital investments: One of the most relevant cost items is the floating substructure. This work focuses on the choice of a floating platform that minimizes the global weight, in order to reduce the material cost, but ensuring buoyancy and static stability. Subsequently, the optimized platform is used to define a wind farm located near the island of Pantelleria, Italy in order to meet the island’s electricity needs. A sensitivity analysis to estimate the Levelized Cost Of Energy is presented, analyzing the parameters that influence it most, like Capacity Factor, Weighted Average Capital Cost (WACC) and number of wind turbines

The Freehand Technique: The Ability of the Human Eye to Identify Implant Sites on the Patient

In implantology, among the key choices, to obtain predictable results, it is essential to establish, using cone beam computed tomography (CBCT), the bone site and where to insert the implants; during the surgical phase, these sites must be identified on the oral mucosa. Surgical templates are a valid aid, especially in complex cases which require the insertion of more than three or four implants. In cases of a single implant, on the other hand, surgical guides are rarely used, and the implant is often inserted freehand; therefore, the identification of the implant site on the oral mucosa (after choosing the location on the CBCT) is more difficult. For this reason, the clinician uses the teeth in the arch as a reference. This study evaluates the ability of the human eye to identify, on the oral mucosa, where the implant collars will be positioned, the position of which has previously been chosen on the CBCT, in cases where the hands-free surgical technique (without surgical guides) is used. The verification of this precision is carried out using particular thermo-printed templates which contain radiopaque metal spheres. The results show that, in the freehand technique, it is difficult to precisely identify the implant sites (chosen via X-ray) on the mucosa, especially when they are far from natural teeth adjacent to the edentulous area. In case of monoedentulism, the freehand implant technique seems to be applicable by expert implantologists with a reduced risk of error; in fact, clinical experience helps to find the correct correspondence between the implant site chosen on the CBCT and its identification on the mucosa. The level of experience is fundamental in the clinician’s decision about whether or not to use surgical guides; in fact, doctors with little experience should use surgical guides even in the simplest cases to reduce the risk of error

Terrestrial laser scanning for 3D archaeological documentation. the prehistoric Cave of Sa Miniera de Santu Josi (Sardinia, Italy)

Caves have a great archaeological importance: they were used as a dwelling, as a shelter of animals, as an occasional refuge both for funerary and religious purposes. A cave survey is the first step towards their exploration. This study describes the San Giorgio cave’s survey that is the object of an archaeological research that concerns both the area above it and the underground environments. The cave, located in the north-west of Sardinia, has an extension of about 140 meters and has a maximum depth (surveyed) of -15 meters. Sixty-two TLS scans were carried out producing 1.5 milliard points. The Poisson surface reconstruction algorithm [3] is used to produce the 3D Model. A 3D model in low resolution can be adopted for aims of public archaeology; however archaeologists should take advantage of all the information available in the original point cloud

Imaging of temporomandibular joint: Approach by direct volume rendering

Materials and Methods: We have studied the temporom-andibular joint anatomy, directly on the living, from 3D images obtained by medical imaging Computed Tomography and Nuclear Magnetic Resonance acquisition, and subsequent re-engineering techniques 3D Surface Rendering and Volume Rendering. Data were analysed with the goal of being able to isolate, identify and distinguish the anatomical structures of the joint, and get the largest possible number of information utilizing software for post-processing work.Results: It was possible to reproduce anatomy of the skeletal structures, as well as through acquisitions of Magnetic Resonance Imaging; it was also possible to visualize the vascular, muscular, ligamentous and tendinous components of the articular complex, and also the capsule and the fibrous cartilaginous disc. We managed the Surface Rendering and Volume Rendering, not only to obtain three-dimensional images for colour and for resolution comparable to the usual anatomical preparations, but also a considerable number of anatomical, minuter details, zooming, rotating and cutting the same images with linking, graduating the colour, transparency and opacity from time to time.Conclusion: These results are encouraging to stimulate further studies in other anatomical districts.Background: The purpose of this study was to conduct a morphological analysis of the temporomandibular joint, a highly specialized synovial joint that permits movement and function of the mandible