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OSTEOGENESI IMPERFETTA: ASPETTI CLINICI E ODONTOIATRICI
No full textOstegenesis imperfecta (OI) is a group of genetic diseases with a wide spectrum of severity, ranging from very mild bone fragility to lethal forms. Without treatment the more severe forms have multiple fractures leading to progressive bone deformities with extreme shortness, frequent skeletal pain and immobilization.
AIMS. The overall aim of these studies were initially to find and later to optimize a symptomatic treatment of patients with OI to find and to monitor treatment.
METHOD AND MATERIALS. The study involves 15 persons with OI of which 9 were treated with bisphosphonates in infusions every three months (disodium pamidronate). 8 patients had dentinogenesys imperfecta. None of the 15 patients reviewed developed osteonecrosis of the jaw. In 46.5% of the cases the teeth had a restaurative treatment (26.6% while the patient had active bisphosphonate treatment); in 20% of the cases the teeth were extracted (none had active bisphosphonate treatment); in 13.2% of the cases the teeth had a not surgical parodontal treatment (6.6% while the patient had active bisphosphonate treatment); in 13.2% of the cases the teeth had a surgical parodontal treatment (none had active bisphosphonate treatment); in 13.2% of the cases the patiens had an implant surgery. Because no complications were reported, we inferred that no osteonecrosis of the jaw occurred.
CONCLUSIONS. One of the greatest challenges for the pediatric dentist is to provide adequate treatment to achieve functional and esthetic restoration in cases of diseases like OSTEOGENESIS imperfecta. Early diagnosis and treatment are essential for obtaining a favorable prognosis, any delay in intervention making the treatment even more complex. The aim is to achieve a good esthetic result and restore function along with preventive measures to establish a more favorable prognosis for such complex anomaly
Characterization of biologically effective UV radiation at mid-latitudes sites: innovative method for the calculation of the human vitamin D exposure
No full textThe Italian territory has the potential for receiving high solar ultraviolet (UV) doses during most of the year. This may represent a serious hazard for human health as UV radiation is responsible for skin cancer: Italy is in the third place, after Australia and USA, for melanoma occurrences. It ought to be remember that UV radiation has well-established beneficial effects on the skin, most notably the synthesis of vitamin D3. However a climatological characterization of biologically effective UV radiation in Italy is still missing.
Given the dual biological effect of UV radiation, we focused on the characterization of erythemal and vitamin D dose rates at two Italian sites with different environmental conditions: Rome (41.9°N,12.5°E, 70 m a.s.l) and Aosta (45.8°N, 7.4°E, 569m a.s.l.). For both sites multi-year series of high quality spectral UV measurements, provided by Brewer spectrophotometers are available, especially at the Rome station which has the longest available spectral measurements of UV irradiances in Italy (more than 15 years).
The climatological characterization of erythemal and vitamin D radiation has been carried out in relation to total ozone, solar zenith angle, and aerosol optical index. In addition, the results of the climatological analysis allowed to study the applicability of an innovative method to derive vitamin D doses based on pholysulphonedosimetry -- normally used to measure erythemal exposures -- and hence to expand the potential applications of the PS dosimetric technique
Mixed effect joint models for longitudinal responses with drop-out: estimation and sensitivity issues.
No full textRole of ERp57 in the regulation of gene expression and its involvement in neurodegeneration
No full textParkinson disease (PD) is a progressive neurodegenerative disorder characterized by a progressive and selective loss of dopaminergic neurons in the Substantia nigra.
Recent studies indicate that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), is strongly neurotoxic and may contribute to the onset and progression of this disease (1). To better understand CysDA contribution to neurodegeneration, it has been evaluated the modulation of the expression, aggregation and cellular localization of proteins known to be involved in the oxidative stress response. In particular, we focused our study on alpha-Synuclein (a-Syn), a protein considered the PD “hallmark” and on ERp57, an endoplasmic reticulum thiol oxidoreductase, known to be implicated in neurodegenerative disease (2).
To achieve these goals, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA and the data were compared to those obtained by the use of 6-hydroxydopamine (6-OHDA), a well known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, without affecting serotonergic or noradrenergic systems, providing in vivo evidence of CysDA specific neurotoxicity at dopaminergic system level.
Both in CD1 mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and Glutathione (GSH) depletion.
Moreover, CysDA treatment induced in CD1 mice an increase of α-Syn aggregated forms in the prefrontal cortex with respect to the striatum and hippocampus. These data are in agreement with previous findings which indicate that α-Syn is overexpressed in the prefrontal cortex in cognitive impairment (3). Conversely, ERp57 protein increase was observed in the striatum after CysDA treatment, the other brain regions were slightly affected.
To assess α-Syn and ERp57 protein levels, aggregation and their cellular distribution, cytoplasm and nuclei fractions were obtained from SH-SY5Y cells treated with CysDA at different times. In the cytosol, α-Syn dimeric forms increased with incubation time, up to 24 hours, whereas the monomeric form was overexpressed within 8 hours, and decreased in prolonged incubations. In the nuclei, only the monomeric form was present. Concerning ERp57, the protein level was increased up to 24 hours in the cytosol, whereas in the nuclei it was transiently increased within 3 hours.
Gene expression analyses have demonstrated that α-Syn and ERp57 mRNAs increased at 6 and 3 hours, respectively from neurotoxins administration.
The overall data suggest that CysDA exerts neurotoxic effects similar to 6-OHDA, supporting the hypothesis that it may be an endogenous parkinsonian mimetic, able to induce α-Syn overexpression and aggregation and ERp57 upregulation.
1. Mosca et al (2006) Neurochem Int. 49:262
2.Coe et al (2010) Int J Biochem Cell Biol 42:796
3.Ferrer et al (2009) Progr Neurobiol 88:8
MORFOFONOLOGIA DEI FENOMENI DI ALLUNGAMENTO VOCALICO IN INDO-ARIO E LATINO
No full textLo scopo del lavoro è quello di indagare da vicino due particolari fenomeni di allungamento vocalico che si manifestano nel ramo indo-ario e nel latino, analizzando nello specifico il comportamento e l'operatività di due leggi fonetiche parecchio problematiche e discusse: la legge di Brugmann per il vedico e la legge di Lachmann per il latino
Numerical study of stability of flows from low to high Mach number
No full textInterest in the study of stability lies in the strong link with the laminar-to-turbulent transition with several implications in the design of new vehicles in the aerospace community. If on one side aeronautics would like to predict and control transition to limit drag, boost efficiency and reduce the fuel consumption on the other hand, space design faces reentry problem where an accurate transition prediction could lead to a better sizing of the thermal protection system, thus enhancing the overall performance of the spacecraft.
Nevertheless one has to keep in mind that transition can occur because of several causes, which make the link between stability and transition not as direct as one would it like to be. On an engineering point of view the use of the eN method has been selected as our preferred way of estimating the onset of transition.
Despite the great amount of software available to study stability of incompressible flows and, to a lesser extent, low supersonic flows, there is a restricted number of codes dealing specifically with hypersonic flows. The objective of this work is then to write a consistent toolkit to be able to study stability of flows at different regimes, from low to high Mach numbers.
The VESTA toolkit (VKI Extensible Stability and Transition Analysis toolkit) gathers a number of codes for different regimes which are based on Chebyshev pseudo-spectral methods. It compares well against literature for the incompressible and compressible flows while hypersonic cases are more difficult to test, because of the narrower body of literature treating them. Nevertheless some comparisons allow us to estimate a reasonable good matching with existing results.
The incompressible study was not limited to the reproduction of standard cases and techniques but included also an original expansion of the -method capable of treating boundary layer flows. Results have been verified against the ones obtained by other methods even if its complexity makes the -method an unideal candidate for the development of the compressible solver.
The compressible linear stability solver is able to cope with both subsonic and supersonic regime and it has been used to verify and expand the current database of neutral stability curves at different Mach, by plotting results for adiabatic flows with different free stream static temperatures.
The compressible solver served as a base for the implementation of the specialized hypersonic code. For this case, when temperature is high enough, air molecules start dissociating and chemical reactions happen between the different species. For this reason air should be considered as a mixture of gases. In the present work this effect is taken into account by means of the Local Thermodynamic Equilibrium (LTE) assumption. A deep investigation has been carried on the effect of free stream temperature and pressure. It turned out that in the investigated range, pressure plays a minor role, while temperature results to be the driving parameter, even more at lower Reynolds numbers. It has been observed that the critical Reynolds number decreases when temperature increases. As the free stream temperature increase the neutral stability curves show also a larger instability area.
Another important aspect of hypersonic flows is the strong shock in front of the body. Its influence on the boundary layer has been modeled as a boundary condition for the calorically perfect gas (CPG) and LTE solver. Nevertheless the latter implementations is new and only simple verifications against a calorically perfect gas was possible. It is already known in literature that the shock stabilizes the flow at low wave numbers. Our computations on chemically reacting flows found out that LTE tends to stabilize it even more, with growth rates as low as three times the respective one for CPG.
Future works will take advantage of the modularity of the VESTA toolkit to add other stability feature like Parabolized Stability Equations and BiGlobal stability. On the numerical side some work will be devoted to the implementation of more general and faster algorithm retaining the same level of accuracy of the present solvers. On a different level the results found in this work could be readily used together with an eN code for the prediction of transition for flight condition and ground testing while the software will be used as the founding brick of an Uncertainty Quantification for transition prediction
Dosaggio del PTH post tiroidectomia e suo valore predittivo di ipocalcemia e terapia sostitutiva a lungo termine
No full textChemioembolizzazione intra-arteriosa con microsfere embolizzanti a rilascio doxorubicina nel trattamento dell'epatocarcinoma monofocale in stadio intermedio
No full textIntroduzione:
La chemioembolizzazione intra-arteriosa epatica (TACE) convenzionale, è un valido approccio terapeutico ampiamente utilizzato in pazienti con epatocarcinoma allo stadio intermedio-avanzato non suscettibili di trattamenti curativi chirurgici o percutanei.
La TACE con utilizzo di microsfere embolizzanti a rilascio di farmaco "DC-Beads", è stata sviluppata per ridurre gli effetti collaterali di questa terapia e migliorarne l'efficacia.
Scopo:
Lo scopo di questo studio prospettico è di presentare i risultati clinici a breve termine della TACE eseguita con l’utilizzo di microsfere embolizzanti a rilascio di doxorubicina (DC Beads) in pazienti con epatocarcinoma monofocale, in stadio intermedio della stadiazione BCLC (Barcelona Clinic LiverCancer), secondo l’algoritmo proposto dalle linee guida ESAL (Europeanassociation for the study of the liver), valutando la sicurezza e l'efficacia del trattamento.
Materiali e Metodi:
Da novembre 2008 a settembre 2011, 42 pazienti (M:F=31/11, età media 62,3± 7,4 anni) con epatopatia cirrotica cronica e HCC (1 nodulo, con diametro medio tra 55 - 70 mm), sono stati sottoposti a TACE con iniezione di microsfere embolizzanti "DC Beads" da 100-300 micron a rilascio di doxorubicina (50-100 mg) fino alla scomparsa di vascolarizzazione del tumore.
Sono stati valutati il tasso di complicanze periprocedurali (sicurezza) e la risposta tumorale al trattamento (efficacia), definita sulla base dei dati di Tomografia Compiuterizzata (TC) trifasica ad 1 e 6 mesi, e classificati secondo i criteri EASL(Europeanassociation for the study of the liver).
Risultati:
1) Complicanze periprocedurali (sicurezza): Il successo tecnico immediato è stato del 100%. Tutti i pazienti sono stati dimessi in 3-5 giorni dopo la procedura. Tra le complicanze maggiori, sono stati osservati 1 su 42 casi ( 2.3%) di formazione ascessuale, che ha richiesto il posizionamento di un drenaggio percutaneo. 12 su 42 pazienti (28.5%) hanno presentato una modesta e breve sindrome post-embolizzazione, con nausea, lievi dolori addominali e talora febbre modesta (38°C) e di breve durata, senza necessità di ricorrere a terapia medica specifica. In 9 su 42 pazienti (21,4%) è stato osservato un modesto e transitorio rialzo degli enzimi epatici (AST, ALT, GGT). Dopo la TACE i livelli di α-FP sono risultati stabiliti o ridotti in tutti i pazienti trattati.
2) Risposta tumorale (efficacia): Per quanto riguardala risposta tumorale ad un mese di follow-up su 42 pazienti, è stata osservata una CR (complete response) in 33/42 casi (78,5%) , una PR (partialresponse) in 9 casi (21.4%). A 6 mesi di follow-up, è stata osservata una CR in 25/42 pazienti (59.5%), una PR in 10/42 casi (23,8%), con progressione di malattia (PD) in 7/42 pazienti (16,6%).
Conclusioni:
La nostra esperienza dimostra che la TACE con microsfere embolizzanti a rilascio di doxorubicina "DC-Beads", risulta una procedura sicura e ben tollerata, con risultati clinici a breve termine promettenti. Inoltre porta ad una riduzione dei livelli plasmatici del farmaco citotossico e quindi minimizza la tossicità sistemica e gli effetti collaterali, rispetto ai dati riportati in letteratura riguardo la TACE convenzionale