L’imaging quantitativo nella clinica nefrologica: i limiti e le potenzialitàdell’elastosonografia [Quantitative imaging in nephrology: limits and potentials of elastosonography]

La patologia renale cronica, indipendentemente dall’eziologia, provoca un sovvertimento strutturale del parenchima con progressivo sviluppo di fibrosi. Il grado di fibrosi renale sembrerebbe correlare con un rischio aumentato di progressione verso l’uremia terminale; pertanto, il monitoraggio nel tempo della fibrosi renale può svolgere un ruolo importante nel follow-up delle patologie renali sia focali che diffuse, e nella valutazione della risposta ai trattamenti. La biopsia renale è l’unica metodica in grado di fornire informazioni oggettive e confrontabili sull’estensione della fibrosi rispetto al parenchima sano ma, data la sua invasività, non è indicata per il follow-up dei pazienti con malattia renale cronica. L’elastosonografia rappresenta una metodica ultrasonografica innovativa e non invasiva che consente la misura dell’elasticità tissutale attraverso la trasmissione di onde meccaniche e la misurazione della loro velocità di propagazione. Sebbene numerosi autori abbiano dimostrato l’utilità delle tecniche elastosonografiche per la quantificazione della fibrosi epatica, pochi sono gli studi sistematici sulle applicazioni dell’elastosonografia nelle patologie renali. Inoltre, fattori quali la profondità dei reni nativi rispetto al piano cutaneo, l’elevata anisotropia del tessuto renale e la possibilità di esaminare solamente una piccola regione di interesse limitano ad oggi la diffusione della metodica nella pratica clinica. Obiettivo di questa review è quello di riesaminare i principi fisici dell’elastosonografia e di passare in rassegna le ultime evidenze circa le possibili applicazioni del modulo ARFI (acoustic radiation force impulse) nello studio delle patologie renali.Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases

Comparison of 3D structural metrics on oyster reefs using unoccupied aircraft photogrammetry and terrestrial LiDAR across a tidal elevation gradient

Abstract Physical structures generated from ecosystem engineers can have a cascade of impacts on the ecological community and the surrounding landscape. The Eastern oyster Crassostrea virginica can form extensive intertidal reefs, whose three‐dimensional structures provide ecosystem services like nursery and foraging habitat for fishes and invertebrates and shoreline stabilization. Measurements of the structural properties of these reefs provide opportunities to quantitatively assess associated services. There is a growing variety of tools available for measuring three‐dimensional (3D) properties of intertidal habitats, including two remote sensing methods that capture 3D structural metrics in a number of environments. We surveyed reefs using a terrestrial laser scanner (TLS, LiDAR) and imagery from unoccupied aircraft systems (UAS, or drones) processed through Structure from Motion photogrammetry. Comparisons of digital elevation models from repetitive flights over an oyster reef to checkpoints yielded mean horizontal and vertical root mean square errors (RMSE) of −0.54 ± 0.47 cm and 0.97 ± 1.0 cm (Mean ± SD), respectively, indicating high accuracy among UAS surveys. Compared to TLS products, point cloud densities from UAS‐derived products were more consistent across the reef elevation gradient and much denser overall except in the low reef zone, which was proximal to most of the TLS scan locations. Comparisons of structural metrics between UAS and TLS showed similarities in metrics like profile and planform curvatures, yet indicated UAS surveys produced higher values of surface complexity and slope. Results indicate that UAS photogrammetry can produce robust oyster reef structural metrics that can be highly useful in oyster conservation and restoration

Neuroprotective effect of different virgin olive oil extracts in SH-SY5Y cells

Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are the largest growing area of neurological research still in search of an effective therapy. Virgin olive oil is a rich source of phenolic compounds that have been demonstrated to interfere with different mechanisms involved in neurodegenerative disorders1. Olive oil polyphenols can be divided into three categories: secoiridoids such as oleocanthal, simple phenols such as hydroxytyrosol and lignanes. Here, we evaluated the neuroprotective effect of four different virgin olive oil extracts against neurodegeneration by determining their effect in modulating oxidative stress and pro-survival pathways. The different olive oil extracts were characterized for their content in tyrosol, hydroxytyrosol, oleacein and oleocanthal by HPLC. SH-SY5Y cells were treated with different concentrations (1-10 μg/mL) of the extracts. Cell viability was evaluated by MTT assay and the results showed that three of the tested extracts significantly increased cell viability. Furthermore, two of these extracts decreased basal reactive oxygen species level measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Interestingly all the extracts increased GSH level measured by monochlorobimane (MCB) assay. These extracts were also able to modulate phase II antioxidant enzymes and MAPK signalling pathways as measured by RT-PCR and immunoblotting. Our findings support the idea that virgin olive oil has a beneficial health effect in counteracting neurodegeneration and these effects are strongly related to the specific pattern of olive oil phenols

Investigation of the anti-inflammatory activity of oleocanthal and oleocanthalic acid in an in vitro model of neuroinflammation

The increase in life expectancy is leading to a consequent rise in the incidence of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, which mainly affect the elderly population. These conditions share several features, such as abnormal protein deposition, oxidative stress, impaired mitochondrial function, and neuroinflammation. The latter plays a crucial role in the pathogenesis of these diseases, and it involves the activation of microglia, the resident immune cells of the brain with an important role in maintaining CNS (central nervous system) homeostasis. In neurodegenerative diseases, microglia are excessively activated, leading to the overproduction of pro-inflammatory mediators such as cytokines, reactive oxygen species, and nitric oxide (NO), causing neuronal death. Extra virgin olive oil (EVOO) has been widely associated with beneficial properties, mainly attributed to its phenols, which exert antioxidant and anti-inflammatory activities. Among them, oleocanthal (OL) is known for its several demonstrated health benefits. Of note, it has a strong anti-inflammatory “ibuprofen-like” activity since it inhibits the cyclooxygenase enzymes. During olive oil shelf-life, phenolic compounds may be modified by different processes. In particular, OL is progressively oxidized to oleocanthalic acid (OA) and this conversion is accelerated by inappropriate storage conditions. To date, the biological effects of OA are completely unknown, and the anti-inflammatory activity of OL has not been characterized in the brain yet. On these bases, the aim of this study was to investigate the potential anti-inflammatory activity of OL and OA in an in vitro model of neuroinflammation. BV-2 microglial cells were treated with OL and OA at different concentrations and after 2 h activated with LPS 100 ng/ml for 24 h. NO production, analyzed with Griess assay, was significantly reduced by OL, but not by OA, compared to cells exposed only to LPS. Furthermore, OL significantly decreased the gene expression of pro-inflammatory factors, namely iNOS, NLRP3, COX2, IL-1β, IL-6 and TNF-α and up-regulated anti-inflammatory mediators such as IL-4 and CD206, compared to LPS. Conversely, OA significantly reduced only the expression of IL-1β and COX2, although to a lesser extent than OL. In addition, the protein levels of iNOS and NLRP3, analyzed by immunoblotting, were significantly reduced by OL compared to LPS, but not by OA. Interestingly, OL was able to completely inhibit p38 MAPK phosphorylation induced by LPS suggesting that the reduction of neuroinflammation triggered by OL could be, at least partially, due to the modulation of this signaling pathway. In conclusion, our data clearly demonstrate that OL exerts a strong anti-inflammatory activity in the brain, by efficiently counteracting microglia activation. This confirms the beneficial role of EVOO consumption for human health. Nonetheless, the strong biological activity of this compound is lost when it’s oxidized to OA. This emphasizes how crucial is to store EVOO in appropriate conditions and highlights the importance of consuming EVOO as fresh as possible to benefit from the health effects of this product

SAR study on Arylmethyloxyphenyl scaffold: looking for a P-gp nanomolar affinity

Starting from the previously developed P-gp ligands 1a and 1b (EC50 ¼ 0.25 mM and 0.65 mM, respectively), new arylmethyloxyphenyl derivatives have been synthesized as P-gp modulators in order to investigate: (i) the effect of small electron-donor groups (OMe) (5e11), (ii) the effect of the replacement of methoxy groups with an electron-withdrawal substituent (Cl) on C-ring (13) (iii) the effect induced by the replacement of C-ring with heteroaromatic cycles such as thiophene and pyrimidine (13, 15, 16), (iv) the effect induced by molecular constriction on C ring (14, 17, 18) on P-gp modulating activity. The results demonstrated that P-gp inhibition potency is strongly correlated to the number of methoxy groups in the A-ring whereas the methoxylation of C-ring seems to poorly affect P-gp activity. The best result was found for compound 10 that displays a nanomolar affinity (EC50 ¼ 7.1 nM) towards P-gp pump and, in the meantime lacks of activity against MRP1 pump

STUDY OF THE NEUROPROTECTIVE EFFECTS OF FOUR DIFFERENT EXTRA VIRGIN OLIVE OILS

Neurodegenerative diseases represent an increasingly public health problem, especially in the aging population, still in search of an effective therapy. The consumption of extra-virgin olive oil represents the main source of phenols from Mediterranean diet. In vitro and in vivo studies demonstrated preventive and protective properties of extra-virgin olive oil against neurodegeneration. In particular, the specific phenolic pattern of different extra virgin olive oils could influence their biological activity such as neuroprotection. To deepen this hypothesis, we investigated the potential differences in neuroprotective effects of four extra virgin olive oil extracts against H2O2-induced oxidative damage in differentiated SH-SY5Y cells by determining their effect in modulating antioxidant enzymes and pro-survival pathways. The different olive oil extracts were characterized for their content in tyrosol, hydroxytyrosol, oleacein and oleocanthal by HPLC. SH-SY5Y were treated with different concentrations (1-500 \ub5g/mL) of the four extracts (corniolo, collina, pianura and spes) in the presence and absence of H2O2. Interestingly, collina is the most effective in counteracting oxidative damage as evaluated by MTT and LDH assays. Collina, pianura and spes reduced the H2O2-induced release of reactive oxygen species level as measured by dichloro-dihydro-fluorescein diacetate assay. Moreover, collina, pianura and spes increased GSH level measured by monochlorobimane assay. The extracts were also able to modulate phase II antioxidant enzymes and BDNF mRNA levels as measured by RT-PCR. Our findings confirm that extra-virgin olive oil possesses beneficial effects in counteracting neurodegeneration and these effects are strongly related to the specific pattern of olive oil phenols presents in the different olive oils. This work was supported by MIUR-PRIN 2015 (No. 20152HKF3Z