Publications by authors named "Gabriele D"

34 Publications

Exploring the variability of radiomic features of lung cancer lesions on unenhanced and contrast-enhanced chest CT imaging.

Phys Med 2021 Feb 12;82:321-331. Epub 2021 Mar 12.

Institute of Radiological Sciences, University of Sassari, Italy.

Purpose: The aim of this methods work is to explore the different behavior of radiomic features resulting by using or not the contrast medium in chest CT imaging of non-small cell lung cancer.

Methods: Chest CT scans, unenhanced and contrast-enhanced, of 17 patients were selected from images collected as part of the staging process. The major T1-T3 lesion was contoured through a semi-automatic approach. These lesions formed the lesion phantoms to study features behavior. The stability of 94 features of the 3D-Slicer package Radiomics was analyzed. Feature discrimination power was quantified by means of Gini's coefficient. Correlation between distance matrices was evaluated through Mantel statistic. Heatmap, cluster and silhouette plots were applied to find well-structured partitions of lesions.

Results: The Gini's coefficient evidenced a low discrimination power, <0.05, for four features and a large discrimination power, around 0.8, for five features. About 90% of features was affected by the contrast medium, masking tumor lesions variability; thirteen features only were found stable. On 8178 combinations of stable features, only one group of four features produced the same partition of lesions with the silhouette width greater than 0.51, both on unenhanced and contrast-enhanced images.

Conclusions: Gini's coefficient highlighted the features discrimination power in both CT series. Many features were sensitive to the use of the contrast medium, masking the lesions intrinsic variability. Four stable features produced, on both series, the same partition of cancer lesions with reasonable structure; this may merit being objects of further validation studies and interpretative investigations.
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http://dx.doi.org/10.1016/j.ejmp.2021.02.014DOI Listing
February 2021

Cardiac and Metabolic Impact of Functional Foods with Antioxidant Properties Based on Whey Derived Proteins Enriched with Hemp Seed Oil.

Antioxidants (Basel) 2020 Oct 30;9(11). Epub 2020 Oct 30.

Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, E. and E.S. (Di.B.E.S.T.), University of Calabria, 87036 Rende (CS), Italy.

The impaired ability to feed properly, evident in oncologic, elderly, and dysphagic patients, may result in malnutrition and sarcopenia. Increasing the consumption of dietary proteins by functional foods and enriching their composition by adding beneficial nutrients may represent an adjuvant therapy. We aimed to evaluate the safety and the positive effects of a standard diet (SD) supplemented with whey-derived protein puddings (WDPP), with appropriate rheological properties, and hemp seed oil (HSO), rich in polyphenols. Rats were assigned to SD, WDPP, WDPP plus hemp seed oil (HSOP), and HSO supplemented diets for eight weeks. "Anthropometric", metabolic, and biochemical variables, oxidative stress, tissue injury, liver histology, and cardiac susceptibility to ischemia/reperfusion were analyzed. All the supplementations did not induce significant changes in biochemical and metabolic variables, also in relation to glucose tolerance, and livers did not undergo morphological alteration and injury. An improvement of cardiac post-ischemic function in the Langendorff perfused heart model and a reduction of infarct size were observed in WDPP and HSOP groups, thanks to their antioxidant effects and the activation of Akt- and AMPK-dependent protective pathways. Data suggest that (i) functional foods enriched with WDPP and HSOP may be used to approach malnutrition and sarcopenia successfully under disabling conditions, also conferring cardioprotection, and that (ii) adequate rheological properties could positively impact dysphagia-related problems.
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http://dx.doi.org/10.3390/antiox9111066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692817PMC
October 2020

Quality indicators for hyperthermia treatment: Italian survey analysis.

Phys Med 2020 Feb 30;70:118-122. Epub 2020 Jan 30.

Radiotherapy Department, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Torino, Italy.

Aim: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field.

Material And Methods: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches.

Results: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed.

Conclusion: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.
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http://dx.doi.org/10.1016/j.ejmp.2020.01.010DOI Listing
February 2020

SLUG/HIF1-α/miR-221 regulatory circuit in endometrial cancer.

Gene 2019 Aug 18;711:143938. Epub 2019 Jun 18.

Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy. Electronic address:

Background And Purpose: The pathogenesis of endometrial cancer (EC) involves many regulatory pathways including transcriptional regulatory networks supported by transcription factors and microRNAs only in part known. The aim of this retrospective study was to explore the possible correlation in the EC microenvironment between master regulators of complex phenomena such as steroid responsiveness through estrogen receptor alpha (ERα) and progesterone receptor (PR), epithelial-to-mesenchymal transition (supported by SLUG transcription factor), hypoxia (with hypoxia inducible factor-1 alpha, HIF-1α), and obesity that has been recognized as a EC risk factor.

Methods: Formalin-Fixed Paraffin-Embedded (FFPE) blocks from University of Ferrara Pathology Archive were used and allocated into 2 groups according to their immunohistochemical positivity to ERα and PR, distinguishing the samples with a more benign prognosis (ERα/PR) from those with a poorer prognosis (ERα/PR). Immunohistochemistry for HIF1-α and SLUG was also performed. Body mass index (BMI) was registered at the time of diagnosis: patients with BMI ≥ 30 kg/m were defined obese (OB). Total RNA was isolated for miR-221 analysis.

Results: We showed a comparable percentage of HIF1-α and SLUG positive samples in the ERα/PR and ERα/PR groups. However, the obesity factor impacted more in the ERα/PR group since the ratio between OB and non-obese (NOB) patients with high expression of HIF1-α and SLUG was higher in ERα/PR than in the ERα/PR group. miR-221 levels were significantly higher in the OB than NOB patients, and, also in this case, obesity impacted more in the ERα/PR group.

Conclusions: A molecular circuit of mutual regulation between ERα, PR, HIF1-α, SLUG and miR-221 is feasible in the EC and was firstly suggested by our research. In this interplay miR-221 seems to be in a nodal point of the regulatory system that is particularly strengthened by the metabolic changes in obesity.
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http://dx.doi.org/10.1016/j.gene.2019.06.028DOI Listing
August 2019

New-onset extrapyramidal symptoms in hepatic cirrhosis without neuroimaging signs of encephalopathy.

Rev Neurol (Paris) 2019 Jun 24;175(6):407-409. Epub 2019 Apr 24.

Department of neurosurgery, campus germaneto, University of Catanzaro 1, VLE europa, 88100 Catanzaro I, Italy.

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http://dx.doi.org/10.1016/j.neurol.2018.10.007DOI Listing
June 2019

Prostate cancer dose-response, fractionation sensitivity and repopulation parameters evaluation from 25 international radiotherapy outcome data sets.

Br J Radiol 2019 Jun 24;92(1098):20180823. Epub 2019 Apr 24.

5 Radiation Therapy, Candiolo Cancer Institute - FPO , IRCCS, Candiolo (To) , Italy.

Objective: This study was undertaken to model the biochemical free survival at 5 years and to evaluate the parameters defining dose-response curve, dose-fractionation radiosensitivity and repopulation.

Methods: It was carried out a literature search on Pubmed to retrieve data sets of patients treated with external beam radiation therapy of 1.8-4.0 Gy per fraction and overall treatment time of 3 to 10 weeks. 10 groups were identified, based on risk class and androgen deprivation therapy (ADT). Dose-response curve (dose at 50% probability of control) and (steepness), (dose-fractionation radiosensitivity), and repopulation parameters, and , were calculated. Bootstrap-based cross-validation was performed and median and 95% CI (confidence interval) were evaluated.

Results: 25 data sets, including 20,310 patients, were considered. The median (95% CI) and values were 62 (CI 53 - 66) Gy and 1.6 (0.8 - 2.4). ADT patients showed lower values of and (57 ± 5 Gy and 1.1 ± 0.4) compared to no-ADT patients (65 ± 2 Gy and 2.3 ± 0.6), with < 0.0001 and = 0.002. If we did not consider any dependence on overall treatment time, the median (95% CI) value of was 1.4 (1.0 - 1.9) Gy with < 0.0001 for all patients. The median values of and were 0.0 to 0.3 Gy/d and 18-40 days.

Conclusion: Dose-response curve resulted dependent on risk class and ADT, with higher steepness for no-ADT patients. Low values of dose-fractionation radiosensitivity were found, supporting the use of moderate hypofractionated radiotherapy in each risk class. A limited dependence on repopulation was observed.

Advances In Knowledge: Prostate cancer response to moderate hypofractionated radiotherapy was reliably quantified considering risk class and androgen deprivation therapy.
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http://dx.doi.org/10.1259/bjr.20180823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592096PMC
June 2019

Key characteristics and modelling of bigels systems: A review.

Mater Sci Eng C Mater Biol Appl 2019 Apr 26;97:932-953. Epub 2018 Dec 26.

Department of Information, Modeling, Electronics and System Engineering (D.I.M.E.S.), University of Calabria, Via P. Bucci, Cubo 39C, I-87036 Rende, CS, Italy. Electronic address:

Bigels are interesting semisolid formulations with better properties for different applications such as cosmetics and pharmaceutical systems. Due to the mixing of two phases of different nature (polar and apolar), bigels possess some interesting features like ability to deliver hydrophilic and hydrophobic drugs, better spreadability and water washability, improved permeability of drugs, enhanced hydration of stratum corneum and ability to manipulate the drug release rate. The main objective of this review article is to provide a thorough insight into the important characteristics of bigels together with the discussion on modelling of bigel systems to relate their properties with individual constituents and different parameters. Moreover, some important applications of bigels are also discussed by considering some examples from the literature.
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http://dx.doi.org/10.1016/j.msec.2018.12.075DOI Listing
April 2019

Occipital Nerve Stimulation for Refractory Pain after Occipitocervical Fusion.

Acta Neurochir Suppl 2019;125:365-367

Department of Neurosurgery, Magna Graecia University of Catanzaro, Catanzaro, Italy.

Occipital nerve stimulation (ONS) is electric stimulation of the distal branches of the greater occipital nerve by cylindrical or paddle leads implanted in subcutaneous occipital tissue. This surgical option has emerged as a promising treatment for different types of disabling medical refractory headache and recently also for residual occipital and nuchal pain after previous occipitocervical fusion. The mechanisms of action have not yet been clearly explained: electrical stimulation of the occipital nerve has both peripheral and central effects on the nervous system, which may modulate nociception. ONS is a well-tolerated and safe procedure in comparison with other invasive modalities of treatment. Lead migration/dislodgement is a common complication, but use of new surgical techniques and leads may reduce the rate of this complication.
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http://dx.doi.org/10.1007/978-3-319-62515-7_52DOI Listing
August 2019

Occipitocervical Fusion.

Acta Neurochir Suppl 2019;125:243-245

Department of Neurosurgery, Magna Graecia University of Catanzaro, Catanzaro, Italy.

Occipitocervical fusion is a surgical technique in continuous evolution due to the innovation of devices, operative and instrumentation techniques. The aetiologies responsible for occipitocervical instability are trauma, neoplastic disease, metabolic disease or congenital disease. A variety of stabilization techniques are currently available depending on the type of patient and surgeon's experience. Each of these techniques requires thorough knowledge of the anatomy of the craniovertebral junction.
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http://dx.doi.org/10.1007/978-3-319-62515-7_34DOI Listing
August 2019

Salvage radiation therapy after radical prostatectomy: survival analysis.

Minerva Urol Nefrol 2019 Jun 23;71(3):240-248. Epub 2018 Jul 23.

Division of Radiation Therapy, University of Sassari, Sassari, Italy.

Background: To evaluate the outcome of patients treated with salvage radiotherapy after radical prostatectomy and to investigate the effects of independent predictors on survival.

Methods: From January 2000 to December 2015, 234 patients with biochemical/clinical recurrences after radical prostatectomy were submitted to salvage radiotherapy (SRT). One hundred and fifty-seven patients (67%) received three-dimensional (3D) conformal radiotherapy while 77 patients (33%) were treated with intensity-modulated radiotherapy (IMRT) or IMRT/image-guided radiotherapy by tomotherapy. The median RT dose to prostate bed was 70.2 Gy (range: 66-79 Gy). The investigated endpoints were biochemical relapse-free survival (BRFS), clinical relapse-free survival (CRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS). Different covariates were considered to investigate predictors of survival.

Results: With a median follow-up of 117 months the BRFS, CRFS, DMFS and PCSS at 10 years were 54%, 84%, 90%, and 94%, respectively. In multivariate analysis (MVA), the pathological Gleason Score (pGS) was the most important factor affecting BRFS, CRFS, DMFS and PCSS (P<0.007, HR>1.55); pathological stage (pT) was predictor of BRFS (P=0.007, HR=1.7) and PCSS (P=0.02, HR=4.2), and the last prostate-specific antigen during follow-up was an important survival predictor of CRFS (P=0.004, HR=1.26) and PCSS (P<0.0001, HR=1.04). The time between surgery and the start of SRT was correlated with BRFS (P<0.0001, HR=0.987) and CRFS (P=0.047, HR=0.989). In univariate analysis (UVA), positive surgical margins at the prostatectomy specimen improved BRFS (P=0.01, HR=0.54), CRFS (P=0.05, HR=0.46) and DMFS (P=0.005, HR=0.13) after SRT.

Conclusions: At long-term follow-up, excellent outcome results of SRT on BRFS, CRFS, DMFS, and PCSS were obtained. Several prognostic factors such as pGS, pT and surgical margin status were found to be predictors of survival.
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http://dx.doi.org/10.23736/S0393-2249.18.03124-7DOI Listing
June 2019

The role of edible oils in low molecular weight organogels rheology and structure.

Food Res Int 2018 09 23;111:399-407. Epub 2018 May 23.

Department of Information, Modeling, Electronics and System Engineering, (D.I.M.E.S.), University of Calabria, Via P. Bucci, Cubo 39C, Rende I-87036, CS, Italy. Electronic address:

In this paper, the role of solvent characteristics on the rheological and physicochemical properties of organogels was investigated using different techniques. Vegetable oils, such as rice, sunflower and castor oil were used as solvents, for producing organogels with monoglycerides of fatty acids or a mixture of fatty alcohols (policosanol) as gelators. Moreover, two non-edible oils (silicon and paraffin oil) were also used for analysing the properties of solvents completely different in nature with respect to the edible ones, for a better interpretation of the given results. Organogels were investigated from a rheological point of view and through a microscopic analysis, given by polarised light (POM) and atomic force (AFM) microscopy, and X-rays to study the crystallinity of the system. The IR technique was used to analyse the intermolecular interactions, resulting in interesting information about the effect of oil polarity on the driving forces promoting structuration. This investigation showed that when solvents of a similar chemical nature are used, their physical properties, mainly oil polarity, are strictly related to the properties of the organogel, such as the onset of crystallisation temperature, the stiffness of the final material and its crystallinity. Anyway, these physical parameters seem insufficient to describe properly the role of solvents when oils of a different chemical nature are compared.
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http://dx.doi.org/10.1016/j.foodres.2018.05.050DOI Listing
September 2018

Effect of the monostearate/monopalmitate ratio on the oral release of active agents from monoacylglycerol organogels.

Food Funct 2018 Jun;9(6):3278-3290

Department of Information, Modelling, Electronics and System Engineering, (D.I.M.E.S.) University of Calabria, Via P. Bucci, Cubo 39C, I-87036 Rende, CS, Italy.

The delivery of active agents from organogels is becoming an important topic owing to the possibility of releasing, in a controlled way, lipophilic agents. Controlled release from foods is a topic with increasing relevance owing to the growing industrial interest towards functional or medical foods, i.e. foods containing nutraceutical agents or drugs. Anyway, release properties are related to the rheological properties of organogels, and, therefore, a deep knowledge of their microstructure and physical characteristics is necessary to design carriers with expected release properties. In this work, two low molecular weight gelators (i.e. glycerol monopalmitate, GMP, and glycerol monostearate, GMS) have been investigated using rheology, microscopy and infrared spectroscopy, IR, aiming at understanding the effects of different gelator ratios on organogel properties. It was observed that GMP, within the range of investigated compositions, seems to be more effective in yielding consistent organogels and this effect was related to differences in microstructure with respect to GMS. Their ability to control the oral release of active agents was investigated, in vitro, using a chemotherapeutic drug for adenocarcinoma of the gastrointestinal tract, 5 fluorouracil (5-FU). A physical model based on carrier erosion was used to describe the release data, evidencing a good agreement with experimental values. Among the tested samples it seems that the use of 90% of GMS (over total organogelator content) yields promising results allowing a good partition of the released drug between the gastric and intestinal tracts with the largest value (although lower than 40% of loaded amount) of the total released drug.
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http://dx.doi.org/10.1039/c8fo00594jDOI Listing
June 2018

Impact of a rectal and bladder preparation protocol on prostate cancer outcome in patients treated with external beam radiotherapy.

Strahlenther Onkol 2017 Sep 15;193(9):722-732. Epub 2017 Jun 15.

Radiotherapy Department, Candiolo Cancer Institute - FPO,IRCCS, Candiolo (To), Italy.

Purpose And Objective: To test the hypothesis that a rectal and bladder preparation protocol is associated with an increase in prostate cancer specific survival (PCSS), clinical disease free survival (CDFS) and biochemical disease free survival (BDFS).

Patients And Methods: From 1999 to 2012, 1080 prostate cancer (PCa) patients were treated with three-dimensional conformal radiotherapy (3DCRT). Of these patients, 761 were treated with an empty rectum and comfortably full bladder (RBP) preparation protocol, while for 319 patients no rectal/bladder preparation (NRBP) protocol was adopted.

Results: Compared with NRBP patients, patients with RBP had significantly higher BDFS (64% vs 48% at 10 years, respectively), CDFS (81% vs 70.5% at 10 years, respectively) and PCSS (95% vs 88% at 10 years, respectively) (log-rank test p < 0.001). Multivariate analysis (MVA) indicated for all treated patients and intermediate high-risk patients that the Gleason score (GS) and the rectal and bladder preparation were the most important prognostic factors for PCSS, CDFS and BDFS. With regard to high- and very high-risk patients, GS, RBP, prostate cancer staging and RT dose were predictors of PCSS, CDFS and BDFS in univariate analysis (UVA).

Conclusion: We found strong evidence that rectal and bladder preparation significantly decreases biochemical and clinical failures and the probability of death from PCa in patients treated without daily image-guided prostate localization, presumably since patients with RBP are able to maintain a reproducibly empty rectum and comfortably full bladder across the whole treatment compared with NRPB patients.
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http://dx.doi.org/10.1007/s00066-017-1163-4DOI Listing
September 2017

Hypertension in kidney transplantation is associated with an early renal nerve sprouting.

Nephrol Dial Transplant 2017 Jun;32(6):1053-1060

Hypertension and Nephrology Unit, Department of Systems Medicine, Tor Vergata University, Rome, Italy.

Background.: Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney.

Methods.: We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls.

Results: . Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves.

Conclusions: . Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation.
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http://dx.doi.org/10.1093/ndt/gfx069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837349PMC
June 2017

Prognostic factors in prostate cancer patients treated by radical external beam radiotherapy.

Panminerva Med 2017 09 3;59(3):210-220. Epub 2017 Mar 3.

Radiotherapy Unit, Candiolo Cancer Institute - FPO, IRCCS, Turin, Italy.

Background: The aim of this paper was to analyze, retrospectively, in prostate cancer patients treated in our Centre with external beam radiotherapy, the prognostic factors and their impact on the outcome in terms of cancer-specific survival (CSS), biochemical disease-free survival (BDFS) and clinical disease-free survival (CDFS).

Methods: From October 1999 and March 2012, 1080 patients were treated with radiotherapy at our Institution: 87% of them were classified as ≤cT2, 83% had a Gleason Score (GS) ≤7, their mean of iPSA was 18 ng/mL, and the rate of clinical positive nodes was 1%. The mean follow-up was 81 months.

Results: The statistically significant prognostic factors for all groups of patients at both, univariate and multivariate analysis, were the GS and the iPSA. In intermediate- and high- or very-high-risk patients at multivariate analysis other prognostic factors for CSS were positive nodes on computed tomography (CT) scan and rectal preparation during the treatment; for BDFS, the prognostic factors were patient risk classification, positive lymph nodes on CT scan and rectal/bladder preparation; for CDFS, the prognostic factors were the number of positive core on biopsy (P=0.003), positive lymph nodes on CT scan, and radiotherapy (RT) dose. In high/very-high risk patient group at multivariate analysis other prognostic factors for CSS were clinical/radiological stage and RT dose, for BDFS they were adjuvant hormone therapy, clinical/radiological stage, and RT dose >77.7 Gy, and for CDFS they were clinical/radiological stage and RT dose >77.7 Gy.

Conclusions: The results of this study confirm the prognostic factors described in the recent literature, with the addition of rectal/bladder preparation, generally known for its effect on toxicity but not yet on outcome.
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http://dx.doi.org/10.23736/S0031-0808.17.03232-3DOI Listing
September 2017

Quality indicators in the intensity modulated/image-guided radiotherapy era.

Crit Rev Oncol Hematol 2016 Dec 2;108:52-61. Epub 2016 Nov 2.

Medical Physics Department of the Candiolo Cancer Center-FPO-, IRCCS, Candiolo, Turin, Italy.

Purpose: To propose new Quality Indicators (QIs) for the Intensity Modulated(IMRT)/Image-Guided(IGRT) Radiotherapy techniques.

Materials And Methods: Two structure, 10 process and 2 outcome QIs were elaborated. A working group including Radiation Oncologist, Medical Physicist and Radiation Technologists was made up. A preliminary set of indicators was selected on the basis of evidenced critical issues; the criteria to identify more relevant and specific QIs for IMRT/IGRT were defined; structure, process and outcome QIs were defined. The elaborated indicators were tested in four Italian Radiotherapy Centers.

Results: Fourteen indicators were proposed. Seven indicators were completely new while a new standard is proposed for four indicators based on Validation Centers (VC) data. No change was reported for 3 indicators. The indicators were applied in the four VC. The VC considered were able to respect all indicators except indicator 2 for one Center.

Discussion And Conclusion: QIs may provide useful measures of workload and service performances.
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http://dx.doi.org/10.1016/j.critrevonc.2016.10.013DOI Listing
December 2016

A rheological and microstructural characterisation of bigels for cosmetic and pharmaceutical uses.

Mater Sci Eng C Mater Biol Appl 2016 Dec 1;69:358-65. Epub 2016 Jul 1.

Department of Information, Modeling, Electronics and System Engineering, (D.I.M.E.S.), University of Calabria, Via P. Bucci, Cubo 39C, I-87036, Rende, CS, Italy. Electronic address:

Bigels are biphasic systems formed by water-based hydrogels and oil-based organogels, mainly studied, in the last few years, for pharmaceutical and cosmetic application focused on the controlled delivery of both lipophilic and hydrophilic active agents. The rheological properties of bigels depend on both the amount and the rheological characteristics of single structured phases. Moreover, it can be expected that, at large fractions of one of the starting gels, systems more complex than oil-in-water or water-in-oil can be obtained, yielding bicontinuous or matrix-in-matrix arrangement. Model bigels were investigated from a microstructural (i.e. microscopy and electrical conductivity tests) and rheological point of view. The hydrogel was prepared by using a low-methoxyl pectin whereas the organogel was prepared by using olive oil and, as gelator, a mixture of glyceryl stearate and policosanol. Model bigels were obtained by increasing the amount of organogel mixed with the hydrogel, and microstructural characterisation evidenced an organogel-in-hydrogel behaviour for all investigated samples, even though at the highest organogel content a more complex structure seems to arise. A semi-empirical model, based on theoretical equations developed for suspensions of elastic spheres in elastic media, was proposed to relate bigel rheological properties to single phase properties and fractions.
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http://dx.doi.org/10.1016/j.msec.2016.06.098DOI Listing
December 2016

A Simple PSA-Based Computational Approach Predicts the Timing of Cancer Relapse in Prostatectomized Patients.

Cancer Res 2016 09;76(17):4941-7

Department of Neuroscience, University of Turin, Torino, Italy.

Recurrences of prostate cancer affect approximately one quarter of patients who have undergone radical prostatectomy. Reliable factors to predict time to relapse in specific individuals are lacking. Here, we present a mathematical model that evaluates a biologically sensible parameter (α) that can be estimated by the available follow-up data, in particular by the PSA series. This parameter is robust and highly predictive for the time to relapse, also after administration of adjuvant androgen deprivation therapies. We present a practical computational method based on the collection of only four postsurgical PSA values. This study offers a simple tool to predict prostate cancer relapse. Cancer Res; 76(17); 4941-7. ©2016 AACR.
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http://dx.doi.org/10.1158/0008-5472.CAN-16-0460DOI Listing
September 2016

The effects of intermolecular interactions on the physical properties of organogels in edible oils.

J Colloid Interface Sci 2016 Dec 3;483:154-164. Epub 2016 Aug 3.

Department of Information, Modeling, Electronics and System Engineering (D.I.M.E.S.), University of Calabria, Via P. Bucci, Cubo 39C, I-87036 Rende, CS, Italy. Electronic address:

The microstructure of organogels based on monoglycerides of fatty acids (MAGs) and policosanol and on different edible oils was investigated by using different techniques (calorimetry, nuclear magnetic resonance, infrared spectroscopy, rheology, polarized light microscopy) towards a better understanding and control of the oil gelation phenomena. Dynamic moduli were related via a fractal model to microstructural information such as solid content and fractal dimension. Infrared spectroscopy evidenced that network structure in MAGs gel is mainly due to hydrogen bonding, whereas in policosanol system is mainly given by van der Waals interactions. Because of the different relative contribution of molecular interactions, the investigated organogelators exhibit a distinguished macroscopic behavior. MAGs are sensitive to the utilized oil and structuration occurs quickly, even though at a temperature lower than policosanol. Policosanol organogels exhibit a behavior independent of the used oil and a slower gelation rate, as a result of the weaker van der Waals interactions. Nevertheless, at lower concentration a stronger final gel is obtained, probably due to of the large number of interactions arising among the long alkyl chains of the fatty alcohols. Obtained results evidenced that policosanol is very effective in gelation of different oils and seems promising for potential commercial uses.
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http://dx.doi.org/10.1016/j.jcis.2016.08.009DOI Listing
December 2016

Administration of palmitoylethanolamide in combination with topiramate in the preventive treatment of nummular headache.

Int Med Case Rep J 2016 18;9:193-5. Epub 2016 Jul 18.

Department of Neurosurgery, University of Catanzaro "Magna Graecia", Catanzaro, Italy.

Nummular headache has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter, not attributed to another disorder. Both size and shape of the painful area remain constant since the onset of symptoms. A 57-year-old woman presented with a history of focal episodic pain in a circumscribed area on the right parietal region. The administration of standard oral doses of palmitoylethanolamide and topiramate in combination showed an improvement in pain symptoms and on pain measuring scales.
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http://dx.doi.org/10.2147/IMCRJ.S106323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957685PMC
August 2016

CYP1A1 3801T>C polymorphism implicated in altered xenobiotic metabolism is not associated with variations in sperm production and function as measured by total motile sperm and fertilization rates with intracytoplasmic sperm injection.

Fertil Steril 2016 08 23;106(2):481-6. Epub 2016 Apr 23.

Division of Reproductive Endocrinology, Department of Obstetrics, Gynecology and Reproductive Science, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Morristown, New Jersey.

Objective: To evaluate the cytochrome P450 3801T>C polymorphism's frequency in relation to semen production, as determined by semen analysis parameters, and sperm function, as determined by fertilization rates with intracytoplasmic sperm injection (ICSI).

Design: Case-control study.

Setting: Academic-affiliated private practice.

Patient(s): This study included patients undergoing IVF from 2004 to 2014 grouped into categories based on semen analysis parameters performed at a single andrology laboratory. Cases were patients with total motile sperm (TMS) counts of ≤20 × 10(6). Frequency-matched controls were selected with TMS of >20 × 10(6).

Intervention(s): The 3801T>C polymorphism was identified using DNA from serum samples with real-time quantitative polymerase chain reaction.

Main Outcome Measure(s): CYP1A1 3801T>C polymorphism frequency in TMS groups and distribution in fertilization rate outcomes with ICSI.

Result(s): A total of 460 cases were identified with ≤20 × 10(6) TMS, and 489 age-matched controls with >20 × 10(6) TMS were selected across the study time frame. For those with <5 × 10(6) vs. >20 × 10(6) TMS there was no difference when comparing heterozygous (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.66-1.40) or homozygous mutant (OR 1.33; 95% CI 0.52-3.20) with the wild-type patients. Additionally, no difference was seen when analyzing subgroups <5 × 10(6), 5-20 × 10(6), and >20 × 10(6) TMS in a similar fashion. Receiver operating characteristic (ROC) curve analysis did not find a significant TMS count based on presence of the polymorphism (area under the ROC curve = 0.51). There were 460 patients who underwent IVF/ICSI, and fertilization rates did not differ with presence of the polymorphism (area under the ROC curve = 0.50).

Conclusion(s): Allele frequency of the 3801T>C polymorphism does not correlate with semen production as determined by TMS counts or sperm function as determined by fertilization rates with ICSI. The use of neither semen analysis parameters nor fertilization rates with ICSI helps identify CYP1A1 polymorphism carriers.
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http://dx.doi.org/10.1016/j.fertnstert.2016.04.003DOI Listing
August 2016

Beyond D'Amico risk classes for predicting recurrence after external beam radiotherapy for prostate cancer: the Candiolo classifier.

Radiat Oncol 2016 Feb 24;11:23. Epub 2016 Feb 24.

Division of Radiation Oncology, FPO-IRCCS Cancer Center of Candiolo (Torino), Candiolo, Italy.

Background: The aim of this work is to develop an algorithm to predict recurrence in prostate cancer patients treated with radical radiotherapy, getting up to a prognostic power higher than traditional D'Amico risk classification.

Methods: Two thousand four hundred ninety-three men belonging to the EUREKA-2 retrospective multi-centric database on prostate cancer and treated with external-beam radiotherapy as primary treatment comprised the study population. A Cox regression time to PSA failure analysis was performed in univariate and multivariate settings, evaluating the predictive ability of age, pre-treatment PSA, clinical-radiological staging, Gleason score and percentage of positive cores at biopsy (%PC). The accuracy of this model was checked with bootstrapping statistics. Subgroups for all the variables' combinations were combined to classify patients into five different "Candiolo" risk-classes for biochemical Progression Free Survival (bPFS); thereafter, they were also applied to clinical PFS (cPFS), systemic PFS (sPFS) and Prostate Cancer Specific Survival (PCSS), and compared to D'Amico risk grouping performances.

Results: The Candiolo classifier splits patients in 5 risk-groups with the following 10-years bPFS, cPFS, sPFS and PCSS: for very-low-risk 90 %, 94 %, 100 % and 100 %; for low-risk 74 %, 88 %, 94 % and 98 %; for intermediate-risk 60 %, 82 %, 91 % and 92 %; for high-risk 43 %, 55 %, 80 % and 89 % and for very-high-risk 14 %, 38 %, 56 % and 70 %. Our classifier outperforms D'Amico risk classes for all the end-points evaluated, with concordance indexes of 71.5 %, 75.5 %, 80 % and 80.5 % versus 63 %, 65.5 %, 69.5 % and 69 %, respectively.

Conclusions: Our classification tool, combining five clinical and easily available parameters, seems to better stratify patients in predicting prostate cancer recurrence after radiotherapy compared to the traditional D'Amico risk classes.
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http://dx.doi.org/10.1186/s13014-016-0599-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765202PMC
February 2016

External beam radiotherapy with dose escalation in 1080 prostate cancer patients: definitive outcome and dose impact.

Panminerva Med 2016 Jun 19;58(2):121-9. Epub 2016 Jan 19.

Department of Radiotherapy, Candiolo Cancer Institute, Candiolo, Turin, Italy -

Background: The aim of this paper was to report definitive outcome of prostate cancer patients treated with dose escalation during a period of 12.5 years.

Methods: From October 1999 to March 2012 we treated 1080 patients affected by prostate cancer, using External Beam Radiotherapy (EBRT). The mean age was 69.2 years. Most of the patients (69%) were staged as cT2, Gleason Score (GS)<7; the mean iPSA 18 ng/mL; the rate of clinical positive nodes was 1%. Our intention to treat was the following: for low risk patients 72 Gy; for intermediate risk patients 75.6 Gy and for high-very high risk patients 79.2 Gy in 1.8 Gy/day fractions. From 2008 we changed the fractionation scheme and the doses were the following: for low risk patients 74 Gy and for intermediate and high-very high risk patients 78 Gy in 2.0 Gy/day fractions. Whole pelvis irradiation was performed in high-very high risk patients with 43.2-50.4 Gy in 1.8 Gy per day. The mean follow-up was 81 months.

Results: For the whole population at 5 and 10 years, the prostate cancer specific overall survival (CSOS) was 96.7% and 92.2% respectively; the clinical disease free survival (CDFS) 88% and 77%; the biochemical disease free survival (BDFS) 75% and 58.5%. The 5 and 10 years CSOS was 98% and 96% respectively for low risk, 96% and 92% for intermediate risk and 89% and 82% for high-very high risk patients. In intermediate and high-very high risk groups at 5 and 10 years the CSOS was 95.2% and 89.2% respectively, the CDFS 84.5% and 70% and the BDFS 70% and 51% respectively. In high-very high risk patients at 5 and 10 years the CSOS were respectively 89% and 82% the CDFS was 78% and 61% and BDFS was 61% and 34%. In whole patient population the BDFS was related with the dose level (P=0.006) as well as the CDFS (P=0.003) with a cut off of 75.6 Gy. In the subgroup of intermediate plus high-very high risk patients the BDFS and the CDFS were dose-related with a cut off of 75.6 Gy (P=0.007 and P=0.0018 respectively). Finally, in the subgroup of high-very high risk patients we found that the CSOS, the BDFS and the CDFS were related to the dose level with a cut-off of 77.7 Gy (P=0.017; P=0.006 and P=0.038, respectively). Overall gastrointestinal (GI) acute and late G2 toxicities were respectively 5 % and 3.8%; GI acute and late >G3 toxicities were respectively 0.5% and 0.9%; acute and late >G2 genitourinary (GU) toxicities were respectively 10.5% and 2.6%; finally GU acute and late >G3 toxicities were respectively 0.6% and 0.5%.

Conclusions: The dose escalation is not relevant for the outcome in low risk patients that can benefit from relatively moderate doses (72-74 Gy). For intermediate and high-very high risk patients the dose becomes significant to levels above 75.6 Gy; particularly in high-very high risk doses >77.7 Gy correlate with an improved outcome. Patients receiving dose >77.7 Gy presented a higher rate of overall GI and GU toxicity, but the number of grade >2 remains low. Our results, consolidated by a long follow-up, corroborate the literature data, confirming that 3D-CRT can allow a safe dose escalation without significantly increasing the severe toxicity.
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June 2016

Is there still a role for computed tomography and bone scintigraphy in prostate cancer staging? An analysis from the EUREKA-1 database.

World J Urol 2016 Apr 15;34(4):517-23. Epub 2015 Aug 15.

Radiation Oncology Division, FPO-IRCCS Cancer Center of Candiolo, Candiolo, Italy.

Purpose: According to the current guidelines, computed tomography (CT) and bone scintigraphy (BS) are optional in intermediate-risk and recommended in high-risk prostate cancer (PCa). We wonder whether it is time for these examinations to be dismissed, evaluating their staging accuracy in a large cohort of radical prostatectomy (RP) patients.

Methods: To evaluate the ability of CT to predict lymph node involvement (LNI), we included 1091 patients treated with RP and pelvic lymph node dissection, previously staged with abdomino-pelvic CT. As for bone metastases, we included 1145 PCa patients deemed fit for surgery, previously staged with Tc-99m methylene diphosphonate planar BS.

Results: CT scan showed a sensitivity and specificity in predicting LNI of 8.8 and 98 %; subgroup analysis disclosed a significant association only for the high-risk subgroup of 334 patients (P 0.009) with a sensitivity of 11.8 % and positive predictive value (PPV) of 44.4 %. However, logistic multivariate regression analysis including preoperative risk factors excluded any additional predictive ability of CT even in the high-risk group (P 0.40). These data are confirmed by ROC curve analysis, showing a low AUC of 54 % for CT, compared with 69 % for Partin tables and 80 % for Briganti nomogram. BS showed some positivity in 74 cases, only four of whom progressed, while 49 patients with negative BS progressed during their follow-up, six of them immediately after surgery.

Conclusions: According to our opinion, the role of CT and BS should be restricted to selected high-risk patients, while clinical predictive nomograms should be adopted for the surgical planning.
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http://dx.doi.org/10.1007/s00345-015-1669-2DOI Listing
April 2016

Olive oil and hyperthermal water bigels for cosmetic uses.

J Colloid Interface Sci 2015 Dec 5;459:70-78. Epub 2015 Aug 5.

Department of Information, Modeling, Electronics and System Engineering (D.I.M.E.S.), University of Calabria, Via P. Bucci, Cubo 39C, I-87036 Rende, CS, Italy. Electronic address:

Bigels are biphasic systems produced with an organogel (or oleogel) and a hydrogel mixed together at high shear rates. These systems are promising for different uses, among them the formulation of new cosmetic matrices for cosmetic agents delivery is under investigation. In the present paper, a common cosmetic formulation for skin care was enriched with increasing fractions of monoglycerides of fatty acids/olive oil organogels, in order to understand the rheology and the microstructure of these systems. Small amplitude oscillation tests, NMR-self diffusion analysis, contrast phase microscopy and electric conductivity confirmed that the addition of the organogel caused a microstructural change of the starting material, which turned from O/W to a more complex system where, probably, a matrix-in-matrix structure is present at the highest fractions of added organogel.
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http://dx.doi.org/10.1016/j.jcis.2015.08.013DOI Listing
December 2015

Percentage of positive prostate biopsies independently predicts biochemical outcome following radiation therapy for prostate cancer.

Panminerva Med 2016 Jun 24;58(2):109-14. Epub 2015 Jul 24.

Neuroscience Department, Human Physiology Section University of Torino, Turin, Italy -

Background: This work aims to definitely show the ability of percentage of positive biopsy cores (%PC) to independently predict biochemical outcome beyond traditional pretreatment risk-factors in prostate cancer (PCa) patients treated with radiotherapy.

Methods: A cohort of 2493 men belonging to the EUREKA-2 retrospective multicentric database on (PCa) and treated with external-beam radiation therapy (EBRT) as primary treatment comprised the study population (median follow-up 50 months). A Cox regression time to prostate-specific antigen (PSA) failure analysis was performed to evaluate the predictive power of %PC, both in univariate and multivariate settings, with age, pretreatment PSA, clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/- ADT as covariates.

Results: P statistics for %PC is lower than 0.001 both in univariate and multivariate models. %PC as a continuous variable yields an AUC of 69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21-50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical relapse (overall log-rank test P<0.0001), with biochemical progression free survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from 80% to 38%.

Conclusions: We strongly affirm the usefulness of %PC information beyond main risk factors (PSA, staging and bGS) in predicting biochemical recurrence after EBRT for PCa. The stratification of patients according to %PC may be valuable to further discriminate cases with favourable or adverse prognosis.
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June 2016

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

Tumori 2016 Nov 11;102(Suppl. 2). Epub 2016 Nov 11.

Radiotherapy Division of the FPO-IRCCS Cancer Center, Candiolo (Turin) - Italy.

Background: Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally.

Methods: A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities.

Results: Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication.

Conclusions: In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.
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http://dx.doi.org/10.5301/tj.5000388DOI Listing
November 2016

Clinical and technical feasibility of ultra-boost irradiation in Dominant Intraprostatic Lesion by Tomotherapy: preliminary experience and revision of literature.

Panminerva Med 2016 Mar 29;58(1):16-22. Epub 2015 Apr 29.

Radiotherapy Division, FPO‑IRCCS Cancer Center, Candiolo, Turin, Italy -

Background: The aim of this paper was to present our experience of dominant intraprostatic lesions (DIL) irradiation up to an EQD2 of 93,2 Gy with helical tomotherapy.

Methods: Between March 2012 and December 2014, 15 staged II-III patients with intermediate-high risk prostate cancer were enrolled in our protocol of DIL dose escalation by Tomotherapy. All patients were submitted to a multiparametric MRI (including DCE and DWI series), in order to visualize DILs. Considering a mean α/β ratio of 3 for prostate cancer the prescribed doses were: 83.2 Gy in 32 fractions of 2.6 per fraction (EQD2=93.2 Gy) on the DILs, 75.2 Gy in 32 fractions of 2.35 Gy per fraction (EQD2=80.5 Gy) on the prostate gland and 67.2 Gy in 32 fraction of 2.1 (EQD2=68.5 Gy) on the seminal vesicles.

Results: With a mean follow-up of 16 months (range 2-39), no overall severe acute toxicities >G3 were observed; one patient out of 15 (6.6%) had acute gastrointestinal (GI) toxicity equal to G2, while two cases (13.3%) had G2 acute genitourinary (GU) toxicity. No >G2 late toxicity was observed. At last follow-up, for all patients, the biochemical disease free survival was 100%.

Conclusions: The irradiation of the whole prostate and seminal vesicles up to an EQD2 of 80.5 Gy and of DILs up to 93.2 Gy was clinically feasible and safe, without acute severe toxicity. Although with a short follow-up, late toxicities are currently absent and no patient relapsed.
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March 2016

Technical and clinical description of a case of extensive anogenital Paget's disease associated with anal cancer treated by tomotherapy.

Tumori 2014 Mar-Apr;100(2):e41-4

In this paper we describe a case of extramammary Paget's disease associated with anal cancer, which was successfully treated by intensity-modulated radiotherapy using tomotherapy with a simultaneous integrated boost and daily image guidance. The main pitfall in this report is the relatively short follow-up (1 year), which means that the evaluated data is promising but not conclusive. Considering the rarity and wide extension of our patient's Paget's disease in the anogenital region, and the lack of literature reports about curative radiotherapy in this particular setting, this case report may be considered the first related to extensive extramammary Paget's disease treated by tomotherapy.
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http://dx.doi.org/10.1700/1491.16431DOI Listing
July 2014

Oxidation of human red blood cells by a free radical initiator: effects on rheological properties.

Clin Hemorheol Microcirc 2015 ;60(4):375-88

Department of Engineering Modelling, Faculty of Chemical Engineering and Materials, University of Calabria, Arcavacata di Rende (CS), Italy.

The main aim of this study was the investigation of the rheological properties of Red Blood Cells (RBCs) obtained from subjects admitted to blood donors, associated with the lipid profile of High-Density Lipoprotein Cholesterol (HDL-C), Low-Density Lipoprotein Cholesterol (LDL-C), Triglyceride (TG) and Total Cholesterol (TOT-C). The deformability index of RBCs was determined by using a Dynamic Stress Rheometer (DSR-500) under oxidative injury induced by 2.2'-azo-bis (2-amidinopropane) dihydrochloride (AAPH). An increased rigidity of RBCs in subjects with borderline level of hyperlipidemia was found, compared with the control group. In order to explain the reason for the reduced deformability, a borderline group was studied for the evaluation of anionic permeability on membrane, haemolysis and morphological changes induced by AAPH, as well as ThioBarbituric Acid Reactive Substances (TBARs) generation. Haemolysis by AAPH indicated a decrease of globular resistance in the borderline group, furthermore, the elevated values of TBARs suggested lipid peroxidative damage to the RBCs membrane associated with morphological changes and anion permeability alterations. Our study shows the correlation between biochemical and morphological parameters of RBCs and their rheological behavior during oxidative injury. Rheological studies might be useful as a clinical and diagnostic monitoring technique and provide support for further research.
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http://dx.doi.org/10.3233/CH-141841DOI Listing
December 2016