Use of amyloid PET/CT with 18F-Florbetaben in the management of patients with Alzheimer's disease.

INTRODUCTION AND AIM: Amyloid PET/CT is an "in vivo" imaging that may radically change management of Alzheimer's disease (AD) thanks to its ability to identify AD at the earliest stage. A diagnosis of dementia is currently made in terms of probability and is based on clinical evaluation (neuropsycological tests) as well as on the results of morphological imaging investigations (MRI) that can be supported by biohumoral (CSF analysis), and functional imaging only in the case of uncertain diagnosis of disease. The present study aimed to evaluate the role of amyloid PET/CT in the management of patients with suspicion of AD, through comparison with instrumental and clinical evaluation. METHODS: 38 consecutive patients with suspicion of AD (23 female, 15 male; median age 63 years old, range 46-72), who performed 18F-florbetaben PET/CT, were retrospectively reviewed. All of them performed a previous instrumental evaluation. A subgroup of patients (24/38) were evaluated with Mini Mental State Examination (MMSE). Cohen's K test was used as a measure of agreement between previous instrumental examinations/clinical evaluation and beta-amyloid PET results. RESULTS: Twenty-five/38 (65.8%) amyloid PET/CT scans resulted positive for amyloid deposition. Among the four target regions, precuneus was the most frequently involved. Previous instrumental evaluation was: MRI in 26/38 patients (24/26 positive for atrophy), CT in 9/38 (8/9 positive for atrophy), perfusion SPECT in 12/38 (8/12 areas of hypo-perfusion), 18F-FDG PET/CT in 2/38 (1/2 hypometabolism in frontal cortex). The agreement between previous instrumental examinations and beta-amyloid PET results was low (K= 0.084). In the subgroup of 24/38 patients, MMSE was scored positive (MMSE<24) in 14/24 (58.4%) and negative (MMSE>24) in 10/24 (41.6%). The agreement between clinical evaluation (MMSE) and beta-amyloid PET results was fair (K= 0.217). CONCLUSION: The low agreement between amyloid PET/CT and previous clinical and instrumental assessments that we found in our study suggests that the amyloid PET/CT provides additional and early information. To perform an early and differential diagnosis of AD could have a great impact on the patient's management and cost of care in order to perform the correct therapeutic interventions and to allow family members to manage adequately the patient's demanding care.

Impact of pre-treatment variables on the completion of 223radium-dichloride therapy in mCRPC patients with bone metastases.

INTRODUCTION: Radium-223 dichloride (223Ra) is an alpha-particle-emitter radiopharmaceutical, approved for metastatic castration-resistant prostate cancer (mCRPC) patients with symptomatic bone metastases and no visceral involvement. Its administration is based on a schedule of intravenous injection (55kBq/kg) every four weeks for up to six cycles. Because the biological effectiveness of 223Ra-therapy is dose-dependent, the main goal is to complete the entire treatment to achieve a better patient outcome. This study aims to identify potential pre-treatment variables that could impact on 223Ra-treatment completion and then be used to improve the clinical and supportive management of mCRPC patients. MATERIALS AND METHODS: 30 consecutive mCRPC patients (mean age 77 years old), who were admitted for Ra223-therapy at our Department from February 2016 to October 2018, were enrolled for the analysis. The population was grouped as patients who completed 223Ra-therapy (group Ra223-C) and patients who do not (group 223Ra-U). For each group, we analyzed the effects of potential pre-treatment variables (age, Gleason Score, tumor burden, "Time From Diagnosis To 223Ra therapy", type and number of previous treatments, hemoglobin level, Alkaline Phosphatase, Prostate Specific Antigen and pain) on the Ra223-therapy completion. Statistical analysis was performed to evaluate the association between the completion of 223Ra therapy and the variables examined. RESULTS: 16/30 (53%) patients were 223Ra-C, conversely 14/30 (47%) patients were 223Ra-U because of an early interrupted treatment. A statistically significant association was found only with tumor burden: 68.7% of patients who completed 223-therapy had less than 20 bone metastases (χ2=4.821, p=0.028). CONCLUSION: Our preliminary analysis demonstrates that the high tumor burden represents the most important pre-treatment factor that could affect treatment completion and that needs to be considered before starting 223Ra-therapy to achieve a better outcome in mCRPC patients.

Microencapsulation of grape skin phenolics for pH controlled release of antiglycation agents.

Grape skin (GS) phenolics can prevent structural damage of proteins due to reducing sugars or dicarbonyl compounds, which is the leading cause of hyperglycaemia damage and is involved in inflammatory diseases. In this study, alginate hydrogel was used to encapsulate GS phenolics as a pH dependent releasing system. Microbeads were obtained by a vibrating nozzle method using calcium chloride as hardening agent. Encapsulation efficiency for total phenolics was 68%. At pH 1.4, the alginate microbeads remained intact and only 13% of total phenolic compounds of the microbeads was released. The percent release depended on the compound: procyanidin B1 release was 74%, catechin and epicatechin release was ~ 50%, while anthocyanin and flavonol release was less than 11%. At pH 7.4, the microbeads were dissolved and formed a viscous solution that showed ability to protect bovine serum albumin from glycation induced by both fructose and methylglyoxal. The antiglycation activity was 246 mmol catechin equivalents (CE)/kg of dry microbeads in the fructose model system and 78 mmol CE/kg of dry microbeads in the methylglyoxal model system. These values corresponded to 68% and 62% of the expected activity, probably due to interaction between phenolics and the alginate carrier. Despite the recovery of antiglycation activity was incomplete, results of this study confirmed the efficiency of alginate to act as a pH controlled released system for GS phenolics. This functionalized polymer could be applied in the prevention of advanced-glycation-endproducts related diseases.

Predictive value of 18F-FDG PET/CT on survival in locally advanced rectal cancer after neoadjuvant chemoradiation.

OBJECTIVE: To evaluate the prognostic value of 18F-FDG PET/CT in terms of survival in patients with locally advanced rectal cancer (LARC) who had undergone surgery preceded by neoadjuvant chemoradiotherapy (nCRT). Moreover, the existence of correlation between Overall Survival (OS) and Disease Free Survival (DFS) with pathological staging ((y)pTNM and TRG) was evaluated. PATIENTS AND METHODS: A total of 58 patients with biopsy-proven of LARC were included. All patients underwent conventional diagnostic/staging procedures to characterize the rectal lesion. The first whole-body 18F-FDG PET/CT was performed 1 week before the beginning of nCRT (baseline scan). The second 18F-FDG PET/CT was scheduled at 5-6 weeks from nCRT completion (post-nCRT scan). Survival was evaluated in 3 different restaging classification systems, based on focusing only on primary lesion (TRG), loco-regional evaluation (ypTNM) and whole-body 18F-FDG PET/CT evaluation (VRA). RESULTS: Among the 58 patients at the end of the observation, 46/58 patients (79.3%) were alive and 12/58 (20.7%) were dead. This work demonstrated a higher percentage of patients with TRG complete response (39.7%) compared to literature (24.6%), with longer Overall Survival (OS) and Disease Free Survival (DFS) in responders even if without statistically significant differences. CONCLUSIONS: The present study highlights the predictive and prognostic potential role of 18F-FDG PET/CT in assisting physicians on personalized decision in the selective risk-adapted treatment strategy, and to schedule the correct follow-up approach.

Modelling the stability of maltodextrin-encapsulated grape skin phenolics used as a new ingredient in apple puree.

Highly soluble maltodextrin-encapsulated grape skin phenolics comprising anthocyanins and less hydrophilic flavonoids were added as an ingredient to apple puree. Upon formulation, heat treatments were applied to achieve 3-14 decimal reductions (D) of the target microorganism (Alicyclobacillus acidoterrestris). A storage study was performed at 15-35°C for 1month. Monomeric anthocyanins were retained at 100% after the 3 D treatment, while anthocyanin retention decreased to 72% with increasing heating intensity until 14 D. During storage, the concentration of monomeric anthocyanins decreased following first-order kinetics (k25°C=34.4d(-1), activation energy=51.0kJ/mol). The flavanols were more stable than the monomeric anthocyanins. The hydroxycinnamic acid, dihydrochalcone and flavonol contents did not change. The fortified puree had a two-fold higher reducing capacity with respect to apple puree. Overall, this ingredient could meet the industrial demand for sustainable colouring agents and health promoting compounds.

Grape skin phenolics as inhibitors of mammalian α-glucosidase and α-amylase--effect of food matrix and processing on efficacy.

Type-2 diabetes is continuously increasing worldwide. Hence, there is a need to develop functional foods that efficiently alleviate damage due to hyperglycaemia complications while meeting the criteria for a sustainable food processing technology. Inhibition of mammalian α-amylase and α-glucosidase was studied for white grape skin samples recovered from wineries and found to be higher than that of the drug acarbose. In white grape skins, quercetin and kaempferol derivatives, analysed by UPLC-DAD-MS, and the oligomeric series of catechin/epicatechin units and their gallic acid ester derivatives up to nonamers, analysed by MALDI-TOF-MS were identified. White grape skin was then used for enrichment of a tomato puree (3%) and a flat bread (10%). White grape skin phenolics were found in the extract obtained from the enriched foods, except for the higher mass proanthocyanidin oligomers, mainly due to their binding to the matrix and to a lesser extent to heat degradation. Proanthocyanidin solubility was lower in bread, most probably due to formation of binary proanthocyanin/protein complexes, than in tomato puree where possible formation of ternary proanthocyanidin/protein/pectin complexes can enhance solubility. Enzyme inhibition by the enriched foods was significantly higher than for unfortified foods. Hence, this in vitro approach provided a platform to study potential dietary agents to alleviate hyperglycaemia damage and suggested that grape skin phenolics could be effective even if the higher mass proanthocyanidins are bound to the food matrix.

Antioxidant activity of tomato products as studied by model reactions using xanthine oxidase, myeloperoxidase, and copper-induced lipid peroxidation.

The antioxidant content and activity of commercial tomato products differing in variety and processing were studied. Two procedures for extracting hydrophilic and lipophilic antioxidants, namely, two-step 0.1 M phosphate buffer (pH 3.0 and 7.4) extraction and tetrahydrofuran extraction followed by petroleum ether fractionation, were developed. Carotenoids (lycopene, beta-carotene, and lutein) and ascorbic acid were analyzed by HPLC with spectrophotometric and electrochemical detectors, respectively. Total phenolics were determined by using the Folin-Ciocalteu reagent. The antioxidant activity was studied by the following three model systems: (a) the xanthine oxidase (XOD)/xanthine system, which generates superoxide radical and hydrogen peroxide; (b) the myeloperoxidase (MPO)/NaCl/H(2)O(2) system, which produces hypochloric acid; and (c) the linoleic acid/CuSO(4) system, which promotes lipid peroxidation. Results showed that the hydrophilic and lipophilic fractions of all tomato products were able to affect model reactions, whatever reactive oxygen species and catalysts were used to drive oxidation. In the XOD/xanthine system both the hydrophilic and lipophilic fractions displayed an inhibitory activity. The hydrophilic fractions were more effective (I(50) ranging from 680 to 3200 microg, dry weight) than the lipophilic fractions (I(50) ranging from 4000 to 7750 microg, dry weight). In the MPO/NaCl/H(2)O(2) system the hydrophilic fractions inhibited oxidation (I(50) ranging from 2300 to 2900 microg, dry weight), whereas the lipophilic fractions had a lower inhibitory effect at the same concentration. Conversely, in the copper-catalyzed lipid peroxidation only the lipophilic fractions were effective (I(50) ranging from 1030 to 2100 microg, dry weight), whereas the hydrophilic fractions had a pro-oxidant effect in the same concentration range. The extent of inhibition varied according to the tomato sample in the superoxide and hydrogen peroxide generating system and in lipid peroxidation, but was substantially the same in the HClO generating system. Fresh tomato varieties differed considerably in the antioxidant activities of their hydrophilic and lipophilic fractions. Processed tomatoes showed a significantly lower antioxidant activity than fresh tomatoes in their hydrophilic fractions but had a high antioxidant activity in their lipophilic fractions. Because the oxidative reactions produced by the above-mentioned model systems are also involved in the pathogenesis of several chronic diseases, the antioxidant activity of tomato fractions might be related to their in vivo activity. Hence, these measurements may be used for optimizing tomato technologies.

Properties of tomato powders as additives for food fortification and stabilization.

The antioxidant activities of two freeze-dried tomato powders as additives for food fortification and stabilization were studied. The two tomato powders were obtained from the whole fruit and from the pulp after "serum" separation, respectively. The antioxidant activity was studied by measuring (a) the inhibition of the singlet oxygen-catalyzed oxidation of alpha-linolenic acid, in the presence or absence of copper ions, as a model of the oxidative processes occurring in foods, and (b) the inhibition of xanthine oxidase (XOD)- and myeloperoxidase (MPO)-catalyzed reactions and copper-induced lipid peroxidation. The partial separation of "serum" decreased the freeze-drying time by 50%. The partially fractionated tomato powder had a 60% lower phenolic content and an 11-fold higher lycopene content than the whole tomato powder, on a dry weight basis. Ascorbic acid was almost completely removed by fractionation. Both the powder obtained from the whole tomato and that obtained from the partially fractionated tomato had antioxidant activity in all the model systems used. Based on these results, we conclude that tomato powders have multifunctional properties, which could address the prevention of oxidative degradations both in foods and in vivo. Therefore, tomato can be regarded as source of food additives for fortification and stabilization, even if it is submitted to technological processes that can cause the loss of the more labile hydrophilic antioxidants.

Evaluation of radical scavenging activity of fresh and air-dried tomatoes by three model reactions.

The radical scavenging activity and the antioxidant content of fresh and air-dried tomatoes were investigated. Tomato halves were dried in a pilot-scale dryer under the following conditions: air temperature, 80 degrees C; air flow rate, 1.5 m/s; drying time, 400 min; final moisture, 25%. Carotenoid (lycopene, beta-carotene, lutein) and ascorbic acid were analyzed by HPLC with a spectrophotometric and an electrochemical detector, respectively. Total phenolics were determined by using the Folin-Ciocalteu reagent. The radical scavenging activity was studied in three model systems: (a) the xanthine oxidase and xanthine system, which generates superoxide radical and hydrogen peroxide; (b) the 3-morpholinosydnonimine system, which releases spontaneously superoxide radical and nitrogen monoxide, forming peroxynitrite; (c) the linoleic acid and CuSO(4) system, which promotes lipid peroxidation. These model systems allow the simulation of key reactions involved in the pathogenesis of certain chronic diseases and may be related to the in vivo activity of tomato antioxidants. Hence, these measurements can be used for optimizing tomato processing and storage. The drying process resulted in a decrease of ascorbic acid content, whereas phenol reagent reducing compounds increased. Carotenoid levels were substantially unchanged upon drying. Fresh and air-dried tomato extracts could act as radical scavengers both in the reactive oxygen species-mediated reactions and in lipid peroxidation. Drying affected the antioxidant effectiveness as measured in the xanthine/xanthine oxidase system, which was found to be the most sensitive method for the measurement of tomato antioxidant activity (lower I(50)) but retained the antioxidant effectiveness in the other two systems.

Protective ability of phenolics from white grape vinification by-products against structural damage of bovine serum albumin induced by glycation.

Grape skins recovered from white grape vinification processes were studied as possible anti-glycation agents. Total phenolics were characterised by the Folin Ciocalteu assay, proanthocyanidins by depolymerisation with n-butanol/HCl, flavonols by HPLC-DAD, reducing capacity by ferric ion reducing antioxidant power assay (FRAP) and anti-glycation activity by a bovine serum albumin (BSA)/fructose model system. Structural modifications of BSA were investigated by 2D isoelectric focusing sodium dodecyl sulfate polyacrylamide gel electrophoresis (IEF/SDS-PAGE) and fluorescence measurements. Both pI and Mr. of BSA were modified upon glycation reaction. These changes attributable to the involvement of free amino groups in Maillard-type reactions were inhibited by the white grape skin extracts. The anti-glycation activity ranged between 250 and 711mmol aminoguanidine Eq/kg. These results raise the interest in the potential health benefits of by-products of white grape vinification that could have a secondary use as an ingredient for new functional foods targeting wellbeing of diabetic and elderly people.