Chairside virtual patient protocol. Part 3: In vitro accuracy of a digital facebow.

OBJECTIVES: The present study aimed to investigate the trueness and precision of an intraoral transfer element (IOTE) designed for matching intraoral and facial scans. METHODS: A mannequin head with a maxillary model in position was used. Cone beam computed tomography (CBCT) was used to construct the master model (MM). A digital impression of the maxillary arch was taken using an intraoral scanner, and the IOTE was used to record the maxillary arch position. Twenty facial scans with and twenty without the IOTE in place were performed with a handheld device (Ipad Pro, Apple) using a dedicated software. Digital mounting was performed to build a scan model (SM). Using software for data processing, the three-dimensional deviation between the MM and SM at the central left incisor (#9#), and the left and right first molars (#3#, #14#) was calculated as trueness and linear deviation precision. . Angular deviation was also calculated at the occlusal plane. RESULTS: The linear deviation trueness at #9#, #3# and #14# was 0.3 ± 0.12 mm, 1.07 ± 0.28 mm, and 0.18 ± 0.34 mm, respectively, whereas the precision was 1.17 ± 0.4 mm, 0.43 ± 0.12 mm, and 0.64 ± 0.28 mm, respectively. Trueness of the angular deviation at the occlusal plane was 2.17 ± 0.46°, whereas the angular deviation precision was 0.64 ± 0.28°. CONCLUSIONS: Based on in vitro findings the proposed IOTE design is accurate and suitable for clinical use. CLINICAL SIGNIFICANCE: Direct virtual mounting is a reliable technique in vitro; however, in vivo tests are required.

Clinical effects of conventional and underprepared drilling preparation of the implant site based on bone density: A systematic review and meta-regression.

PURPOSE: There is no clinical consensus to determine the right balance between underpreparation and marginal bone level changes. The purpose of this systematic review and meta-regression was to investigate the influence of the type of drilling preparation of the implant site in relation to the bone mineral density on the clinical success, expressed in terms of the MBL and implant failure rate. STUDY SELECTION: A thorough search was performed using the digital databases MEDLINE PubMed, EMBASE, and Cochrane Central Register of Controlled Trials by entering research lines or various combinations of free words. The main keywords used were "dental implants", "bone density", and "torque". RESULTS: The mean bone resorption in the conventional preparation group was -0.43 (± 0.28) mm, whereas it was -0.80 (± 0.37) mm in the underprepared group. For the D1/D2/D3 bone group, the slope was significantly different from zero and linearity; the D4 bone group slope was not significantly different from zero and was almost parallel, although it was significantly different from linearity. The box and whiskers plot shows that the MBL in underprepared sites tended to be significantly higher with a higher variation than that in conventionally prepared sites. CONCLUSIONS: Within its limits, our meta-regression analysis showed that MBL is influenced by the type of drilling preparation and bone mineral density. In particular, a lower MBL was observed in the D1 bone with conventional preparation than with underpreparation. Moreover, a greater implant-to-osteotomy site mismatch was positively associated with greater MBLs in the bone densities of D1/D2/D3.

Facial scanning technologies in the era of digital workflow: A systematic review and network meta-analysis.

PURPOSE: The aim of this network meta-analysis is to evaluate the accuracy of various face-scanning technologies in the market, with respect to the different dimensions of space (x, y, and z axes). Furthermore, attention will be paid to the type of technologies currently used and to the best practices for high-quality scan acquisition. MATERIAL AND METHODS: The review was conducted following the PRISMA guidelines and its updates. A thorough search was performed using the digital databases MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials by entering research lines or various combinations of free words. The main keywords used during the search process were "photogrammetry", "laser scanner", "optical scanner", "3D", and "face". RESULTS: None of the included technologies significantly deviated from direct anthropometry. The obtained mean differences in the distances between the considered landmarks range from 1.10 to -1.74 mm. CONCLUSIONS: Limiting the movements of the patient and scanner allows for more accurate facial scans with all the technologies involved. Active technologies such as laser scanners (LS), structured light (SL), and infrared structured light (ISL) have accuracy comparable to that of static stereophotogrammetry while being more cost-effective and less time-consuming.

Chairside virtual patient protocol. Part 2: Management of multiple face scans and alignment predictability.

OBJECTIVES: Face scans are currently used in dentistry to obtain a virtual patient. Find stable and repeatable references for their matching is a fundamental step. Aim of this study is to evaluate matching reliability of multiple face scans using frontal adhesives references. Null hypothesis was that no significant discrepancy could be detected between the references position analyzed both with surface analysis and linear analysis. MATERIALS AND METHODS: Nine patients were enrolled for this study and nine soft tissue adhesives landmarks (APLI Paper S.A.U, 4 mm Ø) placed, equally distributed, on the forehead and glabella. Patients were digitally scanned with a portable scanner (iPad Pro 3rd Gen. Apple Store, Cupertino, CA, USA) using the software Bellus3D (Inc. Campbell, CA, USA) in maximum intercuspation, with a full smile and with a scan reference device. After the scan procedure, a high-definition polygon file format (.ply) was exported, and linear measurements were collected with MeshLab (MeshLab; MeshLab). In order to further evaluate reference accuracy, a surface analysis was performed using a CAD software (GOM inspect, GOM). 3D deviations were calculated as root mean square. Statistical analysis was performed used two repeated-measures ANOVAs. RESULTS: Results showed non-significant differences both for linear measurements (p=.22) and surface analysis (p=.58). Frontal references showed to be clinical reliable landmarks for use during face scans alignment, even with different facial expressions. CONCLUSION: The proposed technique seems to be suitable for the clinical use when superimposition of several face scans is required. CLINICAL SIGNIFICANCE: This study showed the clinical reliability of face scans matching method using adhesives references. These references are cheap and easy to use, allowing for a rapid registration of the patient anatomy.

Influence of vinification process over the composition of volatile compounds and sensorial characteristics of greek wines.

Wine is one of the most traditional consumed alcoholic beverages in the world. Millions of wine enthusiasts worldwide duly appreciate a wine of excellent quality in terms of physicochemical and sensorial properties. Different classes of wines have different volatile compositions and sensorial properties, which can be altered, depending on the vinification process and use of additives. Among the widely employed additives in wine production is sulfite (SO2). The popularity of sulfite lies in its ability to preserve the flavor and freshness of wine; however, depending on the quantity, sulfite can pose serious health risks to consumers and affect the quality of the drink. The present study evaluated and compared the compositions of volatile compounds and sensorial properties of sparkling and traditional wines (with and without SO2) produced from Greek grapes 'Grechetto', 'Greco bianco' and 'Greco di tufo'. The results obtained of the composition of volatile compounds in these wines pointed to differences between SO2-containing, SO2-free and sparkling wines, with different amounts of compounds such as alcohols, esters, fatty acids, phenols and differences in sensorial properties. The 'Grechetto' wine, prepared without SO2, exhibited greater quality, better volatile composition, and better sensorial properties compared to the wines produced with SO2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05160-y.

The function of specialized pro-resolving endogenous lipid mediators, vitamins, and other micronutrients in the control of the inflammatory processes: Possible role in patients with SARS-CoV-2 related infection.

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the "cytokine storm" observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

Soft tissue dimensional changes after alveolar ridge preservation using different sealing materials: a systematic review and network meta-analysis.

BACKGROUND: Alveolar ridge preservation (ARP) is a proactive treatment option aiming at attenuating post-extraction hard and soft tissue dimensional changes. A high number of different types of biomaterials have been utilized during ARP to seal the socket, but their effectiveness in terms of soft tissue outcomes has rarely been investigated and compared in the literature. OBJECTIVE: To evaluate the efficacy of different types of membranes and graft materials in terms of soft tissue outcomes (keratinized tissue width changes, vertical buccal height, and horizontal changes) after ARP, and to assign relative rankings based on their performance. MATERIALS AND METHODS: The manuscript represents the proceedings of a consensus conference of the Italian Society of Osseointegration (IAO). PUBMED (Medline), SCOPUS, Embase, and Cochrane Oral Health's Information Specialist were utilized to conduct the search up to 06 April 2021. English language restrictions were placed and no limitations were set on publication date. Randomized controlled trials that report ARP procedures using different sealing materials, assessing soft tissue as a primary or secondary outcome, with at least 6-week follow-up were included. Network meta-analysis (NMA) was performed using mean, standard deviation, sample size, bias, and follow-up duration for all included studies. Network geometry, contribution plots, inconsistency plots, predictive and confidence interval plots, SUCRA (surface under the cumulative ranking curve) rankings, and multidimensional (MDS) ranking plots were constructed. RESULTS: A total of 11 studies were included for NMA. Overall, the level of bias for included studies was moderate. Crosslinked collagen membranes (SUCRA rank 81.8%) performed best in vertical buccal height (VBH), autogenous soft tissue grafts (SUCRA rank 89.1%) in horizontal width change (HWch), and control (SUCRA rank 85.8%) in keratinized mucosa thickness (KMT). CONCLUSIONS: NMA confirmed that the use of crosslinked collagen membranes and autogenous soft tissue grafts represented the best choices for sealing sockets during ARP in terms of minimizing post-extraction soft tissue dimensional shrinkage. CLINICAL RELEVANCE: Grafting materials demonstrated statistically significantly better performances in terms of soft tissue thickness and vertical buccal height changes, when covered with crosslinked collagen membranes. Instead, soft tissue grafts performed better in horizontal width changes. Non-crosslinked membranes and other materials or combinations presented slightly inferior outcomes.

Sealing materials for post-extraction site: a systematic review and network meta-analysis.

AIM: By means of a systematic review and network meta-analysis, this study aims to answer the following questions: (a) does the placement of a biomaterial over an extraction socket lead to better outcomes in terms of horizontal and vertical alveolar dimensional changes and percentage of new bone formation than healing without coverage? And (b) which biomaterial(s) provide(s) the better outcomes? MATERIALS AND METHODS: Parallel and split-mouth randomized controlled trials treating ≥ 10 patients were included in this analysis. Studies were identified with MEDLINE (PubMed), Embase, Cochrane Central Register of Controlled Trials, and Scopus. Primary outcomes were preservation of horizontal and vertical alveolar dimension and new bone formation inside the socket. Both pairwise and network meta-analysis (NMA) were undertaken to obtain estimates for primary outcomes. For NMA, prediction intervals were calculated to estimate clinical efficacy, and SUCRA was used to rank the materials based on their performance; multidimensional ranking was used to rank treatments based on dissimilarity. The manuscript represents the proceedings of a consensus conference of the Italian Society of Osseointegration (IAO). RESULTS: Twelve trials were included in the qualitative and quantitative analysis: 312 sites were evaluated. Autologous soft tissue grafts were associated with better horizontal changes compared to resorbable membranes. A statistically significant difference in favor of resorbable membranes, when compared to no membrane, was found, with no statistically significant heterogeneity. For the comparison between crosslinked and non-crosslinked membranes, a statistically significant difference was found in favor of the latter and confirmed by histomorphometric NMA analysis. Given the relatively high heterogeneity detected in terms of treatment approaches, materials, and outcome assessment, the findings of the NMA must be interpreted cautiously. CONCLUSIONS: Coverage of the healing site is associated with superior results compared to no coverage, but no specific sealing technique and/or biomaterial provides better results than others. RCTs with larger sample sizes are needed to better elucidate the trends emerged from the present analysis. CLINICAL RELEVANCE: Autologous soft tissue grafts and membranes covering graft materials in post-extraction sites were proved to allow lower hard tissue shrinkage compared to the absence of coverage material with sealing effect. Histomorphometric analyses showed that non-crosslinked membranes provide improved hard tissue regeneration when compared to crosslinked ones.

COVID-19, what could sepsis, severe acute pancreatitis, gender differences, and aging teach us?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a potentially life-threatening disease, defined as Coronavirus Disease 19 (COVID-19). The most common signs and symptoms of this pathological condition include cough, fever, shortness of breath, and sudden onset of anosmia, ageusia, or dysgeusia. The course of COVID-19 is mild or moderate in more than 80% of cases, but it is severe or critical in about 14% and 5% of infected subjects respectively, with a significant risk of mortality. SARS-CoV-2 related infection is characterized by some pathogenetic events, resembling those detectable in other pathological conditions, such as sepsis and severe acute pancreatitis. All these syndromes are characterized by some similar features, including the coexistence of an exuberant inflammatory- as well as an anti-inflammatory-response with immune depression. Based on current knowledge concerning the onset and the development of acute pancreatitis and sepsis, we have considered these syndromes as a very interesting paradigm for improving our understanding of pathogenetic events detectable in patients with COVID-19. The aim of our review is: 1)to examine the pathogenetic mechanisms acting during the emergence of inflammatory and anti-inflammatory processes in human pathology; 2)to examine inflammatory and anti-inflammatory events in sepsis, acute pancreatitis, and SARS-CoV-2 infection and clinical manifestations detectable in patients suffering from these syndromes also according to the age and gender of these individuals; as well as to analyze the possible common and different features among these pathological conditions; 3)to obtain insights into our knowledge concerning COVID-19 pathogenesis. This approach may improve the management of patients suffering from this disease and it may suggest more effective diagnostic approaches and schedules of therapy, depending on the different phases and/or on the severity of SARS-CoV-2 infection.

Microscopic Characterization of Bioactivate Implant Surfaces: Increasing Wettability Using Salts and Dry Technology.

The surface topography of dental implants plays an important role in cell-surface interaction promoting cell adhesion, proliferation and differentiation influencing osseointegration. A hydrophilic implant leads to the absorption of water molecules and subsequently promotes the adhesion of cells to the implant binding protein. Dried salts on the implant surfaces allow one to store the implant surfaces in a dry environment while preserving their hydrophilic characteristics. This process has been identified as "dry technology". The aim of the present study is to describe from a micrometric and nanometric point of view the characteristics of this new bioactivated surface obtained using salts dried on the surface. Topographic analysis, energy-dispersive X-ray spectroscopy, and contact angle characterization were performed on the samples of a sandblasted and dual acid-etched surface (ABT), a nanosurface (Nano) deriving from the former but with the adding of salts air dried and a nanosurface with salts dissolved with distilled water (Nano H2O). The analysis revealed promising results for nanostructured surfaces with increased wettability and a more articulated surface nanotopography than the traditional ABT surface. In conclusion, this study validates a new promising ultra-hydrophilic nano surface obtained by sandblasting, double acid etching and surface salt deposition using dry technology.

The Role of Platelet-Rich Fibrin (PRF) in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ).

Dentoalveolar surgery is probably the major risk factor for MRONJ and for other complications following a tooth extraction, especially in patients affected by systemic diseases. The aim of this retrospective study is to evaluate whether a PRF plug inserted in the post extraction socket can prevent the onset of MRONJ. The patients were divided into two groups according to the surgical protocol that included the insertion or not of the PRF following the extraction and all the anamnestic, and clinical data were analyzed. In the control group, 5 patients developed MRONJ (19.23%) while in the study group, any case of MRONJ was reported. In the control group, patients who developed MRONJ had a CTX with less than 100 pg/mL (5 high-risk patients, Spearman's rank r = .547, p < .001). The use of platelet concentrates in patients with high risk of MRONJ is a user-friendly technique with an excellent cost-benefit ratio in oral surgery.

Correction to: SNP genotyping elucidates the genetic diversity of Magna Graecia grapevine germplasm and its historical origin and dissemination.

An amendment to this paper has been published and can be accessed via the original article.

What Are the Effects of Different Abutment Morphologies on Peri-implant Hard and Soft Tissue Behavior? A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effect of different abutment morphologies on peri-implant hard and soft tissue behavior. MATERIALS AND METHODS: The focus question for this literature search was: What are the effects of different abutment morphology (concave vs convex) on peri-implant hard and soft tissue behavior? Randomized clinical trials (RCTs) with a minimum sample size of 20 implants (10 per group) and a follow-up period of at least 3 months after implant loading were considered eligible for this study. This review excluded studies comparing different abutment heights or surfaces and different implant shapes. Two different meta-analyses were performed: one for marginal bone loss (MBL) to evaluate hard tissue changes, and one for Pink Esthetic Score (PES) as an indicator of soft tissue modifications. RESULTS: Four publications from 12 full texts analyzed were included. The meta-analysis (data from 117 patients and 173 abutments) indicated that a statistically significant difference (P < .00001) was detected from the data regarding MBL between the two groups (mean difference = -0.21 [95% CI: -0.25, -0.16]), but not considering the PES (mean difference = -0.69 [95% CI: -2.08, 0.70]) after a minimum period of 3 months after implant loading. All such evidence was confirmed by the trial sequential analysis on both MBL and PES. CONCLUSION: The results demonstrate that abutment design may have an influence on MBL but no impact on soft tissues. However, the existing evidence is moderate, as few RCTs were conducted and follow-up periods were short.

Microarray data and pathway analyses of peripheral blood mononuclear cells from healthy subjects after a three weeks grape-rich diet.

Using Human Gene Expression Microarrays (Agilent) technologies, we investigated changes of the level of gene expression in peripheral blood mononuclear cells of healthy subjects after 21 days of fresh table grape-rich diet and after an additional 28-day washout. Several hundreds of genes were differentially expressed after grape intake or after washout. The functional analysis of these genes detected significant changes in key processes such as inflammation and immunity, thrombosis, DNA and protein repair, autophagy and mitochondrial biogenesis. Moreover, fresh grape intake was found to influence the expression of many long non-coding RNA genes. The data can be valuable for researchers interested in nutrigenetics and nutrigenomics studies and are related to the research article "Gene expression signature induced by grape intake in healthy subjects reveals wide-spread beneficial effects on PBMCs" [1].

FT-NIR Analysis of Intact Table Grape Berries to Understand Consumer Preference Driving Factors.

Fourier-transform near infrared spectroscopy (FT-NIR) is a technique used in the compositional and sensory analysis of foodstuffs. In this work, we have measured the main maturity parameters for grape (sugars and acids) using hundreds of intact berry samples to build models for the prediction of these parameters from berries of two very different varieties: "Victoria" and "Autumn Royal". Together with the chemical composition in terms of sugar and acidic content, we have carried out a sensory analysis on single berries. Employing the models built for sugars and acids it was possible to learn the sweetness and acidity of each berry before the destructive sensory analysis. The direct correlation of sensory data with FT-NIR spectra is difficult; therefore, spectral data were exported from the spectrometer built-in software and analyzed with R software using a statistical analysis technique (Spearman correlation) which allowed the correlation of berry appreciation data with specific wavelengths that were then related to sugar and acidic content. In this article, we show how it is possible to carry out the analysis of single berries to obtain data on chemical composition parameters and consumer appreciation with a fast, simple, and non-destructive technique with a clear advantage for producers and consumers.

Optimized ultrasonic-assisted extraction of phenolic antioxidants from grape (Vitis vinifera L.) skin using response surface methodology.

Currently, the analysis of bioactive compounds is easily carried out by modern chromatographic and spectrometric techniques, but the success of the procedure still depends on the efficiency of the extraction methods. This work aimed at finding the optimal conditions for ultrasonic-assisted extraction (UAE) of phenolic antioxidants from grape skin using single-factor experimentation combined with response-surface methodology. Our extraction parameters were ethanol concentration, time and temperature. Total phenolic content (TPC and TPC-280), 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and oxygen radical absorbance capacity (ORAC) were dependent variables. A second-order polynomial model satisfactorily described the experimental data. Optimized extraction conditions for UAE from grape skin were: 59.5% ethanol, 113.6 min and 66.8 °C for TPC extraction; 61.1% ethanol, 99.4 min and 66.1 °C for TPC-280 extraction; 57.1% ethanol, 99.5 min and 66.8 °C for DPPH radical-scavenging activity; 60.2% ethanol, 82.4 min and 66.8 °C for ORAC value. Our work provides detailed and useful information to optimize the extraction of grape skin phenols, which are widely used as dietary supplements and nutraceuticals.

SNP genotyping elucidates the genetic diversity of Magna Graecia grapevine germplasm and its historical origin and dissemination.

BACKGROUND: Magna Graecia is the ancient name for the modern geopolitical region of South Italy extensively populated by Greek colonizers, shown by archeological and historical evidence to be the oldest wine growing region of Italy, crucial for the spread of specialized viticulture around Mediterranean shores. Here, the genetic diversity of Magna Graecia grape germplasm was assessed and its role in grapevine propagation around the Mediterranean basin was underlined. RESULTS: A large collection of grapevines from Magna Graecia was compared with germplasm from Georgia to the Iberian Peninsula using the 18 K SNP array. A high level of genetic diversity of the analyzed germplasm was determined; clustering, structure analysis and DAPC (Discriminant Analysis of Principal Components) highlighted the genetic relationships among genotypes from South Italy and the Eastern Mediterranean (Greece). Gene flow from east (Georgia) to west (Iberian Peninsula) was identified throughout the large number of detected admixed samples. Pedigree analysis showed a complex and well-structured network of first degree relationships, where the cultivars from Magna Graecia were mainly involved. CONCLUSIONS: This study provided evidence that Magna Graecia germplasm was shaped by historical events that occurred in the area due to the robust link between South Italian and Greek genotypes, as well as, by the availability of different thermal resources for cultivars growing in such different winegrowing areas. The uniqueness of this ampelographic platform was mainly an outcome of complex natural or human-driven crosses involving elite cultivars.

Phenolic content and in vitro antifungal activity of unripe grape extracts from agro-industrial wastes.

The antifungal activity of unripe grape extracts from agro-industrial wastes has been evaluated against several strains of Candida spp. and dermatophytes. All the extracts tested showed antifungal activity. The geometric mean MIC ranged from 53.58 to 214.31 µg/mL for Candida spp. and from 43.54 to 133.02 µg/mL for dermatophytes. The chemical analyses have been carried out using Liquid Chromatograph equipped with a DAD and MS detectors. Flavan-3-ols were the main metabolites within all samples ranged from 3.3 to 6.8 mg/g fresh weight. For Candida spp. highest negative significant correlation has been found between MICs and polymeric flavan-3-ols (r = -0.842; p < 0.001) and for dermatophytes between MICs and caffeoyl derivatives (r = -0.962; p < 0.01). The results indicate that total extracts obtained from unripe grapes, a large source of waste material derived from the wine industry, could be used as a cheap source of value-added products.

Grape intake reduces thrombin generation and enhances plasma fibrinolysis. Potential role of circulating procoagulant microparticles.

Phytochemicals contained in grapes down-regulate several prothrombotic pathways in vitro. We evaluated the effect of grape consumption on coagulation and fibrinolysis in healthy volunteers. Thirty subjects were enrolled: 20 were given grape (5 g/kg body weight/day for 3 weeks), while 10 served as controls. Blood samples were taken at baseline (T0), at the end of the grape diet (T1) and after 4-week wash-out (T2). Grape intake caused a significant decrease of the procoagulant and inflammatory responses of whole blood and/or mononuclear cells to bacterial lipopolysaccharide at both T1 and T2. At plasma level, grape diet decreased thrombin generation at T1 and T2, largely through a reduction in the number and/or activity of procoagulant microparticles. This anticoagulant effect resulted in the formation of clots that were more susceptible to fibrinolysis, mainly because of a lesser activation of thrombin activatable fibrinolysis inhibitor. No difference in any variables was detected in controls at the time points considered. In conclusion, chronic grape consumption induces sustained anticoagulant and profibrinolytic effects with potential benefits for human health.

Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity.

Grape seed extracts are commonly utilized as dietary supplements for their antioxidant properties, even from cancer patients. However, whether these natural extracts interfere with chemotherapeutics utilized in colon cancer treatment is still poorly investigated. The cytotoxicity of extracts from Italia and Palieri cultivars either alone or in combination with oxaliplatin was evaluated in colon cancer cells. Grape seed extracts displayed anti-proliferative activity depending on the concentration utilized through apoptosis induction. In combination, they affected the activation of Erk1/2 and counteracted the intrinsic and the extrinsic pathway of apoptosis, the DNA damage and the generation of ROS induced by oxaliplatin. Noteworthy grape seed extracts strongly enhanced the uptake of oxaliplatin into all cells, by affecting the cell transport system of platinum. The addition of these natural extracts to oxaliplatin strongly reduced the cellular response to oxaliplatin and allowed a huge accumulation of platinum into cells. Here, we shed light on the chemical biology underlying the combination of grape seed extracts and oxaliplatin, demonstrating that they might be detrimental to oxaliplatin effectiveness in colon cancer therapy.