Techniques for locating the screw access hole in cement-retained implant-supported prostheses: A systematic review.

STATEMENT OF PROBLEM: Different techniques for retrieving cement-retained implant-supported prostheses have been described to minimize damage to the prostheses. Nevertheless, a classification of the described techniques remains ambiguous. PURPOSE: The purpose of this systematic review was to review and classify the described techniques for recording and locating the screw access hole in cement-retained implant-supported prostheses. MATERIAL AND METHODS: A bibliographic search was completed on MEDLINE/PubMed, Web of Science, Scopus, and Cochrane databases. A manual search was also conducted. The articles that described or evaluated techniques for recording and locating the screw access hole of cement-retained implant-supported prostheses were included. Two investigators independently assessed the quality assessment of the studies using the Revised Cochrane risk of bias tool for randomized trials. A third examiner was consulted to resolve the lack of consensus. RESULTS: A total of 30 articles were included. The different methods were classified according to whether the screw access hole location was registered before or after cementation. The precementation techniques were classified into 4 subgroups: identification marks, photographic records, digital files, and precementation screw access hole location guides. The postcementation techniques were subdivided into 2 subgroups: radiographic records and postcementation screw access hole location guides. CONCLUSIONS: Different techniques have been proposed to facilitate the location of the screw access hole in cement-retained implant-supported restorations. Although the evidence is scarce, studies seem to ascertain that some techniques, such as the use of drilling guides, orientation with cone beam computed tomography images, or holes made in the metal framework, can increase the retrievability of cement-retained implant-supported prostheses and decrease complications in the location of the screw access hole. The proposed classification summarizes precementation and postcementation techniques and provides a tool to decide the most suitable for each specific clinical situation.

CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies.

We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19+ malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4-5 × 106 ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin's lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%-67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%-88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583.

Is sphere assay useful for the identification of cancer initiating cells of the ovary?

OBJECTIVE: Current evidence suggests that the presence of tumor-initiating cells (TICs) in epithelial ovarian cancer (EOC) has a role in chemoresistance and relapse. Surface markers such as CD44(+)/CD24(-), CD117(+), and CD133(+) expression have been reported as potential markers for TICs related to ovarian cancer and tumorigenic cell lines. In this study, we have investigated if spheroid forms are TIC specific or whether they can also be produced by somatic stem cells from healthy tissue in vitro. In addition, we also investigated the specificity of surface markers to identify TICs from papillary serous EOC patients. METHODS: Cells were obtained from fresh tumors from 10 chemotherapy-naive patients with EOC, and cells from ovarian and tubal epithelium were obtained from 5 healthy menopausal women undergoing surgery for benign pathology and cultured in standard and in selective medium. Cells forming nonadherent spheroids were considered TICs, and the adherent cells were considered as non-TIC-like. Percentages of CD24(+), CD44(+), CD117(+), CD133(+), and vascular endothelial growth factor receptor (VEGF-R)(+) cell surface markers were analyzed by flow cytometry. RESULTS: Four of 10 EOC cell tissues were excluded from the study. Tumor cells cultured in selective medium developed spheroid forms after 1 to 7 weeks in 5 of 6 EOC patients. No spheroid forms were observed in cultures of cells from healthy women. Unlike previously published data, low levels of CD24(+), CD44(+), CD117(+), and VEGF-R(+) expression were observed in spheroid cells, whereas expression of CD133(+) was moderate but higher in adherent cells from papillary serous EOC cells in comparison with adherent cells from controls. CONCLUSIONS: Papillary serous EOC contains TICs that form spheroids with low expression of CD44(+), CD24(+), CD117(+) and VEGF-R(+). Further research is required to find specific surface markers to identify papillary serous TICs.

Melatonin promotes angiogenesis during repair of bone defects: a radiological and histomorphometric study in rabbit tibiae.

OBJECTIVES: The pineal gland hormone, melatonin, is an immunomodulator and neuroendocrine hormone; it also stimulates monocyte, cytokine and fibroblast proliferations, which influence angiogenesis. The aim of this study was to investigate the effects of melatonin on angiogenesis during bone defect repair by means of radiological and histomorphometric evaluations of bone response to melatonin implants. MATERIALS AND METHODS: Twenty New Zealand rabbits weighing 3,900-4,500 g were used. Twenty melatonin implants were inserted in the proximal metaphyseal area of the animals' right tibia and 20 control areas were located in the left proximal metaphyseal area. Following implantation, the animals were sacrificed in groups of five, after 1, 2, 3 and 4 weeks, respectively. Anteroposterior and lateral radiographs were taken, and radiographic thermal imaging analysis was performed for all groups at different time stages following implant insertion. Samples were sectioned at 5 µm and stained using Hematoxylin-Eosin and Masson's trichrome, supplementing radiographic findings with histomorphometric analysis. RESULTS: After 4 weeks, radiological images showed complete repair of the bone defects. No healed or residual bone alterations attributable to the presence of the melatonin implant were observed. Histomorphometric analysis at 4 weeks showed the presence of a higher density newly formed bone. There were statistically significant differences in the length of cortical formation between the melatonin group and the control group during the first weeks of the study; there were also statistically significant differences in the number of vessels observed in the melatonin groups at the first two study stages. CONCLUSION AND CLINICAL RELEVANCE: Melatonin may have potential beneficial effects on bone defect repair.

Transdermal wires for improved integration in vivo.

Alternative engineering approaches have led the design of implants with controlled physical features to minimize adverse effects in biological tissues. Similar efforts have focused on optimizing the design features of percutaneous VAD drivelines with the aim to prevent infection, omitting however a thorough look on the implant-skin interactions that govern local tissue reactions. Here, we utilized an integrated approach for the biophysical modification of transdermal implants and their evaluation by chronic sheep implantation in comparison to the standard of care VAD drivelines. We developed a novel method for the transfer of breath topographical features on thin wires with modular size. We examined the impact of implant's diameter, surface topography, and chemistry on macroscopic, histological, and physical markers of inflammation, fibrosis, and mechanical adhesion. All implants demonstrated infection-free performance. The fibrotic response was enhanced by the increasing diameter of implants but not influenced by their surface properties. The implants of small diameter promoted mild inflammatory responses with improved mechanical adhesion and restricted epidermal downgrowth, in both silicone and polyurethane coated transdermal wires. On the contrary, the VAD drivelines with larger diameter triggered severe inflammatory reactions with frequent epidermal downgrowth. We validated these effects by quantifying the infiltration of macrophages and the level of vascularization in the fibrotic zone, highlighting the critical role of size reduction for the benign integration of transdermal implants with skin. This insight on how the biophysical properties of implants impact local tissue reactions could enable new solutions on the transdermal transmission of power, signal, and mass in a broad range of medical devices.

Facile and Versatile Method for Micropatterning Poly(acrylamide) Hydrogels Using Photocleavable Comonomers.

We here present a micropatterning strategy to introduce small molecules and ligands on patterns of arbitrary shapes on the surface of poly(acrylamide)-based hydrogels. The main advantages of the presented approach are the ease of use, the lack of need to prefabricate photomasks, the use of mild UV light and biocompatible bioconjugation chemistries, and the capacity to pattern low-molecular-weight ligands, such as peptides, peptidomimetics, or DNA fragments. To achieve the above, a monomer containing a caged amine (NVOC group) was co-polymerized in the hydrogel network; upon UV light illumination using a commercially available setup, primary amines were locally deprotected and served as reactive groups for further functionalization. Cell patterning on various cell adhesive ligands was demonstrated, with cells responding to a combination of pattern shape and substrate elasticity. The approach is compatible with standard traction force microscopy (TFM) experimentation and can further be extended to reference-free TFM.

Antiseizure medication for brain metastasis-related epilepsy: Findings of optimal choice from a retrospective cohort.

OBJECTIVE: To analyze the prevalence of antiseizure medication (ASM) in patients with brain metastasis-related epilepsy (BMRE) treated with radiosurgery and the relationship between ASM and psychiatric comorbidity. MATERIAL AND METHODS: This is a cross-sectional observational design study with retrospective review of medical records of all patients with brain metastases treated with volumetric modulated arc therapy radiosurgery (VMAT-RS) between 2012 and 2018 in a tertiary oncology center. We included those patients with BMRE, analyzing the clinical and demographic data, with special attention to psychiatric comorbidities and the use of ASM. RESULTS: Of the 121 patients with brain metastases included for treatment with VMAT-RS, a total of 38 presented BMRE. The most widely used ASM as first-line treatment was levetiracetam (89%). Only 8% of the patients received sodium channel blockers. The most common psychiatric comorbidity was depression (42.1%). CONCLUSIONS: Levetiracetam is the most widely used ASM in patients with BMRE treated with VMAT-RS. Nevertheless, common psychiatric comorbidities in this population might change the decision-making of ASM choice.

Presence of a critical stenosis in left anterior descending coronary artery alongside a short "P-R" and "Q-T" pattern, in the same electrocardiographic record.

The knowledge of the heart and its functions is increasing every day. However, many cardiac dysfunctions remain undocumented. One of them might be the presence of the Wellens' sign, minimally elevated or isoelectric ST segments, and inverted T waves in the precordial leads, without changes in the QRS complex, together with a shortened of "P-R and Q-T intervals" in the same electrocardiographic record. Both patterns are greatly underdiagnosed. The key to an accurate diagnosis of both dysfunctions must begin with a detailed analysis of all the symptoms reported by the patient. The ECG recording provides an almost definitive confirmation: The T-wave characteristics in precordial derivations. The duration of P-R and Q-T intervals.

Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial.

Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. TCM and TEM were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or TCM phenotype, in average, which are the subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that ex vivo cell expansion leads to reduced numbers of TN, TSCM, and TEFF cells, while TCM cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced ex vivo expansion may yield CAR T-cell products with increased persistence in vivo.

Melatonin plus porcine bone on discrete calcium deposit implant surface stimulates osteointegration in dental implants.

The aim of this study was to evaluate the effect of the topical application of melatonin mixed with collagenized porcine bone to accelerate the osteointegration on the rough discrete calcium deposit (DCD) surface implants in Beagle dogs 3 months after their insertion. In preparation for subsequent insertion of dental implants, lower premolars and molars were extracted from 12 Beagle dogs. Each mandible received three parallel wall implants with discrete calcium deposit (DCD) surface of 4 mm in diameter and 10 mm in length. The implants were randomly assigned to the distal sites on each side of the mandible in three groups: group I implants alone, group II implants with melatonin and group III implants with melatonin and porcine bone. Prior to implanting, 5 mg lyophylized powdered melatonin was applied to one bone hole at each side of the mandible. None was applied at the control sites. Ten histological sections per implant were obtained for histomorphometric studies. After a 4-wk treatment period, melatonin significantly increased the perimeter of bone that was in direct contact with the treated implants (P < 0.0001), bone density (P < 0.0001), new bone formation (P < 0.0001) in comparison with control implants. Topical application of melatonin on DCD surface may act as a biomimetic agent in the placement of endo-osseous dental implants and enhance the osteointegration. Melatonin combined with porcine bone on DCD implants reveals more bone to implant contact at 12 wk (84.5 +/- 1.5%) compared with melatonin treated (75.1 +/- 1.4%) and nonmelatonin treated surface implants (64 +/- 1.4%).

Changes in radiological protection and quality control in Spanish dental installations: 1996-2003.

INTRODUCTION: The European Union has established specific directives concerning radiological protection which are obligatory for member States. In addition, all Spanish dental clinics with radiological equipment are required to have an annual quality control check. OBJECTIVE: To analyze the effect of new European legislation on dental radiological practice in Spain and to determine whether it has resulted in lower doses being administered to patients. MATERIAL AND METHODS: A total of 10,171 official radiological quality control reports on Spanish dental clinics, covering 16 autonomous regions, were studied following the passing of Royal Decree 2071/1995 on quality criteria in radiodiagnostic installations. The reports, compiled by U.T.P.R Asigma S.A., a company authorised by the Nuclear Safety Council, cover the years 1996 to 2003, which has enabled us to monitor the evolution of radiological procedures in dental clinics over a seven year period. RESULTS: According to the reports for 2003, 77.3 % of clinics complied with EU requirements, using equipment of 70 kVp, 8 mA, 1.5 mm Al filters, with a collimator length of 20 cm. However, non-compliance was detected in approximately a third (30.8%) of the equipment inspected: alterations in the kilovoltage used, exposure time, performance of the tubing, dosage, linearity/intensity of current and acoustic-luminous signal 6.86%. The mean skin dose reached 3.11 mGy for patients who received an x-ray of an upper molar, representing a decrease of 18% over the seven years studied. CONCLUSION: there has obviously been a general improvement in the parameters studied, but only 77.3% of the installations complied fully with official EU regulations concerning dental radiological protection.

Nurse's A-Phase-Silicocarnotite Ceramic-Bone Tissue Interaction in a Rabbit Tibia Defect Model.

Calcium phosphate materials are widely used as bone substitutes due to their bioactive and biodegradable properties. Also, the presence of silicon in their composition seems to improve the bioactivity of the implant and promote bone tissue repair. The aim of this study was to develop a novel ceramic scaffold by partial solid-state sintering method with a composition lying in the field of the Nurse's A-phase-silicocarnotite, in the tricalcium phosphate-dicalcium silicate (TCP-C2S) binary system. Also, we evaluated its osteogenic and osteoconductive properties after being implanted into tibia defects in New Zealand rabbits. X-ray, microcomputer tomography, and histomorphometry studies demonstrated that this porous ceramic is highly biocompatible and it has excellent osteointegration. The material was being progressively reabsorbed throughout the study and there was no unspecified local or systemic inflammatory response observed. These results suggest that ceramic imitates the physicochemical characteristics of bone substitutes used in bone reconstruction.

Improvement of quality of life in diabetic patients treated with percutaneous transluminal angioplasty.

To assess the quality of life (QoL) of treated patients in order to evaluate the success of peripheral transluminal angioplasty (PTA) and correlate physical parameters with clinical progress at 6 months post-PTA.According to TASC II classifications, 69 patients were selected for PTA. Clinical evaluation and diagnostic tests were performed before, after and after 6 months following PTA. The SF-36 QoL questionnaire was added as an additional parameter.Fifty one patients were included in the study. The ankle-brachial index (ABI) increased from 0.49 ±â€Š0.11 before PTA, to 0.81 ±â€Š0.14 after PTA (P < .001) and 0.76 ±â€Š0.10 at 6 months following PTA (P < .001). Transcutaneous oxygen pressure (TcPO2) increased from 28.05 ±â€Š3.15 mm Hg before PTA, to 39.89 ±â€Š4.12 after PTA (P < .001) and 46.4 ±â€Š3.81 at 6 months following PTA (P < .001). The lumen of the affected blood vessel increased from 29 ±â€Š18% before PTA, to 81 ±â€Š10.3% after PTA (P < .001). SF-36 values increased from 29 ±â€Š18 before PTA, to 81 ±â€Š10.36 at 6 months following PTA (P < .001).The improvement of QoL is the parameter that best describes the symptoms and functionality of the patient, therefore, should be used to determine the successful PTA. Although ABI and TcPO2 with arteries functionality and tissue oxygenation, they are not show a significant correlation with all parameters determined in the QoL questionnaire.

Degradation of the herbicide 2,4-DP by anodic oxidation, electro-Fenton and photoelectro-Fenton using platinum and boron-doped diamond anodes.

This paper reports the degradation of 2,4-DP (2-(2,4-dichlorophenoxy)-propionic acid) solutions of pH 3.0 by environmentally friendly electrochemical methods such as anodic oxidation, electro-Fenton and photoelectro-Fenton with a Pt or boron-doped diamond (BDD) anode. In the two latter techniques an O(2)-diffusion cathode was used and 1.0mM Fe(2+) was added to the solution to give hydroxyl radical (*OH) from Fenton's reaction between Fe(2+) and H(2)O(2) generated at the cathode. All treatments with BDD are viable to decontaminate acidic wastewaters containing 2,4-DP since they give complete mineralization, with loss of chloride ion, at high current due to the great production of oxidant *OH at the BDD surface favoring the destruction of final carboxylic acids. *OH formed from Fenton's reaction destroys more rapidly aromatic products, making the electro-Fenton and photoelectro-Fenton processes much more efficient than anodic oxidation. UVA light in photoelectro-Fenton with BDD has little effect on the degradation rate of pollutants. The comparative procedures with Pt lead to slower decontamination because of the lower oxidizing power of this anode. The effect of current on the degradation rate and efficiency of all methods is studied. The 2,4-DP decay always follows a pseudo-first-order kinetics. Chlorohydroquinone, chloro-p-benzoquinone and maleic, fumaric, malic, lactic, pyruvic, acetic, formic and oxalic acids are detected as products by chromatographic techniques. A general sequence accounting for by the reaction of all these intermediates with the different oxidizing agents is proposed.

Clinical justification of dental radiology in adult patients: a review of the literature.

Although the radiological doses used by dentists are low individually, patients are often exposed to many repeat dental radiographic examinations. The "routine" use of dental radiography, such as screening of all patients using dental panoramic radiography (DPRs) or a random decision to take a dental radiograph, will inevitable lead to unnecessary patient exposure. The use of Radiographic Referral Criteria has now become a legal requirement for all practitioners following the adoption of European Legislation. All exposures to x-rays should be clinically justified and each exposure should be expected to give the patient a positive net benefit. Recently the European Commission has published guidelines on radiation protection in dental radiology. Guidelines have previously been available in a number of European countries and also within the United States. At the present time, no specific guidelines have been published within Spain. The aim of this review article is to provide the Spanish dentist with guidance as to the appropriateness of different radiographic techniques for a variety of clinical conditions and also the frequency with which they should be taken. It is hoped that this document will act as a useful work tool in daily dental practice.

Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array.

INTRODUCTION: The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. MATERIALS AND METHODS: QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. RESULTS: The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0-16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. CONCLUSION: Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall.

Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients.

BACKGROUND: Autologous tumour lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and, therefore, potential antitumour activity. We designed a phase II randomised trial of ADC + best supportive care (BSC) (experimental arm [EA]) compared with BSC (control arm [CA]), in pre-treated metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with progressive mCRC, at least to two chemotherapy regimens and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, were randomised to EA versus CA. Stratification criteria: ECOG PS (0-1 versus 2) and lactate dehydrogenase (ULN). EA was administered subcutaneously till progressive disease. Primary end-point was progression-free survival (PFS) at 4 months. RESULTS: Fifty-two patients were included (28 EA/24 CA). An interim analysis recommended early termination for futility. No objective radiological response was observed in EA. Median PFS in EA was 2.7 months (95% confidence interval [CI], 2.3-3.2 months) versus 2.3 months (95% CI, 2.1-2.5 months) in CA (p = 0.628). Median overall survival (OS) was 6.2 months (95% CI, 4.4-7.9 months) in EA versus 4.7 months (95% CI, 2.3-7 months) in CA (p = 0.41). No ADC-related adverse events were reported. Immunization induces tumour-specific T-cell response in 21 of 25 (84%) patients. Responder patients have an OS of 7.3 months (95% CI, 5.2-9.4 months) versus 3.8 months (95% CI, 0.6-6.9 months) in non-responders; p = 0.026). CONCLUSION: Our randomised clinical trial comparing ADC + BSC versus BSC in mCRC demonstrates that ADC generates a tumour-specific immune response but not benefit on PFS and OS. Our results do not support the use of ADC alone, in a phase III trial.

Treatment of metastatic melanoma B16F10 by the flavonoids tangeretin, rutin, and diosmin.

Melanoma is one of the most frequently metastasizing malignant neoplasias. This study examines an experimental model of pulmonary metastasis and the B16F10 cell subline, highly metastatic in the lung. Antimetastatic effects of the flavonoids tangeretin, rutin, and diosmin were analyzed, and at the same time an analysis of the metastatic activity of ethanol was performed, considered to be necessary because it is used as a vehicle for administering the flavonoids. Lentini's model, which complements the macroscopic evaluation of nodule numbers by using a stereoscopic microscope and image analysis at the microscopic level, was used. The greatest reduction in the number of metastatic nodules (52%) was obtained with diosmin; similarly, the percentages of implantation, growth index, and invasion index (79.40, 67.44, and 45.23%, respectively), were all compared with those of the ethanol group, considered to be an effective control group. Rutin- and tangeretin-treated groups also showed reductions of the same index compared with the ethanol group. It would seem that structural factors would better explain these results and the antimetastatic activity of each flavonoid and the respective metabolites.

[Experimental model for treating pulmonary metastatic melanoma using grape-seed extract, red wine and ethanol]. / Modelo experimental de tratamiento con extracto de semillas de uva, vino tinto y etanol del melanoma metastásico pulmonar.

INTRODUCTION: Melanoma is one of the neoplasias that most frequently metastasize, especially in the lung, where represents a challenge in oncology since current treatment is ineffective, and mortality is high. MATERIAL AND METHODS: Swiss mice (n = 52) were inoculated with 0.5 x 106 B16F10 cell lines and, later, given an oral administration of grape-seed extract, red wine or ethanol. Metastatic nodules on the lung surface were counted and, after processing for microscopy, five sections were selected for image analysis and the invasion index was calculated. RESULTS: Macroscopic analysis showed that grape-seed extract and red wine reduced the number of metastatic nodules by 26.07 and 20.81%, respectively, compared with a control group treated with ethanol. Microscopically, the reduction in the invasion index was 31.65 for grape-seed extract and 17.57% for red wine. CONCLUSION: Ethanol administration significantly increased pulmonary metastasis while grape-seed extract and red wine led to their reduction.