Remodelling surgery with 3D printed patient specific surgical guides in patients with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible, a case series.

BACKGROUND: Patients with chronic diffuse sclerosing osteomyelitis/tendoperiostitis (DSO/TP) of the mandible may complain about facial asymmetry as a result of mandibular deformity, one of the characteristics of DSO/TP of the mandible. If the disease is fully extinguished, remodelling surgery could be performed to treat complaints of facial asymmetry. This study reports the results of remodelling surgery with three-dimensional (3D) designed- and -printed patient-specific surgical guides. MATERIAL AND METHODS: 3D printed guides were designed and manufactured by using mirroring of the contralateral non-affected mandible. Subsequently, the surgical procedure was performed under general anaesthesia using these surgical guides. RESULTS: Four patients (all female) aged 15 (±2.8) years were included. They all complained about facial asymmetry and were planned for surgery with patient-specific surgical guides. Three of those surgeries were performed, of which two patients were satisfied with the result and the other patient is planned for re-surgery because of persistent aesthetical complaints. The last patient cancelled her surgery, because she eventually accepted her asymmetry with the help of a psychologist. CONCLUSIONS: The use of patient-specific surgical guides in remodelling surgery of the mandible could enable a more predictable and symmetrical outcome, which could minimise the chance for re-surgery and could increase patient satisfaction. Furthermore, it could minimise the chance of iatrogenic damage to the inferior alveolar nerve.

In vitro assessment of the mutagenic and genotoxic potential of a pure stilbene extract.

Stilbenes are secondary metabolites of great interest produced by many plant species due to their important bioactive properties. These phytochemicals have become of increasing interest in the wine industry as a natural alternative to sulphur dioxide, which has been associated with human health risks. However, there is still little toxicological information on stilbenes and the results thus far have been contradictory. Considering the key role of genotoxicity in risk assessment and the need to offer safe products in the market, the aim of this study was to assess the mutagenic and genotoxic potential of a stilbene extract with 99% purity (ST-99 extract). A complete series of different in vitro tests (Ames test, micronucleus (MN) test, and standard and enzyme-modified comet assays) was performed before its use as a preservative in wines. The ST-99 extract induces a significant increase of binucleated cells with micronuclei only in presence of the metabolic fraction S9 at the highest concentration assayed. Neither the Ames test nor the comet assay revealed the extract's genotoxic potential. Further studies are necessary, including in vivo assays, to ensure consumer safety before it can be used.

Dental implants as risk factors for patients with medication-related osteonecrosis of the jaws (MRONJ).

An increasing number of patients with medication-related osteonecrosis of the jaws (MRONJ) has recently been reported. It is still being debated whether the presence or placement of dental implants can lead to MRONJ, so the aim of this study was to find out whether dental implants are a risk factor for MRONJ. From January 2003-January 2019 180 patients with MRONJ were seen at the Leiden University Medical Center. Luxating moments for the onset of MRONJ were calculated retrospectively. We collected clinical data and details of antiresorptive medication and found 22 patients with both dental implants and MRONJ. In 18 patients the implants were in the region of the MRONJ and they were included in this study, 14 who had had implants before using antiresorptive drugs and four who had had antiresorptive drugs before or at the time that the implants were placed. The median times between the placement of implants and the diagnosis of MRONJ in these two groups were 24 months and 6 months, respectively. Among the 47 implants, 30 were located in the necrotic region, and all 30 were either lost spontaneously or had to be removed during treatment of MRONJ. Our results show an increased risk for developing MRONJ in patients with dental implants. Both peri-implantitis around previously placed implants, and insertion of dental implants, are risk factors. Prevention of peri-implantitis and caution when inserting dental implants in patients who take antiresorptive medication are therefore important.

Outcome of different treatments for chronic diffuse sclerosing osteomyelitis of the mandible: a systematic review of published papers.

Treating chronic diffuse sclerosing osteomyelitis (DSO) is challenging and many treatments have been reported. However, we know of no standard protocol or guidelines. In this systematic review of relevant publications we provide an overview of the different treatments used. We made an electronic search of PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases, for papers that described the treatment of DSO of the mandible. The search yielded 48 papers that applied to all inclusion criteria, resulting in 16 case reports, 13 case series, 18 retrospective clinical cohort studies, and one randomised controlled trial. Reported treatment options included different operations; the use of antibiotics, anti-inflammatories, and antiresorptive medication; conservative treatment; and hyperbaric oxygen. Surgical treatment resulted in a low success rate and was associated with higher morbidity than other treatments. Conservative treatment, and that of bisphosphonates, yielded more promising results, so conservative treatment and bisphosphonates seem to be the most promising therapeutic options. However, because of the high risk of bias, no firm conclusions can be drawn, and larger studies with clear inclusion criteria and specified endpoints are needed.

Pyrolysis-gas chromatography-isotope ratio mass spectrometry for monitoring natural additives in polylactic acid active food packages.

Compound-specific isotope analysis (CSIA) usually requires preparative steps (pretreatments, extraction, derivatization) to get amenable chromatographic analytes from bulk geological, biological or synthetic materials. Analytical pyrolysis (Py-GC/MS) can help to overcome such sample manipulation. This communication describe the results obtained by hyphenating analytical pyrolysis (Py-GC) with carbon isotope-ratio mass spectrometry (IRMS) for the analysis of a polylactic acid (PLA) a based bio-plastic extruded with variable quantities of a natural plant extract or oregano essential oil. The chemical structural information of pyrolysates was first determined by conventional analytical pyrolysis and the measure of δ13C in specific compounds was done by coupling a pyrolysis unit to a gas chromatograph connected to a continuous flow IRMS unit (Py-GC-C-IRMS). Using this Py-CSIA device it was possible to trace natural additives with depleted δ13C values produced by C3 photosystem vegetation (cymene: -26.7‰±2.52; terpinene: -27.1‰±0.13 and carvacrol: -27.5‰±1.80 from oregano and two unknown structures: -23.3‰±3.32 and -24.4‰±1.70 and butyl valerate: -24.1‰±3.55 from Allium spp.), within the naturally isotopically enriched bio-plastic backbone derived from corn (C4 vegetation) starch (cyclopentanones: -14.2‰±2.11; lactide enantiomers: -9.2‰±1.56 and larger polymeric units: -17.2‰±1.71). This is the first application of Py-CSIA to characterize a bio-plastic and is shown as a promising tool to study such materials, providing not only a fingerprinting, but also valuable information about the origin of the materials, allowing the traceability of additives and minimizing sample preparation.

A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure.

Development of PLA films containing oregano essential oil (Origanum vulgare L. virens) intended for use in food packaging.

Consumers' concerns about the environment and health have led to the development of new food packaging materials avoiding petroleum-based matrices and synthetic additives. The present study has developed polylactic acid (PLA) films containing different concentrations of essential oil from Origanum vulgare L. virens (OEO). The effectiveness of this new active packaging was checked for use in ready-to-eat salads. A plasticising effect was observed when OEO was incorporated in PLA films. The rest of the mechanical and physical properties of developed films did not show much change when OEO was included in the film. An antioxidant effect was recorded only for films containing the highest percentages of the active agent (5% and 10%). In addition, films exhibited in vitro antibacterial activity against Staphylococcus aureus, Yersinia enterocolitica, Listeria monocytogenes, Enterococcus faecalis and Staphylococcus carnosus. Moreover, in ready-to-eat salads, antimicrobial activity was only observed against yeast and moulds, where 5% and 10% of OEO was the most effective.

Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats.

Proallium AP(®) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP(®) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed-adverse-effect-level (NOAEL) for Proallium AP(®) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging.

Genotoxicity assessment of propyl thiosulfinate oxide, an organosulfur compound from Allium extract, intended to food active packaging.

Essential oils from onion (Allium cepa L.), garlic (Allium sativum L.), and their main components, such as propyl thiosulfinate oxide (PTSO) are being intended for active packaging with the purpose of maintaining and extending food product quality and shelf life. The present work aims to assess for the first time the potential mutagenicity/genotoxicity of PTSO (0-50 µM) using the following battery of genotoxicity tests: (1) the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test, OECD 471); (2) the micronucleus test (OECD 487) (MN) and (3) the mouse lymphoma thymidine-kinase assay (OECD 476) (MLA) on L5178YTk(+/-), cells; and (4) the comet assay (with and without Endo III and FPG enzymes) on Caco-2 cells. The results revealed that PTSO was not mutagenic in the Ames test, however it was mutagenic in the MLA assay after 24 h of treatment (2.5-20 µM). The parent compound did not induce MN on mammalian cells; however, its metabolites (in the presence S9) produced positive results (from 15 µM). Data from the comet assay indicated that PTSO did not induce DNA breaks or oxidative DNA damage. Further in vivo genotoxicity tests are needed to confirm its safety before it is used as active additive in food packaging.

Marble game with optimal ferroelectric switching.

A low coercivity and, consequently, low hysteresis loss are desired properties for ferroelectric materials used in high-power and high-frequency actuators. The coercive field required for the onset of ferroelectric switching is shown to develop a strong directional anisotropy due to peculiarities of an energy surface associated with the polarization rotation. It is found that the ferroelectric anisotropy exhibits 'hard' and 'easy' switching axes similar to magnetic materials. The hard axis corresponds to 180° polarization reversal, whereas the easy axis favors 90° switching. Our results suggest that the intrinsic low coercivity and the full polarization reversal may not be achieved at the same time under uniaxial excitation. A rotating electric field excitation is proposed in order to circumvent this limitation and to guide the polarization switching along a curved path.

Histopathological and immunohistochemical analysis of Tilapia (Oreochromis niloticus) exposed to cylindrospermopsin and the effectiveness of N-Acetylcysteine to prevent its toxic effects.

Cylindrospermopsin (CYN) is a cytotoxic cyanotoxin produced by several cyanobacteria species. It has been demonstrated that CYN is a potent protein and glutathione synthesis inhibitor, and induces genotoxicity and oxidative stress. The present study investigated the protective role of two different doses of N-Acetylcysteine (NAC) (22 and 45 mg/fish/day) against the pathological changes induced in tilapia (Oreochromis niloticus) orally exposed to a single dose of pure CYN or CYN from an Aphanizomenon ovalisporum CYN-producer strain (200 µg/kg of CYN in both cases). Moreover, an immunohistochemical (IHC) analysis was carried out in order to elucidate the CYN distribution in exposed fish. The histological findings were more pronounced when fish were intoxicated with CYN from the cyanobacterial strain, being liver and kidney the main targets for CYN toxicity. NAC pre-treatment was effective reducing the damage induced by CYN, especially at the highest dose employed (45 mg/fish/day), with a total prevention in all organs. The IHC analysis showed that CYN-antigen appeared mainly in the liver and gastrointestinal tract, although it was also present in kidney and gills. In this case, the immunopositive results were more abundant in those fish exposed to pure CYN. NAC reduced the number of immunopositive cases in a dose-dependent way. Therefore, NAC can be considered a useful chemoprotectant in the prophylaxis and treatment of CYN-related intoxications in fish.

Use of nanoclay platelets in food packaging materials: technical and cytotoxicity approach.

Two organo-modified clays for food contact applications were developed to produce hydrophobically modified montmorillonite and hence to obtain better compatibility between the biopolymer and the filler (nanoclay). These nanofillers were characterised by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction and thermogravimetric analysis (TGA) in order to study their composition, structure and thermal stability. The fillers were used to reinforce polylactic acid (PLA) bottles, which were characterised using different techniques such as mechanical and barrier properties, morphology and thermal stability. The results were compared with conventional PLA bottles. The use of the modified clay in PLA bottles was found to lead to an improvement in mechanical and barrier properties. Finally, cytotoxicity tests were carried out with the organo-modified clays using Caco-2 and HepG2 cell lines, with uptake of neutral red as a basal cytotoxicity biomarker.

Evaluación de la seguridad de una arcilla modificada y su extracto de migración en bazo de ratas Wistar expuestas de forma subcrónica / Influence of a subchronical exposure to a modified clay and its migration extract in the spleen of Wistar rats

Las ventajas tecnológicas de la incorporación de arcillas modificadas en polímeros para el envasado de alimentos son bien conocidas, pero aún quedan muchas incertidumbres sobre la seguridad de estos materiales. El Instituto Tecnológico del Embalaje, Transporte y Logística ha desarrollado una arcilla, Clay1, modificando una montmorillonita con una sal de amonio cuaternario. Esta organoarcilla, incorporada al polímero (ácido poliláctico), da lugar a un material nanocompuesto, reforzándose así el material de partida. El principal objetivo de este estudio es evaluar la actividad de biomarcadores de estrés oxidativo en bazo de ratas expuestas durante 90 días a Clay1 (40 mg/kg/día) y al extracto de migración obtenido a partir del material nanocompuesto resultante. Los parámetros evaluados fueron la peroxidación lipídica y las actividades enzimáticas superóxido dismutasa y catalasa. Además, se realizó un análisis del contenido en bazo de los metales más característicos que componen la organoarcilla (Al, Ca, Fe, Mg, Si) para comprobar su posible acumulación. En dicho estudio se trabajó con tres grupos de ratas Wistar (n=10): control (comida estándar + agua como bebida), Clay1 (comida estándar mezclada con 40mg/kg/día de arcilla + agua) y extracto de Clay1 (comida estándar + extracto como bebida). Tras el tiempo de exposición los animales se sacrificaron y se extrajo el bazo. De forma general, no se observaron diferencias significativas en ninguno de los parámetros evaluados con respecto al grupo control, por lo que Clay1 muestra un buen perfil toxicológico respecto a los biomarcadores ensayados con vistas a su uso en la industria alimentaria (AU)

The technological advantages of the incorporation of modified clays into polymers for food packaging are well known. However, there are still many uncertainties about the safety of these materials. The Technological Institute of Packaging, Transport and Logistic has developed Clay1, a modified clay with a quaternary ammonium salt. This organoclay is incorporated into the polymer (polylactic acid), giving a nanocomposite material and reinforcing the bulk material. The aim of this study is to evaluate the activity of several oxidative stress biomarkers in the spleen of rats exposed for 90 days to Clay1 (40 mg/kg/day) and its migration extract obtained from the resultant nanocomposite material. The parameters evaluated were lipid peroxidation and superoxide dismutase and catalase activities. Moreover, the characteristic metallic components of the organoclay (Al, Ca, Fe, Mg, Si) were also analyzed to test the possible accumulation. In this study, three groups of Wistar rats (n=10) were used: control (standard food + water), Clay1 (food with Clay1+water) and Clay1 extract (standard food+ Clay1 extract as water). After the exposure the spleen was removed. In general, no significant differences were observed in any of the parameters evaluated compared to the control group, therefore Clay1 showed a good toxicologic profile regarding the biomarkers assayed for its use in the food industry (AU)

Estudio in vitro de la viabilidad de células Caco-2 en presencia de componentes del aceite esencial de Allium spp / In vitro study of the viability of Caco-2 cells in presence of two compound of Allium spp essential oil

El aceite esencial de los componentes del género Allium, principalmente ajo y cebolla, presenta propiedades antioxidantes y antibacterianas debidas a la presencia de compuestos azufrados en su composición. La industria alimentaria ha comenzado a desarrollar nuevos sistemas de envasado activo a partir de polímeros seleccionados, a los que se incorporan aceites esenciales que, por sus propiedades, contribuyen a aumentar la vida útil de los alimentos perecederos. En este sentido, se hace necesario evaluar la seguridad asociada al uso de estas sustancias en envases alimentarios que van a estar en contacto con el consumidor a través del alimento. El objetivo del presente estudio fue determinar la citotoxicidad producida por dipropil sulfuro y dipropil disulfuro, dos de los componentes del aceite esencial de ajo y cebolla, en la línea celular Caco-2, células humanas procedentes de carcinoma de colon. Los biomarcadores ensayados fueron el contenido total de proteínas, la captación de rojo neutro y la reducción de la sal de tetrazolio (3-(4,5-dimetiltiazol-2- il)-5-(3-carboximetoxifenil)-2-(4sulfofenil)-2H-tetrazolio). Las células fueron expuestas durante 2, 4 y 8 h a concentraciones comprendidas entre 0 y 200 μM. Los resultados no mostraron diferencias significativas frente al control para ninguno de los tres marcadores, lo que demuestra que bajo las condiciones de los ensayos ambos compuestos azufrados no son citotóxicos para esta línea celular gastrointestinal y podrían ser útiles en la industria alimentaria para desarrollar envases activos (AU)

Allium spp. essential oil, mainly from garlic and onion, possesses different beneficial properties, for example antioxidant and antimicrobial effects, due to the presence of sulfur compounds. Food industry is developing new active packaging systems that include the essential oil of garlic in their structure, in order to improve the shelf-life of perishable products. Therefore it is necessary to evaluate the safety associated with the use of these substances in food packaging that will be in contact with the consumer through food. The aim of our study was to evaluate in vitro the cytotoxicity of dipropyl sulfide and dipropyl disulfide. For this purpose, we used the human Caco-2 cell line, from human small intestinal mucosa carcinoma. The assayed cytotoxicity biomarkers were the total protein content, neutral red uptake and reduction of the 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboximethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt. Cells were exposed to dipropyl sulfide and dipropyl disulfide in concentrations between 0-200 μM for 2, 4 and 8 h. After periods of exposure, no alterations were observed in any of the biomarkers assayed. These results suggest that both organosulfur compounds are safety options for food industry and could be a choice in the development of active packaging. (AU)

Suitability of a tumour-mimicking material for the evaluation of high-intensity focused ultrasound ablation under magnetic resonance guidance.

This study tests the suitability of a tumour-mimic for targeting magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU). An agarose-based tumour-mimic was injected as a warm solution that polymerized in tissue. Thermal characteristics and acoustic absorption of the mimic were observed within the values reported for tissues. The relaxation times at 3T were 1679 ± 15 ms for T1 and 41 ± 1 ms for T2. The mimic was clearly visible on in vivo images. With lower contrast the tumour-mimic was visible on T2-weighted images, where it was possible to detect the ablated tissue surrounding the mimic after sonications. HIFU sonications were performed to induce thermal ablation on and around the mimic using a Sonalleve system (Philips). MR thermometry maps were performed during HIFU. The average temperature when the sonication was done at the tumour-mimic was 67.6 ± 8.0 °C in vitro and 67.6 ± 5.0 °C in vivo. The average temperature for sonications at tissues was 68.4 ± 8.7 °C in vitro (liver) and 66.0 ± 2.6 °C in vivo (muscle), with no significant difference between tissue and tumour-mimic (p > 0.05). The tumour-mimic behaviour when using MR-guided HIFU was similar to tissues, showing that this mimic can be used as an alternative to tumour models for validating MR-guided HIFU devices targeting.

La Toxicología en la Universidad de Sevilla / Toxicology at the University of Seville

La docencia del Área de Toxicología en la Universidad de Sevilla se desarrolla en la actualidad en dos titulaciones, Farmacia y Bioquímica. En los planes de estudios actuales la carga lectiva del Área viene dada por las asignaturas de Toxicología (asignatura troncal), y Toxicología Alimentaria (asignatura optativa) en la Licenciatura de Farmacia, y de Toxicología Molecular (asignatura optativa) en la Licenciatura de Bioquímica. Una vez aprobados por la Agencia Nacional de la Evaluación de la Calidad y Acreditación (ANECA) ambos títulos de Grado, la docencia no sólo se mantiene sino que se amplía gracias a la participación en la impartición de dos asignaturas pluridisciplinares de nueva creación en el Grado de Farmacia (AU)

The teaching in the Area of Toxicology at the University of Seville is currently being developed in two degrees, Pharmacy and Biochemistry. In the present curriculum, the teaching load of the area is given by the subjects of Toxicology (compulsory subject), and Food Toxicology (elective subject) in the Bachelor of Pharmacy; and Molecular Toxicology (elective subject) in the Bachelor of Biochemistry. Once approve by the National Agency for Quality Assessment and Accreditation (ANECA) both titles, this teaching is not only maintained but even increased through participation in the teaching of two newly created multidisciplinary subjects in the degree of Pharmacy (AU)

Nuevos riesgos tóxicos por exposición a nanopartículas / New toxic risks due to nanoparticles exposure

La nanotecnología es una ciencia multidisciplinar que está teniendoun gran auge en la actualidad, ya que proporciona productos(nanopartículas) con nuevas propiedades fisicoquímicas, que son lasque hacen que tengan una gran cantidad de aplicaciones. Laexposición humana a estas nanopartículas se puede producirprincipalmente por las vías respiratoria (nanopartículas suspendidasen el aire), dérmica (nanopartículas ambientales, cosméticos) y oral(alimentos, agua). Por vía pulmonar las nanopartículas activan losmecanismos de defensa o son internalizadas en los intersticios. Porvía dérmica se pueden acumular en el estrato córneo o en los folículospilosos, o bien atravesarlo y acumularse en la dermis. Por vía oralpueden ser absorbidas por las células epiteliales del intestino. Laexposición también se puede producir a través de la instrumentaciónmédica o prácticas clínicas, ya que se usan, por ejemplo, en eltratamiento y diagnóstico del cáncer de mama y en el control deinfecciones en cirugía. Una vez las nanopartículas han sidoabsorbidas, se distribuyen por vía sanguínea y linfática, alcanzandodiferentes órganos, tales como huesos, riñones, páncreas, bazo,hígado y corazón, en los que quedan retenidas y ejercen sus efectostóxicos, aunque esto también se utiliza como una forma devectorización de fármacos. La toxicidad de estas nanopartículasdepende, entre otros factores, de su persistencia en los órganos y de siel hospedador puede provocar una respuesta biológica paraeliminarlas. Los mecanismos de toxicidad no se conocen conexactitud, aunque parece ser que se incluyen daño en membranascelulares, disrupción del potencial de membrana, oxidación deproteínas, genotoxicidad, formación de especies reactivas de oxígenoe inflamación. Estudios sobre las vías respiratorias han mostradodisminución de la viabilidad celular in vitro, producción de estrésoxidativo e inflamación...(AU)

Nanotechnology is a multi-disciplinary science which is having a great growth at present, as it provides products (nanoparticles) withnew physico-chemical properties that can have many applications.Human exposure to these nanoparticles can be produced byrespiratory (airborne nanoparticles), dermal (atmosphericnanoparticles, cosmetics) and oral routes (food, water). Byrespiratory route, nanoparticles can stimulate the defensemechanisms or can penetrate into gaps. By dermal route, they can beaccumulated in the stratum corneum or in the hair follicles, or gothrough it and be accumulated in the dermis. By gastrointestinal routethey can be absorbed by the epithelial cells of the intestine. Humancan also be exposed by medical instrumentation or clinic practices, asnanoparticles are used, for example, for treatment and diagnostic ofbreast cancer and to control surgery infections. Once nanoparticleshave been absorbed they are distributed by blood and lymphaticstream, reaching different organs, such as bones, kidneys, pancreas,spleen, liver and heart, where they are retained and can produce theirtoxic effects, although this ability is also used for drugs delivery. Thetoxicity of these nanoparticles depends, among other factors, on theirpermanence in organs and if the host can produce a biologicalresponse to eliminate them. The toxicity mechanisms have not beencompletely elucidated, although they are known to produce cellmembrane damages, membrane potential disruption, proteinsoxidation, genotoxicity, production of reactive oxygen species, andinflammation. Studies on the respiratory exposure have demonstrateda diminution of the cellular viability in vitro, oxidative stressproduction, and inflammation. On skin have been demonstratedtoxicity and oxidative stress, although other authors have shown theabsence of irritation and allergic reactions...(AU)

Dose-dependent antioxidant responses and pathological changes in tenca (Tinca tinca) after acute oral exposure to Microcystis under laboratory conditions.

The effects of cyanobacterial cells containing microcystins (MCs), toxins from cyanobacteria, on oxidative stress biomarkers from liver and kidney of Tenca fish (Tinca tinca) were investigated under laboratory conditions. Moreover, a histopathological study of liver, kidney, heart and intestine tissues was performed. Fish were orally exposed to cyanobacterial cells dosing 0, 5, 11, 25 and 55 microg MC-LR/fish mixed with the food. Results showed a dose-dependent decrease of superoxide dismutase (SOD) activity, and also of catalase (CAT) in the liver. Glutathione levels and protein oxidation, however, were not altered by the exposure to the cyanobacterial material. The microscopic study revealed tissue alterations even at the lower cyanobacterial cells doses. Onion-like hepatocytes in the liver, glomerulopathy in the kidney, loss of myofibrils in the heart and vacuolated enterocytes in the gastrointestinal tract were the main changes observed. These findings suggest that this fresh water fish can be adversely affected by cyanobacterial blooms in their natural habitats.

New integrated imaging high intensity focused ultrasound probe for transrectal prostate cancer treatment.

The present study proposes a new integrated imaging (II) high-intensity focused ultrasound (HIFU) probe intended as an improvement to the Ablatherm prostate cancer treatment. Because of a perforation in the center of the II probe, the expected lesion differs from the one obtained for the original Ablatherm probe. In this paper, the new geometry and the strategy followed to establish the treatment parameters are presented. The original probe has a 40-mm focal length, a 50-mm aperture and is truncated at 31 mm. The II probe has a 45-mm focal length, a 61-mm aperture, a central perforation of 25 mm and is truncated at 31 mm. Both probes operate at 3 MHz. A mathematical model for lesion prediction was used for setting the treatment parameters for the II probe. These parameters should ensure equivalence between the lesions obtained with the original and II probes. Simulation-obtained parameters were validated by in-vitro and in-vivo (on liver of 70 New Zealand rabbits) experiments. The new II probe was used clinically to treat 30 patients. The mean age was 70.9 +/- 5.3 years (SD), the mean prostate volume 26.9 +/- 7.7 mL and the mean serum prostate specific antigen (PSA) concentration before treatment was 9.2 +/- 5.5 ng/mL. Simulations showed that for the II probe acoustical power and duration when the transducer is inactive should be reduced of 14% and 1s. In-vitro and in-vivo experiments confirmed the equivalence between the lesions obtained with the two probes. The lesion volume obtained under in-vitro conditions (for a traversed tissue depth of 16 mm to the focus) was 5 +/- 0.4 cm(3) and 5.1 +/- 0.5 cm(3) for the original and II probes, respectively. Under in-vivo conditions, the lesion volume (for a traversed tissue depth of 18 mm) was 5.3 +/- 1.1 cm(3) and 5.1 +/- 1.1 cm(3) for the original and II probes, respectively. During the clinical trial, a correction of + 1s in the exposure time was required to recreate the same degree of efficacy observed with the original probe (p = 0.97): 66.7 % of negative biopsies and 75% of patients with PSA at 3 mo < or =1 ng/mL. The morbidity observed was minimal and identical to that observed with the original probe.

Efectos tóxicos producidos por las microcistinas en peces / Toxic effects produced by microcystins in fish

Las microcistinas (MC) son toxinas peptídicas producidas, generalmente en medios acuáticos eutróficos, por distintos géneros de cianobacterias, destacando como una de las principales especies productoras Microcystis aeruginosa. Estructuralmente, las MC son heptapéptidos cíclicos y funcionalmente están clasificadas dentro del grupo de las hepatotoxinas. Las MC han originado intoxicaciones a veces incluso fatales tanto en animales como en humanos, por lo que están consideradas como un problema ambiental, ecotoxicológico y principalmente sanitario, destacando su posible actividad carcinógenica. Se ha establecido una Ingesta Diaria Tolerable (IDT) provisional de 0,04 μg/Kg/día de equivalentes de MC-LR y en relación con este valor guía, se considera que la exposición a MC por consumo de alimentos puede ser del orden del20%, una vez reconocida su bioacumulación en algunos tejidos de plantas, moluscos y pescados, ya que las cianobacterias son un importante componente de la dieta de muchos peces cíclidostropicales y ciprínidos. Son diversos los estudios de campo que demuestran la acumulación de MC en pescados, procedentes de la goscon floraciones de cianobacterias tóxicas, incluso en periodos de baja densidad fitoplanctónica, pudiéndose alcanzar valores muy próximosa la IDT anteriormente mencionada. Al ser los peces uno de los organismos más proclives a las intoxicaciones por MC y acumularlas, en los últimos años se ha constatado un aumento considerable de las publicaciones científicas sobre los daños fisiopatológicos inducidos por las mismas a nivel macroscópico, histológico, ultraestructural ymetabólico en peces, en función de la especie piscícola, lo que justifica su revisión (AU)

Microcystins (MCs) are peptidic toxins produced in euthrophicwaters by different genera of cyanobacteria, being Microcystisaeruginosa one of the main toxins-producing species. Structurally MCs are cyclic heptapeptides and are classified as hepatotoxins. MCshave been responsible of fatal intoxications both in humans and animals, and they are considered as an environmental, ecotoxicologic and also a health problem due to their potential carcinogenic activity. A provisional tolerable daily intake (TDI) value of 0.04 μg/kg/day equivalents MC-LR has been established. In this regard, it is considered that the MCs exposure through food ingestion could be around 20%, as they accumulate in different tissues of plants, molluscs and fish, being an important dietary component of many tropical cichlids and cyprinids fish. Different field studies have shown that MCs accumulation in fish from water bodies where toxic cyanobacterial blooms were present can lead to a toxins level near the TDI. Fish are among the organisms more easily prone to suffer from MCs intoxication and to accumulate them. This explains the high increase of scientific publications dealing with pathological damage induced by these toxins at macroscopic, histological, ultra structural and metabolic level in different fish species, and justifies the review of this topic (AU)