Review and new therapeutic alternatives for the treatment of cutaneous Leishmaniasis

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/63704Leishmaniasis comprises a group of diseases caused by protozoa of the genus Leishmania and has two basic clinical forms, visceral Leishmaniasis and cutaneous Leishmaniasis. The clinical features of Leishmaniasis depend on the species of Leishmania, the interaction between host and parasite and the immune response. This work focuses on cutaneous leishmaniosis because although it is not a deadly disease it results in significant scars and facial disfigurements, thus being clinically important. Furthermore, the first-line treatment consists of intravenous or intramuscular administration of intralesional pentavalent antimonials, which are highly toxic, making hospitalization of patients compulsory during treatment, with the associated financial costs. Herein, we review studies on drugs and treatments with fewer side effects and easier routes of administration such as topical administration. Recent research shows that the topical route of administration holds promise for the future treatment of cutaneous leishmaniosis

Mice with hyper-long telomeres show less metabolic aging and longer lifespans

Short telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.S

Exercices, problems and practices of metric geometry

2019/202

Diferents estratègies per augmentar la sensibilitat en eleccroforesi capil·lar. Aplicació a la determinació de fàrmacs antiinflamatoris

La Tesi Doctoral que porta per títol, "Diferents estratègies per augmentar la sensibilitat en electroforesi capil·lar. Aplicació a la determinació de fàrmacs antiinflamatoris", s'ha basat en el desenvolupament de diferents estratègies per a disminuir els límits de detecció (LODs) de l'electroforesi capil·lar (CE) a la determinació de fàrmacs antiinflamatoris. Les estratègies desenvolupades s'han basat en la injecció d'un gran volum de mostra en el capil·lar mitjançant l'aplicació de tècniques de preconcentració tant electroforètiques com cromatogràfiques, i en l'ús de l'espectrometria de masses (MS) com a sistema de detecció per augmentar la capacitat de detecció dels analits. La present Tesi Doctoral s'ha centrat en la determinació de fàrmacs antiinflamatoris no esteroïdals (NSAIDs) en el medi ambient aquàtic a baixos nivells de concentració. L'interès a la determinació d'aquests ha augmentat molt darrerament degut al seu elevat consum tant en espècies humanes com en animals. Aquests fàrmacs arriben a les estacions de tractament d'aigües residuals (EDAR) a través de diferents procedències, i posteriorment aquests poden entrar en el medi ambient aquàtic degut a la seva gran estabilitat. Diferents estudis han demostrat la determinació d'aquests fàrmacs a nivells de baixos ng·L-1 en les aigües superficials. Aquests estudis s'han realitzat principalment tant per cromatografia de gasos (GC) com per cromatografia de líquids (HPLC) emprant l'MS com a sistema de detecció. L'CE també ha estat emprada per la determinació d'aquests fàrmacs, però la seva aplicació principal ha estat en l'anàlisi de mostres biològiques. Tot i els grans avantatges que proporciona la tècnica d'CE, aquesta presenta una baixa sensibilitat que limita la determinació d'analits a baixos nivells de concentració. Aquest fet és degut com a conseqüència del petit volum de mostra que es pot injectar en el capil·lar i del petit camí òptic que tenen els capil·lars que sutilitzen. Amb l'objectiu de millorar la sensibilitat de la tècnica i d'ampliar la seva aplicabilitat en altres camps, com el mediambiental, el desenvolupament de diferents estratègies per a disminuir els LODs són molt importants i són objecte d'estudi de diferents grups d'investigació. En la present Tesi Doctoral s'han aplicat i comparat diferents tècniques de preconcentració electroforètiques per la determinació d'aquests fàrmacs en els diferents modes electroforètics, com l'electroforesi capil·lar per zones (CZE), la cromatografia capil·lar de microemulsió electrocinètica (MEEKC) i la cromatografia capil·lar micel·lar electrocinètica (MEKC). La majoria d'aquestes tècniques s'han basat en la supressió del flux electroosmòtic (EOF) per eliminar la matriu de la mostra del capil·lar desprès d'haver injectat un gran volum de mostra. L'avantatge d'addicionar un supressor de l'EOF al medi electrolític és que aplicant un sol voltatge negatiu es duu consecutivament la preconcentració i la separació electroforètica. L'aplicació d'una tècnica de preconcentració cromatogràfica, basada en l'acoblament in-line entre l'extracció en fase sòlida (SPE) i l'CE, també s'ha aplicat a la determinació de NSAIDs en una mostra d'aigua. El gran potencial de les tècniques de preconcentració tant electroforètiques com cromatogràfiques és que ha permès la determinació d'aquests fàrmacs a nivells de ng·L-1. Aquests resultats s'han obtingut emprant prèviament la tècnica d'SPE off-line per preconcentrar els analits i netejar la matriu de la mostra. Una altra estratègia emprada per la determinació de NSAIDs en el medi ambient aquàtic ha estat l'ús de l'MS com a sistema de detecció. Aquest acoblament permet la confirmació i la identificació dels diferents analits que puguin estar presents en una mostra. D'aquesta manera, ha estat possible la determinació dels fàrmacs en estudi en aigües superficials i la identificació d'aquests en les aigües procedents de diferents estacions EDAR. En aquest cas s'han emprat com a tècniques de pretractament la tècnica d'SPE off-line, i la combinació de l'extracció líquid-líquid (LLE) i l'SPE off-line, respectivament.The entitled Doctoral Thesis, "Diferents estratègies per augmentar la sensibilitat en electroforesi capil·lar. Aplicació a la determinació de fàrmacs antiinflamatoris", has been based on the development of different strategies to decrease the limits of detection (LODs) in capillary electrophoresis (CE) to determine anti-inflammatory drugs. The developed strategies have been based on injecting a large volume of sample into the capillary by application electrophoretic and chromatographic preconcentration techniques, and using the mass spectrometry (MS) as the detection system to increase the detection capacity of the analytes. This Doctoral Thesis has been centred on the determination of nonsteroidal anti-inflammatory drugs (NSAIDs) in the aquatic environment at low concentration levels. In the last years, the interest to determine them has considerably grown due to the high consume in humans and in animals. These drugs arrive in the sewage treatment plants (STPs) by different source, and subsequently these can entry into the aquatic environment due to its high stability. Different studies have demonstrated the determination of these drugs at low ng·L-1 levels in surface waters. These studies have principally carried out by gas chromatography (GC) and liquid chromatography (HPLC) by using mass spectrometry as the detection system. CE has also been used to determine these drugs, but its principal application has been for the analysis of biological samples. Although the high advantages that presents the technique, this shows a low sensitivity that overcomes the determination of analytes at low concentration levels. This is a consequence of the low amount of sample that can be injected into the capillary and the small path length. With the aim of improving the sensitivity and extending the CE applicability in others fields, such as the environmental, then the development of different strategies to decrease the LODs are very important and these are object of studying of different research groups. In this Doctoral Thesis have been applied and compared different electrophoretic preconcentration techniques to determine these drugs in the different electrophoretic modes, such as capillary zones electrophoresis (CZE), microemulsion electrokinetic capillary chromatography (MEEKC) and micellar electrokinetic capillary chromatography (MEKC). Frequently, in these preconcentration techniques the sample matrix has been removed from the capillary by suppressing the electroosmotic flow (EOF). The advantage of adding an EOF suppressor in the electrophoretic medium is that the preconcentration and the electrophoretic separation can consecutively be performed by applying an only negative voltage. The application of a chromatographic preconcentration technique, based on the in-line coupling between solid phase extraction (SPE) and CE, has also been applied to determine NSAIDs in water samples. The high potential of the electrophoretic and the chromatographic preconcentracion techniques, is that allow to determine these drugs at ng·L-1 levels. These results have been obtained by using the technique off-line SPE to preconcentrate the analytes and to clean-up the sample matrix before the application of the preconcentration technique. Other strategy used to determine NSAIDs in the aquatic environment at low levels has been the use of MS as the detection system. This coupling allows confirming and identifying the presence of the analytes in the sample. So, it has been possible the determination of the studied drugs in surface waters and their identification in the STPs. In this study, the technique off-line SPE and the combination of liquid-liquid extraction (LLE) and off-line SPE off-line, respectively, have been used as the sample pretreatment technique

Micronuclei detection by flow cytometry as a high-throughput approach for the genotoxicity testing of nanomaterials

Thousands of nanomaterials (NMs)-containing products are currently under development or incorporated in the consumer market, despite our very limited understanding of their genotoxic potential. Taking into account that the toxicity and genotoxicity of NMs strongly depend on their physicochemical characteristics, many variables must be considered in the safety evaluation of each given NM. In this scenario, the challenge is to establish high-throughput methodologies able to generate rapid and robust genotoxicity data that can be used to critically assess and/or predict the biological effects associated with those NMs being under development or already present in the market. In this study, we have evaluated the advantages of using a flow cytometry-based approach testing micronucleus (MNs) induction (FCMN assay). In the frame of the EU NANoREG project, we have tested six different NMs-namely NM100 and NM101 (TiO2NPs), NM110 (ZnONPs), NM212 (CeO2NPs), NM300K (AgNPs) and NM401 (multi-walled carbon nanotubes (MWCNTs)). The obtained results confirm the ability of AgNPs and MWCNTs to induce MN in the human bronchial epithelial BEAS-2B cell line, whereas the other tested NMs retrieved non-significant increases in the MN frequency. Based on the alignment of the results with the data reported in the literature and the performance of the FCMN assay, we strongly recommend this assay as a reference method to systematically evaluate the potential genotoxicity of NMs

Osteoradionecrosis of the jaws triggered by dental implants placement : a case report

The decision-making process about how to rehabilitate edentulous osseous defects in patients with head and neck cancer history can be complex. Even though, endosseous dental implants could be considered to be the first choice for treating these patients, it is highly important to be aware of the complications that might occur. The aim of this report was to describe the clinical features of mandibular fracture after dental implants placement on a cancer irradiated patient and update the available information about this event. The case describes a 70-year-old man, with medical background of radiotherapy in jaw bones to treat a carcinoma in the floor of the mouth and later on in the soft palate and cheek. One week after dental implant surgery, the patient presented a mandibular osteoradionecrosis that healed in 8 months. A fracture on the right side of the body mandible was diagnosed one year after implant placement. Although several options were suggested in order to repair the fracture, the patient did not accept any further treatment despite the callus formation not being radiographically evident. The implant-supported prosthesis is functionally useful for more than 8 years of follow-up without significant problems. The implant treatment and management of oncologic irradiated patients require special considerations due to the risk of osteoradionecrosis and its possible complications, such as pathologic fracture. It is necessary to provide full information to the patient about risk factors and complications