in vivo toxicity of the ribosome-inactivating lectin ebulin f in elderly mice

Producción CientíficaEbulin f is a ribosome-inactivating protein (RIP) present in green fruits of the dwarf elder (Sambucus ebulus L). Since dwarf elder fruits are used for food and as a medicine, we assessed the study of toxicological effects and safety of ebulin f in elderly mice, comparing these results with those reported in young animals and with other RIPs. Female Swiss mice aged 6 and 12 months of age were intraperitoneally injected with a single dose from 1.4 to 4.5 mg/kg ebulin f. Heart, stomach, intestines, lung, kidney, liver, spleen, pancreas, adrenal gland, uterus, ovary and brain were studied. Histology analysis was carried out by staining with hematoxylin and eosin and Masson's trichrome observed with a light microscope, or apoptosis detection by TUNEL method observed with a confocal laser microscope. Treated animals injected with the lower dose could recover their weights, but after 14 days half of them died. The higher dose caused a progressive loss of body weight leading to death. In the animals of the experimental groups it was found atrophy of Lieberkühn's crypts, pneumonia, nephronal degeneration, myocardial atrophy, centrolobular hepatic necrosis, splenic white pulp necrosis foci and increased rate of apoptosis in the intestines and liver, in which apoptoses were mainly located in the vicinity of the lobular central vein. We conclude that ebulin f affects vital organs in elderly mice.UVa-GIR Inmunotoxinas AntitumoralesUCM-CAM Research group 95024

Unexpected toxicity of green tea polyphenols in combination with the Sambucus RIL ebulin

Producción CientíficaThe safety of concentrated food complements intake is a major health concern. It has been well established that green tea polyphenols (GTPs) consumption promotes healthy effects. However, the ingestion of large amounts of GTPs is a matter of controversy due to reported adverse effects. We underwent a preliminary exploration of the effects of the oral administration of a standardized concentrated GTPs preparation on mice which suffered from reversible intestinal derangement promoted by sublethal amounts of the antiribosomal lectin ebulin f from dwarf elder (Sambucus ebulus L.). Neither independent oral administration of 30 mg/kg body weight Polyphenon 60 nor intraperitoneal administration of 2.5 mg/kg body weight ebulin f triggered lethal toxicity. In contrast, the simultaneous administration of these same doses of both Polyphenon 60 and ebulin f triggered an important and unexpected synergistic toxic action featured by the biphasic reduction of weight, which continued after eight days, reaching a reduction of 40%. Lethality appeared 2 days after the onset of the combined treatment and reached more than 50% after 10 days.Junta de Castilla y León y Consejería de Sanidad (GR106

Models Used by Nurse Case Managers in Different Autonomous Communities in Spain: A Scoping Review

[Background]: The role of the nurse case manager is unknown to the population. The main objective is to analyze the existing differences within the national territory in order to make known the situation in Spain with a view to the recognition of its functions and the creation of the professional profile in an equal manner.[Methods]: A scoping review was conducted in order to achieve the main aim. Selected articles were subjected to a critical reading, and the levels of evidence and grades of recommendation of the Joanna Briggs Institute were verified. The search field was limited to the last ten years.[Results]: Case management models are heterogeneous in different autonomous communities in Spain. Case nurse management is qualified for high-complexity patients, follow up on chronic patients, and coordinate health assistance.[Conclusions]: It concludes that nursing’s role is crucial in the field of case management, being required in the follow-up of chronic patients of high complexity. Despite the proven health benefits, efficacy, and efficiency of case management, there are many heterogeneous models that coexist in Spain. This involves a restriction in the development of a nursing career because of the lack of a definition of its functions and competences.Peer reviewe

Identification of recent tuberculosis exposure using QuantiFERON-TB Gold Plus, a multicenter study.

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB22TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD81 T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-g) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB22TB1 value .0.6 IU ml21 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2.TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB22TB1 result of .0.6 IU ml21 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 5.4%, and 17.7% with close, frequent, and sporadic contact had a TB2.TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB22TB1 difference of .0.6 IU ml21 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Vectorización de fármacos para la optimización del tratamiento de enfermedades inflamatorias intestinales

En el término enfermedad inflamatoria intestinal (EII) se engloban dos trastornos idiopáticos, la enfermedad de Crohn y la colitis ulcerosa. Su tratamiento depende de la gravedad, el subtipo de enfermedad y localización, entre otros. Los corticoides son los fármacos más eficaces para el tratamiento de las EII, destacando la prednisolona, cuya eficacia ha demostrado ser mayor en ensayos clínicos frente a la budesonida. Sin embargo, su uso se limita a los casos graves debido a la aparición de efectos secundarios como consecuencia de su absorción sistémica. El objetivo principal de esta tesis consiste en desarrollar sistemas de liberación modificada de prednisolona vectorizados con SELfd conforme a los condicionantes biofarmacéuticos de las EII. Los objetivos parciales consisten en el aislamiento y caracterización de la lectina dimérica de frutos de Sambucus ebulus L. (SELfd), seguido del estudio de las propiedades bioadhesivas de la SELfd y ebulina f (Ebu f) sobre tejido intestinal de ratón. Para mejorar la vehiculización de prednisolona se pretende elaborar micropartículas empleando como polímeros biocompatibles y biodegradables el PLGA y el quitosano, y se recurre a la funcionalización de los sistemas con SELfd. Por último, se evalúa la formulación seleccionada en el modelo murino de daño-regeneración generado por ebulina-f..

In vivo toxicity of the ribosome- inactivating lectin ebulin f in elderly mice

Ebulin f is a ribosome-inactivating protein (RIP) present in green fruits of the dwarf elder (Sambucus ebulus L). Since dwarf elder fruits are used for food and as a medicine, we assessed the study of toxicological effects and safety of ebulin f in elderly mice, comparing these results with those reported in young animals and with other RIPs. Female Swiss mice aged 6 and 12 months of age were intraperitoneally injected with a single dose from 1.4 to 4.5 mg/kg ebulin f. Heart, stomach, intestines, lung, kidney, liver, spleen, pancreas, adrenal gland, uterus, ovary and brain were studied. Histology analysis was carried out by staining with hematoxylin and eosin and Masson’s trichrome observed with a light microscope, or apoptosis detection by TUNEL method observed with a confocal laser microscope. Treated animals injected with the lower dose could recover their weights, but after 14 days half of them died. The higher dose caused a progressive loss of body weight leading to death. In the animals of the experimental groups it was found atrophy of Lieberkühn’s crypts, pneumonia, nephronal degeneration, myocardial atrophy, centrolobular hepatic necrosis, splenic white pulp necrosis foci and increased rate of apoptosis in the intestines and liver, in which apoptoses were mainly located in the vicinity of the lobular central vein. We conclude that ebulin f affects vital organs in elderly mice

Study of the migration of Fasciola hepatica juveniles across the intestinal barrier of the host by quantitative proteomics in an ex vivo model

22 páginas, 8 figurasFasciola hepatica is a trematode parasite that infects animals and humans causing fasciolosis, a worldwide-distributed disease responsible for important economic losses and health problems. This disease is of growing public health concern since parasite isolates resistant to the current treatment (triclabendazole) have increasingly been described. F. hepatica infects its vertebrate host after ingestion of the encysted parasite (metacercariae), which are found in the water or attached to plants. Upon ingestion, newly excysted juveniles of F. hepatica (FhNEJ) emerge in the intestinal lumen and cross the intestinal barrier, reach the peritoneum and migrate to the biliary ducts, where adult worms fully develop. Despite the efforts made to develop new therapeutic and preventive tools, to date, protection against F. hepatica obtained in different animal models is far from optimal. Early events of host-FhNEJ interactions are of paramount importance for the infection progress in fasciolosis, especially those occurring at the host-parasite interface. Nevertheless, studies of FhNEJ responses to the changing host environment encountered during migration across host tissues are still scarce. Here, we set-up an ex vivo model coupled with quantitative SWATH-MS proteomics to study early host-parasite interaction events in fasciolosis. After comparing tegument and somatic fractions from control parasites and FhNEJ that managed to cross a mouse intestinal section ex vivo, a set of parasite proteins whose expression was statistically different were found. These included upregulation of cathepsins L3 and L4, proteolytic inhibitor Fh serpin 2, and a number of molecules linked with nutrient uptake and metabolism, including histone H4, H2A and H2B, low density lipoprotein receptor, tetraspanin, fatty acid binding protein a and glutathione-S-transferase. Downregulated proteins in FhNEJ after gut passage were more numerous than the upregulated ones, and included the heath shock proteins HSP90 and alpha crystallin, amongst others. This study brings new insights into early host-parasite interactions in fasciolosis and sheds light on the proteomic changes in FhNEJ triggered upon excystment and intestinal wall crossing, which could serve to define new targets for the prevention and treatment of this widespread parasitic disease.The Spanish Ministerio de Ciencia e Innovación (Projects PID2019-108782RB-C22 and PID2019-108782RB-C21), Spanish Ministerio de Economía, Industria y Competitividad (Projects AGL2015-67023-C2-2-R and AGL2015-67023-C2-1-R), and the Project “CLU-2019-05 – IRNASA/CSIC Unit of Excellence”, funded by the Consejería de Educación, Junta de Castilla y León and co-financed by the European Union (ERDF “Europe drives our growth”). the JIN project ‘ULYSSES’ (RTI2018-093463-J-100) funded by the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe

Desarrollo de un modelo in vivo para el estudio proteómico de los mecanismos de invasión del parásito Fasciola hepatica

1 página. -- Comunicación oral presentada en las IX Jornadas de investigadoras de Castilla y León, celebradas en Salamanca, del 9 al 10 de febrero de 2023La fasciolosis producida por Fasciola hepatica es una enfermedad parasitaria que causa grandes pérdidas económicas en la industria ganadera, y una preocupación sanitaria creciente a nivel mundial debido a su carácter zoonótico. Los mecanismos moleculares que rigen la invasión llevada a cabo por el parásito desde el intestino hasta las vías biliares del hospedador siguen planteando grandes incógnitas. Por ello, el objetivo de este trabajo fue establecer un modelo de infección experimental en ratón para identificar las moléculas parasitarias clave durante la migración de los vermes juveniles a través de los tejidos del hospedador. Ratones C57BL/6 se infectaron oralmente con 200 metacercarias de F. hepatica y, posteriormente, los parásitos fueron recuperados a las 24 horas en la cavidad peritoneal (9.38 % tasa de recuperación) y a los 8 días en el parénquima hepático (21.19 % tasa de recuperación). Los extractos parasitarios tegumental y somático y sus respectivos controles se sometieron a proteómica cuantitativa mediante la adquisición secuencial de todos los espectros de masas teóricos o SWATH-MS, de sus siglas en inglés "Sequential Window Acquisition of All Theoretical Mass Spectra". Los resultados proteómicos revelan la presencia de 1180 proteínas en las muestras, de las cuales, 243 proteínas se expresan diferencialmente en los parásitos extraídos en el peritoneo y 543 proteínas en los procedentes del hígado. La anotación ontológica de los términos asociados a estas proteínas apunta principalmente a la relevancia de mecanismos de defensa antioxidante, proteolíticos, de motilidad, metabólicos y de transporte de moléculas en la invasión llevada a cabo por F. hepatica. En conjunto, los avances de este estudio profundizarán en el conocimiento de la interacción parásito-hospedador de la fasciolosis para identificar nuevas dianas moleculares en el desarrollo de vacunas frente a F. hepatica.PID2019-108782RB-C22 y PID2019-108782RB-C21 financiados por MICINN, AEI y FEDER y CL-EI-2021-01 IRNASA-CSIC patrocinado por la JCyL y cofinanciado por FEDERPeer reviewe

Design and Validation of a Questionnaire on Risk Perception, Coping Behaviors and Preventive Knowledge against COVID-19 among Nursing Students

As shown in the previous literature, in view of the future responsibilities of nursing professionals and the consequences for healthcare, it is of great interest to examine their risk perceptions, coping behaviors, and sense of coherency during the COVID-19 pandemic. The purpose of this study is to design and to validate a specific questionnaire that evaluates the factors relating to perceived risk, coping behaviors, and preventive knowledge against COVID-19 infection among nursing students from Spain. This is a psychometric study of a questionnaire's design and its validation in 1562 nursing students at 16 undergraduate nursing institutions in Spain. An ad-hoc survey was designed by a panel of six experts drawing from the literature. After a trial test, the questionnaire was formed with four scales (perception, risk, coping, and knowledge of preventive practices for COVID-19), with a total of 69 items. The final questionnaire was composed of 52 items grouped into four scales, with good psychometric properties to measure risk perception (Cronbach's alpha 0.735), factors related to perceived risk (Cronbach's alpha 0.653), coping behaviors (Cronbach's alpha 0.80), and knowledge of preventive practices against COVID-19 (Cronbach's alpha 0.77). This questionnaire, specifically designed and validated for nursing students, is the first to address four important areas in the development of preventive measures against COVID-19.This research was funding by the Fundación Instituto de InvestigaciónMarqués De Valdecilla.Nursing educationNursing studentsRisk assessmen