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Recently, growing attention has been directed toward stem cell metabolism, with the key observation that the plasticity of stem cells also reflects the plasticity of their energy substrate metabolism. There seems to be a clear link between the self-renewal state of stem cells, in which cells proliferate without differentiation, and the activity of specific metabolic pathways. Differentiation is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration. This metabolic switch of differentiating stem cells is required to cover the energy demands of the different organ-specific cell types. Among other metabolic signatures, amino acid and carbohydrate metabolism is most prominent in undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature is unique in cardiomyocytes derived from embryonic stem cells. Identifying the specific metabolic pathways involved in pluripotency and differentiation is critical for further progress in the field of developmental biology and regenerative medicine. The recently generated knowledge on metabolic key processes may help to generate mature stem cell-derived somatic cells for therapeutic applications without the requirement of genetic manipulation. In the present review, the literature about metabolic features of stem cells and their cardiovascular cell derivatives as well as the specific metabolic gene signatures differentiating between stem and differentiated cells are summarized and discussed.

We report the use of thin film poly(dimethylsiloxane) (PDMS) prints for the arrayed mass production of highly uniform 3-D human HT29 colon carcinoma spheroids. The spheroids have an organotypic density and, as determined by 3-axis imaging, were genuinely spherical. Critically, the array density impacts growth kinetics and can be tuned to produce spheroids ranging in diameter from 200 to 550 µm. The diffusive limit of competition for media occurred with a pitch of ≥1250 µm and was used for the optimal array-based culture of large, viable spheroids. During sustained culture mass transfer gradients surrounding and within the spheroids are established, and lead to growth cessation, altered expression patterns and the formation of a central secondary necrosis. These features reflect the microenvironment of avascularised tumours, making the array format well suited for the production of model tumours with defined sizes and thus defined spatio-temporal pathophysiological gradients. Experimental windows, before and after the onset of hypoxia, were identified and used with an enzyme activity-based viability assay to measure the chemosensitivity towards irinotecan. Compared to monolayer cultures, a marked reduction in the drug efficacy towards the different spheroid culture states was observed and attributed to cell cycle arrest, the 3-D character, scale and/or hypoxia factors. In summary, spheroid culture using the array format has great potential to support drug discovery and development, as well as tumour biology research., Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

PURPOSE: Although the central role of the immune system for tumor prognosis is generally accepted a single robust marker is not yet available. EXPERIMENTAL DESIGN: Based on ROC (receiver operating characteristic) analyses robust markers were identified from a 60 gene B-cell derived metagene and analyzed in gene expression profiles of 1810 breast cancer, 1056 non-small cell lung cancer, 513 colorectal and 426 ovarian cancer patients. Protein and RNA levels were examined in paraffin embedded tissue of 330 breast cancer patients. The cell types were identified using immunohistochemical co-staining and confocal fluorescence microscopy. RESULTS: We identified immunoglobulin kappa C (IGKC) which as a single marker is similarly predictive and prognostic as the entire B-cell metagene. IGKC was consistently associated with metastasis free survival across different molecular subtypes in node-negative breast cancer (n=965) and predicted response to anthracycline-based neoadjuvant chemotherapy (n=845) [P less than 0.001]. In addition, IGKC gene expression was prognostic in non-small cell lung cancer and colorectal cancer. No association was observed in ovarian cancer. IGKC protein expression was significantly associated with survival in paraffin embedded tissues of 330 breast cancer patients. Tumor infiltrating plasma cells were identified as the source of IGKC expression CONCLUSION: Our findings provide IGKC as a novel diagnostic marker for risk stratification in human cancer and support concepts to exploit the humoral immune response for anti-cancer therapy. It could be validated in several independent cohorts and performed similarly well in RNA from fresh frozen as well as from paraffin tissue and on protein level by immunostaining.

En la presente tesis se estudia el tratamiento de la mastitis con fármacos antibacterianos y, en concreto, con el enrofloxacino que es una de las fluoroquinolonas más utlizadas en medicina veterinaria. Se ha desarrollado y puesto a punto una técnica (Ehinger y Kietzmann, 2000a y b; Ehinger et al., 2006) que permite estudiar la distribución de los fármacos en ubres de oveja aisladas y perfundidas. El modelo in vitro propuesto en esta memoria se postula como una alternativa adecuada al empleo de animales vivos en los estudios de eficacia y seguridad de antimicrobianos de aplicación intramamaria formulados en vehículos con distinta capacidad de difusión tisular

[ES] El desarrollo anormal de la articulación coxofemoral es un trastorno hereditario cuyo diagnóstico precoz no es fácil, pero se confirma a través de radiografías. Su tratamiento puede ser conservador o quirúrgico.

[EN] Dietary supplements are commonly used among athletes, and the Internet may be an easy source of these products. Tribulus terrestris is an herbal supplement with multiple properties. Of interest to athletes are reports that its consumption can lead to muscle mass gain and a faster recovery process. The objective of this cross-sectional study was to determine the availability of Tribulus terrestris via the Internet in six countries (Canada, Puerto Rico, Russia, Spain, Ukraine, and the United States of America) via a specifically designed computer program. The characteristics of the websites selling this substance, the country from which it can be purchased, the route of administration, and recommendations for its use were analyzed. The results of the study show that this supplement is marketed mainly in Russia, Ukraine, and Spain on many websites that are mostly dedicated to sports products. Just over half of the webpages (59.14%) identified only distribute this supplement within the same country. The main claims for its consumption refer to sports performance benefits, but there are also claims that it may improve male hormone levels and sexual function. Athletes should be encouraged to seek professional advice prior to ingesting this supplement to ensure that it is suitable for their specific training and sports objectives.

[EN] Background - Animal models are increasingly used in Nursing science to study care approaches. Despite the scientific relevance and the ethical debate surrounding the use of experimental animals, there is a scarcity of scholarly literature exploring this topic in Nursing Schools. Aim - To evaluate perceptions and attitudes of nursing students enrolled in a Pharmacology course on the use of experimental animals and implementation of alternative methods, by comparing the experience for two academic years. An interdisciplinary collaboration has also been developed. Methods - A descriptive cross-sectional, quantitative study was developed. Undergraduate nursing students were enrolled in the Pharmacology subject at the University of Leon (Spain). The study was carried out in the Pharmacology facilities. Students followed a two-session practical class regarding experimental animals and alternative methods in the Pharmacology course (Degree in Nursing) in two different academic years (2019–20/2020–21). At the end of the activity, they answered a questionnaire to assess their opinions on the use of experimental animals and alternative methods in Pharmacology and the 3Rs principle. Results - A comparison of the students’ perception with and without direct participation in the evaluation of promazine effects in mice was made. A total of 190 students participated in the teaching experience, providing high scores in all items (4–5 out of 5 points) regarding the teaching experience. Students became also aware of the advantages and disadvantages on the use of experimental animals, as well as the ethical considerations to bear in mind for their use and the need for alternative methods. Conclusions - In the students’ opinion, the total replacement of animals by alternative techniques was very difficult, and they preferred to do the practice face-to-face. The alternative method designed was useful for the students to accept the employment of experimental animals in biomedical re

[EN] Exotic companion animals have had an important role in our society since ancient times. Preserving animal health is necessary to do a responsible use of veterinary medicines. This study aimed to describe the prescription patterns of drugs in exotic pets and wildlife animals attending the Veterinary Teaching Hospital of the University of León (HVULE). A retrospective study was carried out between 2018 and 2022. Birds were the largest group of exotic animals attending the HVULE. Visits were related to emergency reasons and for musculoskeletal disorders. One-third of the animals were eventually euthanised. Regarding pharmacological treatments, the most frequently active ingredients used were pentobarbital, isoflurane, meloxicam, and within antibiotics, marbofloxacin (category B in the classification of European Medicines Agency).

[EN] Sparfloxacin, a synthetic antibiotic belonging to the third-generation fluoroquinolones, has numerous pharmacokinetic and microbiological advantages which can make it an excellent candidate for the treatment of infections in sheep. The objective of this study was to develop and validate an analytical HPLC method to quantify sparfloxacin in sheep plasma, following the recommendations set out in the Guideline on Bioanalytical Method Validation of the European Union (EMEA/CHMP/EWP/192217/2009). The HPLC mobile phase consisted of acetonitrile and monopotassium phosphate buffer (1.36 g/L) 49:51 (v/v). Genabilic acid was used as internal standard. Mean retention times for sparfloxacin and genabilic acid were 2.6 and 5.8 min, respectively. The method met all specifications of the EMA guideline, being selective and linear in the range of 0.2–10 g/mL (R2 0.99). Within-run precision ranged between 0.00 and 0.88%, with an accuracy of 90.3–118.0% for the lower limit of quantitation (LLOQ). The LLOQ was 0.2 g/mL, and no interference from the biological matrix was found. The stability of sparfloxacin in the biological matrix was demonstrated under different storage conditions. Therefore, the method can be used to determine sparfloxacin concentrations in sheep plasma in different types of studies.

[EN] Menbutone is often used to stimulate the hepato-digestive activity in case of digestive disorders and hepatic insufficiency in different species (cattle, sheep, goats, pigs, horses, dogs) because it has choleretic and cholagogue effects and increases gastric and pancreatic juices. The objective was to develop and validate an HPLC method to quantify menbutone in sheep plasma using sparfloxacin as internal standard. The HPLC mobile phase consisted of acetonitrile:monopotassium phosphate solution. The method was validated according to EMA guideline (EMEA/CHMP/EWP/192217/2009). Mean retention times of menbutone and sparfloxacin were 4.5 and 2.2 min, respectively. The method met all specifications of the EMA guideline, being selective and linear in the range of 0.2–100 g/mL (R2 0.99). The within-run precision range was 0.19–8.21%, with an accuracy of 102.99–119.52% for the lower limit of quantitation (LLOQ). For the other values (LOW, MED, HIGH) the precision range was 0.01–4.77%, with an accuracy of 85.17–109.67%. The LLOQ was 0.2 g/mL, and no interference from the biological matrix was found. Stability of menbutone in the biological matrix at different storage conditions was also demonstrated. Thus, the method can be used to determine menbutone concentrations in plasma sheep in different types of studies

[EN] At present, 19.2% of the Spanish population is aged 65 or older. Polypharmacy is a frequent condition among the elderly, especially in those living in nursing homes, which is associated with adverse outcomes, such as adverse drug events or drug-drug interactions. This study aimed to assess the pattern of polypharmacy in a nursing home in León, one of Spain’s most ageing regions, and its relationship with different drug-related problems. A descriptive, observational, and crosssectional study design was used; 222 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds, BOT PLUS and Drug-Reax. Residents were on a median of 7 medicines. Polypharmacy and inappropriate medications were present in 78.8% and 96.8% of residents, respectively. Drug-related problems were present in almost all the populations evaluated. Drug-drug interactions were very common in participants (81.1%), being severe/moderate in 24.7%. A high prevalence of polypharmacy and drugrelated problems in the nursing home population assessed has been observed. A significantly higher risk of suffering drug-drug interactions was revealed for increasing polypharmacy and anticholinergic risk. A regular evaluation of drug prescribing in nursing home residents is necessary to minimize drug-related problems risk.

[EN] Medicinal plants have been used in veterinary medicine since ancient times, and they are gaining importance in Eastern Europe. The aim of this study was to conduct a survey on the use of medicinal plants in Spain. A cross-sectional study with an online questionnaire was carried out among Spanish small animal veterinarians, to evaluate the use patterns of medicinal plants and attitudes of professionals toward it. 313 veterinarians took part in the study. Most of them were female (80.2%) and age ranged 35–49 (49.5%). 80.3% of respondents use phytotherapy. Musculoskeletal and gastrointestinal disorders were those most frequently treated, with cannabis, aloe and thyme the most often medicinal plants used. The most common pattern of user was women working in clinics.

[EN] The use of supplements containing herbal active ingredients in sport has increased in recent years. Their consumption is explained by the benefits they may provide and because their natural origin do not involve health complications, from the point of view of the consumers. The aim of this study is to analyze the availability of four supplements (caffeine, turmeric, ginseng, cannabidiol) on the internet and understand the nature of these websites. A descriptive, observational, and cross-sectional study design was used. A detailed search was carried out with specifically developed software. The searches and data evaluation took 10 days. The websites consulted correspond to those that sell supplements, or some sport websites in the case of the Spanish ones, whereas those in English belong to pharmacies, parapharmacies, or herbalists. It is concluded that the websites do not provide adequate information to ensure proper consumption and lack advice on the choices of supplements and their administration guidelines

[EN] The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MENwere administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.

[EN] Inappropriate prescribing in the elderly is a risk factor for higher adverse drugs reactions, hospitalisation, and mortality rates. Therefore, it is necessary to identify irrational prescriptions and implement interventions to improve geriatric clinical practices in nursing homes. This study aimed to examine and compare the prevalence of potentially inappropriate medications in nursing home residents using three different updated criteria: 2019 Beers criteria, PRISCUS list, and v2 STOPP criteria, and to determine the prevalence of potential prescribing omissions according to v2 START criteria. A descriptive, observational, and cross-sectional study design was used. A total of 218 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds. Potentially inappropriate medications were present in 96.3%, 90.8%, and 35.3% of residents, according to the STOPP, Beers, and PRISCUS criteria or list, respectively. Inappropriate medication was found to be significantly associated with polypharmacy and severe or moderate drug–drug interactions with the three tools and with pathologies and unnecessary drugs only for STOPP criteria. The most frequent inappropriate medications were benzodiazepines and proton pump inhibitors. A regular use of software to review medications in nursing home residents would help to reduce the risk of these drug-related problem

[EN] In Spain, there has been a progressive increase in aging. Specifically, Leon has been one of the Spanish provinces with the highest aging index. Polypharmacy is highly prevalent among the elderly, with significant consequences for safety. The aim of this study was to assess the consumption of drugs in a nursing home in the province of Leon and establish the relationship between polypharmacy and the most common comorbid diseases. A descriptive, observational, and cross-sectional study design was used. Residents’ information and treatments were collected by reviewing on medical charts, completed with clinical information obtained from the physician of the nursing home. The mean age of residents was 86.8 years, and 63.8% were female. Mean medical consumption amounted to 7.02 prescriptions. Polypharmacy was observed in 54.9% of residents, and excessive polypharmacy in 22.1%. The most commonly used medications (ATC classification) were those acting on the cardiovascular system (84.4%) and the nervous system (82.8%). A high-level of drug consumption was observed in the nursing home. Interventions should focus on those residents hospitalized the last year and with recent contact with a general practitioner. There is a need to develop a comprehensive monitoring system to assess the quality of prescriptions for nursing home residents.

[EN] Background: The Internet has become an important source for easy access to doping substances, where people and athletes may acquire, outside pharmacies and without a (medical) prescription. These online websites do not always offer quality-assured products, and are outside the regular distribution channels of medicines. The aim of this study was to estimate the availability and accessible information on the Internet about the sale of three doping substances (oxandrolone, DHEA, androstenedione). Methods: Cross-sectional exploratory study, being an observation at a point in time of the online availability of these three doping substances (WADA S1 category: anabolic agents), purchased from Spain, Puerto Rico, Canada, United States, Ukraine and Russia. The characteristics of the websites, the countries the webs sold to, the pharmaceutical forms offered and the recommendations for its use were analyzed by using a computer tool designed ad hoc. Results: There were significant differences between countries in the number of webpages that sold the products (Chi-square test, p < 0.05). Oxandrolone was available for purchase mainly when buying from Spain (27.12%) and Ukraine (26.58%), in websites dedicated to sports (77.26%). For DHEA, most of the pages offered it if the search was done from Canada (23.34%) and Russia (21.44%). Products containing androstenedione or DHEA are claimed to enhance sports performance or for sports use without providing details. Compared to the total number of websites checked, the proportion of pharmacies offering these products was low, ranging from 4.86% for DHEA to 15.79% for androstenedione. Conclusion: The three substances selected are easily available without control through the Internet. Only a small number of websites offering them were online pharmacies, and requested a prescription. Most of the doping substances are purchased from the country where they are requested. Product information described benefits for sports performance, but

[EN] The misuse or overuse of antibiotics can favor the emergence of antimicrobial resistance, with a direct impact on human and animal health as well as on ecosystems. In this work, we have analyzed the web pages in which antibiotics for veterinary use can be purchased online. By using a specifically developed software, we carried out a detailed search to know if each individual antibiotic and the families included in the OIE list of antimicrobial agents of veterinary importance (in English and in Spanish) were sold, reviewing the offers according to the administration route and the species for which the antibiotics were intended. The greatest offer of antibiotics was for those compounds considered critically important by OIE. In the search in English, penicillins were available on 55.8% of the sites, tetracyclines on 55.0%, and fluoroquinolones on 52.7%. In Spanish, the families with the greatest presence were fluoroquinolones (67.9% of the sites), tetracyclines (67.9% of the sites), and penicillins (65.4% of the sites). Regarding individual antibiotics, the most offered in both searches were amoxicillin (49.6% of the sites in English and 57.7% in Spanish) and doxycycline (46.5% of the sites in English and 53.8% in Spanish). Most offers were for oral and parenteral administration and intended for cats and dogs and for bovines.