DECLINE OF CLINICAL ART AND TECNOLOGICAL MEDICINE BOOM

Currently there is a consensus that the clinical art have been greatly deteriorating during the past 50 years. This problem has raised worldwide attention through as increase in publications, courses, symposia and congress. The erosion of bedside teaching and the consequent decline of clinical skills, notably wrongfull and inadequate use of new technologies. At as result, it becomes difficult if not impossible obtain an appropiate collection of the synptoms sufferick for the sick. Together with the medical history, the physical examination is mandatory for the correct diagnosis and developing the treatment plan. In this paper, the decline of clinical art is exposed and how this ancient heritage of medical practice can be recovered.

NATURAL PRODUCTS: FROM TRADITIONAL MEDICINE TO LEAD COMPOUNDS FOR DRUG DEVELOPMENT IN THE 21ST CENTURY

Natural products have historically contributed to drug discovery as a source of bioactive molecules, due to their great diversity and structural complexity. They have provided “lead” molecules for the development of drugs in different therapeutic areas, with a very prominent representation in the treatment of pain and inflammation, coagulation disorders, metabolic disorders, as well as in the treatment of cancer and infectious diseases. In recent decades there has been a paradigm shift in drug discovery strategies that has allowed the identification of new active natural products in therapeutic targets. Combinatorial Chemistry and biological tests (High Throughput Screening), together with the development of computational techniques, have contributed decisively to the design and optimization of libraries of natural product derivatives based on their biological activity. In parallel, technological advances in the field of Omics sciences and in data processing lead to a multidimensional approach in the drug discovery process. These powerful tools will allow the analysis of the pharmacological potential of natural products and their derivatives for the conversion of these molecules to active products with low toxicity. In the Precision Medicine era, natural products continue to be molecules with great potential in pharmaceutical development, since, unlike other therapeutic strategies, they have a favorable cost-benefit ratio, which will allow their future use in this discipline.

Historical development of the pharmaceutical industry in Spain prior to Transition

Max Weber (1864-1920), in his classic Die protestantische Ethik und der Geist des Kapitalismus, tried to justify the unequal industrial development of the different European countries based on the religious division of the continent as result of the Lutheran Reformation; According to their approach, the establishment of Protestantism in the north and centre and Catholicism in the south became the northern areas prosperous and the southern areas depressed, encouraging a tendency in the Protestant countries towards factory work, in opposition to the Catholic preference for craftsmanship. As far as the pharmaceutical industry was concerned, this approach led to two different models: the Central European model, Protestant-inspired, and the Mediterranean model, established in mainly Catholic countries such as Spain. The pharmaceutical industry was the driving force behind the new therapeutics that emerged during the 19th century, and it did so by acting on the two fundamental components of the drug: composition and presentation; while the Central European and Anglo-Saxon countries were inclined to promote the composition, the Mediterranean pharmaceutical industry channelled its efforts towards the final consumer product, the “pharmaceutical speciality”. Taking this framework into account, our intention is to offer a general overview of the Spanish pharmaceutical industry prior to the Transition, based on a series of stages ranging from the emergence of drugstore pharmacies in the mid-19th century to the establishment of pharmaceutical laboratories during Franco’s regime, including the classification of what we know as industrial medicines (“secret remedies”, “specific” and “pharmaceutical specialities”), their legal recognition (Stamp Act and health registration), their raw materials and main pharmaceutical forms.

Extracellular vesicles in the host-helminth communication: biomedical applications

Extracellular vesicles participate in intercellular communications, altogether with classic mechanisms like direct contact between cells and the secretion of mediators. They have attracted considerable interest since their discovery in reticulocytes in 1983. The term includes different types of vesicles that vary in size and origin, with exosomes, microvesicles and apoptotic bodies as the major ones. These structures are sorrounded by a lipid membrane, where various types of receptors are located, and can carry different cargo molecules, including sugars, proteins, nucleic acids and metabolites. They have been described in all kingdoms in nature (participating in both intercellular and inter-specific communications), in all types of biological fluids (as part of liquid biopsy). In fact, their presence in samples from both physiological and pathological processes has suggested them as excellent biomarkers. Their role in health and disease is being widely investigated. In this context, the study of extracellular vesicles produced by parasites, and specifically by helminths, constitutes a growing field of research, with great biomedical interest, mainly in the control of infections caused by them. In fact, these vesicles can be used to generate rapid and specific diagnosis systems, to produce new tools for vaccination, and to identify targets for new treatments. The ability of extracellular vesicles to modulate the immune response also opens new possibilities for their use against autoimmune diseases.

OTTO LOEWI: ONE HUNDRED YEARS OF CONFIRMATION OF CHEMICAL NEUROTRANSMISSION

In 1921, Otto Loewi published an experimental study that gave rise to the birth of the chemical theory of nerve transmission, according to which, the nerve current causes, at the end of nerve fibers, the release of a chemical substance called a neurotransmitter. For his discoveries related to the chemical neurotransmission of nerve impulses, Loewi received the Nobel Prize in Physiology or Medicine in 1936.

SUSCEPTIBILITY PROFILES TO ANTIBIOTICS IN STRAINS OF THE GENUS BACILLUS ISOLATED FROM EXTREME AQUATIC ENVIRONMENTS OF ECUADOR

Introduction. The water of aquatic ecosystems considered extreme, given the values of its physicochemical and chemical parameters, such as high concentrations of salts, oligotrophic environments, extreme pH, high radiation and extreme temperatures, there is a bacterial population that has adapted to these conditions and that they can be an important reservoir of natural resistomes. Objective. The objective of the present work was to know the profiles of susceptibility to various antibiotics in strains of the Bacillus genus isolated from mineromedicinal water spas and water from a volcanic crater lake in Ecuador. Materials and methods. A total of 16 mineromedicinal water samples and 32 samples of crater volcanic lake water were analyzed. The isolation of the Bacillus colonies was carried out by the membrane filtration technique, using Millipore filters of 0.45 μm pore, a sample volume of 100 mL and R2A agar. The isolated strains were identified following the schemes of MacFaddin (2004), complemented with the biochemical tests of the Microgen galleries for Bacillus. The antibiotic resistance profile was determined by the plate diffusion method of Kirby and Bauer (1966), interpreted according to the CLSI (2019). Results. 19 Bacillus strains were identified. Most of the strains were resistant and multi-resistant to the antibiotic clindamycin, erythromycin, gentamicin, oxacillin, and penicillin. Conclusions. The results indicate the presence of Bacillus species and resistomes associated with this genus in the water of extreme natural environments in Ecuador, which suggests that these environments may be an important reservoir of bacteria resistant to antibiotics.

EXTENDED-RELEASE DELIVERY SYSTEMS OF OPIOIDS: ANALGESIA AND DEPENDENCE

The consumption of opioid analgesics has increased drastically in the last decades worldwide. This high consumption is linked with a surge in the number of opioid prescriptions for the treatment of chronic pain and a surge in opioid misuse and addiction. Opioid analgesics have a short duration of action, making necessary frequent administrations to provide extended analgesia. The use of prolonged-release formulations enables dosing intervals to be spaced out and drug blood levels to be stabilized, improving therapeutic compliance, and reducing the likelihood of developing addiction. However, these formulations contain higher doses of opioid analgesics which make them more susceptible to be manipulated. Hence, the most recent advances in pharmaceutical technology have been oriented towards the application of abuse deterrent technologies aiming to prevent their administration through alternative routes. Moreover, prolonged- release systems also play an essential role in the treatment of opioid addictions with the development of parenteral dosage forms capable of prolonging opioid release for months that help overcome one of the most important drawbacks in achieving treatment success, namely, patient compliance. We review herein the different prolonged-release opioid dosage forms currently approved in Europe and/or the United States for the treatment of pain and opioid dependence.

REGULATION OF THE INTESTINAL INFLAMMATORY RESPONSE THROUGH THE INGESTION OF MAILLARD COMPOUNDS AND THEIR INTERACTION WITH RAGE AND GPR43 RECEPTORS

Molecular damage signals attract neutrophils to sites of infection or inflammation. The G-protein coupled receptor (GPR43) and the receptor for advanced glicosilation compounds (RAGE) recognize short-chain fatty acids (propionate and butyrate) and AGEs (advanced glycosylation compounds) respectively, both receptors being abundantly expressed in neutrophils and intestinal epithelial cells. The functional role that activation of these receptors plays in the in vivo orchestration of the immune response is unclear. Our work examines the effect of the ingestion of AGEs on the immune response, both in healthy mice and in mice that were induced to colitis, using transgenic mice deficient in GPR43 or RAGE receptors. One of the main findings is that both the GPR43 receptor and RAGE are necessary for the recruitment of neutrophils in a model of intestinal inflammation due to mucosal barrier injury. We have also verified that the AGEs ingested with the diet promote the appearance of an imbalance in the inflammatory balance at the intestinal level, giving rise to a pro-inflammatory status. We have also show that carboxymethylisine (CML), a specific type of AGE, is capable of stimulating the GPR43 receptor and acting as a neutrophil chemoattraction factor. Finally, we have tested the treatment with sRAGE, a protein capable of capturing free AGEs. This procedure could be a promising therapy for the treatment of inflammatory bowel disease.

Euthanasia in Spain. Analysis compared with other legal regulations of the European Union

The publication of Organic Law 3/2021 regulating euthanasia (BOE 03.25.2021), converted Spain in the fourth country in the European Union to decriminalize such practice. In this article we analyze this rule and the introduction of euthanasia in the Health Service of the Spanish National Health System, which guarantees access to the provision. On the other hand, we will carry out a comparative study of other legal systems in the European Union in which this practice is allowed or penalized.

RELATIONSHIP OF THE VIROLOGIST PROFESSOR ADOLFO GARCÍA SASTRE WITH THE UNIVERSITY OF SALAMANCA AND THE ROYAL NATIONAL ACADEMY OF PHARMACY

We give some biographical details of the virologist Professor Adolfo Garcia Sastre, as a Graduate student (1981-1986) in the Biology School of University of Salamanca and during his PhD Thesis (1986-1990) in the Department of Biochemistry and Molecular Biology (Chairman Prof J.A. Cabezas), under the supervision of Prof. Enrique Villlar and obtaining the highest academic marks. The research lines that he established in collaboration with his Thesis director, with Prof. J.A Cabezas and others, as well as his results during his stay at the Pasteur Institute in Paris, are also highlighted. His findings in this period were published in prestigious Virology and Biochemistry journals and presented at national and international meetings. Thereafter, when he moved to Mount Sinai in New York, he met Prof Mariano Esteban, then working at Downstate Medical Center in New York, SUNY, and both, in collaboration with the group of Prof. Ruth Nussenzweig and Fidel Zavala at New York University, set up seminal immunological studies that are the basis for combined vaccination approaches, prime/boost and activation of CD8+ T cells, now widely used in preclinical and clinical studies. The scientific research contributions of Prof. García Sastre are growing at an exponential rate, opening new horizons in understanding the molecular biology of emerging viruses, their pathology, virus-host cell interactions and strategies of virus control.