Salud digital en América Latina: legislación actual y aspectos éticos / Digital health in Latin America: current legislation and ethical aspects / Saúde digital na América Latina: legislação atual e aspectos éticos

[RESUMEN]. Objetivo. Describir la legislación vigente respecto a historia clínica electrónica (HCE) y telesalud de los países latinoamericanos y analizar el tratamiento de la confidencialidad y el secreto profesional. Métodos. Entre marzo y septiembre de 2022, se realizó un relevamiento de la reglamentación vigente en los 21 países latinoamericanos en estudio, en dos niveles: i) la existencia de legislación respecto a la HCE y la telesalud, y ii) el tratamiento de la confidencialidad y el secreto profesional en la HCE y la telesalud. Se con- feccionó una ficha de extracción de datos por país. Se recolectaron datos a partir de fuentes on-line oficiales. Se analizó cualitativamente la información y se sintetizó en forma de tablas cuando fue posible. Resultados. El uso de la HCE está reglamentado legalmente en 16 países. Para el caso de telesalud, son 19 países los que cuentan con legislación en referencia a esta herramienta. Todos los países analizados resguardan la confidencialidad y el secreto profesional a través de reglamentaciones. Sin embargo, en el contexto de telesalud se mencionan en 11 países, en tanto en el contexto de la HCE, solo en 9 países. Conclusiones. Desde el inicio del segundo milenio América Latina ha avanzado respecto a la legislación de herramientas digitales en la atención en salud como la HCE y la telesalud. Se observa a su vez un interés por las cuestiones éticas relacionadas con el uso de la HCE y la telesalud, en particular de la confidencialidad y secreto profesional, aunque dichos aspectos deben ser fortalecidos en la salud digital.

[ABSTRACT]. Objectives. Describe the current legislation on electronic medical records (EMR) and telehealth in Latin Ame- rican countries and analyze the treatment of confidentiality and professional secrecy. Methods. Between March and September 2022, a survey of the regulations in force in 21 Latin American countries was conducted at two levels: the existence of legislation on EMR and telehealth, and the treatment of confidentiality and professional secrecy in EMR and telehealth. A data extraction form was prepared for each country. Data were collected from official on-line sources. The information was analyzed qualitatively and synthesized in tables when possible. Results. The use of EMR is legally regulated in 16 countries. Nineteen countries have legislation on telehealth. All the countries analyzed safeguard confidentiality and professional secrecy through regulations. However, confidentiality and professional secrecy are mentioned in 11 countries in the context of telehealth, and in only nine countries in the context of EMR. Conclusions. Since the start of this century, Latin America has made progress in the legislation of digital tools for health care, such as EMR and telehealth. There is also interest in ethical issues related to the use of EMR and telehealth, particularly confidentiality and professional secrecy, aspects that should be strengthened in digital health.

[RESUMO]. Objetivo. Descrever a legislação vigente sobre prontuários eletrônicos e telessaúde nos países da América Latina e analisar o tratamento da confidencialidade e do sigilo profissional. Métodos. Entre março e setembro de 2022, realizou-se um levantamento sobre a regulamentação vigente nos 21 países latino-americanos incluídos no estudo, em dois níveis: i) existência de legislação sobre prontuários eletrônicos e telessaúde; e ii) tratamento da confidencialidade e do sigilo profissional em prontuários eletrônicos e telessaúde. Uma planilha para extração de dados foi elaborada para cada país. Os dados foram coletados de fontes oficiais disponíveis on-line. Foi realizada uma análise qualitativa das informações, que foram resumidas em tabelas, quando possível. Resultados. O uso dos prontuários eletrônicos é legalmente regulamentado em 16 países. Quanto à telessaúde, 19 países têm legislação sobre essa ferramenta. Todos os países analisados protegem a confidencialidade e o sigilo profissional por meio de regulamentação. No entanto, no contexto da telessaúde, eles são mencionados em 11 países; já no contexto dos prontuários eletrônicos, em apenas 9 países. Conclusões. Desde o início dos anos 2000, a América Latina vem avançando em relação à legislação sobre ferramentas digitais na atenção à saúde, como prontuários eletrônicos e telessaúde. Há também interesse nas questões éticas relacionadas ao uso de prontuários eletrônicos e telessaúde, especialmente em relação à confidencialidade e ao sigilo profissional, embora esses aspectos precisem ser reforçados na saúde digital.

The Skin and Natural Cannabinoids-Topical and Transdermal Applications.

The chemical constituents of the Cannabis plant known as cannabinoids have been extensively researched for their potential therapeutic benefits. The use of cannabinoids applied to the skin as a potential method for both skin-related benefits and systemic administration has attracted increasing interest in recent years. This review aims to present an overview of the most recent scientific research on cannabinoids used topically, including their potential advantages for treating a number of skin conditions like psoriasis, atopic dermatitis, and acne. Additionally, with a focus on the pharmacokinetics and security of this route of administration, we investigate the potential of the transdermal delivery of cannabinoids as a method of systemic administration. The review also discusses the restrictions and difficulties related to the application of cannabinoids on the skin, emphasizing the potential of topical cannabinoids as a promising route for both localized and systemic administration. More studies are required to fully comprehend the efficacy and safety of cannabinoids in various settings.

Nanocarriers of shRNA-Runx2 directed to collagen IV as a nanotherapeutic system to target calcific aortic valve disease.

Runx2 is a key transcription factor involved in valvular interstitial cells (VIC) osteodifferentiation, a process actively entwined with the calcific aortic valve disease (CAVD). We hypothesize that a strategy intended to silence Runx2 could be a valuable novel therapeutic option for CAVD. To this intent, we aimed at (i) developing targeted nanoparticles for efficient delivery of short hairpin (sh)RNA sequences specific for Runx2 to the aortic valve employing a relevant mouse model for CAVD and (ii) investigate their therapeutic potential in osteoblast-differentiated VIC (oVIC) cultivated into a 3D scaffold. Since collagen IV was used as a target, a peptide that binds specifically to collagen IV (Cp) was conjugated to the surface of lipopolyplexes encapsulating shRNA-Runx2 (Cp-LPP/shRunx2). The results showed that Cp-LPP/shRunx2 were (i) cytocompatible; (ii) efficiently taken up by 3D-cultured oVIC; (iii) diminished the osteodifferentiation of human VIC (cultured in a 3D hydrogel-derived from native aortic root) by reducing osteogenic molecules expression, alkaline phosphatase activity, and calcium concentration; and (iv) were recruited in aortic valve leaflets in a murine model of atherosclerosis. Taken together, these data recommend Cp-LPP/shRunx2 as a novel targeted nanotherapy to block the progression of CAVD, with a good perspective to be introduced in practical use.

The Roles of Imaging Biomarkers in the Management of Chronic Neuropathic Pain.

Chronic neuropathic pain (CNP) affects around 10% of the general population and has a significant social, emotional, and economic impact. Current diagnosis techniques rely mainly on patient-reported outcomes and symptoms, which leads to significant diagnostic heterogeneity and subsequent challenges in management and assessment of outcomes. As such, it is necessary to review the approach to a pathology that occurs so frequently, with such burdensome and complex implications. Recent research has shown that imaging methods can detect subtle neuroplastic changes in the central and peripheral nervous system, which can be correlated with neuropathic symptoms and may serve as potential markers. The aim of this paper is to review available imaging methods used for diagnosing and assessing therapeutic efficacy in CNP for both the preclinical and clinical setting. Of course, further research is required to standardize and improve detection accuracy, but available data indicate that imaging is a valuable tool that can impact the management of CNP.

Reflexiones sobre el primer caso de triple filiación desde el nacimiento en Argentina. Por qué es importante establecer diferencias con la adopción y la subrogación del embarazo / Reflexions sobre el primer cas de triple filiació des del naixement a l'Argentina. Per què és important establir diferències amb l'adopció i la subrogació de l'embaràs / Reflections on the first case of triple filiation from birth in Argentina. Why it is important to establish differences between adoption and surrogacy of pregnancy

El presente artículo tiene el propósito de reflexionar sobre un reciente caso de triple filiación desde el nacimiento en Argentina que constituye una nueva forma de coparentalidad. Para ello, en primer lugar, realizo una descripción de los hechos y la sentencia. En segundo lugar, refiero que los feminismos y los movimientos por la diversidad han colaborado en comprensiones y prácticas más respetuosas y dinámicas de lainstitución familiar en clara oposición al neoconservadurismo. Luego planteo que la defensa de dicho dinamismo familiar fundado no debiera llevarnos a defender cualquier camino para la consecución del proyecto familiar, puntualmente en el caso de varones solos o en pareja. Por ello, diferencio los modos que usualmente tienen para alcanzar la paternidad con el objetivo de mostrar cómo la coparentalidad y la adopción son moralmente aceptables mientras que la subrogación del embarazo es cuestionable éticamente.(AU)

El present article té el propòsit de reflexionar sobre un recent cas de triple filiació des del naixement a l'Argentina que constitueix una nova forma de coparentalitat. Per a això, en primer lloc, realitzo una descripció dels fets i la sentència. En segon lloc, refereixo que els feminismes i els moviments per la diversitat han col·laborat en comprensions i pràctiques més respectuoses i dinàmiques de la institució familiar en clara oposició al neoconservadurisme. Després plantejo que la defensa d'aquest dinamisme familiar fundat no hagués de portar-nos a defensar qualsevol camí per a la consecució del projecte familiar, puntualment en el cas d'homes sols o en parella. Per això, diferencio les maneres que usualment tenen per a aconseguir la paternitat amb l'objectiu de mostrar com la coparentalitat i l'adopció són moralment acceptables mentre que la subrogació de l'embaràs és qüestionable èticament.(AU)

The purpose of this article is to analyze on a recent case of triple filiation from birth in Argentina, whichconstitutes a new form of co-parenting. In order to do so, firstly, I describe the facts and the judicial sentence. Secondly, I explain that feminisms and diversity movements have collaborated in more respectful and dynamic understandings and practices of the family institution in clear opposition to neoconservatism. Then I argue that the defense of such family dynamism should not lead us to defend any path for the achievement of the family project, especially in the case of single men or couples. Therefore, I differentiate the ways they usually have to achieve parenthood in order to show how co-parenting and adoption are morally acceptable while pregnancy surrogacy is ethically questionable.(AU)

Pros and cons of NRF2 activation as adjunctive therapy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease with an important inflammatory component accompanied by deregulated redox-dependent signaling pathways that are feeding back into inflammation. In this context, we bring into focus the transcription factor NRF2, a master redox regulator that exerts exquisite antioxidant and anti-inflammatory effects. The review does not intend to be exhaustive, but to point out arguments sustaining the rationale for applying an NRF2-directed co-treatment in RA as well as its potential limitations. The involvement of NRF2 in RA is emphasized through an analysis of publicly available transcriptomic data on NRF2 target genes and the findings from NRF2-knockout mice. The impact of NRF2 on concurrent pathologic mechanisms in RA is explained by its crosstalk with major redox-sensitive inflammatory and cell death-related pathways, in the context of the increased survival of pathologic cells in RA. The proposed adjunctive therapy targeted to NRF2 is further sustained by the existence of promising NRF2 activators that are in various stages of drug development. The interference of NRF2 with conventional anti-rheumatic therapies is discussed, including the cytoprotective effects of NRF2 for alleviating drug toxicity. From another perspective, the review presents how NRF2 activation would be decreasing the efficacy of synthetic anti-rheumatic drugs by increasing drug efflux. Future perspectives regarding pharmacologic NRF2 activation in RA are finally proposed.

VCAM-1 Targeted Lipopolyplexes as Vehicles for Efficient Delivery of shRNA-Runx2 to Osteoblast-Differentiated Valvular Interstitial Cells; Implications in Calcific Valve Disease Treatment.

Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface of oVIC was used as a target, and a peptide with high affinity for VCAM-1 was coupled to the surface of lipopolyplexes encapsulating C60-PEI/shRunx2 (V-LPP/shRunx2). We report here that V-LPP/shRunx2 lipopolyplexes are cyto- and hemo-compatible and specifically taken up by oVIC. These lipopolyplexes are functional as they downregulate the Runx2 gene and protein expression, and their uptake leads to a significant decrease in the expression of osteogenic molecules (OSP, BSP, BMP-2). These results identify V-LPP/shRunx2 as a new, appropriately directed vehicle that could be instrumental in developing novel strategies for blocking the progression of CAVD using a targeted nanomedicine approach.

Alquiler o sustitución del embarazo? Sobre la importancia de los significantes en la construcción de sentido / Lloguer o substitució de l'embaràs? Sobre la importància dels significants en la construcció de sentit / Pregnancy Contract or Womb for Rent? About the importance of terms in the construction of meaning

In this article I will present the importance of critically revising the common uses of the terms to nominate the link established between those who gestate for other people and those who request gestation to acquire a baby. It is my intention to propose amore adequate term: relationship ofsurrogacy/ pregnancyreplacement. To do so, first, I will briefly mention how the use of language in assisted reproduction is far from neutral. Secondly, I will examine the most usednomenclatures in Spanish such as “contract pregnancy”, “womb for rent”, among others, and I will analyze them considering two criteria:the role of the pregnant person and the kind of relationship between that who gestates and that/those who want/s to be the baby’s mother/s and father/s. Finally, I will use both criteria to propose a new term.(AU)

En este artículo presentaré la importancia de revisar críticamente los términos usuales utilizados para denominar al vínculo que se establece entre quien gesta para otras personas y quienes solicitan la gestación para adquirir un bebé, con la intención de proponer un significante, a mi entender, más adecuado: relación dealquiler/sustitución del embarazo. Para ello, en primer lugar, aludiré sucintamente a cómoel uso del lenguaje en reproducción asistida no es neutral. En segundo lugar, examinaré las nomenclaturas más utilizadas en lengua castellana como por ejemplo “alquiler de vientre” y “gestación por sustitución”, entre otras, y las analizaré a través de dos criterios: el rol de la persona gestante y el tipo de relación entre quien gesta y quien/es quieren ser madre/s y/o padre/s.Por último, utilizaré ambos criterios para proponer el nuevo significante.(AU)

En aquest article presentaré la importància de revisar críticament els termes usuals utilitzats per a denominar al vincle que s'estableix entre qui gesta per a altres persones i els qui sol·liciten la gestació per a adquirir un bebè, amb la intenció de proposarun significant, al meu entendre, més adequat: relació delloguer/substitució de l'embaràs. Per a això, en primer lloc, al·ludiré succintament a com l'ús del llenguatge en reproducció assistida no és neutral. En segon lloc, examinaré les nomenclatures més utilitzades en llengua castellana com per exemple “lloguer de ventre” i “gestació per substitució”, entre altres, i les analitzaré a través de dos criteris: el rol de la persona gestant i el tipus de relació entre qui gesta i qui/és volen ser mare/s i/o pare/s.Finalment, utilitzaré tots dos criteris per a proposar el nou significant.(A)

Feixe de intervenções na manutenção do cateter venoso central: saberes e práticas de enfermeiros numa unidade de cuidados intensivos / Bundle of interventions in central venous catheter maintenance: knowledge and practices of nurses in an intensive care unit

O uso de cateter venoso central (CVC) e a sua manutenção associa-se a infeções, locais ou sistémicas, aumentando a probabilidade de infeção, principalmente, por agentes multirresistentes. As infeções associadas ao CVC são muito frequentes e responsáveis pelo aumento de custos para a instituição com maior tempo de internamento e com aumento de taxas de morbimortalidade, nomeadamente em utentes que se encontram nas UCI. O objetivo principal deste estudo foi analisar a associação entre os saberes e as práticas dos enfermeiros relativos ao feixe de intervenções na manutenção do CVC numa UCI de adultos polivalente de um hospital universitário do Norte de Portugal. O método adotado foi o quantitativo, tendo-se desenhado um estudo descritivo-correlacional, com uma amostra de voluntários e como instrumentos de recolha de dados utilizou-se o questionário e a observação. A amostra, composta por 42 enfermeiros, é predominantemente do sexo feminino (76,2%). O grupo etário mais representado foi dos 31-40 anos (45,2%) e a maioria é casado(a)/união de facto (57,1%). Predominam os enfermeiros licenciados (73,8%), com especialidade (54;8%), sendo a Enfermagem Médico-Cirúrgica (91,3%) a especialidade mais registada. Os resultados demonstraram que a formação sobre o feixe de intervenções na manutenção do CVC foi reportada por 21,4% dos enfermeiros. Destes, 55,6% frequentou a formação em serviço de implementação da Bundle. Relativamente aos saberes dos enfermeiros, os resultados demonstraram que 100% reconhece a importância de: avaliar diariamente a necessidade de manter o CVC e identificar o motivo; higienizar as mãos antes de manusear o CVC; realizar tratamento da ferida na periodicidade adequada utilizando técnica asséptica. Com valores inferiores, 83,3% reconhece a fricção com solução antisséptica com base alcoólica (SABA) como técnica na higienização das mãos. Ainda em relação aos saberes, os resultados revelaram que os enfermeiros reconhecem a importância de: garantir o orifício de inserção limpo e sem sangue; utilizar máscara cirúrgica, luvas esterilizadas, campo esterilizado de suporte para material de pensos; utilizar cloro-hexidina a 2% com álcool na antissepsia da pele e datar o penso; bem como proceder à substituição dos sistemas de perfusão, datando a sua substituição. Face às práticas observou-se uma adesão de 69,0% à utilização da fricção com SABA. 97,6% utilizam cloro-hexidina a 2% com álcool, para a descontaminação das conexões de manuseamento e dos pontos de acesso dos sistemas e prolongadores. 100% da amostra identificou o(s) motivo(s) para a realização do tratamento da ferida e procede ao seu tratamento dentro da periodicidade adequada e com técnica asséptica cirúrgica. Na observação da prática, e à semelhança dos resultados dos saberes, os enfermeiros também garantem o orifício de inserção limpo e sem sangue, utilizam máscara cirúrgica e realizam os restantes procedimentos. Após a análise, não se verificou uma associação estatisticamente significativa entre as práticas e os saberes dos enfermeiros relativos ao feixe de intervenções na manutenção do CVC. Conclui-se que os enfermeiros possuem elevado conhecimento do feixe de intervenções na manutenção e manipulação do CVC e que na sua prática profissional quotidiana recorrem à sua implementação.

The use of central venous catheter (CVC) and its maintenance is associated with infections, local or systemic, increasing the probability of infection, mainly by multidrug-resistant agents. Infections associated with CVC are very frequent and responsible for the increase in costs for the institution with longer hospital stays and increase morbidity and mortality rates, particularly in users who are in the ICU. The main objective of this study was to analyze the association between nurses' knowledge and practices regarding the range of interventions in CVC maintenance in a multipurpose adult ICU of a university hospital in Northern Portugal. The method adopted was the quantitative one, having been designed a descriptive-correlational study, with a sample of volunteers and as instruments of data collection it was used the questionnaire and the observation. The sample, consisting of 42 nurses, is predominantly female (76.2%). The most represented age group was between 31-40 years old (45.2%) and the majority is married/covenant (57.1%). There is a predominance of licensed nurses (73.8%), with a specialty (54.8%), with Medical-Surgical Nursing (91.3%) being the most registered specialty. The results showed that training on the range of interventions in CVC maintenance was reported by 21.4% of nurses. Of these, 55.6% attended Bundle implementation in-service training. Regarding the nurses' knowledge, the results showed that 100% recognize the importance of: daily assessing the need to maintain the CVC and identifying the reason; sanitize your hands before handling the CVC; perform wound treatment at the appropriate frequency using aseptic technique. With lower values, 83.3% recognize rubbing with an alcohol-based solution (SABA) as a technique for hand hygiene. Still in relation to knowledge, the results revealed that nurses recognize the importance of: ensuring the insertion hole is clean and free of blood; use surgical mask, sterile gloves, sterile field support for dressing material; use 2% chlorhexidine with alcohol for skin antisepsis and date the dressing; as well as proceeding with the replacement of the infusion systems, dating their replacement. In view of the practices, there was an adherence of 69.0% to the use of rubbing with an alcoholic-based solution (SABA). 97.6% use 2% chlorhexidine, with alcohol for the decontamination of handling connections and access points of systems and extensions. 100% of the sample identified the reason(s) for performing the treatment of the wound and proceeded with its treatment within the proper frequency and with aseptic surgical technique. In observing the practice, and similarly to the results of knowledge, nurses also ensure the insertion hole is clean and free of blood, use a surgical mask and perform the remaining procedures. After the analysis, there was no statistically significant association between nurses' practices and knowledge regarding the range of interventions in CVC maintenance. It is concluded that nurses have a high knowledge of the range of interventions in the maintenance and handling of the CVC and that in their daily professional practice they resort to its implementation.

Clinical and pathological considerations in lumbar herniated disc associated with inflammatory lesions.

Lumbar herniated disc is the most frequent cause for lumbar pain. It is caused by degenerative, macroscopic and microscopic changes of the intervertebral discs. It is a chronic disease, with periods of exacerbation and remission under drug and physiotherapeutic treatment. When the disc lesions are large, with intense symptoms, reduced or impossible movements, with pain radiating to the sciatic nerve trajectory, a surgical treatment is required, to remove the herniated nucleus pulposus and decompress the nerve roots. Patients who present high inflammatory signs, high inflammatory serous markers, may have a longer postoperative recovery period, while the motor recovery may be late and incomplete. We analyzed a group of 24 patients with lumbar herniated disc that required discectomy, with clear inflammatory signs, together with histopathological and immunohistochemical changes present in the herniated disc.

Nano-Polyplexes Mediated Transfection of Runx2-shRNA Mitigates the Osteodifferentiation of Human Valvular Interstitial Cells.

Calcific aortic valve disease (CAVD) is a progressive disorder that increases in prevalence with age. An important role in aortic valve calcification is played by valvular interstitial cells (VIC), that with age or in pathological conditions acquire an osteoblast-like phenotype that advances the disease. Therefore, pharmacological interventions aiming to stop or reverse the osteoblastic transition of VIC may represent a therapeutic option for CAVD. In this study, we aimed at developing a nanotherapeutic strategy able to prevent the phenotypic switch of human aortic VIC into osteoblast-like cells. We hypothesize that nanocarriers designed for silencing the Runt-related transcription factor 2 (Runx2) will stop the progress or reverse the osteodifferentiation of human VIC, induced by high glucose concentrations and pro-osteogenic factors. We report here the potential of fullerene (C60)-polyethyleneimine (PEI)/short hairpin (sh)RNA-Runx2 nano-polyplexes to efficiently down-regulate Runx2 mRNA and protein expression leading subsequently to a significant reduction in the expression of osteogenic proteins (i.e. ALP, BSP, OSP and BMP4) in osteoblast-committed VIC. The data suggest that the silencing of Runx2 could represent a novel strategy to impede the osteoblastic phenotypic shift of VIC and the ensuing progress of CAVD.

Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers.

Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics.

Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy.

Cannabis has been used in pain management since 2900 BC. In the 20th century, synthetic cannabinoids began to emerge, thus opening the way for improved efficacy. The search for new forms of synthetic cannabinoids continues and, as such, the aim of this review is to provide a comprehensive tool for the research and development of this promising class of drugs. Methods for the in vitro assessment of cytotoxic, mutagenic or developmental effects are presented, followed by the main in vivo pain models used in cannabis research and the results yielded by different types of administration (systemic versus intrathecal versus inhalation). Animal models designed for assessing side-effects and long-term uses are also discussed. In the second part of this review, pharmacokinetic and pharmacodynamic studies of synthetic cannabinoid biodistribution, together with liquid chromatography-mass spectrometric identification of synthetic cannabinoids in biological fluids from rodents to humans are presented. Last, but not least, different strategies for improving the solubility and physicochemical stability of synthetic cannabinoids and their potential impact on pain management are discussed. In conclusion, synthetic cannabinoids are one of the most promising classes of drugs in pain medicine, and preclinical research should focus on identifying new and improved alternatives for a better clinical and preclinical outcome.

Vibrational Spectroscopy Fingerprinting in Medicine: from Molecular to Clinical Practice.

In the last two decades, Fourier Transform Infrared (FTIR) and Raman spectroscopies turn out to be valuable tools, capable of providing fingerprint-type information on the composition and structural conformation of specific molecular species. Vibrational spectroscopy's multiple features, namely highly sensitive to changes at the molecular level, noninvasive, nondestructive, reagent-free, and waste-free analysis, illustrate the potential in biomedical field. In light of this, the current work features recent data and major trends in spectroscopic analyses going from in vivo measurements up to ex vivo extracted and processed materials. The ability to offer insights into the structural variations underpinning pathogenesis of diseases could provide a platform for disease diagnosis and therapy effectiveness evaluation as a future standard clinical tool.

CD 36: Focus on Epigenetic and Post-Transcriptional Regulation.

CD36 is a transmembrane protein involved in fatty acid translocation, scavenging for oxidized fatty acids acting as a receptor for adhesion molecules. It is expressed on macrophages, as well as other types of cells, such as endothelial and adipose cells. CD36 participates in muscle lipid uptake, adipose energy storage, and gut fat absorption. Recently, several preclinical and clinical studies demonstrated that upregulation of CD36 is a prerequisite for tumor metastasis. Cancer metastasis-related research emerged much later and has been less investigated, though it is equally or even more important. CD36 protein expression can be modified by epigenetic changes and post-transcriptional interference from non-coding RNAs. Some data indicate modulation of CD36 expression in specific cell types by epigenetic changes via DNA methylation patterns or histone tails, or through miRNA interference, but this is largely unexplored. The few papers addressing this topic refer mostly to lipid metabolism-related pathologies, whereas in cancer research, data are even more scarce. The aim of this review was to summarize major epigenetic and post-transcriptional mechanisms that impact CD36 expression in relation to various pathologies while highlighting the areas in need of further exploration.

Osteopontin - a biomarker of disease, but also of stage stratification of the functional myocardial contractile deficit by chronic ischaemic heart disease.

The study analyses the significance of the plasmatic values of the OPN dosed to 91 people suffering from diastolic cardiac dysfunction with preserved ejection fraction, thus revealing significant growths of its level compared to the normal value. Despite being a clinical research, its conclusions are a breakthrough, differing from the results of other studies published in the relevant medical literature. We can make this assertion because this study analyses the clinical information given by the circulating values of the OPN, based on experimental models (animals), or on patients with congestive heart failure, which can be identified with the existence of a low systolic flow. The results of our study allow us to assert that the plasmatic values of this glycoprotein lead to its acceptance in the medical practice as a new biomarker that provides indicators regarding the stratification of risk with the patients suffering from heart failure of the diastolic dysfunction type, but whose systolic flow is preserved.

Myeloperoxidase, a possible biomarker for the early diagnosis of cardiac diastolic dysfunction with preserved ejection fraction.

The current study was conducted on a sample of 91 patients diagnosed with diastolic dysfunction (DD) with preserved systolic function caused by a painful chronic ischaemic cardiopathy - angina pectoris stable at the effort. The diagnosis was established following anamnesis, electrocardiogram, and echocardiography. Myeloperoxidase (MPO) serum levels were assessed in all patients and then these values were correlated with some of the echocardiography parameters that proved the mentioned diagnosis. In conclusion, the execution of this investigation triad (electrocardiogram, echocardiography, and MPO) allows: Stratifying the patients depending on the disease risk by early detecting of any possible DD with preserved systolic function. The use of the MPO increased circulating levels as a biomarker for diagnosis and risk due to the statistically significant correlation between those and the results of the other two aforementioned paraclinical investigation.

Development of new 5-(chromene-3-yl)methylene-2,4-thiazolidinediones as antimicrobial agents.

BACKGROUND AND AIMS: In the context of the increasing phenomenon of microbial resistance to usual drugs, the development of new treatment strategies and new therapeutic protocols is a constant need. Thiazolidinedione and chromone represent two important scaffolds in medicinal chemistry due to their large pharmacological applicability. METHODS: We synthesized a new 5-(chromene-3-yl)methylene-2,4-thiazolidinedione starting from 6,8-dichloro-4-oxo-4H-chromene-3-carbaldehyde. Then, by treating with different α-bromoalkylarylketones, we obtained N-substituted derivatives. All new compounds were investigated for their antimicrobial potential, using the diffusion method, against Listeria monocytogenes ATCC 13932, Staphylococcus aureus ATCC 49444, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028 and Candida albicans ATCC 10231. Three concentrations, 10 mg/ml, 5 mg/ml and 1 mg/ml of compounds were used. The results were evaluated by the measurement of the inhibition zone diameters and compared to those of gentamicin and fluconazole respectively, as reference drugs. RESULTS: All new synthesized compounds were characterized using physico-chemical and spectrometric methods. They displayed modest to good antimicrobial activity. New molecules 8, 9 and 10 may represent promising candidates, showing zone inhibition diameters superior to those of reference drugs. CONCLUSIONS: This work presents chemical synthesis, characterization and investigation of the antibacterial and antifungal potential of 5-(chromene-3-yl)methylene-2,4-thiazolidinedione derivatives, which may be worthy of future research for designing new chemical entities.

Helleborus purpurascens-Amino Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties of the Extracted Compounds.

There is a strong drive worldwide to discover and exploit the therapeutic potential of a large variety of plants. In this work, an alcoholic extract of Helleborus purpurascens (family Ranunculaceae) was investigated for the identification of amino acids and peptides with putative antiproliferative effects. In our work, a separation strategy was developed using solvents of different polarity in order to obtain active compounds. Biochemical components were characterized through spectroscopic (mass spectroscopy) and chromatographic techniques (RP-HPLC and GC-MS). The biological activity of the obtained fractions was investigated in terms of their antiproliferative effects on HeLa cells. Through this study, we report an efficient separation of bioactive compounds (amino acids and peptides) from a plant extract dependent on solvent polarity, affording fractions with unaffected antiproliferative activities. Moreover, the two biologically tested fractions exerted a major antiproliferative effect, thereby suggesting potential anticancer therapeutic activity.

Dynamics of telopodes (telocyte prolongations) in cell culture depends on extracellular matrix protein.

Telocytes (TC) are cells with telopodes (Tp), very long prolongations (up to 100 µm) with an uneven caliber ( www.telocytes.com ). Factors determining the dynamics of cellular prolongations are still unknown, although previous studies showed telopode motility in TC cultures. We comparatively investigated, by time-lapse videomicroscopy, the dynamics of Tp of mouse heart TC seeded on collagen, fibronectin, and laminin. Under our experimental conditions, TC and fibroblasts (cell line L929) behaved differently in terms of adherence, spreading, and prolongation extension. Fibroblasts showed lower spreading on the matrix proteins used. The time needed for spreading was 2-4 h for TC, versus 8-10 h for fibroblasts. The values for final cell surface area after spreading were between 200 and 400 µm(2) for fibroblasts and 800-2,000 µm(2) for TC. TC showed a more than three times higher ability to spread on the tested matrix proteins. An extremely low capacity to extend prolongations with lengths shorter than cell bodies was noted for fibroblasts, while TC extended prolongations longer than the cell body length, with a moniliform appearance. The stronger adherence and spreading were noted for TC seeded on fibronectin, while the lowest were on laminin. Collagen determined an intermediate adherence and spreading for TC, but the highest dynamics in Tp extensions. In conclusion, TC behave differently than fibroblasts in terms of adherence, spreading, and cell prolongation extension when seeded on various matrix proteins in cell culture.