Pub Date : 2022-06-30DOI: 10.53519/analesranf.2022.88.02.03
J. García Marín
According to World Health Organization (WHO) cancer is one of top non- infectious death causes worldwide. In this context, as such the searching of new potent and safe anticancer drugs is a hot point for pharmacy industry and academic investigation. Despite protein kinases have been one of the most explored anticancer targets, its evolutionary degenerated parents, pseudokinases, have attracted the attention of scientific community during the last decade. Integrin Linked Kinase (ILK) is a member of the human pseudokinome that has been claimed and validated as a prommissing target for neoplastic diseases. The only well-known ILK inhibitor, CPD22, has probed its activity in phenotypic assays, however very few knowledge regarding its mechanism of action at molecular level is available. Using chemoinformatic and molecular modelling techniques we were able to elucidate if this molecule is able to bind to ILK and how. Additionally, our model explains the SAR raised from the optimization campaign, and SPR experiments have probed, by first time, that this molecule binds to ILK, thus supporting the hypothesis of inhibition by direct binding and the computational model as well.
{"title":"Deciphering the inhibition mechanism of a pseudokinase: integrin-bound kinase and cpd22","authors":"J. García Marín","doi":"10.53519/analesranf.2022.88.02.03","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.02.03","url":null,"abstract":"According to World Health Organization (WHO) cancer is one of top non- infectious death causes worldwide. In this context, as such the searching of new potent and safe anticancer drugs is a hot point for pharmacy industry and academic investigation. Despite protein kinases have been one of the most explored anticancer targets, its evolutionary degenerated parents, pseudokinases, have attracted the attention of scientific community during the last decade. Integrin Linked Kinase (ILK) is a member of the human pseudokinome that has been claimed and validated as a prommissing target for neoplastic diseases. The only well-known ILK inhibitor, CPD22, has probed its activity in phenotypic assays, however very few knowledge regarding its mechanism of action at molecular level is available. Using chemoinformatic and molecular modelling techniques we were able to elucidate if this molecule is able to bind to ILK and how. Additionally, our model explains the SAR raised from the optimization campaign, and SPR experiments have probed, by first time, that this molecule binds to ILK, thus supporting the hypothesis of inhibition by direct binding and the computational model as well.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42672672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-30DOI: 10.53519/analesranf.2022.88.02.04
María González Amor, Ana Belén García Redondo
Hypertension and obesity are major health problems worldwide with significant consequences on morbidity and mortality. In fact, both hypertension and obesity are important risk factors for the development of cardiovascular diseases. Endothelial dysfunction, vascular remodeling, and alterations in vascular mechanics are common aspects of vascular damage in hypertension, obesity, and aneurysms. During the last decades, the importance of low-grade inflammation in vascular damage associated with cardiovascular diseases has been demonstrated. This inflammation is characterized by the accumulation of inflammatory cells in the vasculature, as well as by the increase of local and circulating pro-inflammatory cytokines. Therefore, the identification of new inflammatory mediators involved in this damage has become a very important area of research. Interferón-γ (IFNγ) or tumor necrosis tumoral-α (TNFα) are important cytokines involved in the vascular damage associated with hypertension. Furthermore, it is accepted that TNFα is a key mediator involved in insulin resistance and vascular damage observed in obesity. Both cytokines induce the expression of interferon-stimulated gene 15 (ISG15), a protein similar to ubiquitin that induces a reversible post-translational modification (ISGylation) and that can also be secreted as a free form. The functions of ISG15 are mainly related to the immune response against infections, however, it could also be an interesting new target for cardiovascular damage.
{"title":"Interferon-stimulated gene 15, a common link of vascular damage in hypertension, obesity and aortic aneurysms","authors":"María González Amor, Ana Belén García Redondo","doi":"10.53519/analesranf.2022.88.02.04","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.02.04","url":null,"abstract":"Hypertension and obesity are major health problems worldwide with significant consequences on morbidity and mortality. In fact, both hypertension and obesity are important risk factors for the development of cardiovascular diseases. Endothelial dysfunction, vascular remodeling, and alterations in vascular mechanics are common aspects of vascular damage in hypertension, obesity, and aneurysms. During the last decades, the importance of low-grade inflammation in vascular damage associated with cardiovascular diseases has been demonstrated. This inflammation is characterized by the accumulation of inflammatory cells in the vasculature, as well as by the increase of local and circulating pro-inflammatory cytokines. Therefore, the identification of new inflammatory mediators involved in this damage has become a very important area of research.\u0000\u0000Interferón-γ (IFNγ) or tumor necrosis tumoral-α (TNFα) are important cytokines involved in the vascular damage associated with hypertension. Furthermore, it is accepted that TNFα is a key mediator involved in insulin resistance and vascular damage observed in obesity. Both cytokines induce the expression of interferon-stimulated gene 15 (ISG15), a protein similar to ubiquitin that induces a reversible post-translational modification (ISGylation) and that can also be secreted as a free form. The functions of ISG15 are mainly related to the immune response against infections, however, it could also be an interesting new target for cardiovascular damage.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48524179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-30DOI: 10.53519/analesranf.2022.88.02.06
Pau Antich Isern, Juan Aparicio Blanco
Medical devices cover a wide range of products essential for healthcare. In 2017 a new European regulation covering them was approved that fully applies from 2021 onwards. In it, their legal definition, classification, conformity assessment procedures, requirements for the clinical investigations that asses their safety and/or performance, and European database are specified. Despite the efforts for systematizing the legal definition of medical device in the new regulation, the determination of the legal status of devices known as ‘borderline products’, for which different regulations may apply (like in the borderline with food supplements, cosmetics, personal care products, biocides, personal protective equipment and consumer products), is not without difficulties. On account of their therapeutic significance, this review delves into the borderline between medicinal products and medical devices, and differentiates them from presentations where medicinal products and medical devices are used in combination, without constituting a borderline. Establishing updated definitions, promoting transparency in the sector and preventing conflicts of interest should motivate all stakeholders to the periodic review of the regulation in a field in continuous technological evolution and development.
{"title":"The borderline with medical devices in the current Spanish legal framework","authors":"Pau Antich Isern, Juan Aparicio Blanco","doi":"10.53519/analesranf.2022.88.02.06","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.02.06","url":null,"abstract":"Medical devices cover a wide range of products essential for healthcare. In 2017 a new European regulation covering them was approved that fully applies from 2021 onwards. In it, their legal definition, classification, conformity assessment procedures, requirements for the clinical investigations that asses their safety and/or performance, and European database are specified.\u0000Despite the efforts for systematizing the legal definition of medical device in the new regulation, the determination of the legal status of devices known as ‘borderline products’, for which different regulations may apply (like in the borderline with food supplements, cosmetics, personal care products, biocides, personal protective equipment and consumer products), is not without difficulties. On account of their therapeutic significance, this review delves into the borderline between medicinal products and medical devices, and differentiates them from presentations where medicinal products and medical devices are used in combination, without constituting a borderline.\u0000Establishing updated definitions, promoting transparency in the sector and preventing conflicts of interest should motivate all stakeholders to the periodic review of the regulation in a field in continuous technological evolution and development.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42262198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-30DOI: 10.53519/analesranf.2022.88.02.01
F. J. Puerto Sarmiento
En el año 2011, la Academia entregó la Medalla Carracido, en su clase de oro, a Raúl Guerra Garrido, farmacéutico y novelista, autor multipremiado entre otras distinciones con el Premio Nadal, el de las Letras de Castilla y León y el Nacional de las Letras Españolas. Once años después, José Félix Olalla presentaba su último libro en nuestra institución. Sin la precisión requerida a un historiador, creo que es la primera vez en la cual se produce tal hecho, por lo cual me pareció oportuno escribir una presentación especial y hoy publicarla en el órgano de difusión académica para dejar constancia, también escrita, de lo sucedido.
2011年，该学院将卡拉西多奖章(golden class Carracido medal)授予raul Guerra Garrido，他是药剂师和小说家，曾多次获得纳达尔奖(Premio纳达尔)、卡斯提尔文学奖(Castilla y leon)和西班牙国家文学奖(national de las Letras espanolas)等奖项。11年后，jose felix Olalla在我们学院展示了他的最后一本书。在没有历史学家所要求的精确程度的情况下，我认为这是第一次发生这样的事件，所以我认为写一篇特别的报告是合适的，并在今天的学术传播机构上发表，以记录所发生的事情。
{"title":"José Félix Olalla and his book, La trama del cielo: A poet at the Academy","authors":"F. J. Puerto Sarmiento","doi":"10.53519/analesranf.2022.88.02.01","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.02.01","url":null,"abstract":"En el año 2011, la Academia entregó la Medalla Carracido, en su clase de oro, a Raúl Guerra Garrido, farmacéutico y novelista, autor multipremiado entre otras distinciones con el Premio Nadal, el de las Letras de Castilla y León y el Nacional de las Letras Españolas.\u0000\u0000Once años después, José Félix Olalla presentaba su último libro en nuestra institución. Sin la precisión requerida a un historiador, creo que es la primera vez en la cual se produce tal hecho, por lo cual me pareció oportuno escribir una presentación especial y hoy publicarla en el órgano de difusión académica para dejar constancia, también escrita, de lo sucedido.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42381938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-30DOI: 10.53519/analesranf.2022.88.02.02
J. A. Almeida Villegas, José Alfonso Gutiérrez Gutiérrez, Silvia León Quirino, Patricia Albarrán Calzonzín, Alejandro Acosta Ramírez, Carlos Alberto Rubén Castillo Nava, María del Carmen Guzmán Márquez
Objetive: Description of the different isolated microorganisms and their prevalence in infections associated with health care, in addition to determining their patterns of resistance to antibiotics in patients admitted with a confirmed or suspected diagnosis of COVID-19 in the Intensive Care Unit, during a third-level medical center with hospital reconversion. Method: Patient demographic data was obtained from the clinical record, with defined criteria. Antibiotic resistance patterns were evaluated as well as the identification of isolated bacteria in cultures of expectoration, pleural fluid, catheter tips. For bacterial identification and resistance mechanisms, automated equipment and phenotypic tests were used, following the CLSI (Clinical & Laboratory Standards Institute) criteria. Results: A total of 100 patients with bacterial infection added to the main COVID-19 picture were obtained, representing pneumonia, urinary tract infection, catheter infections and bacteremia. A total of 100 strains were isolated, of which 84 are Extremely Drug Resistant, 12 Multidrug Resistant and only 4 variable sensitivity. The bacteria with the highest prevalence is Staphylococcus aureus with, followed by Pseudonomas aeruginosa and Stenotrophomonas maltophilia. 100% of the patients admitted to the ICU (Intensive Care Unit) had death. Conclusion: The increase in resistance to antibiotics in the COVID-19 pandemic has set off alarms due to the complication that this brings, and the improper use of drugs as prophylaxis or attempted treatment only generates selective pressure that leads to an increase in resistance as observed in the isolated strains in this study, where the vast majority present enzymes as well as other resistance mechanisms that confer them to be XDR (Extremely Drug Resistant).
{"title":"Antibiotic resistance patterns in infections associated with health care in a Third Level Center with hospital reconversion in the COVID-19 pandemic","authors":"J. A. Almeida Villegas, José Alfonso Gutiérrez Gutiérrez, Silvia León Quirino, Patricia Albarrán Calzonzín, Alejandro Acosta Ramírez, Carlos Alberto Rubén Castillo Nava, María del Carmen Guzmán Márquez","doi":"10.53519/analesranf.2022.88.02.02","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.02.02","url":null,"abstract":"Objetive: Description of the different isolated microorganisms and their prevalence in infections associated with health care, in addition to determining their patterns of resistance to antibiotics in patients admitted with a confirmed or suspected diagnosis of COVID-19 in the Intensive Care Unit, during a third-level medical center with hospital reconversion.\u0000Method: Patient demographic data was obtained from the clinical record, with defined criteria. Antibiotic resistance patterns were evaluated as well as the identification of isolated bacteria in cultures of expectoration, pleural fluid, catheter tips. For bacterial identification and resistance mechanisms, automated equipment and phenotypic tests were used, following the CLSI (Clinical & Laboratory Standards Institute) criteria.\u0000Results: A total of 100 patients with bacterial infection added to the main COVID-19 picture were obtained, representing pneumonia, urinary tract infection, catheter infections and bacteremia. A total of 100 strains were isolated, of which 84 are Extremely Drug Resistant, 12 Multidrug Resistant and only 4 variable sensitivity. The bacteria with the highest prevalence is Staphylococcus aureus with, followed by Pseudonomas aeruginosa and Stenotrophomonas maltophilia. 100% of the patients admitted to the ICU (Intensive Care Unit) had death.\u0000Conclusion: The increase in resistance to antibiotics in the COVID-19 pandemic has set off alarms due to the complication that this brings, and the improper use of drugs as prophylaxis or attempted treatment only generates selective pressure that leads to an increase in resistance as observed in the isolated strains in this study, where the vast majority present enzymes as well as other resistance mechanisms that confer them to be XDR (Extremely Drug Resistant).","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42429228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.53519/analesranf.2022.88.01.01
Sara Benedito Castellote
Cerebrovascular disease is one of the complications of long-term diabetes mellitus. While the structure and function of the great cerebral vessels may be more easily studied, the cerebral microcirculation is difficult to assess. However, a simple eye fundus examination with an ophthalmoscope enables to visualize the microvascular abnormalities that characterize diabetic retinopathy, which isth e most common microvascular complication of diabetes. The anatomical and functional similarity between retinal and cerebral microcirculation supports the hypothesis that alterations in retinal vascular reactivity could be considered as an early marker of cerebral microvascular dysfunction in diabetes. The initiating factor of diabetic angiopathies is endothelial dysfunction. Endothelial dysfunction results in a reduced bioavailability of nitric oxide (NO), as a consequence of decreased NO synthesis and/or increased production of free oxygen radicals that are NO scavengers. Diabetes also stimulates the production of endothelial-derived contractile factors such as superoxide anions and hydroxyl radicals, endothelin and certain cyclooxygenase (COX) derivatives. COX activation is related to a high level of oxidative stress. Oxidative stress participates in the inflammatory response involved in the diabetic vascular dysfunction. These pathogenic mechanisms have been shown in both cerebral and retinal arteries, mainly through in vitro vascular reactivity studies, suggesting that diabetes induces a profound change in microvascular regulatory mechanisms. The association between the degree of retinal perfusion, brain injuries and altered cognitive function indicates a certain parallelism in the degree of impairment of both retinal and brain circulations. In addition, prospective studies conclude that diabetic retinopathy predicts ischemic cerebrovascular disease independently of other risk factors, supporting the importance of cerebral microvascular disease in diabetics. Further research on the vascular abnormalities is needed to understand the pathogenic mechanisms underlying retinopathies and cerebrovascular disease in diabetes. In the near future, the use of fully automated methods to detect signs of retinopathy will not only facilitate the efficient evaluation of vascular changes in the retina but will also help to reduce cerebral vascular morbidity and mortality.
{"title":"The retina, a window of cerebrovascular disease in diabetes","authors":"Sara Benedito Castellote","doi":"10.53519/analesranf.2022.88.01.01","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.01.01","url":null,"abstract":"Cerebrovascular disease is one of the complications of long-term diabetes mellitus. While the structure and function of the great cerebral vessels may be more easily studied, the cerebral microcirculation is difficult to assess. However, a simple eye fundus examination with an ophthalmoscope enables to visualize the microvascular abnormalities that characterize diabetic retinopathy, which isth e most common microvascular complication of diabetes. The anatomical and functional similarity between retinal and cerebral microcirculation supports the hypothesis that alterations in retinal vascular reactivity could be considered as an early marker of cerebral microvascular dysfunction in diabetes. The initiating factor of diabetic angiopathies is endothelial dysfunction. Endothelial dysfunction results in a reduced bioavailability of nitric oxide (NO), as a consequence of decreased NO synthesis and/or increased production of free oxygen radicals that are NO scavengers. Diabetes also stimulates the production of endothelial-derived contractile factors such as superoxide anions and hydroxyl radicals, endothelin and certain cyclooxygenase (COX) derivatives. COX activation is related to a high level of oxidative stress. Oxidative stress participates in the inflammatory response involved in the diabetic vascular dysfunction. These pathogenic mechanisms have been shown in both cerebral and retinal arteries, mainly through in vitro vascular reactivity studies, suggesting that diabetes induces a profound change in microvascular regulatory mechanisms. The association between the degree of retinal perfusion, brain injuries and altered cognitive function indicates a certain parallelism in the degree of impairment of both retinal and brain circulations. In addition, prospective studies conclude that diabetic retinopathy predicts ischemic cerebrovascular disease independently of other risk factors, supporting the importance of cerebral microvascular disease in diabetics. Further research on the vascular abnormalities is needed to understand the pathogenic mechanisms underlying retinopathies and cerebrovascular disease in diabetes. In the near future, the use of fully automated methods to detect signs of retinopathy will not only facilitate the efficient evaluation of vascular changes in the retina but will also help to reduce cerebral vascular morbidity and mortality.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71087559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.53519/analesranf.2022.88.01.02
Santiago Cuéllar Rodríguez
Measuring designates the process by which a system is interacted with in order to represent some of its aspects by means of abstract terms or those that have a merely ideal character, establishing common references that allow comparison with a predetermined pattern and bounded by predetermined margins of uncertainty. Obviously, measurement is an essential component of science; one of its hallmarks, a primary source of knowledge and the essential link between theory and experimentation, allowing them to feed off each other and continuously improve. In the scientific study of any phenomenon, the intervention of the observer and the very fact of the observation disturb the phenomenon studied. For this reason, it is always necessary to take into consideration the degree of disturbance it produces, something that in clinical research can be particularly complex due to the multiplicity and variability of human manifestations. The complexity of the observed subject (human being), given his condition as a thinking, emotional, moral and social entity, multiplies the uncertainty of his responses, both individual and collective, and extreme methodological and ethical demands of the scientist; In addition, the response of each individual to a clinical intervention incorporates multiple other factors unrelated to the effects objectively attributable to the intervention, but which must be duly weighed. For all these reasons, in order to scientifically measure the effect of an intervention in a clinical trial, it is essential to previously define and justify the minimum magnitude of the change that can give rise to an effect that is clinically relevant for the patient and for the observer.
{"title":"Epistemology of measurement","authors":"Santiago Cuéllar Rodríguez","doi":"10.53519/analesranf.2022.88.01.02","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.01.02","url":null,"abstract":"Measuring designates the process by which a system is interacted with in order to represent some of its aspects by means of abstract terms or those that have a merely ideal character, establishing common references that allow comparison with a predetermined pattern and bounded by predetermined margins of uncertainty. Obviously, measurement is an essential component of science; one of its hallmarks, a primary source of knowledge and the essential link between theory and experimentation, allowing them to feed off each other and continuously improve. In the scientific study of any phenomenon, the intervention of the observer and the very fact of the observation disturb the phenomenon studied. For this reason, it is always necessary to take into consideration the degree of disturbance it produces, something that in clinical research can be particularly complex due to the multiplicity and variability of human manifestations. The complexity of the observed subject (human being), given his condition as a thinking, emotional, moral and social entity, multiplies the uncertainty of his responses, both individual and collective, and extreme methodological and ethical demands of the scientist; In addition, the response of each individual to a clinical intervention incorporates multiple other factors unrelated to the effects objectively attributable to the intervention, but which must be duly weighed. For all these reasons, in order to scientifically measure the effect of an intervention in a clinical trial, it is essential to previously define and justify the minimum magnitude of the change that can give rise to an effect that is clinically relevant for the patient and for the observer.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71087641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.53519/analesranf.2022.88.01.05
A. Martín González, L. M. Martín Arias, R. Sanz Fadrique, Esther Salgueiro Vázquez
Introduction: the aim of this study is to review the current evidence on the clinical use of NSAIDs, coxibs and nonselective, and to evaluate its cardiovascular (CVR) and gastrointestinal risk (GIR) by means of a meta-analytic procedure. Materials and methods: cohort and case-control studies showing CVR and GIR associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Results: both coxibs (RR, 1.22 [95%CI, 1.17-1.28]) and nonselective NSAIDs (RR 1.18 [95%CI, 1.12-1.24]) were associated with an increased CVR. The coxibs CVR remained even for low-dose and low-baseline CVR subgroups. Analysis by drug disclosed that rofecoxib (RR 1.39 [95%CI, 1.31- 1.47]), along with diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Gastrointestinal risk meta-analysis showed that coxibs were associated with a GIR increment [RR1.64 (95% CI 1.44-1.86)]. Analysis by drug disclosed that etoricoxib [RR 4.48 (95% CI 2.98-6.75)]presented the highest GIR followed by rofecoxib [RR 2.02 (95% CI 1.56-2.61)] and celecoxib [RR1.62 (95% CI 1.46-1.78)]. GIR was also high for <65 year-old and low-dose coxibs subgroups. Conclusion: according to our study the use of NSAIDs (coxibs and nonselective) are associated with a similar CVR increment, even for low-dose and low-baseline CVR subgroups. On the other hand, the use of coxibs is associated with a GIR increased, which would be high even for low-dose coxibs and <65-year-old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib. Keywords: adverse drug reactions; nonsteroidal anti-inflammatory drugs; cardiovascular risk; meta-analysis; observational studies; cyclo-oxygenase 2 inhibitor; gastrointestinal events
简介:本研究的目的是回顾目前关于非甾体抗炎药、coxibs和非选择性抗炎药临床应用的证据，并通过荟萃分析方法评估其心血管(CVR)和胃肠道风险(GIR)。材料和方法:选择了显示非甾体抗炎药与未治疗相关的CVR和GIR的队列和病例对照研究。我们估计了所有非甾体抗炎药作为整体和单独的合并RR和95%置信区间(CI)。结果:coxib (RR, 1.22 [95%CI, 1.17-1.28])和非选择性非甾体抗炎药(RR, 1.18 [95%CI, 1.12-1.24])均与CVR升高相关。在低剂量和低基线CVR亚组中，coxibs的CVR保持不变。药物分析显示，罗非昔布(RR为1.39 [95%CI, 1.31 ~ 1.47])、双氯芬酸(RR为1.34 [95%CI, 1.26 ~ 1.42])和依托昔布(RR为1.27 [95%CI, 1.12 ~ 1.43])是CVR最高的非甾体抗炎药。胃肠道风险荟萃分析显示，coxib与GIR增加相关[RR1.64 (95% CI 1.44-1.86)]。药物分析显示，依托昔布的GIR最高[RR 4.48 (95% CI 2.98 ~ 6.75)]，其次是罗非昔布[RR 2.02 (95% CI 1.56 ~ 2.61)]和塞来昔布[RR1.62 (95% CI 1.46 ~ 1.78)]。65岁以下和低剂量coxibs亚组的GIR也很高。结论:根据我们的研究，使用非甾体抗炎药(coxib和非选择性)与相似的CVR增量相关，即使是低剂量和低基线CVR亚组。另一方面，使用coxibs与GIR增加相关，即使对于低剂量coxibs和<65岁亚组，GIR也会很高。依托昔布的风险高于塞来昔布和罗非昔布。关键词:药物不良反应;非甾体类抗炎药;心血管疾病的风险;荟萃分析;观察性研究;环加氧酶2抑制剂;胃肠道事件
{"title":"Analysis and evaluation of cardiovascular and gastrointestinal risk of nonsteroidal anti-inflammatory drugs selective and non-selective cyclooxygenase inhibitors","authors":"A. Martín González, L. M. Martín Arias, R. Sanz Fadrique, Esther Salgueiro Vázquez","doi":"10.53519/analesranf.2022.88.01.05","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.01.05","url":null,"abstract":"Introduction: the aim of this study is to review the current evidence on the clinical use of NSAIDs, coxibs and nonselective, and to evaluate its cardiovascular (CVR) and gastrointestinal risk (GIR) by means of a meta-analytic procedure. Materials and methods: cohort and case-control studies showing CVR and GIR associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Results: both coxibs (RR, 1.22 [95%CI, 1.17-1.28]) and nonselective NSAIDs (RR 1.18 [95%CI, 1.12-1.24]) were associated with an increased CVR. The coxibs CVR remained even for low-dose and low-baseline CVR subgroups. Analysis by drug disclosed that rofecoxib (RR 1.39 [95%CI, 1.31- 1.47]), along with diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Gastrointestinal risk meta-analysis showed that coxibs were associated with a GIR increment [RR1.64 (95% CI 1.44-1.86)]. Analysis by drug disclosed that etoricoxib [RR 4.48 (95% CI 2.98-6.75)]presented the highest GIR followed by rofecoxib [RR 2.02 (95% CI 1.56-2.61)] and celecoxib [RR1.62 (95% CI 1.46-1.78)]. GIR was also high for <65 year-old and low-dose coxibs subgroups. Conclusion: according to our study the use of NSAIDs (coxibs and nonselective) are associated with a similar CVR increment, even for low-dose and low-baseline CVR subgroups. On the other hand, the use of coxibs is associated with a GIR increased, which would be high even for low-dose coxibs and <65-year-old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib. Keywords: adverse drug reactions; nonsteroidal anti-inflammatory drugs; cardiovascular risk; meta-analysis; observational studies; cyclo-oxygenase 2 inhibitor; gastrointestinal events","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71087926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.53519/analesranf.2022.88.01.00
Pedro Pablo Medina Vico
Since the discovery of the central dogma of Molecular Biology, ribonucleic acid (RNA) was postulated as a messenger molecule, which transmitted the information of protein synthesis from DNA, in the cell nucleus, to the cytoplasm. However, research work has shown that RNA also performs functions beyond that of acting as a messenger. Thus, today it is known that there is a large number of non-protein coding RNA molecules that play a fundamental role in the cell. MicroRNAs (miRNAs) belong to this non-protein-coding RNA and their study has revolutionized our knowledge about the functionality of RNAs. MicroRNAs are gene expression regulatory molecules that help determine when or where genes are translated into protein. As their name indicates, these molecules are composed of nucleic acids (RNA) and not protein, in contrast to previously known regulators of gene expression. Due to their small size (human genes are encoded by thousands of nucleotides and microRNAs by only twenty) and their peculiar nature, microRNAs were discovered in the human genome once it was sequenced. MicroRNAs play a fundamental role in establishing cell identity. Components of the microRNA synthesis machinery, or microRNAs per se, have been associated with human pathologies. MicroRNAs have been found to play an important role in many cellular processes that are altered in cancer, such as differentiation, proliferation, and apoptosis. Thus, genes that code for microRNAs have been found in chromosomal regions frequently gained or lost in cancer. Some microRNAs have altered expression levels in cancer and have demonstrated their ability to affect cell transformation, carcinogenesis, and metastasis by acting as oncogenes or tumor suppressors. These microRNAs that are involved in tumor development have been called onco-microRNAs, and their name gives the title to this work. We are only at the beginning of understanding the functional implications of the gain or loss of a particular microRNA in cancer, and early pharmacological applications for cancer treatment are still being tested. Despite everything, this field is providing a series of promising medical applications in the diagnosis, prognosis and treatment of cancer that could provide new tools for the medicine of the future.
{"title":"OncomicroARNs and their future pharmacological applications","authors":"Pedro Pablo Medina Vico","doi":"10.53519/analesranf.2022.88.01.00","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.01.00","url":null,"abstract":"Since the discovery of the central dogma of Molecular Biology, ribonucleic acid (RNA) was postulated as a messenger molecule, which transmitted the information of protein synthesis from DNA, in the cell nucleus, to the cytoplasm. However, research work has shown that RNA also performs functions beyond that of acting as a messenger. Thus, today it is known that there is a large number of non-protein coding RNA molecules that play a fundamental role in the cell. MicroRNAs (miRNAs) belong to this non-protein-coding RNA and their study has revolutionized our knowledge about the functionality of RNAs. MicroRNAs are gene expression regulatory molecules that help determine when or where genes are translated into protein. As their name indicates, these molecules are composed of nucleic acids (RNA) and not protein, in contrast to previously known regulators of gene expression. Due to their small size (human genes are encoded by thousands of nucleotides and microRNAs by only twenty) and their peculiar nature, microRNAs were discovered in the human genome once it was sequenced. MicroRNAs play a fundamental role in establishing cell identity. Components of the microRNA synthesis machinery, or microRNAs per se, have been associated with human pathologies. MicroRNAs have been found to play an important role in many cellular processes that are altered in cancer, such as differentiation, proliferation, and apoptosis. Thus, genes that code for microRNAs have been found in chromosomal regions frequently gained or lost in cancer. Some microRNAs have altered expression levels in cancer and have demonstrated their ability to affect cell transformation, carcinogenesis, and metastasis by acting as oncogenes or tumor suppressors. These microRNAs that are involved in tumor development have been called onco-microRNAs, and their name gives the title to this work. We are only at the beginning of understanding the functional implications of the gain or loss of a particular microRNA in cancer, and early pharmacological applications for cancer treatment are still being tested. Despite everything, this field is providing a series of promising medical applications in the diagnosis, prognosis and treatment of cancer that could provide new tools for the medicine of the future.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":"18 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71088007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.53519/analesranf.2022.88.01.04
Silvia Enríquez Fernández
Dispensing is the act carried out by a pharmacist or under his supervision, aimed at ensuring that patients receive the medicines in the precise doses according to their individual requirements, for the appropriate period, with the information for their correct use, and in accordance with current regulations. To understand this act, the concept of medicine, the studies that a pharmacist must take, the regulation of the concepts of pharmaceutical management, as well as the pharmacy offices in the European Union have been previously analyzed. Finally, compare the act of dispensing in each of the countries of the European Union. To make that comparison, each of the rules directly affecting the act of dispensing medicinal products in each Member State has been translated, analysed and interpreted. The aspects that have been investigated have been: the obligatory presence of a pharmacist in the pharmacy office; the sale of medicinal products in establishments other than pharmacies; the ability to replace those medicinal products subject to medical prescription by the pharmacist; and, the regulation of the online sale of medicines subject to medical prescription. Although it is true that it has been concluded that the presence of the pharmacist is mandatory in 99% of the countries, no total harmony has been found in the regulations of the rest of the parameters subject to comparison in this research work.
{"title":"Comparative legal framework for the dispensing of medicinal products in pharmacies in the different member states of the European Union","authors":"Silvia Enríquez Fernández","doi":"10.53519/analesranf.2022.88.01.04","DOIUrl":"https://doi.org/10.53519/analesranf.2022.88.01.04","url":null,"abstract":"Dispensing is the act carried out by a pharmacist or under his supervision, aimed at ensuring that patients receive the medicines in the precise doses according to their individual requirements, for the appropriate period, with the information for their correct use, and in accordance with current regulations. To understand this act, the concept of medicine, the studies that a pharmacist must take, the regulation of the concepts of pharmaceutical management, as well as the pharmacy offices in the European Union have been previously analyzed. Finally, compare the act of dispensing in each of the countries of the European Union. To make that comparison, each of the rules directly affecting the act of dispensing medicinal products in each Member State has been translated, analysed and interpreted. The aspects that have been investigated have been: the obligatory presence of a pharmacist in the pharmacy office; the sale of medicinal products in establishments other than pharmacies; the ability to replace those medicinal products subject to medical prescription by the pharmacist; and, the regulation of the online sale of medicines subject to medical prescription. Although it is true that it has been concluded that the presence of the pharmacist is mandatory in 99% of the countries, no total harmony has been found in the regulations of the rest of the parameters subject to comparison in this research work.","PeriodicalId":50795,"journal":{"name":"Anales De La Real Academia Nacional De Farmacia","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71088026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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