Questioning Established Theories and Treatment Methods Related to Iron and Other Metal Metabolic Changes, Affecting All Major Diseases and Billions of Patients.

The medical and scientific literature is dominated by highly cited historical theories and findings [...].

Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends Towards Future Drugs.

BACKGROUND: Cancer continues to be a global burden, despite the advancement of various technological and pharmaceutical improvements over the past two decades. Methods for treating cancer include surgery, radiotherapy and chemotherapy in addition to other specialized techniques. On the other hand, medicinal plants have been traditionally employed either as the complementary medicine or dietary agents in the treatment and management of cancer. Medicinal plants are a rich source of secondary metabolites with interesting biological and pharmacological activities. Among these metabolites, glycosides are naturally occurring substances and have outstanding therapeutic potential and clinical utility. METHODS: Different medical research engines such as, GoogleScholar, PubMed, SpringerLink, ScienceDirect were used to collect related literature on the subject matter. In this regard, only peer-reviewed journals were considered. RESULTS: Emerging results showed that numerous glycosides isolated from various plants possessed marked anticancer activity against a variety of cancer cell lines. Accordingly, the aim of the present review is to shed light on the anticancer effects of glycosides, analyze possible mechanisms of action, and highlight the role of these natural agents as complementary and alternative medicine in combating and managing cancer. CONCLUSION: The glycosides isolated from different plants demonstrated potent cytotoxic effects against various cancer cell lines in initial preclinical studies. The anticancer effect was mediated through multiple mechanisms; however further detailed studies are needed to understand the full potential of glycosides for clinical utility.

An update and systematic review on the treatment of primary dysmenorrhea.

OBJECTIVES: Primary dysmenorrhea is a painful uterine contraction caused by endometrial laceration. Drug therapies and complementary medicine have been used to treat dysmenorrhea. The aim of this study was to investigate and offer an updated perspective on the treatments for dysmenorrhea. METHODS: The present study was conducted in accordance with the PRISMA checklist for systematic reviews and meta-analyses. The required information was collected based on searches for the following keywords: treatment, primary dysmenorrhea, medicinal plants, chemical drugs, and herbs. Searches were performed on databases Pubmed, Web of Sciences, Scopus, Iran medex, and SID by March 2018 to find literature in the English and Persian languages on this subject without a time limit. RESULTS: This review included 17 papers, 10 of which on complementary medicine, three on drug therapies, and four on acupuncture and acupressure. The largest and smallest samples had 303 and 24 patients, respectively. Length of treatment ranged from one to six months and the measures most commonly used in the studies were the visual analogue scale and clinical efficacy. Reported complications included gastrointestinal events, nausea, vomiting, diarrhea, abdominal pain, and liver and kidney disorders. CONCLUSION: Medicinal plants, drugs, and acupressure seem to suppress pain by reducing the level of prostaglandins, mediating nitric oxide, increasing beta-endorphin levels, blocking the calcium channel, and enhancing circulatory flow through the uterine pathway. Further trials are required to confirm the benefits of the procedures described and ensure the absence of complications.

Agonistas parciales, moduladores bioquímicos con múltiples aplicaciones / Partial agonists: biochemical modulators with multiple applications

En general, los diferentes tratados de farmacología se organizan en torno a una clasificación anatómica-terapéutica-química. Los tratados de «química farmacéutica» suelen organizarse, además, poniendo énfasis en la naturaleza química de los fármacos, así como en los procesos bioquímicos involucrados en su acción. En otras ocasiones, cuando se contempla la fitoterapia desde un punto de vista botánico, como hace la «botánica medicinal», la exposición se realiza mediante un viaje a través de los diferentes taxones que contienen especies con relevancia terapéutica. En cambio, en este artículo de revisión se va a hablar de un grupo de fármacos que, desde los enfoques expositivos anteriores, no tienen mucho que ver pero que, sin embargo, poseen mecanismos farmacodinámicos muy similares, a pesar de que actúen sobre diferentes receptores. Se trata de los agonistas (y antagonistas) parciales. Lógicamente no se revisarán todos en este artículo, sino aquellos que al autor le han parecido más curiosos e interesantes para ilustrar su relación mutua en cuanto al funcionamiento farmacodinámico: vareniclina, buprenorfina, diazepinonas, aripiprazol, memantina. Este es el objetivo de este artículo: la revisión de un grupo de fármacos desde un punto de vista novedoso, como es su mecanismo de acción farmacodinámico común. Entre las conclusiones, está la indicación de este tipo de fármacos cuando se va a intervenir en sistemas bioquímicos y fisiológicos tan complicados que las funciones a tratar no deben ni inhibirse ni potenciarse desmedidamente, sino simplemente modularse. Este es el caso de muchas dolencias que afectan al sistema nervioso (AU)

In general the different treatises of pharmacology are organised around an anatomical-therapeutic-chemical classification. Treatises about «medicinal chemistry» are organised, not only around this, but also emphasise the chemical nature of the drugs, as well as the biochemical processes involved in their action. Furthermore, when herbal medicine is contemplated from a botanical point of view, as does the «medical botany», exposure is performed by a journey through the different taxa containing species with therapeutic relevance. Nevertheless, in this review article a group of drugs is discussed that, from the previous points of view, do not have anything to do with each other. However, they have very similar pharmacodynamic mechanisms, despite acting on different receptors. These are partial agonists (and antagonists). Obviously not all of these will be reviewed in this article, but those more interesting to illustrate their relationship in terms of pharmacodynamic performance: varenicline, buprenorphine, diazepinones, aripiprazole, memantine. This is the purpose of this article: A review of a group of drugs from a novel point of view, such as their common pharmacodynamic mechanism of action. Among the conclusions, is the indication of these drugs to intervene in such complicated biochemical and physiological systems that functions to be treated should neither be inhibited nor enhanced, but simply modulated. This is the case of many diseases that affect the nervous system (AU)

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board.

Poor adherence to treatment regimens has long been recognized as a substantial roadblock to achieving better outcomes for patients. Non-adherence to medications affects the quality and length of life and has been associated with negative health outcomes and increasing healthcare costs. The problem of non-adherence is particularly troublesome in older patients who are affected by multiple chronic diseases and for this reason receive multiple treatments. To date, no single intervention strategy has been shown to be effective in improving adherence across all patients, conditions, and settings. Between September and October 2014, a group of experts in geriatrics, pharmacology, epidemiology, and public health applied a modified RAND appropriateness method to reach a consensus on the possible best interventions to improve adherence in older individuals. Seven interventions were identified, classified based on their target (patient, therapy, and public health/society): (1) Comprehensive Geriatric Assessment, (2) patient (and caregiver) education to improve patient empowerment, (3) optimization of treatment, (4) use of adherence aids, (5) physician and other healthcare professionals' education, (6) adherence assessment, (7) facilitating access to medicine by service integration. For each intervention, experts assessed (a) target population, (b) health professionals potentially involved in the intervention, (c) strategies/instruments needed for implementation, and (d) time of the intervention. Interventions that target adherence must combine different approaches targeting the complex aspects of older adults in a holistic approach. Tackling non-adherence, with its complexity, requires a multi-stakeholder patient-centred approach acting in a defined framework of interactions in which the different players may provide different services but are integrated with one another.

Impact of Changing Trends in Medical Therapy on Transurethral Resection of the Prostate: Two Decades of Change in China.

OBJECTIVE: To retrospectively assess that over the 2 decades, whether medical therapy has changed indications, patient characteristics, and outcomes in men undergoing transurethral resection of the prostate (1992-2013). METHODS: At our institution, medical history of all patients undergoing surgery before 1998, between 2001 and 2003, and between 2011 and 2013 was reviewed. Patient demographics, preoperative clinical profile, clinical management, and operative complications were assessed. RESULTS: A total of 1157 patients were enrolled in the study. Mean ages of patients increased from 67.0 to 70.4 years old over the past 2 decades. Furthermore, comorbidities increased significantly as well. Although prostate size and weight of resected tissue increased from 57.3 to 92.3 g and from 24.3 to 36.6 g, the surgical time decreased from 78.21 to 72.29 minutes. From 2011 to 2013, patients undergoing surgery had their catheters remove earlier (from 5.7 to 4.5 days), whose postoperative days in hospital were shorter (from 9.3 to 4.4 days). Although operative complications decreased from 12.3% to 5.7%, especially bleeding, re-operation due to bleeding increased from 0.4% to 2.7%. Moreover, no statistical difference was observed in operative complications between patients with medical therapy and those without medical therapy. CONCLUSION: The increasing application of medical therapy resulted in surgical interventions delay. The prostate size was significantly greater, as was the weight of resected tissue. Although patients with medication were older with more comorbidities and larger prostates, surgical technique advancements have benefited them and transurethral resection of the prostate is still considered as a safe and recommendable surgical treatment.

Recent developments in therapeutic applications of Cyanobacteria.

The cyanobacteria (blue-green algae) are photosynthetic prokaryotes having applications in human health with numerous biological activities and as a dietary supplement. It is used as a food supplement because of its richness in nutrients and digestibility. Many cyanobacteria (Microcystis sp, Anabaena sp, Nostoc sp, Oscillatoria sp., etc.) produce a great variety of secondary metabolites with potent biological activities. Cyanobacteria produce biologically active and chemically diverse compounds belonging to cyclic peptides, lipopeptides, fatty acid amides, alkaloids and saccharides. More than 50% of the marine cyanobacteria are potentially exploitable for extracting bioactive substances which are effective in killing cancer cells by inducing apoptotic death. Their role as anti-viral, anti-tumor, antimicrobial, anti-HIV and a food additive have also been well established. However, such products are at different stages of clinical trials and only a few compounds have reached to the market.

[New therapeutics]. / Nouvelles thérapeutiques.

Daily medical practice triggers reflexes in the use of drugs which must nevertheless always be adapted to new knowledge. Physician assistants and residents in the clinical ward of Internal Medicine of Sion Hospital summarize six recently published clinical treatments to which primary care physicians or in hospital-based internal medicine have to pay a particular attention. Quinolones are widely used but associated with QT interval widening, morphine delays and attenuate ticagrelor action in patients with myocardial infarction, evolocumab, a monoclonal antibody impact in reducing lipids and cardiovascular events, impact of statins on influenza vaccine effectiveness, vitamin D treatment for the prevention of functional decline, high dose dexamethasone for the treatment of immune thrombocytopenia.

La pratique médicale quotidienne suscite des réflexes dans l'utilisation de médicaments qui doivent sans cesse être adaptés aux nouvelles connaissances. Les médecins du Service de médecine interne de Sion résument six publications sur des traitements auxquels le praticien ambulatoire ou hospitalier doit porter une attention particulière. L'effet des quinolones sur l'intervalle QT, l'administration concomitante de morphine et de ticagrélor en cas de syndrome coronarien aigu, la place d'un anticorps monoclonal pour abaisser le taux de cholestérol, l'impact des statines sur l'efficacité vaccinale, la rôle de la vitamine D à haute dose pour ralentir le déclin de la performance physique, le stéroïde de choix en cas de thrombopénie auto-immune.

Alternativa terapéutica para el retinoblastoma: quimioterapia intraarterial con melfalán / Alternative treatment for retinoblastoma: Intra-arterial chemotherapy with melphalan

CASO CLÍNICO: Un lactante de 10 meses fue remitido para estudio de leucocoria izquierda de un mes de evolución. En la exploración se detectó un retinoblastoma que ocupaba el área macular. Fue tratado con quimioterapia intraarterial con 6 mg de melfalán, sin requirir posteriores intervenciones para el control de la enfermedad. DISCUSIÓN: El melfalán es un agente quimioterápico muy efectivo, con uso limitado por la toxicidad sistémica que genera. La quimioterapia intraarterial permite la liberación selectiva en la arteria oftálmica, lo que limita la toxicidad sistémica. Esta combinación de eficacia, seguridad y precisión la hacen una alterativa terapéutica atractiva para el manejo del retinoblastoma

CASE REPORT: A 10-month old infant was referred for the study of a leukocoria of the left eye of one month onset. On examination, a retinoblastoma occupying the macular area was detected. Treatment with intra-arterial chemotherapy (melphalan 6 mg) was performed, with no further intervention required for disease control. DISCUSSION: Melphalan is an effective chemotherapeutic agent. However, its use is limited by the systemic toxicity that may occur. Intra-arterial chemotherapy allows the selective release of melphalan into the ophthalmic artery, thus limiting its systemic toxicity. This combination of efficiency, safety and accuracy makes it an attractive therapeutic alternative for the management of retinoblastoma

Heart failure: novel therapeutic approaches.

Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorders that impairs the ability of the ventricle to fill with or eject blood. Despite effective medical interventions, mortality and morbidity remain substantial. There have been significant advances in the therapy of HF in recent decades, such as the introduction of beta-blockers and antagonists of the renin-angiotensin system but still there is a major unmet need for better therapies for HF. In the present era, pathophysiology of HF has been explored. Various novel pathways, molecular sites have been identified, which contribute to the progression of the disease. By targeting these sites, newer pharmacological agents have been developed, which can play a promising role in the treatment of HF. This article focuses on recent advancements in pharmacotherapy of HF, which include agents targeting myocardial contractility, cytokines and inflammation, fibrosis and remodeling, myocardial metabolism, oxidative stress, and other newly defined pathways.

[Progress of serum pharmacochemistry of traditional Chinese medicine and further development of its theory and method].

Serum pharmacochemistry of traditional Chinese medicine (TCM) is designed to screen the efficacy material base of TCMs from the constituents absorbed into the blood after oral administration. The theory and method is in accordance with the effect characteristics of TCMs, and reflects the interaction between the body and the drugs, has become an effective pathway for researching the efficacy material base of TCMs which has been recognized and used widely. In the paper, the previous research contents and methods of the serum pharmacochemistry of TCM were reviewed, and on the basis of the further validity of the special administration form of the TCM formula and the corresponding property to TCM syndrome, the new strategy of serum pharmacochemistry of TCM integrating the metabonomics technologies was put forward. According to the strategy, we take the biological characters of TCM syndrome as a research starting point, taking TCM formula as object, using the metabolic biomarkers of syndromes or disease to evaluate the therapeutic effect of formula and screen the compounds of TCMs in serum which are highly correlated with the metabolic biomarkers through the correlation analysis, and by further biological validation to finally confirm the efficacy material basis of TCMs. Integrating with the systems biology technologies, the theory and method of serum pharmacochemistry of TCM will further develop, and open a new chapter in the interpretation of the theory of TCM.

[Economic perspectives of the research on advanced therapies]. / Perspectivas económicas de la investigación en terapia avanzada.

Since a new advanced therapy medicinal product is discovered until finally allowed its sale in the domestic market, it has to overcome a series of stages. Biomedical research is the first phase, currently its situation is encouraging to the increase in the number of clinical trials in Spain and in the rest of the world, despite the economic situation and the various difficulties that have faced the pharmaceutical laboratories. The next phase consists in obtaining the authorization of marketing of the European Medicines Agency. After authorization, will attempt to set a fair and moderate price for inclusion in the list of health provision of Social Security. A price for a drug that provides added value to health and society, a price that is generated profits for the pharmaceutical companies that hope to make up for the years of work and investment. Commitment to advanced therapy must be clear and forceful, to fund ongoing research projects and encouraging their creation with economic aid.

Desde que un nuevo medicamento de terapia avanzada sale a la luz hasta que finalmente se permite su venta en el mercado nacional, tiene que superar una serie de fases. La investigación biomédica es la primera fase, actualmente su situación resulta alentadora por el aumento del número de ensayos clínicos en España y en el resto del mundo a pesar de la coyuntura económica y de las diversas dificultades a las que tienen que enfrentarse los laboratorios farmacéuticos. La siguiente fase consiste en la obtención de la autorización de comercialización por parte de Agencia Europea del Medicamento. Tras dicha autorización, se intentará fijar un precio justo y moderado para la inclusión en el listado de prestación sanitaria por parte de la Seguridad Social. Un precio por un medicamento que aporta valor añadido a la salud y la sociedad, con el se generán ganancias para las empresas farmacéuticas que esperan compensar los años de trabajo e inversión. La apuesta por la terapia avanzada debe ser clara y contundente, financiando los proyectos de investigación en curso y animando a su creación con ayudas económicas.

[Situation analysis for drug clinical trial institutions].

Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.

¿Cómo comparar fármacos biológicos? / How to compare biologic drugs

El presente documento de consenso revisa la evidencia sobre evaluación de fármacos biológicos. Las conclusiones principales del grupo son: a) la evidencia actual sobre comparación de biológicos se basa en comparaciones indirectas y es, en general, poco fiable y con importantes limitaciones metodológicas; por ello, b) se considera necesario modificar las directivas regulatorias en el sentido de favorecer decididamente los estudios aleatorizados de no inferioridad comparando cara a cara los nuevos biológicos con los actuales estándares de tratamiento, evitando los ensayos frente a placebo; c) un elemento clave en este proceso será la determinación por consenso entre las agencias reguladoras, las sociedades científicas, la industria farmacéutica y las autoridades sanitarias de las diferencias clínicas que deben considerarse relevantes en cada una de las patologías evaluadas (AU)

This consensus document reviews the evidence on the evaluation of biological drugs. The main conclusions of the group are: a) the current evidence on biological comparisons is based on indirect comparisons and is generally unreliable and with important methodological limitations. Therefore, b) it is considered necessary to amend the regulatory directives in the sense of strongly favoring randomized non-inferiority studies comparing face to face the new biological treatment with current standards, avoiding trials versus placebo, c) a key element in this process will be determined by consensus among regulatory agencies, scientific societies, the pharmaceutical industry and health authorities regarding the clinical differences that should be considered relevant in each of the conditions tested (AU)

Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.

The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections.

Mechanisms of aortic aneurysm formation: translating preclinical studies into clinical therapies.

Aneurysms are common in the abdominal and thoracic regions of the aorta. While generally asymptomatic, progression of aneurysms is associated with the devastating consequences of aortic rupture. Current therapeutic options to prevent rupture are restricted to surgical repair, as there remains a lack of validated pharmaceutical approaches. Absence of proven medical therapies may be a consequence of the paucity of knowledge on mechanisms of aneurysmal initiation, progression and rupture. Many potential therapeutic targets have been identified in several widely used animal models of these diseases. A small number of these targets are currently under clinical evaluation, while many more are in preclinical stages of evaluation. The purpose of this review is to: (1) overview current understanding of mechanisms of aneurysmal initiation and progression and (2) summarise medical therapies that have been investigated clinically, as well as highlight future therapeutic targets.

Compounds from Chinese herbal medicines as reversal agents for P-glycoprotein-mediated multidrug resistance in tumors

Multidrug resistance (MDR) is a major obstacle to successful cancer chemotherapy. One of the main underlying mechanisms of this resistance is the over-expression of P-glycoprotein (P-gp), an ATP-dependent transmembrane transporter protein encoded by the MDR1 gene. P-gp might transport anti-cancer drugs out of cancer cells and decrease effective intracellular drug concentrations. An effective approach to overcome MDR is to inhibit the function of P-gp or its expression on the surface of cancer cells. Thus, application of MDR reversal agents can be seen as a potentially important means by which to overcome the clinical drug resistance of tumour cells and improve the efficacy of chemotherapy. Recently, research efforts worldwide have focused on reversal mechanisms for MDR and on the identification of reversal agents. Chinese scholars have performed a great deal of exploratory work by screening for efficacy and low toxicity in drug resistance reversal compounds. These compounds may provide more lead compounds with greater activity, leading to the development of more effective therapies for MDR cancer cells. In this review, the function and efficiency of novel compounds derived from traditional Chinese medicines are described (AU)

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Evolving use of new oral anticoagulants for treatment of venous thromboembolism.

The new oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, are poised to replace warfarin for treatment of the majority of patients with venous thromboembolism (VTE). With a rapid onset of action and the capacity to be administered in fixed doses without routine coagulation monitoring, NOACs streamline VTE treatment. In phase 3 trials in patients with acute symptomatic VTE, NOACs have been shown to be noninferior to conventional anticoagulant therapy for prevention of recurrence and are associated with less bleeding. Rivaroxaban and dabigatran are already licensed for VTE treatment in the United States, and apixaban and edoxaban are under regulatory consideration for this indication. As the number of approved drugs increases, clinicians will need to choose the right anticoagulant for the right VTE patient. To help with this decision, this review (1) compares the pharmacologic profiles of the NOACs, (2) outlines the unique design features of the phase 3 trials that evaluated the NOACs for VTE treatment, (3) reviews the results of these trials highlighting similarities and differences in the findings, (4) provides perspective about which VTE patients should receive conventional treatment or are candidates for NOACs, and (5) offers suggestions about how to choose among the NOACs.

Novetats farmacològiques en pediatria a Espanya: any 2011 / No disponible

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