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Diffusion-weighted imaging (DWI) is an established MRI technique that can investigate tissue microstructure at the scale of a few micrometers. Musculoskeletal tissues typically have a highly ordered structure to fulfill their functions and therefore represent an optimal application of DWI. Even more since disruption of tissue organization affects its biomechanical properties and may indicate irreversible damage. The application of DWI to the musculoskeletal system faces application-specific challenges on data acquisition including susceptibility effects, the low T2 relaxation time of most musculoskeletal tissues (2-70 msec) and the need for sub-millimetric resolution. Thus, musculoskeletal applications have been an area of development of new DWI methods. In this review, we provide an overview of the technical aspects of DWI acquisition including diffusion-weighting, MRI pulse sequences and different diffusion regimes to study tissue microstructure. For each tissue type (growth plate, articular cartilage, muscle, bone marrow, intervertebral discs, ligaments, tendons, menisci, and synovium), the rationale for the use of DWI and clinical studies in support of its use as a biomarker are presented. The review describes studies showing that DTI of the growth plate has predictive value for child growth and that DTI of articular cartilage has potential to predict the radiographic progression of joint damage in early stages of osteoarthritis. DTI has been used extensively in skeletal muscle where it has shown potential to detect microstructural and functional changes in a wide range of muscle pathologies. DWI of bone marrow showed to be a valuable tool for the diagnosis of benign and malignant acute vertebral fractures and bone metastases. DTI and diffusion kurtosis have been investigated as markers of early intervertebral disc degeneration and lower back pain. Finally, promising new applications of DTI to anterior cruciate ligament grafts and synovium are presented. The review ends with an overview of the use of DWI in clinical routine. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 3.
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Doenças da Medula Óssea , Sistema Musculoesquelético , Fraturas da Coluna Vertebral , Criança , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Sistema Musculoesquelético/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fraturas da Coluna Vertebral/patologiaRESUMO
Acute respiratory infection is the third most frequent cause of mortality worldwide, causing over 4.25 million deaths annually. Although most diagnosed acute respiratory infections are thought to be of viral origin, the aetiology often remains unclear. The advent of next-generation sequencing (NGS) has revolutionised the field of virus discovery and identification, particularly in the detection of unknown respiratory viruses. We systematically reviewed the application of NGS technologies for detecting respiratory viruses from clinical samples and outline potential barriers to the routine clinical introduction of NGS. The five databases searched for studies published in English from 01 January 2010 to 01 February 2021, which led to the inclusion of 52 studies. A total of 14 different models of NGS platforms were summarised from included studies. Among these models, second-generation sequencing platforms (e.g., Illumina sequencers) were used in the majority of studies (41/52, 79%). Moreover, NGS platforms have proven successful in detecting a variety of respiratory viruses, including influenza A/B viruses (9/52, 17%), SARS-CoV-2 (21/52, 40%), parainfluenza virus (3/52, 6%), respiratory syncytial virus (1/52, 2%), human metapneumovirus (2/52, 4%), or a viral panel including other respiratory viruses (16/52, 31%). The review of NGS technologies used in previous studies indicates the advantages of NGS technologies in novel virus detection, virus typing, mutation identification, and infection cluster assessment. Although there remain some technical and ethical challenges associated with NGS use in clinical laboratories, NGS is a promising future tool to improve understanding of respiratory viruses and provide a more accurate diagnosis with simultaneous virus characterisation.
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COVID-19 , Vírus da Influenza A , Infecções Respiratórias , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Vírus da Influenza B , Infecções Respiratórias/diagnóstico , SARS-CoV-2RESUMO
Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However CAR T-cell therapy of R/R T-ALL has unique challenges, such as the lack of specific tumor antigens, cell fratricide and T cell aplasia, in comparison with that of R/R B-ALL. Despite promising therapeutic outcomes in R/R B-ALL, application of this therapy is limited by high relapse rates and immunological toxicities. Recent studies suggest patients who underwent allogeneic hematopoietic stem cell transplantation post-CAR T-cell therapy would achieve durable remission and better survival, but this remains controversial. Herein, I briefly review published data on the clinical use of CAR T-cells in treating ALL.
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Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Imunoterapia Adotiva , Linfócitos T/patologia , Antígenos de Neoplasias , Doença AgudaRESUMO
BACKGROUND: Immune cell dysfunction is a central part of immune paralysis in sepsis. Granulocyte concentrate (GC) transfusions can induce tissue damage via local effects of neutrophils. The hypothesis of an extracorporeal plasma treatment with granulocytes is to show beneficial effects with fewer side effects. Clinical trials with standard GC have supported this approach. This ex vivo study investigated the functional properties of purified granulocyte preparations during the extracorporeal plasma treatment. METHODS: Purified GC were stored for up to 3 days and compared with standard GC in an immune cell perfusion therapy model. The therapy consists of a plasma separation device and an extracorporeal circuit. Plasma is perfused through the tubing system with donor immune cells of the GC, and only the treated plasma is filtered for re-transfusion. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Efficacy of granulocytes regarding phagocytosis, oxidative burst as well as cell viability and metabolic parameters were assessed. RESULTS: In pGC, the metabolic surrogate parameters of cell functionality showed comparable courses even after a storage period of 72 h. In particular, glucose and oxygen consumption were lower after extended storage. The course of lactate dehydrogenase concentration yields no indication of cell impairment in the extracorporeal circulation. The cells were viable throughout the entire study period and exhibited preserved phagocytosis and oxidative burst functionality. CONCLUSION: The granulocytes demonstrated full functionality in the 6 h extracorporeal circuits after 3 days storage and in septic shock plasma. This is demonstrating the functionality of the system and encourages further clinical studies.
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Sepse , Choque Séptico , Humanos , Granulócitos/metabolismo , Neutrófilos , Sepse/terapia , Transfusão de Sangue , Circulação ExtracorpóreaRESUMO
Potency can be described as the quantitative measure of biological activity, that is, the ability of an Advanced Therapy Medicinal Product (ATMP) to elicit the intended effect necessary for clinical efficacy. Potency testing is part of the quality control strategy necessary for batch release and is required for market approval application of an ATMP. Thus, it is crucial to develop a reliable and accurate potency assay. As a prerequisite for potency assay development, it is essential to define the mode of action of the product and thereby also the relevant biological activity that should be measured. The establishment of a potency assay should be initiated already during early product development followed by its progressive implementation into an ATMP's manufacturing, quality control and release process. Potency testing is indispensable for clinical use with a wide range of applications. A potency assay is a valuable tool to determine the product's stability, detect the impact of changes in the manufacturing process on the product, demonstrate quality and manufacturing consistency from batch to batch, estimate clinical efficacy and define the effective dose. This chapter describes the requirements and challenges to be considered for potency assay development and the importance of a well-established potency assay for clinical use.
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Controle de Qualidade , Resultado do TratamentoRESUMO
BACKGROUND: The SII (systemic immune-inflammation index) has been extensively reported to have a prognostic value in prostate cancer (PCa), despite the unconformable results. The purpose of this meta-analysis is to quantify the effect of pretreatment SII on survival outcomes in patients with PCa. METHODS: The following databases were searched: Web of Science, Cochrane Library, PubMed, Embase, and China National Knowledge Infrastructure (CNKI). For exploration of the SII's correlations with the overall survival (OS) and the progression-free survival/biochemical recurrence-free survival (PFS/bRFS) in PCa, the pooled hazard ratios (HRs) were assessed within 95% confidence intervals (CIs). RESULTS: The present meta-analysis covered 10 studies with 8133 patients. Among the PCa population, a high SII was linked significantly to poor OS (HR = 2.63, 95% CI = 1.87-3.70, p < 0.001), and worse PFS/bRFS (HR = 2.49, 95% CI = 1.30-4.77, p = 0.006). However, a high SII was not linked significantly to T stage (OR = 1.69, 95% CI = 0.86-3.33, p = 0.128), the metastasis to lymph node (OR = 1.69, 95% CI = 0.69-4.16, p = 0.251), age (OR = 1.41, 95% CI = 0.88-2.23, p = 0.150), or the Gleason score (OR = 1.32, 95% CI = 0.88-1.96, p = 0.178). CONCLUSIONS: For the PCa sufferers, the SII might be a promising prognostic biomarker, which is applicable to the high-risk subgroup identification, and provide personalized therapeutic strategies.
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Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/patologia , Modelos de Riscos Proporcionais , Inflamação , Intervalo Livre de ProgressãoRESUMO
OBJECTIVES: To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. METHODS: Amniotic fluid was collected by laparotomy - a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. RESULTS: Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. CONCLUSIONS: The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe.
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Líquido Amniótico , Células-Tronco , Gravidez , Feminino , Humanos , Células Cultivadas , Diferenciação CelularRESUMO
Glycyrrhizae Radix et Rhizoma is a well-known herbal medicine with a wide range of pharmacological functions that has been used throughout Chinese history. This review presents a comprehensive introduction to this herb and its classical prescriptions. The article discusses the resources and distribution of species, methods of authentication and determination chemical composition, quality control of the original plants and herbal medicines, dosages use, common classical prescriptions, indications, and relevant mechanisms of the active content. Pharmacokinetic parameters, toxicity tests, clinical trials, and patent applications are discussed. The review will provide a good starting point for the research and development of classical prescriptions to develop herbal medicines for clinical use.
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Medicamentos de Ervas Chinesas , Plantas Medicinais , Medicina Tradicional Chinesa , Medicina Herbária , Medicamentos de Ervas Chinesas/uso terapêutico , PrescriçõesRESUMO
Environmental biophysical interactions are recognized to play an essential part in the human biological processes associated with trauma recovery. Many studies over several decades have furthered our understanding of the effects that Pulsed Electromagnetic Fields (PEMF) have on the human body, as well as on cellular and biophysical systems. These investigations have been driven by the observed positive clinical effects of this non-invasive treatment on patients, mainly in orthopedics. Unfortunately, the diversity of the various study setups, with regard to physical parameters, molecular and cellular response, and clinical outcomes, has made it difficult to interpret and evaluate commonalities, which could, in turn, lead to finding an underlying mechanistic understanding of this treatment modality. In this review, we give a birds-eye view of the vast landscape of studies that have been published on PEMF, presenting the reader with a scaffolded summary of relevant literature starting from categorical literature reviews down to individual studies for future research studies and clinical use. We also highlight discrepancies within the many diverse study setups to find common reporting parameters that can lead to a better universal understanding of PEMF effects.
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Campos Eletromagnéticos , Magnetoterapia , HumanosRESUMO
Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.
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COVID-19 , Influenza Humana , Humanos , Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Pandemias , Zanamivir/efeitos adversosRESUMO
BACKGROUND: Despite the increasing adoption rate of tracking technologies in hospitals in the United States, few empirical studies have examined the factors involved in such adoption within different use contexts (eg, clinical and supply chain use contexts). To date, no study has systematically examined how governance structures impact technology adoption in different use contexts in hospitals. Given that the hospital governance structure fundamentally governs health care workflows and operations, understanding its critical role provides a solid foundation from which to explore factors involved in the adoption of tracking technologies in hospitals. OBJECTIVE: This study aims to compare critical factors associated with the adoption of tracking technologies for clinical and supply chain uses and examine how governance structure types affect the adoption of tracking technologies in hospitals. METHODS: This study was conducted based on a comprehensive and longitudinal national census data set comprising 3623 unique hospitals across 50 states in the United States from 2012 to 2015. Using mixed effects population logistic regression models to account for the effects within and between hospitals, we captured and examined the effects of hospital characteristics, locations, and governance structure on adjustments to the innate development of tracking technology over time. RESULTS: From 2012 to 2015, we discovered that the proportion of hospitals in which tracking technologies were fully implemented for clinical use increased from 36.34% (782/2152) to 54.63% (1316/2409), and that for supply chain use increased from 28.58% (615/2152) to 41.3% (995/2409). We also discovered that adoption factors impact the clinical and supply chain use contexts differently. In the clinical use context, compared with hospitals located in urban areas, hospitals in rural areas (odds ratio [OR] 0.68, 95% CI 0.56-0.80) are less likely to fully adopt tracking technologies. In the context of supply chain use, the type of governance structure influences tracking technology adoption. Compared with hospitals not affiliated with a health system, implementation rates increased as hospitals affiliated with a more centralized health system-1.9-fold increase (OR 1.87, 95% CI 1.60-2.13) for decentralized or independent hospitals, 2.4-fold increase (OR 2.40, 95% CI 2.07-2.80) for moderately centralized health systems, and 3.1-fold increase for centralized health systems (OR 3.07, 95% CI 2.67-3.53). CONCLUSIONS: As the first of such type of studies, we provided a longitudinal overview of how hospital characteristics and governance structure jointly affect adoption rates of tracking technology in both clinical and supply chain use contexts, which is essential for developing intelligent infrastructure for smart hospital systems. This study informs researchers, health care providers, and policy makers that hospital characteristics, locations, and governance structures have different impacts on the adoption of tracking technologies for clinical and supply chain use and on health resource disparities among hospitals of different sizes, locations, and governance structures.
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Atenção à Saúde , Hospitais , Humanos , Estudos Longitudinais , Tecnologia , Estados UnidosRESUMO
The pandemic spread of an infectious disease poses a plethora of challenges to society, clinicians, health care providers and regulating authorities. In order to mount a rapid response and to provide hope in a potentially catastrophic situation as the current COVID-19 pandemic, emergency plans, regulations and funding strategies have to be developed on regional, national and international levels. The speed needed to establish rapid response programs is challenged by the dynamics of the spread of the disease, the concurrent and competing development of different and potentially more effective treatment options, and not the least by regulatory uncertainty. Convalescent plasma, that is plasma collected from patients who have recovered from COVID-19 infections, has emerged as one of the first potential treatment options in the absence of drugs or vaccines with proven efficacy against SARS-CoV-2. The societal aspects of convalescent plasma and the public awareness gave an additional boost to the rapid employment of convalescent plasma donation platforms immediately after the SARS-CoV-2 outbreak. At the same time, uncertainty remains as to the efficacy of convalescent plasma. With evidence mostly limited to empirical reports, convalescent plasma has been used for decades for the prophylaxis and treatment of various infectious diseases. Clinical trials have addressed different infectious agents, stages of disease, target groups of patients and yielded sometimes inconclusive results. The aim of this short review is to delineate the regulatory background for the emergency use of convalescent plasma in the USA, in the European Union and in Germany, and the transition to the setting of clinical trials. In addition, we describe observations made in the process of collecting COVID-19 convalescent plasma (herein referred to as CCP), and formulate proposals to further improve the framework for rapid responses in future emergency situations.
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OBJECTIVE: To identify challenges to the use of Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in the ambulatory pediatric setting and possible solutions to these challenges. STUDY DESIGN: Eighteen semistructured telephone interviews of health system leaders, measurement implementers, and ambulatory pediatric clinicians were conducted. Five coders used applied thematic analysis to iteratively identify and refine themes in interview data. RESULTS: Most interviewees had roles in leadership or the implementation of patient-centered outcomes; 39% were clinicians. Some had experience using PROMIS clinically (44%) and 6% were considering this use. Analyses yielded 6 themes: (1) selection of PROMIS measures, (2) method of administration, (3) use of PROMIS Parent Proxy measures, (4) privacy and confidentiality of PROMIS responses, (5) interpretation of PROMIS scores, and (6) using PROMIS scores clinically. Within the themes, interviewees illuminated specific unique considerations for using PROMIS with children, including care transitions and privacy. CONCLUSIONS: Real-world challenges continue to hamper PROMIS use. Ongoing efforts to disseminate information about the integration of PROMIS measures in clinical care is critical to impacting the health of children.
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Instituições de Assistência Ambulatorial , Sistemas de Informação , Medidas de Resultados Relatados pelo Paciente , Pediatria/normas , Criança , HumanosRESUMO
The International Society for Cell & Gene Therapy mesenchymal stromal cell (MSC) committee has been an interested observer of community interests in all matters related to MSC identity, mechanism of action, potency assessment and etymology, and it has regularly contributed to this conversation through a series of MSC pre-conferences and committee publications dealing with these matters. Arising from these reflections, the authors propose that an overlooked and potentially disruptive perspective is the impact of in vivo persistence on potency that is not predicted by surrogate cellular potency assays performed in vitro and how this translates to in vivo outcomes. Systemic delivery or extravascular implantation at sites removed from the affected organ system seems to be adequate in affecting clinical outcomes in many pre-clinical murine models of acute tissue injury and inflammatory pathology, including the recent European Medicines Agency-approved use of MSCs in Crohn-related fistular disease. The authors further propose that MSC viability and metabolic fitness likely dominate as a potency quality attribute, especially in recipients poised for salutary benefits as defined by emerging predictive biomarkers of response.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Terapia Baseada em Transplante de Células e Tecidos , Terapia Genética , CamundongosRESUMO
Bacterial vaginosis (BV) is a common disease among women of reproductive age, with a serious impact on their daily life and health. At present, the most common treatment for BV is to take antibiotics, which results in good short-term treatment effects, but poor long-term effects. Traditional Chinese medicine (TCM) has been used to treat BV for over a millennium, with little risk of triggering drug resistance and adverse effects. Based on syndrome differentiation, there are three oral TCM treatment strategies for BV, including invigorating spleen, clearing dampness and heat, and nourishing kidney. The oral TCM prescriptions, such as Yi Huang decoction, Longdan Xiegan decoction, Zhibai Dihaung decoction, and so on are commonly used. Topical TCM treatment is also popular in China. According to the research results of pharmacological effects of active TCM ingredients, the most potential mechanisms of TCM for BV treatment are immune-enhancement effects, antibacterial activity, and estrogen-liked effects. Nonetheless, the multi-constituent of herbs may result in possible disadvantages to BV treatment, and the pharmacological mechanisms of TCM need further study. Here, we provide an overview of TCM compounds and their preparations used for BV, based on the pathogenesis and the potential therapeutic mechanisms, therefore providing a reference for further studies.
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Medicamentos de Ervas Chinesas , Vaginose Bacteriana , China , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Medicina Tradicional Chinesa , Vaginose Bacteriana/tratamento farmacológicoRESUMO
Combined with the clinical use condition of MR in use in Shanghai Sixth People's Hospital, MR components are divided into scanning type I and scanning type II. At the same time, combined with the main loss force of MR components, the research divides MR components into dynamic components and electric thermal components. In this study, a complete set of MR system reliability indexes and implementation methods are given, including system reliability index determination, system reliability allocation, component reliability index realization, system reliability prediction and system reliability verification. At the same time, this study also gives the methods of reliability prediction and reliability verification, and gives the MTBF calculation method of MR system based on clinical use data statistics.
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Imageamento por Ressonância Magnética , China , Humanos , Espectroscopia de Ressonância Magnética , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: The aim of this study is to propose and evaluate a new method of volumetric perfusion computed tomography (PCT) incorporated into pancreatic multiphasic contrast enhanced (CE)-CT in the clinical setting. METHODS: In this ethically approved study, PCT was incorporated into our existing scanning protocol in 17 patients and effective doses related to PCT were evaluated. CT values and signal-to-noise ratio (SNR) of anatomical structure were compared in diagnostic images that were acquired using 320-detector volumetric scan mode and 64-detector helical scan mode. In addition, focal lesion depiction was qualitatively assessed in the two groups. Perfusion parameters in normal pancreas were measured by two radiologists and the interobserver-reliability was assessed. RESULTS: The effective dose of PCT was 5.1 ± 0.3 mSv. The actual effective dose (AED) including the dose used in volumetric scans for diagnostic imaging was 22.8 ± 5.3 mSv and the putative effective dose (PED) was 21.9 ± 9.1 mSv on average. There was no significant difference between AED and PED (p = 0.404). Compared with conventional helical scans, volumetric scans did not decrease CT values or SNR, but rather significantly increased those of the aorta in the arterial phase. Both groups had acceptable qualitatively assessed image quality with no significant difference in the depiction of each structure. There was almost perfect interobserver agreement in the measurement of perfusion parameters (mean ICCs > 0.9). CONCLUSIONS: Our scanning protocol for pancreatic perfusion CT provides high-quality images while requiring lower radiation doses than conventional methods.
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Meios de Contraste , Pâncreas/diagnóstico por imagem , Imagem de Perfusão/métodos , Lesões por Radiação/prevenção & controle , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Neoplasias Pancreáticas/diagnóstico por imagem , Doses de Radiação , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
Rhizoma Picrorhizae (RP) is a traditional Chinese medicine, which has always been used to treat many diseases like infantile epilepsy and malnutrition. In modern applications, it has been used to treat hepatitis B and various liver injuries with remarkable curative effects. So far, more than 90 chemical components have been reported in RP, mainly including iridoid glycosides, cucurbitacins, phenylethanoid glycosides, and phenolic glycosides. Among these, iridoid glycosides are the most important active ingredients, and about 30 such compounds have been isolated at present. In pharmacology, RP is beneficial to the choleresis, liver protection, anti-inflammation, asthma relief, immune regulation, and protection of heart, brain, kidney, and other organs. There have been many investigations on this medicinal herb in recent years, and it has attracted much attention in the medicine domain. In this paper, through systematically consulting the relevant books and electronic databases, we analyzed, arranged, and summarized the available information on this herb to provide reference for its further research.
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Medicina Tradicional Chinesa/métodos , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , Animais , Humanos , Extratos Vegetais/farmacologiaRESUMO
Antibiotic resistance has become the most significant threat to human health across the globe. Polymyxins are often used as the only available therapeutic option against Gram-negative 'superbugs', namely Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The limited pharmacological and clinical knowledge on the polymyxins in the old literature substantially limited optimizing their clinical use. The current chapter provides a general introduction to this first-ever polymyxin book which comprehensively reviews the significant progress over the last two decades in the chemistry, microbiology, pharmacology, clinical use and drug discovery of polymyxins. In particular, recent pharmacological results have led to the first scientifically-based dosing recommendations and facilitated the discovery of new-generation polymyxins. Future challenges in polymyxin research are highlighted, aiming at improving the clinical utility of this last-line defence.
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Antibacterianos/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Polimixinas/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Humanos , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
: Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s and recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies.