scholarly journals The Smart Solution for DNA Removal in Biopharmaceutical Production by Benzonase Endonuclease

2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Zhu Yang ◽  
Mingxin Li ◽  
Wen Chen ◽  
Alexander Peters
Keyword(s):  
Mammalian Cells ◽  
Rna World ◽  
Rapid Development ◽  
World Health ◽  
Base Pairs ◽  
Biological Products ◽  
Continuous Cell Lines ◽  
Dna And Rna ◽  
Biomedical Technologies ◽  
Health Organization

<p>More and more mammalian cells especially continuous cell lines were used to produce vaccines and therapeutic biological products with the rapid development of biomedical technologies. Therefore, more attention should be paid from drug regulatory authorities to the safety of biological products especially quality control of residual DNA and RNA. World Health Organization has evaluated the methods commonly used in vaccine manufacture for their ability to reduce the biological activity of DNA. Benzonase endonuclease is frequently used during the production of vaccines and can degrade all nucleic acid sequences down to oligonucleotides of approximately 3 to 5 base pairs.</p>

Effects of chloroquine on Plasmodium knowlesi in vitro

Parasitology ◽  
1972 ◽  
Vol 64 (1) ◽  
pp. 37-45 ◽  
Author(s):  
W. E. Gutteridge ◽  
P. I. Trigg ◽  
P. M. Bayley
Keyword(s):  
Mammalian Cells ◽  
Thermal Denaturation ◽  
Technical Assistance ◽  
Plasmodium Knowlesi ◽  
Fluorescence Emission ◽  
World Health ◽  
Isosbestic Point ◽  
Dna And Rna ◽  
Health Organization

The binding of chloroquine to DNA isolated from P. knowlesi has been investigated. In the presence of increasing concentrations of malarial DNA, the absorption spectrum of chloroquine exhibited strong hypochromism in the range 325–350 nm, small red shifts of the absorption maxima and an isosbestic point at 300 nm. The fluorescence emission of the drug at 380 nm (excitation 330 nm) was quenched five-fold by malarial DNA. Chloroquine itself protected malarial DNA from thermal denaturation. These data are consistent with binding of the drug to malarial DNA as has been suggested from studies with DNA from bacteria and mammalian cells. The binding affinity for malarial DNA is of the same order as that for mammalian DNA.The effect of chloroquine on the metabolism of P. knowlesi in culture was also investigated. There was a direct correlation between concentrations of drug which affect the morphology of parasites and those which affect markedly the incorporation of 3H-adenosine into DNA and RNA, 14C-isoleucine incorporation into protein and the formation of lactate as a result of respiration. However, all processes were inhibited to the same extent, indicating that binding to DNA is not the only action of the drug.The mode of action of chloroquine and the question of resistance to it are discussed.One of us (P. I. T.) received financial assistance from the World Health Organization. We thank Dr F. Hawking and Dr J. Williamson for many helpful discussions, Dr K. N. Brown for reading through the manuscript, and Miss Jane Dunnett, Mrs A. C. Gutteridge and Mr T. Scott-Finnigan for skilled technical assistance.

scholarly journals Strengths and weaknesses of the Brazilian regulation on biosimilars: A critical view of the regulatory requirements for biosimilars in Brazil

2018 ◽  
Vol 10 (12) ◽  
pp. 253-259 ◽  
Author(s):  
Marcos Renato de Assis ◽  
Valdair Pinto
Keyword(s):  
Conflicts Of Interest ◽  
Expression System ◽  
World Health ◽  
Regulatory Requirements ◽  
Biological Products ◽  
Synthetic Drugs ◽  
Comparability Exercise ◽  
The Face ◽  
The Usa ◽  
Health Organization

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

scholarly journals Relative Abundance of SARS-CoV-2 Entry Genes in the Enterocytes of the Lower Gastrointestinal Tract

2020 ◽  
Author(s):  
Jaewon J. Lee ◽  
Scott Kopetz ◽  
Eduardo Vilar ◽  
John Paul Shen ◽  
Ken Chen ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
Mammalian Cells ◽  
World Health ◽  
Lower Gastrointestinal Tract ◽  
Gi Tract ◽  
Single Cell Rna Sequencing ◽  
The World ◽  
Health Organization ◽  
Different Parts

COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world and was declared a pandemic by the World Health Organization, thus leading to a rapid surge in the efforts to understand the mechanisms of transmission, methods of prevention, and potential therapies. While COVID-19 frequently manifests as a respiratory infection,1 there is evidence for infection of the gastrointestinal (GI) tract1–4 with documented viral RNA shedding in the stool of infected patients.2,4 In this study, we aimed to investigate the expression of ACE2 and TMPRSS2, which are required for SARS-CoV-2 entry into mammalian cells,5 from single-cell RNA sequencing (scRNA-seq) datasets of five different parts of the GI tract: esophagus, stomach, pancreas, small intestine, and colon/rectum.

Overview of non-innovator biological products in India

2020 ◽  
Vol 9 (1) ◽  
pp. 30-36 ◽  
Author(s):  
G R Soni
Keyword(s):  
Patent Protection ◽  
Recombinant Dna ◽  
Regulatory System ◽  
Poor Quality ◽  
New Drugs ◽  
World Health ◽  
Clinical Tests ◽  
Regulatory Requirements ◽  
Biological Products ◽  
Health Organization

As per regulatory requirements, biosimilar drugs must show high similarity to their reference product in quality, preclinical and clinical tests. It is by these means that biosimilars are considered to be safe and efficacious. In India, any major deviation(s) from science-based principles in the manufacturing of a recombinant DNA-derived therapeutic biological product leads to its classification as a ‘non-innovator’ biological, which are approved as ‘New Drugs’. According to the World Health Organization (WHO), these biological products have uncertain safety and efficacy when compared to the reference biological and are therefore not recommended for use. However, these so-called non-innovator biological products continue to be developed in India, for reasons including brief and poorly implemented guidelines on biologicals, a lack of expertise on biosimilars amongst drug regulatory committees, lack of coordination among government departments working on biosimilars, poor quality accreditation in testing laboratories, and a lack of patent protection for innovator drugs. There is an urgent need to identify deficiencies in the ministries responsible for biosimilars in India, which could be through a scientific audit. Compliance with such an audit could strengthen the Indian regulatory system and thus increase the provision of affordable, high quality biosimilars in India.

scholarly journals Capsaicin inhibits arginine kinase and exerts anti-Trypanosoma cruzi activity

2020 ◽  
Author(s):  
Edward A. Valera-Vera ◽  
Chantal Reigada ◽  
Melisa Sayé ◽  
Fabio A. Digirolamo ◽  
Mariana R. Miranda ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Stress Responses ◽  
Mammalian Cells ◽  
Arginine Kinase ◽  
Chronic Phase ◽  
New Drugs ◽  
World Health ◽  
Neglected Diseases ◽  
Health Organization

ABSTRACTTrypanosoma cruzi is the causative agent of Chagas disease, considered within the list of twenty neglected diseases according to the World Health Organization. There are only two therapeutic drugs for Chagas disease, both of them unsuitable for the chronic phase, therefore the development of new drugs is a priority.T. cruzi arginine kinase (TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previous study from our laboratory, possible TcAK inhibitors were identified through computer simulations, resulting in the best-scoring compounds cyanidin derivatives and capsaicin. Considering these results, in this work we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Although capsaicin produced a weak inhibition on the recombinant TcAK activity (IC50 ≈ 800 µM), it had a strong trypanocidal effect on epimastigotes and trypomastigotes (IC50 = 6.26 µM and 0.26 µM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Epimastigotes that overexpress TcAK were 37% more resistant to capsaicin than wild type parasites, suggesting that trypanocidal activity could be due, in part, to the enzyme inhibition. However, the difference between the concentrations at which the enzyme is inhibited and the parasite death is caused implies the presence of other targets. In this sense, the prohibitin-2 and calmodulin were identified as other possible capsaicin targets. Capsaicin is a strong and selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower than benznidazole, the drug currently used for treating Chagas disease.

scholarly journals Standardization of DNA Residual Quantification Method of Vero Cell Rabies Vaccine for Human Use

2017 ◽  
Vol 11 (1) ◽  
pp. 66-80 ◽  
Author(s):  
Janeth del Carmen Arias Palacios ◽  
Carlos Alberto Barrero Barreto ◽  
José Salvador Montaña Lara ◽  
Ángela María Londoño Navas
Keyword(s):  
Real Time ◽  
Repetitive Sequences ◽  
Housekeeping Gene ◽  
Vero Cells ◽  
Rabies Vaccine ◽  
World Health ◽  
Continuous Cell Lines ◽  
Highly Repetitive Dna ◽  
Standard Set ◽  
Health Organization

Objectives: Normalize the quantification of residual DNA from Vero cells in the rabies vaccine for use in human VAHV I, by quantitative PCR in real time and the design of primers that amplified, highly repetitive sequences of Cercopithecus aethiops and a constitutive gene according to sequences reported in the GenBank and quantifying the residual DNA in the vaccine VAHV I in three consecutive batches according to the standard set by the World Health Organization. Methods: A real time quantitative method based on SYBR Green chemistry has been applied for the quantification of residual DNA (resDNA) using highly repetitive DNA (Alu) and a housekeeping gene (B-actin) as target sequences. Results: The sensitivity achieved with this white sequence is within the reported limits and who are between 5 and 50 pg. For real time PCR optimization with Alu-p53, different concentrations of MgCl2 (0.5, 0.75, 1.0, 1.25 and 1.5 mm) in combination with three different concentrations of primers (75, 100 and 150nM) were used. pDNA in concentration of 1x107 copies / ul was used as template. Optimal concentrations were 1.25 mM MgCl2 and 100nM primers. To level of detection of 1.53 ng/ul was found for p53-Alu and Alu-Glob and 0.39 ng/ul for B-actin with gDNA curves. Conclusion: Quantification of resDNA of vaccine VAHV I with close-ups of B-actin was normalized. Reached a sensitivity of 30 pg of resDNA/dose VAHV I, with close-ups of B-actin. Found, in three consecutive batches, an amount less than 10 ng/dose, these results suggest that the production process ensures vaccine resDNA removal, meeting international requirements for biological products for use in humans that use continuous cell lines for production.

scholarly journals Emerging infectious diseases: A proactive approach

2017 ◽  
Vol 114 (16) ◽  
pp. 4055-4059 ◽  
Author(s):  
David E. Bloom ◽  
Steven Black ◽  
Rino Rappuoli
Keyword(s):  
Infectious Diseases ◽  
New Technologies ◽  
Population Aging ◽  
Rapid Development ◽  
Emerging Infectious Diseases ◽  
Point Of View ◽  
Leadership Role ◽  
World Health ◽  
Regulatory Processes ◽  
Health Organization

Infectious diseases are now emerging or reemerging almost every year. This trend will continue because a number of factors, including the increased global population, aging, travel, urbanization, and climate change, favor the emergence, evolution, and spread of new pathogens. The approach used so far for emerging infectious diseases (EIDs) does not work from the technical point of view, and it is not sustainable. However, the advent of platform technologies offers vaccine manufacturers an opportunity to develop new vaccines faster and to reduce the investment to build manufacturing facilities, in addition to allowing for the possible streamlining of regulatory processes. The new technologies also make possible the rapid development of human monoclonal antibodies that could become a potent immediate response to an emergency. So far, several proposals to approach EIDs have been made independently by scientists, the private sector, national governments, and international organizations such as the World Health Organization (WHO). While each of them has merit, there is a need for a global governance that is capable of taking a strong leadership role and making it attractive to all partners to come to the same table and to coordinate the global approach.

scholarly journals Rare and unknown canine systemic mastocytosis: clinical and laboratory features of an aberrant c-Kit mutation neoplasia

2021 ◽  
Vol 58 ◽  
pp. e175896
Author(s):  
Carla Sofia Soares ◽  
Leonor Delgado ◽  
Sónia Morgado ◽  
Pedro Pires Carvalho ◽  
Luís Carlos Barros
Keyword(s):  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasms ◽  
World Health ◽  
Base Pairs ◽  
Kit Mutation ◽  
Laboratory Features ◽  
Exon 11 ◽  
Serra Da Estrela ◽  
Health Organization ◽  
Reported Data

Systemic mastocytosis (SM) pathology is extremely rare in canine practice, with insufficient reported data. The knowledge of the clinical behavior of this pathology is scarce. In human medicine, SM has been widely investigated, being defined as a rare hematopoietic disorder by the World Health Organization (2016), within the type of myeloproliferative neoplasms. Herein, we describe a systemic mastocytosis case in a Portuguese Serra-da-Estrela dog, where a cutaneous grade III/high-grade MCT was also diagnosed. The clinical decline of the animal and owner’s insistence throughout anamnesis that the dog was markedly different after the cytologic exam performed in another clinic, along with both severe eosinophilia and hepatomegaly, led to the clinical suspicion of SM. The animal passed away 7 days later. Post-mortem investigation confirmed SM pathology, and a deletion of 15 base pairs change on c-Kit gene exon 11 was identified. Contemplating the low number of cases described in the literature, this publication aims to disclose clinical and laboratory features of rare and poorly described canine SM, taking into consideration human outcomes described in the literature.

Research in Integrated Health Care and Publication Trends from the Perspective of Global Informatics

2019 ◽  
Vol 82 (12) ◽  
pp. 1018-1030
Author(s):  
Zhong Li ◽  
Liang Zhang ◽  
Zijin Pan ◽  
Yan Zhang
Keyword(s):  
Health Care ◽  
Integrated Care ◽  
Rapid Development ◽  
Economic Incentive ◽  
The United States ◽  
World Health ◽  
Scientometric Analysis ◽  
Performance Measurements ◽  
Publication Number ◽  
Health Organization

Abstract Background Integrated care has gained popularity in recent decades and is advocated by the World Health Organization. This study examined the global progress, current foci, and the future of integrated care. Methods We conducted a scientometric analysis of data exported from the Web of Science database. Publication number and citations, co-authorship between countries and institutions and cluster analysis were calculated and clustered using Histcite12.03.07 and VOS viewer1.6.4. Results We retrieved 6127 articles from 1997 to 2016. We found the following. (1) The United States, United Kingdom, and Canada had the most publications, citations, and productive institutions. (2) The top 10 cited papers and journals were crucial for knowledge distribution. (3) The 50 author keywords were clustered into 6 groups: digital medicine and e-health, community health and chronic disease management, primary health care and mental health, healthcare system for infectious diseases, healthcare reform and qualitative research, and social care and health policy services. Conclusions This paper confirmed that integrated care is undergoing rapid development: more categories are involved and collaborative networks are being established. Various research foci have formed, such as economic incentive mechanisms for integration, e-health data mining, and quantitative studies. There is an urgent need to develop performance measurements for policies and models.

scholarly journals Regulatory outlook from concept to commercialization of Biosimilars in Brazil market

2020 ◽  
Vol 8 (2) ◽  
pp. 67-74
Author(s):  
Raj Shekhar ◽  
P Muralidharan ◽  
Namrata Hallur ◽  
Sangamesh B Puranik
Keyword(s):  
Reference Product ◽  
Expression System ◽  
Living Organism ◽  
World Health ◽  
Biological Products ◽  
Synthetic Drugs ◽  
Choice Of Treatment ◽  
Comparability Exercise ◽  
Health Organization ◽  
Market Valuations

Biological products or biopharmaceuticals are medicinal products derived from living organism systems and manufactured by using modern biotechnology that differ widely from the conventional synthetic drugs. They are much larger and more complex molecules with inherent diversity; hence, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilars endeavor to copy the original technology leading to the production of innovative biotechnological medicines to obtain a product which is similar to the reference product. These products reported to improve the treatment landscape for multiple diseases, particularly in the areas of oncology, blood disorders, rheumatology, endocrinology and are becoming choice of treatment regimen due to policy push by governments for it’s affordability without comprising on quality, safety and efficacy. Pharmaceutical exports from Brazil increased by around 41% between 2009 and 2013, touching a high of U.S. $1.516 billion. The valuation of Brazilian pharma markets has shown double digit growth in the past decade. Between 2012 and 2015, market valuations have increased from U.S. $25.2 billion to U.S. $35.3 billion. Biosimilarity is based on a comprehensive comparability exercise wherein unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency shadows the key principles established by the World Health Organization for the assessment of biosimilarity. However, the regulations also widen the gap by having standalone application pathway that does not require the usual comparability exercise with the reference product, originating non-biosimilar copies. Interchangeability and the use of nonproprietary names are not regulated. The objective of this manuscript is to explore the Brazilian Regulatory outlook from concept to commercialization of Biosimilars.  

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