Drug development

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  • Proteins are the driving force for all cellular processes. They regulate several cellular events through binding to different partners in the cell. They are capable of binding to other proteins, peptides, DNA, and also RNA. These interactions are essential in the regulation of cell fates and could be important in drugs development. For example RNA interacting proteins regulate gene expression through the binding to different mRNAs. These mRNAs could be involved in important cellular processes such as cell survival or apoptosis.

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  • Despite massive efforts in drug discovery fueled by combinatory chemistry, recombinant DNA technology, and highthroughput screening, surprisingly few molecules make it through the drug development process. While the reasons are debated, it is certain that many new chemical entities (NCEs) suffer from recurring problems that hinder development— low water solubility, instability, or inadequate pharmacokinetics. An estimated 43% of NCEs are poorly water-soluble.

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  • This book "New Insights into Toxicity and Drug Testing" covers all emerging technologies (profiling technologies, 3D cultures, next generation sequencing etc.), available methods and models to evaluate candidate drugs and medicinal plants with reference to toxicity, drug testing and development. This book is an original contribution of experts from different parts of the globe and the in-depth information will be a significant resource for scientists and physicians who are directly dealing with drugs / medicines and human life....

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  • Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Equipoise, design bias, and randomized controlled trials: the elusive ethics of new drug development...

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  • The discovery of efficacious new human therapeutic agents is one of humanity’s most vital tasks. It is an enormously demanding activity that requires creativity, a vast range of scientific knowledge, and great persistence. It is also an exceedingly expensive activity. In an ideal world, no education would be complete without some exposure to the ways in which new medicines are discovered and developed. For those young people interested in science or medicine, such knowledge is arguably mandatory....

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  • The primary focus of this chapter in on general approaches and considerations toward development of high-performance liquid chromatography (HPLC) methods for separation of pharmaceutical compounds, which may be applied within the various functions in the drug development continuum. It is very important to understand the aim of analysis and the requirements for a particular method to be developed. The aim of analysis of each HPLC method may vary for each developmental area in the drug development process and specific examples are given in Section 8.2.

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  • Introduction: Forensic autopsy is an important task for proving crimes medically; unfortunately, every department of legal medicine of Japanese universities is suffering from insufficient staffs and budget. About 30 years ago, one of the authors started the analysis of drugs and poisons at the Department of Legal Medicine, Hiroshima University School of Medicine. At that time, the author did not have much knowledge about poison analysis; but it is a good memory that many good friends of toxicological societies gave the author many useful suggestions on analytical methods.

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  • Preclinical drug development. Discovery of new drugs in the laboratory is an exercise in prediction • Techniques of discovery. Sophisticated molecular modelling allows precise design of potential new therapeutic substances and new technologies have increased the rate of development of potential medicines. Studies in animals and in humans Prediction. Failures of prediction occur and a drug may be abandoned at any stage, including after marketing. New drug development is a colossally expensive and commercially driven activity. ...

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  • Introduction: An organophosphorus nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate, Figure 2.1) shows potent inhibitory action on acetylcholinesterase; its development, production, stockpiling and use are being prohibited by the CWC international treaty as a chemical weapon together with those of sarin and soman. In addition, even material compounds for VX synthesis are being also controlled strictly. In the world history, there had been no records on the use of VX in any international dispute.

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  • Drugs Acting on Motor Systems spinal disorders. Benzodiazepines enhance the effectiveness of the inhibitory transmitter GABA (p. 226) at GABAA receptors. Baclofen stimulates GABAB receptors. !2-Adrenoceptor agonists such as clonidine and tizanidine probably act presynaptically to inhibit release of excitatory amino acid transmitters. The convulsant toxins, tetanus toxin (cause of wound tetanus) and strychnine diminish the efficacy of interneuronal synaptic inhibition mediated by the amino acid glycine (A).

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  • Introduction: Organophosphorus pesticides (organophosphate pesticides) are being most widely used as insecticides, and thus cause poisoning cases frequently. The organophosphorus pesticides at the early stage, such as parathion and TEPP, had powerful insecticidal effects and high toxicity for both humans and beasts, and caused poisoning accidents during spraying. Although many less toxic organophosphorus pesticides were then developed, the resistance to the pesticides was acquired by insects during their repeated use, resulting in less effectiveness of the pesticides.

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  • Introduction: Chemical weapons (chemical warfare agents), such as sarin and soman, were developed to kill or injure humans by their toxic actions. They are called “nuclear weapon of the poor”, because the weapons are relatively stable during storage, cheap for production and relatively easily synthesized with basic knowledge on organic chemistry. Main advanced countries are making efforts to reduce chemical weapons existing in the world on the basis of the Chemical Weapons Convention (CWC), after the Iran-Iraq War and the Gulf War.

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  • Introduction: Pyrethroids are the general term for insecticide pyrethrins and their analogs (cinerins and jasmolins) being included in the flowers of pyrethrum or chrysanthemum. Trace concentrations of pyrethroids exert rapid toxic effects on insects, but are rapidly metabolized for detoxification in warm-blooded animals; they are insecticides with very high safety for humans. On the basis of clarification of chemical structures of the effective components of the pyrethrum, many of new synthetic pyrethroids were developed.

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  • In the drug discovery area, a compound with desired therapeutic properties is identified, and its structure may be modified by synthetic alterations to enhance potency and specificity or to decrease toxicity and undesired side effects. The lead drug candidate is then transitioned into the drug development area. Only small amounts of drug (typically less than a gram) are required to support the required studies in the Drug Discovery area. However larger amounts are required to support the studies conducted in the Drug Development area.

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  • It has been a privilege to watch the growth of RNA interference technology over the last ten years. Starting with a mixture of curiosity and chagrin, the field has grown into a substantial enterprise which impacts (and utilizes resources from) virtually every field of biomedical research. Research in RNAi derives from a set of apparently unconnected observations: strange pigment patterns in plants, unexpected failures and successes in antisense and overexpression studies, small regulatory RNAs in bacteria.

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  • In a certain sense, the field of drug metabolism (DM) is standing still. More specifically, the basic experiment of drug metabolism (i.e., administering a new drug to an animal or human and determining the structures, amounts, and disposition of the metabolites) has changed very little over a period of decades. Remarkably, the experimental design and resulting data set from a typical absorption, distribution, metabolism, and excretion (ADME) study conducted today would be instantly recognized and understood by DM scientists from 50 years ago.

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  • The subspecialty of population pharmacokinetics was introduced into clinical pharmacology / pharmacy in the late 1970s as a method for analyzing observational data collected during patient drug therapy in order to estimate patient-based pharmacokinetic parameters. It later became the basis for dosage individualization and rational pharmacotherapy. The population pharmacokinetics method (i.e., the population approach) was later extended to the characterization of the relationship between pharmacokinetics and pharmacodynamics, and into the discipline of pharmacometrics.

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  • Theviewsexpressedtherein,thedesignationsemployedaswellasthepresentationof materialinthispaperdonotimplytheexpressionsofanyopinionwhatsoeveronthepartof theSecretariatoftheUnitedNationsIndustrialDevelopmentOrganizationconcerningthe legalstatusofanycountry,territory,cityorareaorofitsauthorities,orconcerningthe delimitationofitsfrontiersorboundaries.

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  • Addiction is a terrible thing. It consumes and controls us, makes us deny important truths and blinds us to the consequences of our actions. Our world is in the grip of a dangerous carbon habit. Coal and oil paved the way for the developed world’s industrial progress.

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  • This study was designed to describe the radiological findings of extensively drug-resistant (XDR) pulmonary tuberculosis (TB) and to compare the observed findings with findings of drug-sensitive (DS) and non-XDR multidrug- resistant (MDR) TB in non-AIDS patients. Materials and Methods: From September 1994 to December 2007, 53 MDR TB patients (M:F = 32:21; mean age, 38 years) and 15 XDR TB non-AIDS patients (M:F = 8:7; mean age, 36 years) were enrolled in the study. All of the MDR TB patients had received no treatment or less than one month of anti-TB treatment.

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