Oligodendrocytes, or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of some vertebrates, equivalent to the function performed by Schwann cells in the peripheral nervous system. Oligodendrocytes do this by creating the myelin sheath, 80% lipid and 20% protein. A single oligodendrocyte can extend its processes to 50 axons, wrapping 1 μm of myelin sheath around each axon; each oligodendrocyte forms one segment of myelin for several adjacent axons. Oligodendrocytes are found only in the central nervous system, which comprises the brain and spinal cord; these cells were thought to have been produced in the ventral neural tube. They are the last cell type to be generated in the CNS, they were discovered by Pío del Río Hortega. Oligodendroglia, types of glial cells, arise during development from oligodendrocyte precursor cells, which can be identified by their expression of a number of antigens, including the ganglioside GD3, the NG2 chondroitin sulfate proteoglycan, the platelet-derived growth factor-alpha receptor subunit.
Most oligodendrocytes develop during embryogenesis and early postnatal life from restricted periventricular germinal regions. Oligodendrocyte formation in the adult brain is associated with glial-restricted progenitor cells, known as oligodendrocyte progenitor cells. SVZ cells migrate away from germinal zones to populate both developing white and gray matter, where they differentiate and mature into myelin-forming oligodendroglia. However, it is not clear. Between midgestation and term birth in human cerebral white matter, three successive stage of the human oligodendroglial cell lineage are found, viz the pre oligodendrocytes, the immature oligodendrocytes, the mature oligodendrocytes, it has been suggested that some undergo apoptosis and others fail to differentiate into mature oligodendroglia but persist as adult oligodendroglial progenitors. Remarkably, oligodendrocyte population originated in the subventricular zone can be expanded by administering epidermal growth factor; as part of the nervous system, oligodendrocytes are related to nerve cells, like all other glial cells, oligodendrocytes provide a supporting role for neurons as well as trophic support by the production of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, or insulin-like growth factor-1.
In addition, the nervous system of mammals depends crucially on myelin sheaths, which reduce ion leakage and decrease the capacitance of the cell membrane. Myelin increases impulse speed, as saltatory propagation of action potentials occurs at the nodes of Ranvier in between Schwann cells and oligodendrocytes. Furthermore, impulse speed of myelinated axons increases linearly with the axon diameter, whereas the impulse speed of unmyelinated cells increases only with the square root of the diameter; the insulation must be proportional to the diameter of the fibre inside. The optimal ratio of axon diameter divided by the total fiber diameter is 0.6. In contrast, satellite oligodendrocytes are functionally distinct from other oligodendrocytes, they are not attached to neurons and, therefore, do not serve an insulating role. They remain opposed to regulate the extracellular fluid. Satellite oligodendrocytes are considered to be a part of the grey matter whereas myelinating oligodendrocytes are a part of the white matter.
Myelination continues into adulthood. The entire process is not complete until about 25–30 years of age. Myelination is an important component of intelligence. Neuroscientist Vincent J. Schmithorst proposes that there is a correlation with white matter and intelligence. People with greater white matter had higher IQs. A study done with rats by Janice M. Juraska showed that rats that were raised in an enriched environment had more myelination in their corpus callosum. Diseases that result in injury to the oligodendroglial cells include demyelinating diseases such as multiple sclerosis and various leukodystrophies. Trauma to the body, e.g. spinal cord injury, can cause demyelination. The immature oligodendrocytes, which increase in number during mid-gestation, are more vulnerable to hypoxic injury and are involved in periventricular leukomalacia; this congenital condition of damage to the newly forming brain can therefore lead to cerebral palsy. In cerebral palsy, spinal cord injury and multiple sclerosis, oligodendrocytes are thought to be damaged by excessive release of the neurotransmitter, glutamate.
Damage has been shown to be mediated by N-methyl-D-aspartate receptors. Oligodendrocyte dysfunction may be implicated in the pathophysiology of schizophrenia and bipolar disorder. Oligodendroglia are susceptible to infection by the JC virus, which causes progressive multifocal leukoencephalopathy, a condition that affects white matter in immunocompromised patients. Tumors of oligodendroglia are called oligodendrogliomas; the chemotherapy agent Fluorouracil causes damage to the oligodendrocytes in mice, leading to both acute central nervous system damage and progressively worsening delayed degeneration of the CNS. 2',3'-Cyclic-nucleotide 3
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are overactivated by glutamatergic storm. Excitotoxins like NMDA and kainic acid which bind to these receptors, as well as pathologically high levels of glutamate, can cause excitotoxicity by allowing high levels of calcium ions to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases and proteases such as calpain; these enzymes go on to damage cell structures such as components of the cytoskeleton, DNA. Excitotoxicity may be involved in spinal cord injury, traumatic brain injury, hearing loss, in neurodegenerative diseases of the central nervous system such as multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, alcoholism or alcohol withdrawal and over-rapid benzodiazepine withdrawal, Huntington's disease.
Other common conditions that cause excessive glutamate concentrations around neurons are hypoglycemia. Blood sugars are the primary glutamate removal method from inter-synaptic spaces at the NMDA and AMPA receptor site. Persons in excitotoxic shock must never fall into hypoglycemia. Patients should be given 5% glucose IV drip during excitotoxic shock to avoid a dangerous build up of glutamate around NMDA and AMPA neurons; when 5% glucose IV drip is not available high levels of fructose are given orally. Treatment is administered during the acute stages of excitotoxic shock along with glutamate antagonists. Dehydration should be avoided as this contributes to the concentrations of glutamate in the inter-synaptic cleft and "status epilepticus can be triggered by a build up of glutamate around inter-synaptic neurons." The harmful effects of glutamate on the central nervous system were first observed in 1954 by T. Hayashi, a Japanese scientist who noted that direct application of glutamate to the CNS caused seizure activity, though this report went unnoticed for several years.
D. R. Lucas and J. P. Newhouse, after noting that "single doses of 20-30gm have... been administered intravenously without permanent ill-effects", observed in 1957 that a subcutaneous dose described as "a little less than lethal", destroyed the neurons in the inner layers of the retina in newborn mice. In 1969, John Olney discovered that the phenomenon was not restricted to the retina, but occurred throughout the brain, coined the term excitotoxicity, he assessed that cell death was restricted to postsynaptic neurons, that glutamate agonists were as neurotoxic as their efficiency to activate glutamate receptors, that glutamate antagonists could stop the neurotoxicity. Excitotoxicity can occur from substances produced within the body. Glutamate is a prime example of an excitotoxin in the brain, it is the major excitatory neurotransmitter in the mammalian CNS. During normal conditions, glutamate concentration can be increased up to 1mM in the synaptic cleft, decreased in the lapse of milliseconds.
When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called apoptosis. This pathologic phenomenon can occur after brain injury and spinal cord injury. Within minutes after spinal cord injury, damaged neural cells within the lesion site spill glutamate into the extracellular space where glutamate can stimulate presynaptic glutamate receptors to enhance the release of additional glutamate. Brain trauma or stroke can cause ischemia. Ischemia is followed by accumulation of glutamate and aspartate in the extracellular fluid, causing cell death, aggravated by lack of oxygen and glucose; the biochemical cascade resulting from ischemia and involving excitotoxicity is called the ischemic cascade. Because of the events resulting from ischemia and glutamate receptor activation, a deep chemical coma may be induced in patients with brain injury to reduce the metabolic rate of the brain and save energy to be used to remove glutamate actively..
Increased extracellular glutamate levels leads to the activation of Ca2+ permeable NMDA receptors on myelin sheaths and oligodendrocytes, leaving oligodendrocytes susceptible to Ca2+ influxes and subsequent excitotoxicity. One of the damaging results of excess calcium in the cytosol is initiating apoptosis through cleaved caspase processing. Another damaging result of excess calcium in the cytosol is the opening of the mitochondrial permeability transition pore, a pore in the membranes of mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release reactive oxygen species and other proteins that can lead to apoptosis; the pore can cause mitochondria to release more calcium. In addition, production of adenosine triphosphate may be stopped, ATP synthase may in fact begin hydrolysing ATP instead of producing it. Inadequate ATP production resulting from brain trauma can eliminate electrochemical gradients of certain ions. Glutamate transporters require the maintenance of these ion gradients to remove glutamate from the extracellular space.
The loss of ion gradients results in not only the halting of glutamate uptake, but in the reversal of the transporters. The Na+-glutamate transporters on ne
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP and NADH. Glycolysis is a sequence of ten enzyme-catalyzed reactions. Most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates; the intermediates may be directly useful. For example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen-independent metabolic pathway; the wide occurrence of glycolysis indicates. Indeed, the reactions that constitute glycolysis and its parallel pathway, the pentose phosphate pathway, occur metal-catalyzed under the oxygen-free conditions of the Archean oceans in the absence of enzymes. In most organisms, glycolysis occurs in the cytosol; the most common type of glycolysis is the Embden–Meyerhof–Parnas, discovered by Gustav Embden, Otto Meyerhof, Jakub Karol Parnas.
Glycolysis refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway; the glycolysis pathway can be separated into two phases: The Preparatory/Investment Phase – wherein ATP is consumed. The Pay Off Phase – wherein ATP is produced; the overall reaction of glycolysis is: The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, charges. Atom balance is maintained by the two phosphate groups: Each exists in the form of a hydrogen phosphate anion, dissociating to contribute 2 H+ overall Each liberates an oxygen atom when it binds to an ADP molecule, contributing 2 O overallCharges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxyl groups of ADP dissociate into −O− and H+, giving ADP3−, this ion tends to exist in an ionic bond with Mg2+, giving ADPMg−.
ATP behaves identically except that it has four hydroxyl groups, giving ATPMg2−. When these differences along with the true charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP. Most cells will carry out further reactions to'repay' the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+. Cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis; these further aerobic reactions use pyruvate and NADH + H+ from glycolysis. Eukaryotic aerobic respiration produces 34 additional molecules of ATP for each glucose molecule, however most of these are produced by a vastly different mechanism to the substrate-level phosphorylation in glycolysis; the lower-energy production, per glucose, of anaerobic respiration relative to aerobic respiration, results in greater flux through the pathway under hypoxic conditions, unless alternative sources of anaerobically oxidizable substrates, such as fatty acids, are found.
The pathway of glycolysis as it is known today took 100 years to discover. The combined results of many smaller experiments were required in order to understand the pathway as a whole; the first steps in understanding glycolysis began in the nineteenth century with the wine industry. For economic reasons, the French wine industry sought to investigate why wine sometime turned distasteful, instead of fermenting into alcohol. French scientist Louis Pasteur researched this issue during the 1850s, the results of his experiments began the long road to elucidating the pathway of glycolysis, his experiments showed. While Pasteur's experiments were groundbreaking, insight into the component steps of glycolysis were provided by the non-cellular fermentation experiments of Eduard Buchner during the 1890s. Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast; this experiment not only revolutionized biochemistry, but allowed scientists to analyze this pathway in a more controlled lab setting.
In a series of experiments, scientists Arthur Harden and William Young discovered more pieces of glycolysis. They discovered the regulatory effects of ATP on glucose consumption during alcohol fermentation, they shed light on the role of one compound as a glycolysis intermediate: fructose 1,6-bisphosphate. The elucidation of fructose 1,6-bisphosphate was accomplished by measuring CO2 levels when yeast juice was incubated with glucose. CO2 production increased then slowed down. Harden and Young noted that this process would restart if an inorganic phosphate was added to the mixture. Harden and Young deduced that this process produced organic phosphate esters, further experiments allowed them to extract fructose diphosphate. Arthur Harden and William Young along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction and a heat-insensitive low-molecular-weight cytoplasm fraction are required together for fermenta
Clinical trials are experiments or observations done in clinical research. Such prospective biomedical or behavioral research studies on human participants are designed to answer specific questions about biomedical or behavioral interventions, including new treatments and known interventions that warrant further study and comparison. Clinical trials generate data on efficacy, they are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial – their approval does not mean that the therapy is'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators enroll volunteers or patients into small pilot studies, subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, they can involve a single research center or multiple centers, in one country or in multiple countries.
Clinical study design aims to ensure the scientific reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug; the sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become an approved drug; some clinical trials involve healthy subjects with no pre-existing medical conditions. Other clinical trials pertain to patients with specific health conditions who are willing to try an experimental treatment; when participants are healthy volunteers who receive financial incentives, the goals are different than when the participants are sick. During dosing periods, study subjects remain under supervision for one to 40 nights. Pilot experiments are conducted to gain insights for design of the clinical trial to follow.
There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy" or "effectiveness". Neither is an absolute criterion; the benefits must outweigh the risks. For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care, are used for a life-threatening condition. In the US, the elderly constitute 14 % of the population. People over 55 are excluded from trials because their greater health issues and drug use complicate data interpretation, because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are frequently excluded. Pregnant women are excluded due to potential risks to the fetus; the sponsor designs the trial in coordination with a panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type of patients might benefit.
If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study. During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment and collect data on the subjects' health for a defined time period. Data include measurements such as vital signs, concentration of the study drug in the blood or tissues, changes to symptoms, whether improvement or worsening of the condition targeted by the study drug occurs; the researchers send the data to the trial sponsor, who analyzes the pooled data using statistical tests. Examples of clinical trial goals include assessing the safety and relative effectiveness of a medication or device: On a specific kind of patient, for example, a patient, diagnosed with Alzheimer's disease At varying dosages, for example, a 10 milligram dose instead of a 5 milligram dose For a new indication Evaluation for improved efficacy in treating a patient's condition as compared to the standard therapy for that condition Evaluation of the study drug or device relative to two or more approved/common interventions for that condition, for example, device A versus device B, or therapy A versus therapy B)While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a placebo.
Except for small, single-location trials, the design and objectives are specified in a document called a clinical trial protocol. The protocol is the trial's "operating manual" and ensures that all researchers perform the trial in the same way on similar subjects and that the data is comparable across all subjects; as a trial is designed to test hypotheses and rigorously monitor and assess outcomes, it can be seen as an application of the scientific method the experimental step. The most common clinical trials evaluate new pharmaceutical products, medical devices, psychological therapies, or other interventions. Clinical trials may be required before a national regulatory authority approves marketing of the innovation. To drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket appr
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm