1.
Food and Drug Administration
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The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription drug user fee act and these include regulating lasers, cellular phones, condoms and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice, the Commissioner reports to the Secretary of Health and Human Services. Dr. Robert M. Califf, MD is the current commissioner, who took over in February 2016 for Dr. Stephen Ostroff, the FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, in 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. The site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak, the first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the facility was kept. All other buildings are new construction, the project is slated to be completed by 2017, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. The Office of Regulatory Affairs is considered the eyes and ears of the agency, the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based roughly on the divisions of the federal court system. Each district comprises a main office and a number of Resident Posts. ORA also includes the Agencys network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and dont focus on aspects of the regulated industries. In many cases, OCI pursues cases involving Title 18 violations, OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works with federal agencies, including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection. Often local and state government agencies also work with the FDA to provide regulatory inspections, the FDA regulates more than US$1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States
2.
Germany
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Germany, officially the Federal Republic of Germany, is a federal parliamentary republic in central-western Europe. It includes 16 constituent states, covers an area of 357,021 square kilometres, with about 82 million inhabitants, Germany is the most populous member state of the European Union. After the United States, it is the second most popular destination in the world. Germanys capital and largest metropolis is Berlin, while its largest conurbation is the Ruhr, other major cities include Hamburg, Munich, Cologne, Frankfurt, Stuttgart, Düsseldorf and Leipzig. Various Germanic tribes have inhabited the northern parts of modern Germany since classical antiquity, a region named Germania was documented before 100 AD. During the Migration Period the Germanic tribes expanded southward, beginning in the 10th century, German territories formed a central part of the Holy Roman Empire. During the 16th century, northern German regions became the centre of the Protestant Reformation, in 1871, Germany became a nation state when most of the German states unified into the Prussian-dominated German Empire. After World War I and the German Revolution of 1918–1919, the Empire was replaced by the parliamentary Weimar Republic, the establishment of the national socialist dictatorship in 1933 led to World War II and the Holocaust. After a period of Allied occupation, two German states were founded, the Federal Republic of Germany and the German Democratic Republic, in 1990, the country was reunified. In the 21st century, Germany is a power and has the worlds fourth-largest economy by nominal GDP. As a global leader in industrial and technological sectors, it is both the worlds third-largest exporter and importer of goods. Germany is a country with a very high standard of living sustained by a skilled. It upholds a social security and universal health system, environmental protection. Germany was a member of the European Economic Community in 1957. It is part of the Schengen Area, and became a co-founder of the Eurozone in 1999, Germany is a member of the United Nations, NATO, the G8, the G20, and the OECD. The national military expenditure is the 9th highest in the world, the English word Germany derives from the Latin Germania, which came into use after Julius Caesar adopted it for the peoples east of the Rhine. This in turn descends from Proto-Germanic *þiudiskaz popular, derived from *þeudō, descended from Proto-Indo-European *tewtéh₂- people, the discovery of the Mauer 1 mandible shows that ancient humans were present in Germany at least 600,000 years ago. The oldest complete hunting weapons found anywhere in the world were discovered in a mine in Schöningen where three 380, 000-year-old wooden javelins were unearthed
3.
Action potential
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In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of cells, called excitable cells, which include neurons, muscle cells. In other types of cells, their function is to activate intracellular processes. In muscle cells, for example, a potential is the first step in the chain of events leading to contraction. In beta cells of the pancreas, they provoke release of insulin, action potentials in neurons are also known as nerve impulses or spikes, and the temporal sequence of action potentials generated by a neuron is called its spike train. A neuron that emits an action potential is often said to fire, action potentials are generated by special types of voltage-gated ion channels embedded in a cells plasma membrane. When the channels open they allow a flow of sodium ions, which changes the electrochemical gradient. This then causes more channels to open, producing an electric current across the cell membrane. The process proceeds explosively until all of the ion channels are open. The rapid influx of ions causes the polarity of the plasma membrane to reverse. As the sodium channels close, sodium ions can no longer enter the neuron, potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, in animal cells, there are two primary types of action potentials. One type is generated by voltage-gated sodium channels, the other by voltage-gated calcium channels, sodium-based action potentials usually last for under one millisecond, whereas calcium-based action potentials may last for 100 milliseconds or longer. In some types of neurons, slow calcium spikes provide the force for a long burst of rapidly emitted sodium spikes. In cardiac muscle cells, on the hand, an initial fast sodium spike provides a primer to provoke the rapid onset of a calcium spike. Nearly all cell membranes in animals, plants and fungi maintain a voltage difference between the exterior and interior of the cell, called the membrane potential. A typical voltage across a cell membrane is –70 mV. In most types of cells the membrane potential usually stays fairly constant, some types of cells, however, are electrically active in the sense that their voltages fluctuate over time
4.
Intramuscular injection
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Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of alternative methods for the administration of medications. Muscles have larger and more vessels than subcutaneous tissue and injections here usually have faster rates of absorption than subcutaneous injections or intradermal injections. Depending on the site, an administration is limited to between 2 and 5 milliliters of fluid. Platelet-rich plasma injections can be administered intramuscularly, certain substances are injected intramuscularly for recreational purposes. Possible sites for IM injection include, deltoid, dorsogluteal, rectus femoris, vastus lateralis, sites that are bruised, tender, red, swollen, inflamed or scarred are avoided. The deltoid muscle site is recommended for use with injections of small volume, usually equal or less than 1 ml and this site is not recommended for repeated injections, due to its small area, it is difficult to rotate the injection site. To locate the site, palpate the lower edge of the acromion process, inject in the upside down triangle that forms with its base at the acromion process and its midpoint in line with the axilla. The ventrogluteal site is recommended for injections requiring a larger volume to be administered, greater than 1 ml and it is also given for narcotic, antibiotic, sedative and anti-emetic medications. To locate the site, place the palm of your hand over the greater trochanter. The right hand is used for the hip and left hand is used for the right hip. Place the index finger on the superior iliac spine and run the middle finger back along the iliac crest. The injection is given in the center of the triangle that is formed, the vastus lateralis site is the recommended site for infants less than 7 months old and those unable to walk, with loss of muscular tone. To locate the site, divide the front thigh into thirds vertically and horizontally to make nine squares and inject in the outer middle square. Use of this site is associated with skin and tissue trauma, muscle fibrosis and contracture, haematoma, nerve palsy and paralysis, as well as infectious processes such as abscess and gangrene. The injection site is located by dividing the buttock into four with a plus shaped cross, the selected site is cleansed with an antimicrobial and is allowed to dry. It is injected with the dominant hand using a quick, darting motion perpendicular to the body at an angle between 72 and 90 degrees, as a faster injection is less painful. The needle is then stabilized with the nondominant hand while the dominant hand slides to the plunger to slowly instill the medication, the CDC does not recommend the outdated practice of aspirating for blood to rule out injecting into a blood vessel
5.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
6.
Electrical resistance and conductance
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The electrical resistance of an electrical conductor is a measure of the difficulty to pass an electric current through that conductor. The inverse quantity is electrical conductance, and is the ease with which a current passes. Electrical resistance shares some parallels with the notion of mechanical friction. The SI unit of resistance is the ohm, while electrical conductance is measured in siemens. An object of uniform cross section has a proportional to its resistivity and length. All materials show some resistance, except for superconductors, which have a resistance of zero and this proportionality is called Ohms law, and materials that satisfy it are called ohmic materials. In other cases, such as a diode or battery, V and I are not directly proportional. The ratio V/I is sometimes useful, and is referred to as a chordal resistance or static resistance, since it corresponds to the inverse slope of a chord between the origin and an I–V curve. In other situations, the derivative d V d I may be most useful, in the hydraulic analogy, current flowing through a wire is like water flowing through a pipe, and the voltage drop across the wire is like the pressure drop that pushes water through the pipe. Conductance is proportional to how much flow occurs for a given pressure, the voltage drop, not the voltage itself, provides the driving force pushing current through a resistor. In hydraulics, it is similar, The pressure difference between two sides of a pipe, not the pressure itself, determines the flow through it, for example, there may be a large water pressure above the pipe, which tries to push water down through the pipe. But there may be a large water pressure below the pipe. If these pressures are equal, no water flows, in the same way, a long, thin copper wire has higher resistance than a short, thick copper wire. A pipe filled with hair restricts the flow of more than a clean pipe of the same shape. The difference between copper, steel, and rubber is related to their structure and electron configuration. In addition to geometry and material, there are other factors that influence resistance and conductance, such as temperature. Substances in which electricity can flow are called conductors, a piece of conducting material of a particular resistance meant for use in a circuit is called a resistor. Conductors are made of high-conductivity materials such as metals, in particular copper, Resistors, on the other hand, are made of a wide variety of materials depending on factors such as the desired resistance, amount of energy that it needs to dissipate, precision, and costs
7.
Chloride channel
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Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions, several families of voltage-gated channels and ligand-gated channels have been characterized in humans. Based on sequence homology the chloride channels can be subdivided into a number of groups, voltage-gated chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Cl− as well as other such as HCO−3, I−, SCN−. The structure of these channels are not like other known channels, the chloride channel subunits contain between 1 and 12 transmembrane segments. Some chloride channels are activated only by voltage wrong the proper term will indifinte structure, while others are activated by Ca2+, other extracellular ligands, the CLC family of chloride channels contains 10 or 12 transmembrane helices. Each protein forms a single pore and it has been shown that some members of this family form homodimers. In terms of structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals, CLCN1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two CBS domains, Chloride channels are also important for maintaining safe ion concentrations within plant cells. The CLC channel structure has not yet resolved, however the structure of the CLC exchangers has been resolved by x-ray crystallography. Because the primary structure of the channels and exchangers are so similar, each channel or exchanger is composed of two similar subunits—a dimer—each subunit containing one pore. The proteins are formed from two copies of the same protein—a homodimer—though scientists have artificially combined subunits from different channels to form heterodimers, each subunit binds ions independently of the other, meaning conduction or exchange occur independently in each subunit. Each subunit consists of two related halves oriented in opposite directions, forming an ‘antiparallel’ structure and these halves come together to form the anion pore. The pore has a filter through which chloride and other anions can pass and these water-filled pores filter anions via three binding sites—Sint, Scen, and Sext—which bind chloride and other anions. The names of these binding sites correspond to their positions within the membrane, sint is exposed to intracellular fluid, Scen lies inside the membrane or in the center of the filter, and Sext is exposed to extracellular fluid. Each binding site binds different chloride anions simultaneously, in the exchangers, these chloride ions do not interact strongly with one another, due to compensating interactions with the protein. In the channels, the protein does not shield chloride ions at one binding site from the negatively charged chlorides
8.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list
9.
Hypnotic
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This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects they are often referred to collectively as sedative-hypnotic drugs. Hypnotic drugs are prescribed for insomnia and other sleep disorders. When prescribed, hypnotic medication should be used for the shortest period of time necessary, most hypnotics prescribed today are either benzodiazepines or nonbenzodiazepines. Among individuals with sleep disorders,13. 7% are taking or prescribed nonbenzodiazepines, while 10. 8% are taking benzodiazepines, early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism, falling outside of the above-mentioned categories, the neuro-hormone melatonin has a hypnotic function. Research about using medications to treat insomnia evolved throughout the last half of the 20th century, treatment for insomnia in psychiatry dates back to 1869 when chloral hydrate was first used as a soporific. Barbiturates emerged as the first class of drugs that emerged in the early 1900s, although the best drug family at the time they were dangerous in overdose. During the 1970s, quinazolinones and benzodiazepines were introduced as alternatives to replace barbiturates. Benzodiazepines are not without their drawbacks, substance dependence is possible, questions have been raised as to whether they disturb sleep architecture. Nonbenzodiazepines are the most recent development, although its clear that they are less toxic than their predecessors, barbiturates, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine, however some psychiatrists recommend these drugs, other sleep remedies that may be considered sedative-hypnotics exist, psychiatrists will sometimes prescribe medicines off-label if they have sedating effects. Examples of these include mirtazapine, clonidine, quetiapine, and the over-the-counter sleep aid diphenhydramine, off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe. Barbiturates are drugs that act as central nervous system depressants, and can produce a wide spectrum of effects. They are also effective as anxiolytics, hypnotics, and anticonvulsants, barbiturates also have analgesic effects, however, these effects are somewhat weak, preventing barbiturates from being used in surgery in the absence of other analgesics. They have dependence liability, both physical and psychological, however, barbiturates are still used in general anesthesia, for epilepsy, and assisted suicide. Barbiturates are derivatives of barbituric acid, the principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABAA receptors. Examples include amobarbital, pentobarbital, phenobarbital, secobarbital, and sodium thiopental, quinazolinones are also a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core
10.
In vitro
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In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. In contrast, in studies are those conducted in animals, including humans. In vitro studies are conducted using components of an organism that have been isolated from their biological surroundings, such as microorganisms, cells. For example, microrganisms or cells can be studied in artificial culture media, colloquially called test-tube experiments, these studies in biology, medicine, and their subdisciplines are traditionally done in test tubes, flasks, Petri dishes, etc. They now involve the range of techniques used in molecular biology. In contrast, studies conducted in living beings are called in vivo, polymerase chain reaction is a method for selective replication of specific DNA and RNA sequences in the test tube. Protein purification involves the isolation of a protein of interest from a complex mixture of proteins. In vitro fertilization is used to allow spermatozoa to fertilize eggs in a culture dish before implanting the resulting embryo or embryos into the uterus of the prospective mother and these ADME process parameters can then be integrated into so called physiologically based pharmacokinetic models or PBPK. In vitro studies permit a species-specific, simpler, more convenient, just as studies in whole animals more and more replace human trials, so are in vitro studies replacing studies in whole animals. This complexity makes it difficult to identify the interactions between individual components and to explore their basic biological functions, in vitro work simplifies the system under study, so the investigator can focus on a small number of components. Another advantage of in vitro methods is that cells can be studied without extrapolation from an experimental animals cellular response. Investigators doing in vitro work must be careful to avoid over-interpretation of their results, for example, scientists developing a new viral drug to treat an infection with a pathogenic virus may find that a candidate drug functions to prevent viral replication in an in vitro setting. However, before this drug is used in the clinic, it must progress through a series of in vivo trials to determine if it is safe and effective in intact organisms. Results obtained from in vitro experiments cannot usually be transposed, as is, building a consistent and reliable extrapolation procedure from in vitro results to in vivo is therefore extremely important. However, increasingly sophisticated in vitro experiments collect increasingly numerous, complex, mathematical models, such as systems biology models, are much needed here. In pharmacology, IVIVE can be used to approximate pharmacokinetics or pharmacodynamics and that indicates that extrapolating effects observed in vitro needs a quantitative model of in vivo PK. Physiologically based PK models are generally accepted to be central to the extrapolations, in these conditions, developing a simple PD model of the dose–response relationship observed in vitro, and transposing it without changes to predict in vivo effects is not enough
11.
William Bleckwenn
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William Jefferson Bleckwenn was an American neurologist, psychiatrist, and military physician, who was instrumental in developing the treatment known as narcoanalysis or narcosynthesis. The lay-description for that process is the administration of truth serum, Bleckwenn was born in Astoria in New York City, in 1895. He received his elementary and secondary education there in public city schools and he then enrolled at the University of Wisconsin–Madison in 1913, earning a B. S. - Med. degree in 1917 as part of an accelerated medical course of study. As an undergraduate, Bleckwenn was an athlete in track & field. Because UW did not have a four-year degree-granting medical school until the mid-1920s and he received his M. D. from that institution in 1920. Bleckwenn then pursued training at Bellevue Hospital in New York. At WPI, he came under the tutelage of William Lorenz, upon completion of his training, Bleckwenn was asked to join Lorenz and Reese on the staff of WPI, which had by then become part of the UW Department of Neuropsychiatry. He quickly acquired skill as an administrator and researcher, becoming assistant director of the Institute in the late 1920s, around that time, Bleckwenn also began investigational studies on the use of barbiturates to treat catatonic mutism, a particularly disabling form of schizophrenia. The latter benefit of the treatment was given the names narcoanalysis or narcosynthesis, in a short time, the amytal-induced lucid interval became a proof-positive test for the diagnosis of catatonia. Periods of from four to fourteen hours of a lucid interval have been a constant result of the treatment. Bleckwenn was forward-thinking regarding the documentation of these effects, making motion pictures of the process. Of those, Fink says His silent films show the patients as mute, posturing, rigid, with heads raised fixedly from the pillow, the films were convincing, and amobarbital was quickly and widely used to obtain clinical histories and to allow feeding and self-care. Psychiatrists across the world became enthused by sodium amytal therapy, in his text entitled A Historical Dictionary of Psychiatry, Shorter states that Some observers view Bleckwenns procedure as the real beginning of psychopharmacology. As an extension of his work on barbiturate therapy, Bleckwenn and they found that dilute intravenous solutions of picrotoxin -- a neurostimulatory plant product—were effective as an antidote in that setting. However, over time, the therapeutic window associated with picrotoxin administration—which can also induce seizures—resulted in its disuse. Bleckwenn had enlisted in the Wisconsin Army National Guard as a medical student, in 1941, Bleckwenn was called to active duty and attached to the 135th medical regiment. That unit operated as part of the U. S, Sixth Army and was tasked with management of frontline casualties. After the United States entered the war, the 135th shipped out to the Pacific Theater of Operations in March 1942, Bleckwenn was its commanding officer, with the rank of Colonel
