Scientific method
The scientific method is an empirical method of acquiring knowledge that has characterized the development of science since at least the 17th century. It involves careful observation, applying rigorous skepticism about what is observed, given that cognitive assumptions can distort how one interprets the observation, it involves formulating hypotheses, via induction, based on such observations. These are principles of the scientific method, as distinguished from a definitive series of steps applicable to all scientific enterprises. Though diverse models for the scientific method are available, there is in general a continuous process that includes observations about the natural world. People are inquisitive, so they come up with questions about things they see or hear, they develop ideas or hypotheses about why things are the way they are; the best hypotheses lead to predictions. The most conclusive testing of hypotheses comes from reasoning based on controlled experimental data. Depending on how well additional tests match the predictions, the original hypothesis may require refinement, expansion or rejection.
If a particular hypothesis becomes well supported, a general theory may be developed. Although procedures vary from one field of inquiry to another, they are the same from one to another; the process of the scientific method involves making conjectures, deriving predictions from them as logical consequences, carrying out experiments or empirical observations based on those predictions. A hypothesis is a conjecture, based on knowledge obtained while seeking answers to the question; the hypothesis might be specific, or it might be broad. Scientists test hypotheses by conducting experiments or studies. A scientific hypothesis must be falsifiable, implying that it is possible to identify a possible outcome of an experiment or observation that conflicts with predictions deduced from the hypothesis; the purpose of an experiment is to determine whether observations agree with or conflict with the predictions derived from a hypothesis. Experiments can take place anywhere from a garage to CERN's Large Hadron Collider.
There are difficulties in a formulaic statement of method, however. Though the scientific method is presented as a fixed sequence of steps, it represents rather a set of general principles. Not all steps take place in every scientific inquiry, they are not always in the same order; some philosophers and scientists have argued. Robert Nola and Howard Sankey remark that "For some, the whole idea of a theory of scientific method is yester-year's debate, the continuation of which can be summed up as yet more of the proverbial deceased equine castigation. We beg to differ." Important debates in the history of science concern rationalism as advocated by René Descartes. The term "scientific method" emerged in the 19th century, when a significant institutional development of science was taking place and terminologies establishing clear boundaries between science and non-science, such as "scientist" and "pseudoscience", appeared. Throughout the 1830s and 1850s, by which time Baconianism was popular, naturalists like William Whewell, John Herschel, John Stuart Mill engaged in debates over "induction" and "facts" and were focused on how to generate knowledge.
In the late 19th and early 20th centuries, a debate over realism vs. antirealism was conducted as powerful scientific theories extended beyond the realm of the observable. The term "scientific method" came into popular use in the twentieth century, popping up in dictionaries and science textbooks, although there was little scientific consensus over its meaning. Although there was a growth through the middle of the twentieth century, by the end of that century numerous influential philosophers of science like Thomas Kuhn and Paul Feyerabend had questioned the universality of the "scientific method" and in doing so replaced the notion of science as a homogeneous and universal method with that of it being a heterogeneous and local practice. In particular, Paul Feyerabend argued against there being any universal rules of science. Historian of science Daniel Thurs maintains that the scientific method is a myth or, at best, an idealization; the scientific method is the process. As in other areas of inquiry, science can build on previous knowledge and develop a more sophisticated understanding of its topics of study over time.
This model can be seen to underlie the scientific revolution. The ubiquitous element in the model of the scientific method is empiricism, or more epistemologic sensualism; this is in opposition to stringent forms of rationalism: the scientific method embodies that reason alone cannot solve a particular scientific problem. A strong formulation of the scientific method is not always aligned with a form of empiricism in which the empirical data is put forward in the form of experience or other abstracted forms of knowledge; the scientific method is of necessity als
Hearing
Hearing, or auditory perception, is the ability to perceive sounds by detecting vibrations, changes in the pressure of the surrounding medium through time, through an organ such as the ear. The academic field concerned with hearing is auditory science. Sound may be heard through liquid, or gaseous matter, it is one of the traditional five senses. In humans and other vertebrates, hearing is performed by the auditory system: mechanical waves, known as vibrations are detected by the ear and transduced into nerve impulses that are perceived by the brain. Like touch, audition requires sensitivity to the movement of molecules in the world outside the organism. Both hearing and touch are types of mechanosensation. There are three main components of the human ear: the outer ear, the middle ear, the inner ear; the outer ear includes the pinna, the visible part of the ear, as well as the ear canal which terminates at the eardrum called the tympanic membrane. The pinna serves to focus sound waves through the ear canal toward the eardrum.
Because of the asymmetrical character of the outer ear of most mammals, sound is filtered differently on its way into the ear depending on what vertical location it is coming from. This gives these animals the ability to localize sound vertically; the eardrum is an airtight membrane, when sound waves arrive there, they cause it to vibrate following the waveform of the sound. The middle ear consists of a small air-filled chamber, located medial to the eardrum. Within this chamber are the three smallest bones in the body, known collectively as the ossicles which include the malleus and stapes, they aid in the transmission of the vibrations from the eardrum into the cochlea. The purpose of the middle ear ossicles is to overcome the impedance mismatch between air waves and cochlear waves, by providing impedance matching. Located in the middle ear are the stapedius muscle and tensor tympani muscle, which protect the hearing mechanism through a stiffening reflex; the stapes transmits sound waves to the inner ear through the oval window, a flexible membrane separating the air-filled middle ear from the fluid-filled inner ear.
The round window, another flexible membrane, allows for the smooth displacement of the inner ear fluid caused by the entering sound waves. The inner ear consists of the cochlea, a spiral-shaped, fluid-filled tube, it is divided lengthwise by the organ of Corti, the main organ of mechanical to neural transduction. Inside the organ of Corti is the basilar membrane, a structure that vibrates when waves from the middle ear propagate through the cochlear fluid – endolymph; the basilar membrane is tonotopic, so that each frequency has a characteristic place of resonance along it. Characteristic frequencies are high at the basal entrance to the cochlea, low at the apex. Basilar membrane motion causes depolarization of the hair cells, specialized auditory receptors located within the organ of Corti. While the hair cells do not produce action potentials themselves, they release neurotransmitter at synapses with the fibers of the auditory nerve, which does produce action potentials. In this way, the patterns of oscillations on the basilar membrane are converted to spatiotemporal patterns of firings which transmit information about the sound to the brainstem.
The sound information from the cochlea travels via the auditory nerve to the cochlear nucleus in the brainstem. From there, the signals are projected to the inferior colliculus in the midbrain tectum; the inferior colliculus integrates auditory input with limited input from other parts of the brain and is involved in subconscious reflexes such as the auditory startle response. The inferior colliculus in turn projects to the medial geniculate nucleus, a part of the thalamus where sound information is relayed to the primary auditory cortex in the temporal lobe. Sound is believed to first become consciously experienced at the primary auditory cortex. Around the primary auditory cortex lies Wernickes area, a cortical area involved in interpreting sounds, necessary to understand spoken words. Disturbances at any of these levels can cause hearing problems if the disturbance is bilateral. In some instances it can lead to auditory hallucinations or more complex difficulties in perceiving sound. Hearing can be measured by behavioral tests using an audiometer.
Electrophysiological tests of hearing can provide accurate measurements of hearing thresholds in unconscious subjects. Such tests include auditory brainstem evoked potentials, otoacoustic emissions and electrocochleography. Technical advances in these tests have allowed hearing screening for infants to become widespread; the hearing structures of many species have defense mechanisms against injury. For example, the muscles of the middle ear in many mammals contract reflexively in reaction to loud sounds which may otherwise injure the hearing ability of the organism. There are several different types of hearing loss: Conductive hearing loss, sensorineural hearing loss and mixed types. Conductive hearing loss Sensorineural hearing loss Mixed hearing lossThere are defined degrees of hearing loss: Mild hearing loss - People with mild hearing loss have difficulties keeping up with conversations in noisy surroundings; the most quiet sounds that people with mild hearing loss can hear with their better ear are between 25 and 40 dB HL.
Moderate hearing loss - People with moderate hearing loss have difficulty keeping up with conversations when they are not using a hearing aid. On average, the most quiet sounds heard by
5-HT receptor
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both inhibitory neurotransmission; the serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand. The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, epinephrine / norepinephrine, acetylcholine, as well as many hormones, including oxytocin, vasopressin, cortisol and substance P, among others; the serotonin receptors influence various biological and neurological processes such as aggression, appetite, learning, mood, nausea and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, anorectics, gastroprokinetic agents, antimigraine agents and entactogens. Serotonin receptors are found in all animals and are known to regulate longevity and behavioral aging in the primitive nematode, Caenorhabditis elegans.
5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors are found in the central and peripheral nervous systems. They can be divided into 7 families of G protein-coupled receptors except for the 5-HT3 receptor, a ligand-gated ion channel, which activate an intracellular second messenger cascade to produce an excitatory or inhibitory response. In 2014, a novel 5-HT receptor was isolated from the small white butterfly, Pieris rapae, named pr5-HT8, it does not occur in mammals and shares low similarity to the known 5-HT receptor classes. The 7 general serotonin receptor classes include a total of 14 known serotonin receptors; the specific types have been characterized as follows: Note that there is no 5-HT1C receptor since, after the receptor was cloned and further characterized, it was found to have more in common with the 5-HT2 family of receptors and was redesignated as the 5-HT2C receptor. Nonselective agonists of 5-HT receptor subtypes include ergotamine, which activates 5-HT1A, 5-HT1D, 5-HT1B, D2 and norepinephrine receptors.
LSD is a 5-HT2A, 5-HT2C, 5-HT5A, 5-HT5, 5-HT6 agonist. The genes coding for serotonin receptors are expressed across the mammalian brain. Genes coding for different receptors types follow different developmental curves. There is a developmental increase of HTR5A expression in several subregions of the human cortex, paralleled by a decreased expression of HTR1A from the embryonic period to the post-natal one. A number of receptors were classed as "5-HT1-like" - by 1998 it was being argued that, since these receptors were "a heterogeneous population of 5-HT1B, 5-HT1D and 5-HT7" receptors the classification was redundant. Serotonin+Receptors at the US National Library of Medicine Medical Subject Headings "5-Hydroxytryptamine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Rubenstein LA, Lanzara RG. "Activation of G protein-coupled receptors entails cysteine modulation of agonist binding". Cogprints. Retrieved 2008-04-11. Paterson LM, Kornum BR, Nutt DJ, Pike VW, Knudsen GM.
"5-HT radioligands for human brain imaging with PET and SPECT". Med Res Rev. 33: 54–111. Doi:10.1002/med.20245. PMC 4188513. PMID 21674551
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A potent drug evokes a given response at low concentrations, while a drug of lower potency evokes the same response only at higher concentrations. Higher potency does not mean more side effects; the IUPHAR has stated that'potency' is "an imprecise term that should always be further defined", for instance as EC 50, IC 50, ED50, LD50 and so on. Harris, Robert. "Formulating High Potency Drugs". Contract Pharma. Retrieved 2013-11-13. Walker MG, Page CP, Hoffman BF, Curtis M. Integrated Pharmacology. St. Louis: Mosby. ISBN 978-0-323-04080-8
Dopamine
Dopamine is an organic chemical of the catecholamine and phenethylamine families. It functions both as a hormone and a neurotransmitter, plays several important roles in the brain and body, it is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA, synthesized in the brain and kidneys. Dopamine is synthesized in plants and most animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons to send signals to other nerve cells; the brain includes several distinct dopamine pathways, one of which plays a major role in the motivational component of reward-motivated behavior. The anticipation of most types of rewards increases the level of dopamine in the brain, many addictive drugs increase dopamine release or block its reuptake into neurons following release. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones; these pathways and cell groups form a dopamine system, neuromodulatory.
In popular culture and media, dopamine is seen as the main chemical of pleasure, but the current opinion in pharmacology is that dopamine instead confers motivational salience. Outside the central nervous system, dopamine functions as a local paracrine messenger. In blood vessels, it acts as a vasodilator. With the exception of the blood vessels, dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it. Several important diseases of the nervous system are associated with dysfunctions of the dopamine system, some of the key medications used to treat them work by altering the effects of dopamine. Parkinson's disease, a degenerative condition causing tremor and motor impairment, is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra, its metabolic precursor L-DOPA can be manufactured. There is evidence that schizophrenia involves altered levels of dopamine activity, most antipsychotic drugs used to treat this are dopamine antagonists which reduce dopamine activity.
Similar dopamine antagonist drugs are some of the most effective anti-nausea agents. Restless legs syndrome and attention deficit hyperactivity disorder are associated with decreased dopamine activity. Dopaminergic stimulants can be addictive in high doses, but some are used at lower doses to treat ADHD. Dopamine itself is available as a manufactured medication for intravenous injection: although it cannot reach the brain from the bloodstream, its peripheral effects make it useful in the treatment of heart failure or shock in newborn babies. A dopamine molecule consists of a catechol structure with one amine group attached via an ethyl chain; as such, dopamine is the simplest possible catecholamine, a family that includes the neurotransmitters norepinephrine and epinephrine. The presence of a benzene ring with this amine attachment makes it a substituted phenethylamine, a family that includes numerous psychoactive drugs. Like most amines, dopamine is an organic base; as a base, it is protonated in acidic environments.
The protonated form is water-soluble and stable, but can become oxidized if exposed to oxygen or other oxidants. In basic environments, dopamine is not protonated. In this free base form, it is less water-soluble and more reactive; because of the increased stability and water-solubility of the protonated form, dopamine is supplied for chemical or pharmaceutical use as dopamine hydrochloride—that is, the hydrochloride salt, created when dopamine is combined with hydrochloric acid. In dry form, dopamine hydrochloride is a fine colorless powder. Dopamine is synthesized in a restricted set of cell types neurons and cells in the medulla of the adrenal glands; the primary and minor metabolic pathways are: Primary: L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine Minor: L-Phenylalanine → L-Tyrosine → p-Tyramine → Dopamine Minor: L-Phenylalanine → m-Tyrosine → m-Tyramine → DopamineThe direct precursor of dopamine, L-DOPA, can be synthesized indirectly from the essential amino acid phenylalanine or directly from the non-essential amino acid tyrosine.
These amino acids are found in nearly every protein and so are available in food, with tyrosine being the most common. Although dopamine is found in many types of food, it is incapable of crossing the blood–brain barrier that surrounds and protects the brain, it must therefore be synthesized inside the brain to perform its neuronal activity. L-Phenylalanine is converted into L-tyrosine by the enzyme phenylalanine hydroxylase, with molecular oxygen and tetrahydrobiopterin as cofactors. L-Tyrosine is converted into L-DOPA by the enzyme tyrosine hydroxylase, with tetrahydrobiopterin, O2, iron as cofactors. L-DOPA is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase, with pyridoxal phosphate as the cofactor. Dopamine itself is used as precursor in the synthesis o
Cannabidiol
Cannabidiol is a phytocannabinoid discovered in 1940. It is one of some 113 identified cannabinoids in cannabis plants, accounting for up to 40% of the plant's extract; as of 2018, preliminary clinical research on cannabidiol included studies of anxiety, movement disorders, pain. Cannabidiol can be taken into the body in multiple ways, including by inhalation of cannabis smoke or vapor, as an aerosol spray into the cheek, by mouth, it may be supplied as CBD oil containing only CBD as the active ingredient, a full-plant CBD-dominant hemp extract oil, dried cannabis, or as a prescription liquid solution. CBD does not have the same psychoactivity as THC, may affect the actions of THC. Although in vitro studies indicate CBD may interact with different biological targets, including cannabinoid receptors and other neurotransmitter receptors, as of 2018 the mechanism of action for its biological effects has not been determined. In the United States, the cannabidiol drug Epidiolex has been approved by the Food and Drug Administration for treatment of two epilepsy disorders.
The side effects of long-term use of the drug include somnolence, decreased appetite, fatigue, weakness, sleeping problems. The U. S. Drug Enforcement Administration has assigned Epidiolex a Schedule V classification, while non-Epidiolex CBD remains a Schedule I drug prohibited for any use. Cannabidiol is not scheduled under any United Nations drug control treaties, in 2018 the World Health Organization recommended that it remain unscheduled. There has been little high-quality research into the use of cannabidiol for epilepsy, what there is is limited to refractory epilepsy in children. While the results of using medical-grade cannabidiol in combination with conventional medication shows some promise, they did not lead to seizures being eliminated, were associated with some minor adverse effects. An orally administered cannabidiol solution was approved by the US Food and Drug Administration in June 2018 as a treatment for two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome.
Preliminary research on other possible therapeutic uses for cannabidiol include several neurological disorders, but the findings have not been confirmed by sufficient high-quality clinical research to establish such uses in clinical practice. Preliminary research indicates that cannabidiol may reduce adverse effects of THC those causing intoxication and sedation, but only at high doses. Safety studies of cannabidiol showed it is well-tolerated, but may cause tiredness, diarrhea, or changes in appetite as common adverse effects. Epidiolex documentation lists sleepiness and poor quality sleep, decreased appetite and fatigue. Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. In vitro, cannabidiol inhibited receptors affecting the activity of voltage-dependent sodium and potassium channels, which may affect neural activity. A small clinical trial reported that CBD inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC.
Little is known about potential drug interactions but CBD-mediates decrease in clobazam metabolism. Cannabidiol has low affinity for the cannabinoid CB2 receptors. Cannabidiol may be an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor, expressed in the caudate nucleus and putamen in the brain, it may act as an inverse agonist of GPR3, GPR6, GPR12. CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist, this action may be involved in its antidepressant and neuroprotective effects, it is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD may involve PPARγ intracellular calcium release; the oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45%. The elimination half-life of CBD is 18–32 hours. Cannabidiol is metabolized in the liver as well as in the intestines by CYP2C19 and CYP3A4 enzymes, UGT1A7, UGT1A9, UGT2B7 isoforms. CBD may have a wide margin in dosing.
Nabiximols is a patented medicine containing THC in equal proportions. The drug was approved by Health Canada in 2005 for prescription to treat central neuropathic pain in multiple sclerosis, in 2007 for cancer related pain. In New Zealand, Sativex is "approved for use as an add-on treatment for symptom improvement in people with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication." Cannabidiol is soluble in organic solvents such as pentane. At room temperature, it is a colorless crystalline solid. In basic media and the presence of air, it is oxidized to a quinone. Under acidic conditions it cyclizes to THC, which occurs during pyrolysis; the synthesis of cannabidiol has been accomplished by several research groups. Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase. Cannabinoids were isolated from the cannabis plant in 1940 by Roger Adams, its chemical structure was established in 1963.
Cannabidiol is the generic name of the drug and its INN. Food and beverage products containing CBD were introduced in the United States in 2017. Similar to energy drinks and protein bars which may contain vitamin or herbal additives and beverage items can be infused with CBD as an alternative means of ingesting the substance. In the United S
Szilveszter E. Vizi
Szilveszter E. Vizi is a Hungarian physician, neuroscientist and university professor who served as President of the Hungarian Academy of Sciences between 2002 and 2008, he issues some of his papers under E. Sylvester Vizi. Vizi was born in Budapest, he is the father of two children. His wife, Veronika Ádám, is a professor of biochemistry at the Semmelweis University and a full member of the Hungarian Academy of Sciences. Thought his studies had started in Pécs at the University of Medicine, he moved to Budapest in 1956, where he graduated in 1961 in Semmelweis University, the oldest medical school in Hungary. After graduation Vizi remained at the university, where at first he became an assistant professor and in 1965, an associate professor at the Department of Pharmacology, he earned the title Candidate of Sciences in 1969. Vizi received his evaluation as professor of pharmacology in 1976. One year he earned the title Doctor of Sciences; the same year Vizi was named deputy chairman of the medical research council department at the Ministry of Health in Hungary.
He held both posts until 1981, when he became the deputy director at the Institute of Experimental Medicine of the Hungarian Academy of Sciences and Chair of the Department of Pharmacology and Therapy at the Imre Haynal University of Health. He was named director of the institute in 1989 and held this post until 2002, he was elected to the Academy as a corresponding member in 1985 and as a full member in 1990. Vizi worked as vice president of the Academy from 1996 to 2002, when he became the president of the Academy, he held his position until 2008. He was inducted to the Academia Europaea in 1992. In 2010, he was elected to the board of the Hungarian Football Association. Vizi was a Riker Fellow at the Department of Pharmacology of the University of Oxford from 1967 to 1969, where he worked alongside Sir William Paton, he was visiting professor at the universities of Parma. He taught at the Albert Einstein College of Medicine of Yeshiva University as a visiting professor since 1984. Vizi works as Editor-in-chief of Neurochemistry International and as Section Editor of the Brain Research Bulletin.
Phenylisopropylmethylpropynylamine, a monoaminoxidase inhibitor antagonising the effect of tyramin The inhibitory action of norandrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip The mechanism of acetylcholine release from parasympathetic nerves Evidence That Acetylcholine Released by Gastrin and Related Polypeptides Contributes to Their Effect on Gastrointestinal Motility The Inhibitory Effect of Adenosine and Related Nulceotids on the Release of Acetylcholine Na~~+-K~~+-activated adenosinetriphosphatase as a trigger in transmitter release Changes in total and quantal release of acetylcholine in the mouse diaphragm during activation and inhibiton of membrane ATPase Presynaptic Modulation of Neurochemical Transmission Non-Synaptic Interactions between Neurons Effect of nicotine on extracellular levels of neurotransmitters assessed by microdialysis in various brain regions: Role of glutamic acid Science in the Future of Europe Adenosine receptor agonists differentially regulate IL-10, TNF-~a, nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice Neurochemistry and pharmacology of the major hippocampal transmitter systems: Synaptic and nonsynaptic interactions Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons Modulatory role of presynaptic nicotinic receptors in synaptic and non-synaptic chemical communication in the nervous system The sympathetic nerve-an integrative interface between two supersystems: The brain and the immune system Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the nervous system Nitric oxide: a novel link between synaptic and nonsynaptic transmission Handbook of neurochemistry and molecular neurobiology: Neurotransmitter systems Non-synaptic receptors and transporters involved in brain functions and targets of drug treatment List of Vizi's publications
