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Friday, November 24, 2017

Nicotine

From Wikipedia, the free encyclopedia

Nicotine.svg
Nicotine-3D-vdW.png
Clinical data
Trade names Nicorette, Nicotrol
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: D
  • US: D (Evidence of risk)
Dependence
liability
Physical: low–moderate
Psychological: moderate–high[1][2]
Addiction
liability
High[3]
Routes of
administration
Inhalation; insufflation; oral – buccal, sublingual, and ingestion; transdermal; rectal
ATC code
Legal status
Legal status
  • AU: Unscheduled
  • CA: Unscheduled
  • DE: Unscheduled
  • NZ: Unscheduled
  • UK: Unscheduled
  • US: Unscheduled
  • UN: Unscheduled
Pharmacokinetic data
Protein binding <5 td="">
Metabolism Primarily hepatic: CYP2A6, CYP2B6, FMO3, others
Metabolites Cotinine
Biological half-life 1-2 hours; 20 hours active metabolite
Excretion Urine (10-20% (gum), pH-dependent; 30% (inhaled); 10-30% (intranasal))
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
ECHA InfoCard 100.000.177
Chemical and physical data
Formula C10H14N2
Molar mass 162.23 g/mol
3D model (JSmol)
Chirality Chiral
Density 1.01 g/cm3
Melting point −79 °C (−110 °F)
Boiling point 247 °C (477 °F)
 Yes (what is this?)  (verify)

Nicotine is a potent parasympathomimetic stimulant and an alkaloid found in the nightshade family of plants. Nicotine acts as an agonist at most nicotinic acetylcholine receptors (nAChRs),[4][5] except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.[4] Nicotine is found in the leaves of Nicotiana rustica, in amounts of 2–14%; in the tobacco plant, Nicotiana tabacum; in Duboisia hopwoodii; and in Asclepias syriaca.[6]

Nicotine constitutes approximately 0.6–3.0% of the dry weight of tobacco.[7] It also occurs in edible plants, such Solanaceae, which include eggplants, potatoes, and tomatoes, but at trace levels generally under 200 nanograms per gram, dry weight (less than .00002%).[8][9][10] Nicotine functions as an antiherbivore chemical; consequently, nicotine was widely used as an insecticide in the past,[11][12] and neonicotinoids, such as imidacloprid, are widely used.

Nicotine is highly addictive.[13][14] An average cigarette yields about 2 mg of absorbed nicotine; in lesser doses of that order, the substance acts as a stimulant in mammals, while high amounts (50–100 mg) can be harmful.[15][16][17] This stimulant effect is a contributing factor to the addictive properties of tobacco smoking. Nicotine's addictive nature includes psychoactive effects, drug-reinforced behavior, compulsive use, relapse after abstinence, physical dependence and tolerance.[18]

Beyond addiction, both short and long-term nicotine exposure have not been established as dangerous to adults,[19] except among certain vulnerable groups.[20] At high-enough doses, nicotine is associated with poisonings and is potentially lethal.[17][21] Nicotine as a tool for quitting smoking has a good safety history.[22] There is inadequate research to show that nicotine itself is associated with cancer in humans.[21] Nicotine in the form of nicotine replacement products is less of a cancer risk than smoking.[21] Nicotine is linked to possible birth defects.[23] During pregnancy, there are risks to the child later in life for type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[22] The use of electronic cigarettes, which are designed to be refilled with nicotine-containing e-liquid, has raised concerns over nicotine overdoses, especially with regard to the possibility of young children ingesting the liquids.[24]

Psychoactive effects

Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[25] First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness.[26]

When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates nicotinic acetylcholine receptors; this indirectly promotes the release of many chemical messengers such as acetylcholine, norepinephrine, epinephrine, arginine vasopressin, serotonin, dopamine, and beta-endorphin in parts of the brain.[27][28] Nicotine also extends the duration of positive effects of dopamine and increases the sensitivity of the brain's reward system to rewarding stimuli.[29][30] Most cigarettes contain 1–3 milligrams of inhalable nicotine.[31][unreliable source?] Studies suggest that when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.[32][needs update]

Nicotine is unusual in comparison to most drugs, as its profile changes from stimulant to sedative with increasing dosages, a phenomenon known as "Nesbitt's paradox" after the doctor who first described it in 1969.[33][34] At very high doses it dampens neuronal activity.[35]

Uses

Medical

A 21 mg patch applied to the left arm. The Cochrane Collaboration finds that nicotine replacement therapy increases a quitter's chance of success by 50% to 70%.[36]

The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence. Studies have found that these therapies increase the chance of success of quitting by 50 to 70%,[36] though reductions in the population as a whole have not been demonstrated.[37]

Enhancing performance

Nicotine is frequently used for its performance-enhancing effects on cognition, alertness, and focus.[38] A meta-analysis of 41 double-blind, placebo-controlled studies concluded that nicotine or smoking had significant positive effects on aspects of fine motor abilities, alerting and orienting attention, and episodic and working memory.[39] A 2015 review noted that stimulation of the α4β2 nicotinic receptor is responsible for certain improvements in attentional performance;[40] among the nicotinic receptor subtypes, nicotine has the highest binding affinity at the α4β2 receptor (ki=1 nM), which is also the biological target that mediates nicotine's addictive properties.[41] Nicotine has potential beneficial effects, but it also has paradoxical effects, which may be due to its inverted U-shape or pharmacokinetic features.[42]

Recreational

Nicotine is commonly consumed as a recreational drug for its stimulant effects.[43] Recreational nicotine products include chewing tobacco, cigars, cigarettes, e-cigarettes, snuff, pipe tobacco, and snus.

Adverse effects

Limited data exists on the health effects of long-term use of pure nicotine, because nicotine is usually consumed via tobacco products.[44] The long-term use of nicotine in the form of snus incurs a slight risk of cardiovascular disease compared to tobacco smoking[44] and is not associated with cancer.[45][not in citation given] Nicotine is one of the most rigorously studied drugs.[46] The complex effects of nicotine are not entirely understood.[23] Studies of continued use of nicotine replacement products in those who have stopped smoking found no adverse effects from months to several years, and that people with cardiovascular disease were able to tolerate them for 12 weeks.[44] The general medical position is that nicotine itself, in small doses[failed verification], poses few health risks, except among certain vulnerable groups.[20] A 2016 Royal College of Physicians report found "nicotine alone in the doses used by smokers represents little if any hazard to the user".[47] A 2014 American Heart Association policy statement found that some health concerns relate to nicotine.[44] Experimental research suggests that adolescent nicotine use may harm brain development.[21] Children exposed to nicotine may have a number of lifelong health issues.[14] Administration of nicotine to guinea pigs has been shown to cause harm to cells of the inner ear.[48][unreliable medical source?] As medicine, nicotine is used to help with quitting smoking and has good safety in this form.[22]

Metabolism and body weight

By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.[49][50] By increasing metabolic rate and inhibiting the usual compensatory increase in appetite, the body weight of smokers is lower on average than that of non-smokers. When smokers quit, they gain on average 5–6 kg weight, returning to the average weight of non-smokers.[51]

Vascular system

Human epidemiology studies show that nicotine use is not a significant cause of cardiovascular disease.[52] A 2015 review found that nicotine is associated with cardiovascular disease.[23] A 2016 review suggests that "the risks of nicotine without tobacco combustion products (cigarette smoke) are low compared to cigarette smoking, but are still of concern in people with cardiovascular disease."[53] Some studies in people show the possibility that nicotine contributes to acute cardiovascular events in smokers with established cardiovascular disease, and induces pharmacologic effects that might contribute to increased atherosclerosis.[53] Prolonged nicotine use seems not to increase atherosclerosis.[53] Brief nicotine use, such as nicotine medicine, seems to incur a slight cardiovascular risk, even to people with established cardiovascular disease.[53] A 2015 review found "Nicotine in vitro and in animal models can inhibit apoptosis and enhance angiogenesis, effects that raise concerns about the role of nicotine in promoting the acceleration of atherosclerotic disease."[54] A 2012 Cochrane review found no evidence of an increased risk of cardiovascular disease with nicotine replacement products.[55] A 1996 randomized controlled trial using nicotine patches found that serious adverse events were not more frequent among smokers with cardiovascular disease.[55] A meta-analysis shows that snus consumption, which delivers nicotine at a dose equivalent to that of cigarettes, is not associated with heart attacks.[56] Hence, it is not nicotine, but tobacco smoke's other components which seem to be implicated in ischemic heart disease.[56] Nicotine increases heart rate and blood pressure[57] and induces abnormal heart rhythms.[58] Nicotine can also induce potentially atherogenic genes in human coronary artery endothelial cells.[59] Microvascular injury can result through its action on nicotinic acetylcholine receptors (nAChRs).[60] Nicotine does not adversely affect serum cholesterol levels,[52] but a 2015 review found it may elevate serum cholesterol levels.[23] Many quitting smoking studies using nicotine medicines report lowered dyslipidemia with considerable benefit in HDL/LDL ratios.[53] Nicotine supports clot formation and aids in plaque formation by enhancing vascular smooth muscle.[23]

Cancer

Possible side effects of nicotine.[61]

Although there is insufficient evidence to classify nicotine as a carcinogen, there is an ongoing debate about whether it functions as a tumor promoter.[62] In vitro studies have associated it with cancer, but carcinogenicity has not been demonstrated in vivo.[23] There is inadequate research to demonstrate that nicotine is associated with cancer in humans, but there is evidence indicating possible oral, esophageal, or pancreatic cancer risks.[21] Nicotine in the form of nicotine replacement products is less of a cancer risk than smoking.[21] Nicotine replacement products have not been shown to be associated with cancer in the real world.[23]

While no epidemiological evidence directly supports the notion that nicotine acts as a carcinogen in the formation of human cancer, research has identified nicotine's indirect involvement in cancer formation in animal models and cell cultures.[63][64][65] Nicotine increases cholinergic signalling and adrenergic signalling in the case of colon cancer,[66] thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-lipoxygenase (5-LOX), and epidermal growth factor (EGF). Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization.[67][68] In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), metastasis (nine-fold increase), and tumor recurrence (threefold increase).[69] N-Nitrosonornicotine (NNN), classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen, has been shown to form in vitro from nornicotine in human saliva, indicating nornicotine is a carcinogen precursor.[70] The IARC has not evaluated pure nicotine or assigned it to an official carcinogenic classification.
In cancer cells, nicotine promotes the epithelial–mesenchymal transition which makes the cancer cells more resistant to drugs that treat cancer.[71]

Fetal development

In pregnancy, a 2013 review noted that "nicotine is only 1 of more than 4000 compounds to which the fetus is exposed through maternal smoking. Of these, ∼30 compounds have been associated with adverse health outcomes. Although the exact mechanisms by which nicotine produces adverse fetal effects are unknown, it is likely that hypoxia, undernourishment of the fetus, and direct vasoconstrictor effects on the placental and umbilical vessels all play a role. Nicotine also has been shown to have significant deleterious effects on brain development, including alterations in brain metabolism and neurotransmitter systems and abnormal brain development." It also notes that "abnormalities of newborn neurobehavior, including impaired orientation and autonomic regulation and abnormalities of muscle tone, have been identified in a number of prenatal nicotine exposure studies" and that there is weak data associating fetal nicotine exposure with newborn facial clefts, and that there is no good evidence for newborns suffering nicotine withdrawal from fetal exposure to nicotine.[72]

Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to cause developmental toxicity.[73]

Nicotine is not safe to use in any amount during pregnancy.[74] Questions exist regarding nicotine use during pregnancy and their potential consequences on fetal growth and mortality.[47] Nicotine negatively affects pregnancy outcomes and fetal brain development.[21] Risks to the child later in life via nicotine exposure during pregnancy include type 2 diabetes, obesity, hypertension, neurobehavioral defects, respiratory dysfunction, and infertility.[22] Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke.[75]

Reinforcement disorders

Nicotine dependence involves aspects of both psychological dependence and physical dependence, since discontinuation of extended use has been shown to produce both affective (e.g., anxiety, irritability, craving, anhedonia) and somatic (mild motor dysfunctions such as tremor) withdrawal symptoms.[1] Withdrawal symptoms peak in the first day or two[76] and can persist for several weeks.[77] Nicotine has clinically significant cognitive-enhancing effects at low doses, particularly in fine motor skills, attention, and memory. These beneficial cognitive effects may play a role in the maintenance of tobacco dependence.[77]
Nicotine is highly addictive,[13][14][78] comparable to heroin or cocaine.[20] Nicotine activates the mesolimbic pathway and induces long-term ΔFosB expression in the nucleus accumbens when inhaled or injected at sufficiently high doses, but not necessarily when ingested.[79][80][81] Consequently, repeated daily exposure (possibly excluding oral route) to nicotine can result in accumbal ΔFosB overexpression, in turn causing nicotine addiction.[79][80]

In dependent smokers, smoking during withdrawal returns cognitive abilities to pre-withdrawal levels, but chronic use may not offer cognitive benefits over not smoking.[21][82]

Use of other drugs

In animals it is relatively simple to determine if consumption of a certain drug increases the later attraction of another drug. In humans, where such direct experiments are not possible, longitudinal studies can show if the probability of a substance use is related to earlier use of other substances.[83]
In mice nicotine increased the probability of later consumption of cocaine and the experiments permitted concrete conclusions on the underlying molecular biological alteration in the brain.[84] The biological changes in mice correspond to the epidemiological observations in humans that nicotine consumption is coupled to an increased probability of later use of cannabis and cocaine.[85]

In rats cannabis consumption – earlier in life – increased the later self-administration of nicotine.[86] A study of drug use of 14,577 US 12th graders showed that alcohol consumption was associated with an increased probability of later use of tobacco, cannabis, and other illegal drugs.[87]

Overdose

Nicotine is regarded as a potentially lethal poison.[88] The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans.[15][89] However, the widely used human LD50 estimate of 0.5–1.0 mg/kg was questioned in a 2013 review, in light of several documented cases of humans surviving much higher doses; the 2013 review suggests that the lower limit causing fatal outcomes is 500–1000 mg of ingested nicotine, corresponding to 6.5–13 mg/kg orally.[17] Nevertheless, nicotine has a relatively high toxicity in comparison to many other alkaloids such as caffeine, which has an LD50 of 127 mg/kg when administered to mice.[90]
At high-enough doses, it is associated with nicotine poisoning.[21] Today nicotine is less commonly used in agricultural insecticides, which was a main source of poisoning. More recent cases of poisoning typically appear to be in the form of Green Tobacco Sickness or due to accidental ingestion of tobacco or tobacco products or ingestion of nicotine-containing plants.[91][92][93] People who harvest or cultivate tobacco may experience Green Tobacco Sickness (GTS), a type of nicotine poisoning caused by dermal exposure to wet tobacco leaves. This occurs most commonly in young, inexperienced tobacco harvesters who do not consume tobacco.[91][94] People can be exposed to nicotine in the workplace by breathing it in, skin absorption, swallowing it, or eye contact. The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for nicotine exposure in the workplace as 0.5 mg/m3 skin exposure over an 8-hour workday. The US National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit (REL) of 0.5 mg/m3 skin exposure over an 8-hour workday. At environmental levels of 5 mg/m3, nicotine is immediately dangerous to life and health.[95]

It is unlikely that a person would overdose on nicotine through smoking alone. The US Food and Drug Administration (FDA) stated in 2013 that "There are no significant safety concerns associated with using more than one OTC NRT at the same time, or using an OTC NRT at the same time as another nicotine-containing product—including a cigarette."[96]

The rise in the use of electronic cigarettes, many forms of which are designed to be refilled with nicotine-containing e-liquid supplied in small plastic bottles, has raised concerns over nicotine overdoses, especially in the possibility of young children ingesting the liquids.[24] A 2015 Public Health England report noted an "unconfirmed newspaper report of a fatal poisoning of a two-year old child" and two published case reports of children of similar age who had recovered after ingesting e-liquid and vomiting.[24] They also noted case reports of suicides by nicotine.[24] Where adults drank liquid containing up to 1,500 mg of nicotine they recovered (helped by vomiting), but an ingestion apparently of about 10,000 mg was fatal, as was an injection.[24] They commented that "Serious nicotine poisoning seems normally prevented by the fact that relatively low doses of nicotine cause nausea and vomiting, which stops users from further intake."[24]

Pharmacology

Pharmacodynamics

Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs),[4][5] except at two nicotinic receptor subunits (nAChRα9 and nAChRα10) where it acts as a receptor antagonist.[4]

Central nervous system

Effect of nicotine on dopaminergic neurons.

By binding to nicotinic acetylcholine receptors in the brain, nicotine elicits its psychoactive effects and increases the levels of several neurotransmitters in various brain structures – acting as a sort of "volume control."[medical citation needed] Nicotine has a higher affinity for nicotinic receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis.[97] Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.[98]

Nicotine activates nicotinic receptors (particularly α4β2 nicotinic receptors) on neurons that innervate the ventral tegmental area and within the mesolimbic pathway where it appears to cause the release of dopamine.[99][100] This nicotine-induced dopamine release occurs at least partially through activation of the cholinergic–dopaminergic reward link in the ventral tegmental area.[100] Nicotine also appears to induce the release of endogenous opioids that activate opioid pathways in the reward system, since naltrexone – an opioid receptor antagonist – blocks nicotine self-administration.[99] These actions are largely responsible for the strongly reinforcing effects of nicotine, which often occur in the absence of euphoria;[99] however, mild euphoria from nicotine use can occur in some individuals.[99] Chronic nicotine use inhibits class I and II histone deacetylases in the striatum, where this effect plays a role in nicotine addiction.[101][102]

Sympathetic nervous system

Effect of nicotine on chromaffin cells.

Nicotine also activates the sympathetic nervous system,[103] acting via splanchnic nerves to the adrenal medulla, stimulating the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream.

Adrenal medulla

By binding to ganglion type nicotinic receptors in the adrenal medulla, nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.[104]

Pharmacokinetics

Urinary metabolites of nicotine, quantified as average percentage of total urinary nicotine.[105]

As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation.[106] The elimination half-life of nicotine in the body is around two hours.[107]

The amount of nicotine absorbed by the body from smoking can depend on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. However, it has been found that the nicotine yield of individual products has only a small effect (4.4%) on the blood concentration of nicotine,[108] suggesting "the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation".

Nicotine has a half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood with a half-life of 18–20 hours, making it easier to analyze.[109]

Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6) and FMO3, which selectively metabolizes (S)-nicotine. A major metabolite is cotinine. Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.[110] Under some conditions, other substances may be formed such as myosmine.[111]

Glucuronidation and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine in vivo.[112]

Chemistry

NFPA 704
fire diamond
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 4: Very short exposure could cause death or major residual injury. E.g., VX gas Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
1
4
0
The fire diamond hazard sign for nicotine.[113]

Nicotine is a hygroscopic, colorless to yellow-brown, oily liquid, that is readily soluble in alcohol, ether or light petroleum. It is miscible with water in its base form between 60 °C and 210 °C. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C.[114]

Nicotine is readily volatile (vapor pressure 5.5 ㎩ at 25 ℃) and dibasic (Kb1 = 1×10⁻⁶, Kb2 = 1×10⁻¹¹).[6]

Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [α]D = –166.4° ((−)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine.[115] The salts of (+)-nicotine are usually dextrorotatory. The hydrochloride and sulphate salts become optically inactive if heated in a closed vessel above 180 °C.[116]

On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (vitamin B3), and methylamine.[116]

Occurrence and biosynthesis

Nicotine biosynthesis

Nicotine is a natural product of tobacco, occurring in the leaves in a range of 0.5 to 7.5% depending on variety.[117] Nicotine also naturally occurs in smaller amounts in plants from the family Solanaceae (such as potatoes, tomatoes, and eggplant).[9]

The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin (nicotinic acid) while the pyrrolidone is derived from N-methyl-Δ1-pyrrollidium cation.[118][119] Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for niacin and the tropane pathway for N-methyl-Δ1-pyrrollidium cation.

The NAD pathway in the genus nicotiana begins with the oxidation of aspartic acid into α-imino succinate by aspartate oxidase (AO). This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form niacin mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce niacin via the conversion of nicotinamide by the enzyme nicotinamidase.[citation needed]

The N-methyl-Δ1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-Δ1-pyrrollidium cation.[citation needed]

The final step in the synthesis of nicotine is the coupling between N-methyl-Δ1-pyrrollidium cation and niacin. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of niacin into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-Δ1-pyrrollidium cation to form enantiomerically pure (−)-nicotine.[120]

Detection in body fluids

Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a forensic autopsy. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids.[121][122] Nicotine use is not regulated in competitive sports programs.[123]

History

Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560, presented to the French King,[124] and who promoted their medicinal use. Smoking was believed to protect against illness, particularly the plague.[124]
Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals.[12]

Currently, nicotine, even in the form of tobacco dust, is prohibited as a pesticide for organic farming in the United States.[125][126]

In 2008, the EPA received a request, from the registrant, to cancel the registration of the last nicotine pesticide registered in the United States.[127] This request was granted, and since 1 January 2014, this pesticide has not been available for sale.[128]

Chemical identification

Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison.[129][130] Its chemical empirical formula was described by Melsens in 1843,[131] its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,[132][133][134][clarification needed] and it was first synthesized by Amé Pictet and A. Rotschy in 1904.[135]

Society and culture

The nicotine content of popular American-brand cigarettes has increased over time, and one study found that there was an average increase of 1.78% per year between the years of 1998 and 2005.[136]

Research

While acute/initial nicotine intake causes activation of nicotine receptors, chronic low doses of nicotine use leads to desensitisation of nicotine receptors (due to the development of tolerance) and results in an antidepressant effect, with early research showing low dose nicotine patches could be an effective treatment of major depressive disorder in non-smokers.[137] However, the original research concluded that: "Nicotine patches produced short-term improvement of depression with minor side effects. Because of nicotine's high risk to health, nicotine patches are not recommended for clinical use in depression."[138]

Though tobacco smoking is associated with an increased risk of Alzheimer's disease,[139] there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.[140]
Research into nicotine's most predominant metabolite, cotinine, suggests that some of nicotine's psychoactive effects are mediated by cotinine.[141][142]

Little research is available in humans but animal research suggests there is potential benefit from nicotine in Parkinson's disease.[143]

Thursday, November 23, 2017

Ascorbic acid

From Wikipedia, the free encyclopedia
L-Ascorbic acid
L-Ascorbic acid.svg
Ascorbic-acid-from-xtal-1997-3D-balls.png
Names
IUPAC name
(5R)-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one
Other names
Vitamin C
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
EC Number 200-066-2
KEGG
PubChem CID
UNII
Properties
C6H8O6
Molar mass 176.12 g·mol−1
Appearance White or light yellow solid
Density 1.65 g/cm3
Melting point 190 to 192 °C (374 to 378 °F; 463 to 465 K) decomposes
330 g/L
Solubility in ethanol 20 g/L
Solubility in glycerol 10 g/L
Solubility in propylene glycol 50 g/L
Solubility in other solvents insoluble in diethyl ether, chloroform, benzene, petroleum ether, oils, fats
Acidity (pKa) 4.10 (first), 11.6 (second)
Pharmacology
A11GA01 (WHO) G01AD03 (WHO), S01XA15 (WHO)
Hazards
Safety data sheet JT Baker
NFPA 704
Flammability code 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g., canola oil Health code 1: Exposure would cause irritation but only minor residual injury. E.g., turpentine Reactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g., liquid nitrogen Special hazards (white): no codeNFPA 704 four-colored diamond
1
1
0
Lethal dose or concentration (LD, LC):
LD50 (median dose)
11.9 g/kg (oral, rat)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
 verify (what is Yes ?)
Infobox references



Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form ("vitamer") of vitamin C. It was originally called L-hexuronic acid, but, when it was found to have vitamin C activity in animals ("vitamin C" being defined as a vitamin activity, not then a specific substance), the suggestion was made to rename it. The new name, ascorbic acid, is derived from a- (meaning "no") and scorbutus (scurvy), the disease caused by a deficiency of vitamin C. Because it is derived from glucose, many animals are able to produce it, but humans require it as part of their nutrition. Other vertebrates which lack the ability to produce ascorbic acid include some primates, guinea pigs, teleost fishes, bats, and some birds, all of which require it as a dietary micronutrient (that is, in vitamin form).[2]

History

From the middle of the 18th century, it was noted that lemon and lime juice could help prevent sailors from getting scurvy. At first, it was supposed that the acid properties were responsible for this benefit; however, it soon became clear that other dietary acids, such as vinegar, had no such benefits. In 1907, two Norwegian physicians reported an essential disease-preventing compound in foods that was distinct from the one that prevented beriberi. These physicians were investigating dietary-deficiency diseases using the new animal model of guinea pigs, which are susceptible to scurvy. The newly discovered food-factor was eventually called vitamin C.

From 1928 to 1932, the Hungarian research team led by Albert Szent-Györgyi, as well as that of the American researcher Charles Glen King, identified the antiscorbutic factor as a particular single chemical substance. Szent-Györgyi isolated the chemical hexuronic acid first from plants and later from animal adrenal glands. He suspected it to be the antiscorbutic factor but could not prove it without a biological assay. This assay was finally conducted at the University of Pittsburgh in the laboratory of King, which had been working on the problem for years, using guinea pigs. In late 1931, King's lab obtained adrenal hexuronic acid indirectly from Szent-Györgyi and, using their animal model, proved that it is vitamin C, by early 1932.

This was the last of the compound from animal sources, but, later that year, Szent-Györgyi's group discovered that paprika pepper, a common spice in the Hungarian diet, is a rich source of hexuronic acid. He sent some of the now more available chemical to Walter Norman Haworth, a British sugar chemist.[3] In 1933, working with the then-Assistant Director of Research (later Sir) Edmund Hirst and their research teams, Haworth deduced the correct structure and optical-isomeric nature of vitamin C, and in 1934 reported the first synthesis of the vitamin.[4] In honor of the compound's antiscorbutic properties, Haworth and Szent-Györgyi now proposed the new name of "a-scorbic acid" for the compound. It was named L-ascorbic acid by Haworth and Szent-Györgyi when its structure was finally proven by synthesis.[5]

In 1937, the Nobel Prize for chemistry was awarded to Haworth for his work in determining the structure of ascorbic acid — shared with Paul Karrer, who received his award for work on vitamins — and the prize for Physiology or Medicine that year went to Albert Szent-Györgyi for his studies of the biological functions of L-ascorbic acid.

The American physician Fred R. Klenner, M.D. promoted vitamin C as a cure for many diseases in the 1950s by elevating the dosages greatly to as much as tens of grams vitamin C daily orally and by injection. From 1967 on, Nobel prize winner Linus Pauling recommended high doses of ascorbic acid as a prevention against cold and cancer. However, modern evidence does not support a role for high-dose vitamin C in the treatment of cancer or the prevention of the common cold in the general population.[6][7]

Acidity

Canonical structures for the ascorbate anion
Ascorbic acid is classed as a reductone. The ascorbate anion is stabilized by electron delocalization, as shown above in terms of resonance between two canonical forms. For this reason, ascorbic acid is much more acidic than would be expected if the compound contained only isolated hydroxyl groups.

Antioxidant mechanism

Semidehydroascorbate acid radical

The ascorbate ion is the predominant species at typical biological pH values. It is a mild reducing agent and antioxidant. It is oxidized with loss of one electron to form a radical cation and then with loss of a second electron to form dehydroascorbic acid. It typically reacts with oxidants of the reactive oxygen species, such as the hydroxyl radical. Such radicals are damaging to animals and plants at the molecular level due to their possible interaction with nucleic acids, proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions by electron transfer. Ascorbic acid is special because it can transfer a single electron, owing to the resonance-stabilized nature of its own radical ion, called semidehydroascorbate. The net reaction is:
RO + C
6
H
7
O
6
→ RO + C6H7O
6
→ ROH + C6H6O6[8]
The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage.
However, being a good electron donor, excess ascorbate in the presence of free metal ions can not only promote but also initiate free radical reactions, thus making it a potentially dangerous pro-oxidative compound in certain metabolic contexts.

On exposure to oxygen, ascorbic acid will undergo further oxidative decomposition to various products including diketogulonic acid, xylonic acid, threonic acid and oxalic acid.[9]

Reactions

Nucleophilic attack of ascorbic enol on proton to give 1,3-diketone

Food chemistry

Ascorbic acid and its sodium, potassium, and calcium salts are commonly used as antioxidant food additives. These compounds are water-soluble and, thus, cannot protect fats from oxidation: For this purpose, the fat-soluble esters of ascorbic acid with long-chain fatty acids (ascorbyl palmitate or ascorbyl stearate) can be used as food antioxidants. Eighty percent of the world's supply of ascorbic acid is produced in China.[10]

The relevant European food additive E numbers are:
  1. E300 ascorbic acid (approved for use as a food additive in the EU[11] USA[12] and Australia and New Zealand)[13]
  2. E301 sodium ascorbate (approved for use as a food additive in the EU[11] USA[14] and Australia and New Zealand)[13]
  3. E302 calcium ascorbate (approved for use as a food additive in the EU[11] USA[12] and Australia and New Zealand)[13]
  4. E303 potassium ascorbate
  5. E304 fatty acid esters of ascorbic acid (i) ascorbyl palmitate (ii) ascorbyl stearate.
It creates volatile compounds when mixed with glucose and amino acids in 90 °C.[15]

It is a cofactor in tyrosine oxidation.[16]

Niche, non-food uses

  • Ascorbic acid is easily oxidized and so is used as a reductant in photographic developer solutions (among others) and as a preservative.
  • In fluorescence microscopy and related fluorescence-based techniques, ascorbic acid can be used as an antioxidant to increase fluorescent signal and chemically retard dye photobleaching.[17]
  • It is also commonly used to remove dissolved metal stains, such as iron, from fiberglass swimming pool surfaces.
  • In plastic manufacturing, ascorbic acid can be used to assemble molecular chains more quickly and with less waste than traditional synthesis methods.[18]
  • Heroin users are known to use ascorbic acid as a means to convert heroin base to a water-soluble salt so that it can be injected.[19]
  • As justified by its reaction with iodine, it is used to negate the effects of iodine tablets in water purification. It reacts with the sterilized water, removing the taste, color, and smell of the iodine. This is why it is often sold as a second set of tablets in most sporting goods stores as Portable Aqua-Neutralizing Tablets, along with the potassium iodide tablets.
  • Intravenous high-dose ascorbate is being used as a chemotherapeutic and biological response modifying agent.[20] Currently it is still under clinical trials.[21]

Biosynthesis

Ascorbic acid is found in plants and animals where it is produced from glucose.[22] Animals must either produce it or digest it, otherwise a lack of vitamin C may cause scurvy, which may eventually lead to death. Reptiles and older orders of birds make ascorbic acid in their kidneys. Recent orders of birds and most mammals make ascorbic acid in their liver where the enzyme L-gulonolactone oxidase is required to convert glucose to ascorbic acid.[22] Humans, other higher primates, guinea pigs and most bats require dietary ascorbic acid because the enzyme L-gulonolactone oxidase catalysing the last step in the biosynthesis is highly mutated and non-functional, therefore, unable to make ascorbic acid. Synthesis and signalling properties are still under investigation.[23]

Animal ascorbic acid biosynthesis pathway

The biosynthesis of ascorbic acid starts with the formation of UDP-glucuronic acid. UDP-glucuronic acid is formed when UDP-glucose undergoes two oxidations catalyzed by the enzyme UDP-glucose 6-dehydrogenase. UDP-glucose 6-dehydrogenase uses the co-factor NAD+ as the electron acceptor. The transferase UDP-glucuronate pyrophosphorylase removes a UMP and glucuronokinase, with the cofactor ADP, removes the final phosphate leading to D-glucuronic acid. The aldehyde group of this is reduced to a primary alcohol using the enzyme glucuronate reductase and the cofactor NADPH, yielding L-gulonic acid. This is followed by lactone formation with the hydrolase gluconolactonase between the carbonyl on C1 and hydroxyl group on C4. L-Gulonolactone then reacts with oxygen, catalyzed by the enzyme L-gulonolactone oxidase (which is nonfunctional in humans and other Haplorrhini primates) and the cofactor FAD+. This reaction produces 2-oxogulonolactone, which spontaneously undergoes enolization to form ascorbic acid.[24]

Plant ascorbic acid biosynthesis pathway

There are many different biosynthesis pathways for ascorbic acid in plants. Most of these pathways are derived from products found in glycolysis and other pathways. For example, one pathway goes through the plant cell wall polymers.[23] The plant ascorbic acid biosynthesis pathway most principal seems to be L-galactose. L-Galactose reacts with the enzyme L-galactose dehydrogenase, whereby the lactone ring opens and forms again but with between the carbonyl on C1 and hydroxyl group on the C4, resulting in L-galactonolactone.[24] L-Galactonolactone then reacts with the mitochondrial flavoenzyme L-galactonolactone dehydrogenase.[25] to produce ascorbic acid.[24] L-Ascorbic acid has a negative feedback on L-galactose dehydrogenase in spinach.[26] Ascorbic acid efflux by embryo of dicots plants is a well-established mechanism of iron reduction, and a step obligatory for iron uptake.[27]

Yeasts do not make L-ascorbic acid but rather its stereoisomer, erythorbic acid[28]

Industrial preparation

Ascorbic acid is prepared in industry from glucose in a method based on the historical Reichstein process. In the first of a five-step process, glucose is catalytically hydrogenated to sorbitol, which is then oxidized by the microorganism Acetobacter suboxydans to sorbose. Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of the product with acetone in the presence of an acid catalyst converts four of the remaining hydroxyl groups to acetals. The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidant TEMPO (regenerated by sodium hypochloritebleaching solution). Historically, industrial preparation via the Reichstein process used potassium permanganate as the bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups and ring-closing lactonization. This step yields ascorbic acid. Each of the five steps has a yield larger than 90%.[29]

A more biotechnological process, first developed in China in the 1960s, but further developed in the 1990s, bypasses the use of acetone-protecting groups. A second genetically modified microbe species, such as mutant Erwinia, among others, oxidises sorbose into 2-ketogluconic acid (2-KGA), which can then undergo ring-closing lactonization via dehydration. This method is used in the predominant process used by the ascorbic acid industry in China, which supplies 80% of world's ascorbic acid.[30] American and Chinese researchers are competing to engineer a mutant that can carry out a one-pot fermentation directly from glucose to 2-KGA, bypassing both the need for a second fermentation and the need to reduce glucose to sorbitol.[31]

There exists a D-ascorbic acid, which does not occur in nature but can be synthesized artificially. To be specific, L-ascorbate is known to participate in many specific enzyme reactions that require the correct enantiomer (L-ascorbate and not D-ascorbate). L-Ascorbic acid has a specific rotation of [α]20
D
 = +23°.[32]

The outdated, but historically important industrial synthesis of ascorbic acid from glucose via the Reichstein process.

Determination

The traditional way to analyze the ascorbic acid content is the process of titration with an oxidizing agent, and several procedures have been developed, mainly relying on iodometry. Iodine is used in the presence of a starch indicator. Iodine is reduced by ascorbic acid, and, when all the ascorbic acid has reacted, the iodine is then in excess, forming a blue-black complex with the starch indicator. This indicates the end-point of the titration. As an alternative, ascorbic acid can be treated with iodine in excess, followed by back titration with sodium thiosulfate using starch as an indicator.[33] The preceding iodometric method has been revised to exploit reaction of ascorbic acid with iodate and iodide in acid solution. Electrolyzing the solution of potassium iodide produces iodine, which reacts with ascorbic acid. The end of process is determined by potentiometric titration in a manner similar to Karl Fischer titration. The amount of ascorbic acid can be calculated by Faraday's law.

An uncommon oxidising agent is N-bromosuccinimide (NBS). In this titration, the NBS oxidizes the ascorbic acid in the presence of potassium iodide and starch. When the NBS is in excess (i.e., the reaction is complete), the NBS liberates the iodine from the potassium iodide, which then forms the blue-black complex with starch, indicating the end-point of the titration.

Friday, November 17, 2017

Ethnobiology

From Wikipedia, the free encyclopedia
 

Ethnobiology is the scientific study of the way living things are treated or used by different human cultures. It studies the dynamic relationships between people, biota, and environments, from the distant past to the immediate present.[1]

"People-biota-environment" interactions around the world are documented and studied through time, across cultures, and across disciplines in a search for valid, reliable answers to two 'defining' questions: "How and in what ways do human societies use nature, and how and in what ways do human societies view nature?"[2]

History

Beginnings (15th century–19th century)

16th-century English map of the world showing extent of western geographic knowledge in 1599

Naturalists have been interested in local biological knowledge since the time Europeans started colonising the world, from the 15th century onwards. Paul Sillitoe wrote that:[3]
Europeans not only sought to understand the new regions they intruded into but also were on the look-out for resources that they might profitably exploit, engaging in practices that today we should consider tantamount to biopiracy. Many new crops .. entered into Europe during this period, such as the potato, tomato, pumpkin, maize, and tobacco.[3] (Page 121)
Local biological knowledge, collected and sampled over these early centuries significantly informed the early development of modern biology:[3]

Phase I (1900s–1940s)

Ethnobiology itself, as a distinctive practice, only emerged during the 20th century as part of the records then being made about other peoples, and other cultures. As a practice, it was nearly always ancillary to other pursuits when documenting others' languages, folklore, and natural resource use. Roy Ellen commented that:
At its earliest and most rudimentary, this comprised listing the names and uses of plants and animals in native non-Western or 'traditional' populations often in the context of salvage ethnography ..[ie] ethno-biology as the descriptive biological knowledge of 'primitive' peoples.[4]
This 'first phase' in the development of ethnobiology as a practice has been described as still having an essentially utilitarian purpose, often focusing on identifying those 'native' plants, animals and technologies of some potential use and value within increasingly dominant western economic systems[4][5]

Phase II (1950s–1970s)

Arising out of practices in Phase I (above) came a 'second phase' in the development of 'ethnobiology', with researchers now striving to better document and better understand how other peoples' themselves "conceptualise and categorise" the natural world around them.[4] In Sillitoe's words:
By the mid-20th century .. utilitarian-focussed studies started to give way to more cognitively framed ones, notably studies that centred on elucidating classificatory schemes.[3] (Page 122)
Some Mangyan (who count the Hanunóo among their members) men, on Mindoro island, Philippines, where Harold Conklin did his ethnobiological work
This 'second' phase is marked:[4]

Present (1980s–2000s)

By the turn of the 21st century ethnobiological practices, research, and findings have had a significant impact and influence across a number of fields of biological inquiry including ecology,[10] conservation biology,[11][12] development studies,[13] and political ecology.[14]

The Society of Ethnobiology advises on its web page:
Ethnobiology is a rapidly growing field of research, gaining professional, student, and public interest .. internationally
Ethnobiology has come out from its place as an ancillary practice in the shadows of other core pursuits, to arise as a whole field of inquiry and research in its own right: taught within many tertiary institutions and educational programmes around the world;[4] with its own methods manuals,[15] its own readers,[16] and its own textbooks[17]

Subjects of inquiry

Usage

All societies make use of the biological world in which they are situated, but there are wide differences in use, informed by perceived need, available technology, and the culture's sense of morality and sustainability.[citation needed] Ethnobiologists investigate what lifeforms are used for what purposes, the particular techniques of use, the reasons for these choices, and symbolic and spiritual implications of them.

Taxonomy

Different societies divide the living world up in different ways. Ethnobiologists attempt to record the words used in particular cultures for living things, from the most specific terms (analogous to species names in Linnean biology) to more general terms (such as 'tree' and even more generally 'plant'). They also try to understand the overall structure or hierarchy of the classification system (if there is one; there is ongoing debate as to whether there must always be an implied hierarchy.[18]

Cosmological, moral and spiritual significance

Societies invest themselves and their world with meaning partly through their answers to questions like "how did the world happen?", "how and why did people come to be?", "what are proper practices, and why?", and "what realities exist beyond or behind our physical experience?" Understanding these elements of a societies' perspective is important to cultural research in general, and ethnobiologists investigate how a societies' view of the natural world informs and is informed by them.

Traditional ecological knowledge

In order to live effectively in a given place, a people needs to understand the particulars of their environment, and many traditional societies have complex and subtle understandings of the places in which they live.[citation needed] Ethnobiologists seek to share in these understandings, subject to ethical concerns regarding intellectual property and cultural appropriation.

Cross-cultural ethnobiology

In cross cultural ethnobiology research, two or more communities participate simultaneously. This enables the researcher to compare how a bio-resource is used by different communities.[19]

Subdisciplines

Ethnobotany

Ethnobotany investigates the relationship between human societies and plants: how humans use plants – as food, technology, medicine, and in ritual contexts; how they view and understand them; and their symbolic and spiritual role in a culture.

Ethnozoology

The subfield ethnozoology focuses on the relationship between animals and humans throughout human history. It studies human practices such as hunting, fishing and animal husbandry in space and time, and human perspectives about animals such as their place in the moral and spiritual realms.[citation needed]

Ethnoecology

Ethnoecology refers to an increasingly dominant 'ethnobiological' research paradigm focused, primarily, on documenting, describing, and understanding how other peoples perceive, manage, and use whole ecosystems.

Other disciplines

Studies and writings within ethnobiology draw upon research from fields including archaeology, geography, linguistics, systematics, population biology, ecology, cultural anthropology, ethnography, pharmacology, nutrition, conservation, and sustainable development.[1]

Ethics

Through much of the history of ethnobiology, its practitioners were primarily from dominant cultures, and the benefit of their work often accrued to the dominant culture, with little control or benefit invested in the indigenous peoples whose practice and knowledge they recorded.

Just as many of those indigenous societies work to assert legitimate control over physical resources such as traditional lands or artistic and ritual objects, many work to assert legitimate control over their intellectual property.

In an age when the potential exists for large profits from the discovery of, for example, new food crops or medicinal plants, modern ethnobiologists must consider intellectual property rights, the need for informed consent, the potential for harm to informants, and their "debt to the societies in which they work".[20]

Furthermore, these questions must be considered not only in light of western industrialized nations' common understanding of ethics and law, but also in light of the ethical and legal standards of the societies from which the ethnobiologist draws information.[21]

Moon

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Moon   Near side of the Moon , lunar ...