Dopaminergic (modern diseases)

Dopaminergic

Main article: Dopamine

The chemical structure of the neurotransmitter dopamine

Look up dopaminergic in Wiktionary, the free dictionary.

Dopaminergic means related to the neurotransmitter dopamine.^[1] For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT₂), and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes which regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylasemonoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Lastly, any endogenous or exogenous chemical substance which acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids which enhance dopamine release indirectly in the reward pathways, and amphetamines, which enhance dopamine release directly by binding to, and inhibiting VMAT₂. (DDC),

[edit] Supplements and drugs

A complete list of dopaminergic substances used as supplements and drugs includes:

• Dopamine (DA; Intropan, Inovan, Revivan, Rivimine, Dopastat, Dynatra, etc) itself, which is used in the treatment of severe hypotension, circulatory shock, and cardiac arrest as a vasopressor or antihypotensive agent.

• Precursors including L-phenylalanine (PHE), L-tyrosine (TYR), and L-DOPA (Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc; also found in Mucuna pruriens (Velvet Bean)), which are all used as dietary supplements, and the latter of which is also used in the treatment of Parkinson’s disease (PD).

• Cofactors including ferrous iron (Fe²⁺), tetrahydrobiopterin (THB, BH₄), vitamin B₃ (niacin, niacinamide) → NADPH, vitamin B₆ (pyridoxine, pyridoxamine, pyridoxal → pyridoxal phosphatevitamin B₉ (folic acid) → tetrahydrofolic acid (THFA, H₄FA), vitamin C (ascorbic acid), and zinc (Zn²⁺), which are used as dietary supplements. (PLP),

• Dopamine receptor agonists such as apomorphine (Apokyn, Uprima), bromocriptine (Parolodel), cabergoline (Dostinex), dihydrexidine (LS-186,899), dopamine (Intropin, Revivan), fenoldopampiribedil (Trivastal), lisuride (Dopergin), pergolide (Permax), pramipexole (Mirapex), ropinirole (Requip), and rotigotine (Neupro), which are used in the treatment of Parkinson’s diseaserestless legs syndrome (RLS), hyperprolactinemia (HPA), and sexual dysfunction (SD), as well as are being investigated in the treatment of depression and anxiety as antidepressants and anxiolytics, respectively. (Corlopam), (PD),

• Dopamine receptor antagonists including typical antipsychotics such as chlorpromazine (Thorazine), fluphenazine (Prolixin), haloperidol (Haldol), loxapine (Loxitane), molindone (Moban), perphenazinepimozide (Orap), thioridazine (Mellaril), thiothixene (Navane), and trifluoperazineatypical antipsychotics such as amisulpride (Solian), clozapine (Clozaril), olanzapinequetiapine (Seroquel), risperidone (Risperdal), sulpiride (Dogmatil), and ziprasidoneantiemetics like domperidone, metoclopramide (Reglan), and prochlorperazineschizophrenia (SCZ) and bipolar disorder (BD) as antipsychotics, and nausea and vomiting. (Trilafon), (Stelazine), the (Zyprexa), (Geodon), and (Compazine), among others, which are used in the treatment of schizophrenia (SCZ) and bipolar disorder (BD) as antipsychotics, and nausea and vomiting.

• Dopamine reuptake inhibitors (DRIs) or dopamine transporter (DAT) inhibitors such as methylphenidate (Ritalin, Focalin, Concerta), bupropion (Wellbutrin, Zyban), amineptine (Survector, Maneon, Directin), and nomifensine (Merital, Alival), as well as cocaine (“Coke”, “Crack”, etc), methylenedioxypyrovalerone (MDPV; “Sonic”), ketamine (K; Ketalar, Ketanest, Ketaset; “Special-K”, “Kit Kat”, etc), and phencyclidine (PCP; Sernyl; “Angel Dust”, “Rocket Fuel”, etc), among others, which are used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics, respectively, drug addiction as anticraving agents, and sexual dysfunction, as well as illicitstreet drugs.

• Dopamine releasing agents (DRAs) such as amphetamine (Adderall, Dexedrine; “Speed”), lisdexamfetamine (Vyvanse), methamphetamine (Desoxyn; “Meth”, “Crank”, “Crystal”, etc), methylenedioxymethamphetamine (MDMA; “Ecstasy”, “E”, “X”, “XTC”, etc), phenmetrazine (Preludin; “Prellies”), pemoline (Cylert), 4-methylaminorex (4-MAR; “Ice”, “Euphoria”, etc), and benzylpiperazineattention-deficit hyperactivity disorder (ADHD) and narcolepsy as psychostimulants, obesity as anorectics, depression and anxiety as antidepressants and anxiolytics, respectively, drug addiction as anticraving agents, and sexual dysfunction, as well as illicit street drugs. (BZP; “Bennies”, “A2”, “Sunrise”, “Frenzy”, etc), among many others, which, like DRIs, are used in the treatment of

• Dopamine activity enhancers such as BPAP and PPAP, which are currently only research chemicals, but are being investigated for clinical development in the treatment of a number of medical disorders.

• Vesicular monoamine transporter 2 (VMAT₂) inhibitors such as reserpine (Serpasil), tetrabenazinedeserpidine (Harmonyl), which are used as sympatholytics or antihypertensives, and in the past as antipsychotics. (Nitoman, Xenazine), and

• Monoamine oxidase (MAO) inhibitors (MAOIs) including nonselective agents such as phenelzinetranylcypromine (Parnate), and isocarboxazid (Marplan), MAO_A selective agents like moclobemide (Aurorix, Manerix), and MAO_B selective agents such as selegiline (Eldepryl, Zelapar, Emsam), rasagiline (Azilect), and pargyline (Eutonyl), as well as the harmala alkaloids like harmine, harmaline, tetrahydroharmine, harmalol, harman, and norharman, which are found to varying degrees in Nicotiana tabacum (Tobacco; also cigarettes, cigars, chew, hookah, etc), Banisteriopsis caapiPeganum harmala (Harmal, Syrian Rue), Passiflora incarnata (Passion Flower), and Tribulus terrestris (Puncture Vine), among others, which are used in the treatment of depression and anxiety as antidepressants and anxiolytics, respectively, in the treatment of Parkinson’s disease (PD) and dementia, and for the recreational purpose of boosting the effects of certain drugsphenethylamine (PEA) and psychedelics like dimethyltryptamine (DMT) via inhibiting their metabolism. (Nardil), (Ayahausca, Caapi, Yage), like

• Catechol O-methyl transferase (COMT) inhibitors such as entacapone (Comtan, Stalevo) and tolcapone (Tasmar), which are used in the treatment of Parkinson’s disease (PD).

• Dopamine β-hydroxylase (DBH) inhibitors like disulfiram (Antabuse), which is used in the treatment of drug addiction as an anticraving agent.

• Phenylalanine hydroxylase (PAH) inhibitors like 3,4-dihydroxystyrene (DHS) which is currently only a research chemical with no suitable therapeutic indications, likely on account of the fact that such drugs would induce the potentially highly dangerous hyperphenylalaninemia (HPA) and/or phenylketonuria (PKU).

• Tyrosine hydroxylase (TH) inhibitors like metirosine (Demser), which is used in the treatment of pheochromocytoma (PCC) as a sympatholytic or antihypertensive agent.

• Aromatic L-amino acid decarboxylase (AAAD) or DOPA decarboxylase (DDC) inhibitors including benserazide (Prolopa, Madopar, etc), carbidopa (Lodosyn, Atamet, Parcopa, Sinemet, Stalevo, etc), and methyldopa (Aldomet, Aldoril, Dopamet, Dopegyt, etc), which are used in the treatment of Parkinson’s disease (PD) in augmentation of L-DOPA ((Levodopa; Sinemet, Parcopa, Atamet, Stalevo, Madopar, Prolopa, etc)) to block the peripheral conversion of dopamine thereby inhibiting undesirable side effects, and as sympatholytic or antihypertensive agents.

Others such as hyperforin and adhyperforin (both found in Hypericum perforatum (St. John’s Wort (SJW))), L-theanine (found in Camellia sinensis (Tea Plant, also known as Black, White, Oolong, Pu-erh, or Green Tea)), and S-adenosyl-L-methionine (SAMe), which are all dietary supplements used mainly  for the remedification of depression and anxietyantidepressants and anxiolytics, respectively.

Dopamine Dopaminergic system (misinformation included)

 Dopamine

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For other uses, see Dopamine (disambiguation).

Dopamine
IUPAC name[hide] 4-(2-aminoethyl)benzene-1,2-diol
Other names[hide] 2-(3,4-dihydroxyphenyl)ethylamine; 3,4-dihydroxyphenethylamine; 3-hydroxytyramine; DA; Intropin; Revivan; Oxytyramine
Identifiers
CAS number	51-61-6 Y, 62-31-7 (hydrochloride)
PubChem	681
ChemSpider	661
UNII	VTD58H1Z2X Y
SMILES	[show] c1cc(c(cc1CCN)O)O
InChI	[show] 1/C8H11NO2/c9-4-3-6-1-2-7(10)8(11)5-6/h1-2,5,10-11H,3-4,9H2
InChI key	[show] VYFYYTLLBUKUHU-UHFFFAOYAA
Properties
Molecular formula	C8H11NO2
Molar mass	153.18 g/mol
Density	1.26 g/cm3
Melting point	128 °C, 401 K, 262 °F
Boiling point	decomposes
Solubility in water	60.0 g/100 ml
Hazards
R-phrases	R36/37/38
S-phrases	S26 S36
(what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)Y
Infobox references

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors—D₁, D₂, D₃, D₄, and D₅—and their variants. Dopamine is produced in several areas of the brain, including the substantia nigra and the ventral tegmental area.^[1] Dopamine is also a neurohormonehypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary. released by the

Dopamine is available as an intravenous medication acting on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure. However, because dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system. To increase the amount of dopamine in the brains of patients with diseases such as Parkinson’s disease and dopa-responsive dystonia, L-DOPA, which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.

Contents [show] 1 History 2 Biochemistry 2.1 Name and family 2.2 Biosynthesis 2.3 Inactivation and degradation 3 Functions in the brain 3.1 Anatomy 3.2 Tonic and phasic activity 3.3 Movement 3.4 Cognition and frontal cortex 3.5 Regulating prolactin secretion 3.6 Motivation and pleasure 3.6.1 Reinforcement 3.6.2 Reuptake inhibition, expulsion 3.6.3 Incentive salience 3.6.4 Dopamine, learning, and reward-seeking behavior 3.6.5 Animal studies 3.6.6 The effects of drugs that reduce dopamine activity 3.6.7 Opioid and cannabinoid transmission 3.6.8 Sociability 3.6.9 Processing of pain 3.6.10 Salience 3.6.11 Behavior disorders 3.7 Latent inhibition and creative drive 3.8 Chemoreceptor trigger zone 3.9 Dopaminergic mind hypothesis 4 Links to psychosis 5 Therapeutic use 6 Nonneural functions 6.1 Immunoregulatory 6.2 Peripheral effects 6.3 Renal effects 7 Dopamine and fruit browning 8 See also 9 References 10 External links

[edit] History

Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England.^[2] It was named dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine (L-DOPA). Dopamine’s function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden.^[3] Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not just a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but a neurotransmitter as well.

[edit] Biochemistry

Biosynthesis of dopamine

[edit] Name and family

Dopamine has the chemical formula C₆H₃(OH)₂-CH₂-CH₂-NH₂. Its chemical name is “4-(2-aminoethyl)benzene-1,2-diol” and its abbreviation is “DA.”
As a member of the catecholamine family, dopamine is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline) in the biosynthetic pathways for these neurotransmitters.

The effects of drugs that reduce dopamine activity

In humans, drugs that reduce dopamine activity (neuroleptics, e.g. antipsychotics) have been shown to reduce motivation, cause anhedonia (inability to experience pleasure), and long-term use has been associated with the irreversible movement disorder, tardive dyskinesia.^[26] Furthermore, antipsychotic drugs are associated with weight gain, diabetes, lactation, gynecomastia, drooling, dysphoria, fatigue, sexual dysfunction, and heart rhythm problems. Selective D2/D3 agonists pramipexole and ropinirole, used to treat restless legs syndrome^[27] (RLS), have limited anti-anhedonic properties as measured by the Snaith-Hamilton Pleasure Scale (SHAPS).

[edit] Opioid and cannabinoid transmission

Opioid and cannabinoid transmission instead of dopamine may modulate consummatory pleasure and food palatability (liking).^[28] This could explain why animals’ “liking” of food is independent of brain dopamine concentration. Other consummatory pleasures, however, may be more associated with dopamine. One study found that both anticipatory and consummatory measures of sexual behavior (male rats) were disrupted by DA receptor antagonists.^[29] Libido can be increased by drugs that affect dopamine, but not by drugs that affect opioid peptides or other neurotransmitters.

[edit] Sociability

Sociability is also closely tied to dopamine neurotransmission. Low D2 receptor-binding is found in people with social anxiety. Traits common to negative schizophrenia (social withdrawal, apathy, anhedonia) are thought to be related to a hypodopaminergic state in certain areas of the brain. In instances of bipolar disorder, manic subjects can become hypersocial, as well as hypersexual.^{[citation needed]} This is credited to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics.^[30]

[edit] Processing of pain

Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central nervous system including the spinal cord,^[31] periaqueductal gray (PAG),^[32] thalamus,^[33] basal ganglia,^[34][35] insular cortex,^[36][37] and cingulate cortex.^[38] Accordingly, decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson’s disease.^[39] Abnormalities in dopaminergic neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome,^[40] fibromyalgia,^[41][42] and restless legs syndrome.^[43] In general, the analgesic capacity of dopamine occurs as a result of dopamine D2 receptor activation; however, exceptions to this exist in the PAG, in which dopamine D1 receptor activation attenuates pain presumably via activation of neurons involved in descending inhibition.^[44] In addition, D1 receptor activation in the insular cortex appears to attenuate subsequent pain-related behavior.

[edit] Salience

Dopamine may also have a role in the salience of potentially important stimuli, such as sources of reward or of danger.^[45] This hypothesis argues that dopamine assists decision-making by influencing the priority, or level of desire, of such stimuli to the person concerned.

[edit] Behavior disorders

Deficient dopamine neurotransmission is implicated in attention-deficit hyperactivity disorder, and stimulant medications used to successfully treat the disorder increase dopamine neurotransmission, leading to decreased symptoms.^[46] Consistent with this hypothesis, dopaminergic pathways have a role in inhibitory action control and the inhibition of the tendency to make unwanted actions.^[47]

The long term use of levodopa in Parkinson’s disease has been linked to dopamine dysregulation syndrome.^[48]

[edit] Latent inhibition and creative drive

Dopamine in the mesolimbic pathway increases general arousal and goal directed behaviors and decreases latent inhibition; all three effects increase the creative drive of idea generation. This has led to a three-factor model of creativity involving the frontal lobes, the temporal lobes, and mesolimbic dopamine.^[49]

[edit] Chemoreceptor trigger zone

Dopamine is one of the neurotransmitters implicated in the control of nausea and vomiting via interactions in the chemoreceptor trigger zone. Metoclopramide is a D2-receptor antagonist that functions as a prokinetic/antiemetic.

[edit] Dopaminergic mind hypothesis

The dopaminergic mind hypothesis seeks to explain the differences between modern humans and their hominid relatives by focusing on changes in dopamine.^[50] It theorizes that increased levels of dopamine were part of a general physiological adaptation due to an increased consumption of meat around two million years ago in Homo habilis, and later enhanced by changes in diet and other environmental and social factors beginning approximately 80,000 years ago. Under this theory, the “high-dopamine” personality is characterized by high intelligence, a sense of personal destiny, a religious/cosmic preoccupation, an obsession with achieving goals and conquests, an emotional detachment that in many cases leads to ruthlessness, and a risk-taking mentality. High levels of dopamine are proposed to underlie increased psychological disorders in industrialized societies. According to this hypothesis, a “dopaminergic society” is an extremely goal-oriented, fast-paced, and even manic society, “given that dopamine is known to increase activity levels, speed up our internal clocks and create a preference for novel over unchanging environments.”^[50] In the same way that high-dopamine individuals lack empathy and exhibit a more masculine behavioral style, dopaminergic societies are “typified by more conquest, competition, and aggression than nurturance and communality.”^[50] Although behavioral evidence and some indirect anatomical evidence (e.g., enlargement of the dopamine-rich striatum in humans)^[51] support a dopaminergic expansion in humans, there is still no direct evidence that dopamine levels are markedly higher in humans relative to other apes.^[52] However, recent discoveries about the sea-side settlements of early man may provide evidence of dietary changes consistent with this hypothesis.^[53]

[edit] Links to psychosis

Main article: Dopamine hypothesis of schizophrenia

Abnormally high dopaminergic transmission has been linked to psychosis and schizophrenia.^[54] Increased dopaminergic functional activity, specifically in the mesolimbic pathway, is found in schizophrenic individuals. Anti-psychotic medications act largely as dopamine antagonists, inhibiting dopamine at the receptor level, and thereby blocking the effects of the neurochemical in a dose-dependant manner. The older, so-called typical antipsychotics most commonly act on D2 receptors,^[55] while the atypical drugs also act on D1, D3 and D4 receptors.^[56][57] The finding that drugs such as amphetamines, methamphetamine and cocaine, which can increase dopamine levels by more than tenfold,^[58] can temporarily cause psychosis, provides further evidence for this link.^[5

Therapeutic use

Main article: L-DOPA

Levodopa is a dopamine precursor used in various forms to treat Parkinson’s disease and dopa-responsive dystonia. It is typically co-administered with an inhibitor of peripheral decarboxylation (DDC, dopa decarboxylase), such as carbidopa or benserazide. Inhibitors of alternative metabolic route for dopamine by catechol-O-methyl transferase are also used. These include entacapone and tolcapone.

Arsenic poisoning [can cause arsenic skin lesions]

Arsenic poisoning

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Arsenic Poisoning
Classification and external resources
ICD–10	T57.0
ICD–9	985.1
eMedicine	emerg/42
MeSH	D020261

Arsenic Poisoning interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase (PDH) complex which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD⁺. With the enzyme inhibited, the energy system of the cell is disrupted resulting in a cellular apoptosis episode. Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the blood increase the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide. Arsenic in cells clearly stimulates the production of hydrogen peroxide (H₂O₂). When the H₂O₂ reacts with certain metals such as iron or manganese it produces a highly reactive hydroxyl radical. Inorganic Arsenic trioxide found in ground water particularly affects voltage-gated potassium channels,^[1] disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged qt interval, neutropenia, high blood pressure,^[2] central nervous system dysfunction, anemia, Leukemia,^[3] and death. Arsenic trioxide is a ubiquitous molecule present in American drinking water.^[4]

“	Arsenic exposure plays a key role in the pathogenesis of vascular endothelial dysfunction as it inactivates endothelial nitric oxide synthase, leading to reduction in the generation and bioavailability of nitric oxide. In addition, the chronic arsenic exposure induces high oxidative stress, which may affect the structure and function of cardiovascular system. Further, the arsenic exposure has been noted to induce atherosclerosis by increasing the platelet aggregation and reducing fibrinolysis. Moreover, arsenic exposure may cause arrhythmia by increasing the QT interval and accelerating the cellular calcium overload. The chronic exposure to arsenic upregulates the expression of tumor necrosis factor-α, interleukin-1, vascular cell adhesion molecule and vascular endothelial growth factor to induce cardiovascular pathogenesis.	”
—Pitchai Balakumar1 and Jagdeep Kaur, “Arsenic Exposure and Cardiovascular Disorders: An Overview”, Cardiovascular Toxicology, December 2009[5]

Contents [show] 1 Toxicity 2 Symptoms of Arsenic Poisoning 3 Pathophysiology 4 Diagnosis 5 Treatment 6 Unintentional poisoning 6.1 Occupational exposures 6.2 Arsenicosis: chronic arsenic poisoning from drinking water 7 Intentional poisoning 7.1 Detection in biological fluids 8 Famous victims (known and alleged) 8.1 Francesco I de’ Medici, Grand Duke of Tuscany 8.2 George III of Great Britain 8.3 Napoleon Bonaparte 8.4 Simón Bolívar 8.5 Charles Francis Hall 8.6 Huo Yuan Jia 8.7 Clare Boothe Luce 8.8 Impressionist painters 8.9 The Emperor Guangxu 8.10 Phar Lap 9 See also 10 Footnotes 11 External links

[edit] Toxicity

Research has shown that the inorganic arsenites (trivalent forms) in drinking water have a much higher acute toxicity than organic arsenates (pentavalent forms).^[6] The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day.^[7] Most reported arsenic poisonings are caused by one of arsenic’s compounds, also found in drinking water, arsenic trioxide which is 500 times more toxic than pure arsenic.

Arsenic is related to the first five leading causes of non-accidental death in the United States, bringing the total to 1,525,675 related mortalities. EPA efforts are underway to reduce drinking water exposure to zero.^[8][9] heart disease^[10] (hypertension related cardiovascular), cancer,^[11] stroke^[12] (cerebrovascular diseases), chronic lower respiratory diseases,^[13] and diabetes. These diseases are all related to the alteration of voltage dependent potassium channels. Researchers, led by Ana Navas-Acien, MD, PhD, of the Johns Hopkins Bloomberg School of Health, studied 788 adults who had their urine tested for arsenic exposure in the 2003-2004 National Health and Nutrition Examination Survey. Participants with type 2 diabetes had a 26% higher level of total arsenic in their urine than those without the disease.^{[citation needed]} Diabetes is also related to alteration of voltage dependent potassium channels due in part to the function of insulin and potassium in the cellular metabolism of glucose. Due to the regular appearance of arsenic in public drinking water supplies, it is likely that arsenic plays a part in about thirty percent of total all cause mortality in the United States.^{[citation needed]} Arsenic prevalence in the water has been related to the occurrence of hypertension, erectile dysfunction and related conditions. Leading causes of mortality in the world are all related to arsenic. These are

Chronic exposure to inorganic arsenic may lead to hypertension, involuntary muscular dysfunction (including incontinence), diabetes, neuropathy, depression, obesity and any other condition related to the altered role of intercellular voltage-dependent potassium channels, including cutaneous hyperpigmentation.^[14]:859

[edit] Symptoms of Arsenic Poisoning

Symptoms of arsenic poisoning begin with headaches, confusion and drowsiness. As the poisoning develops, convulsions and changes in fingernail pigmentation may occur. When the poisoning becomes acute, symptoms may include diarrhea, vomiting, blood in the urine, cramping muscles, hair loss, stomach pain, and more convulsions. The organs of the body that are usually affected by arsenic poisoning are the lungs, skin, kidneys, and liver. The final result of arsenic poisoning is coma or death.

[edit] Pathophysiology

Main article: Arsenic toxicity

Tissue culture studies have shown that arsenic blocks both IKr and Iks channels and, at the same time, activates IK-ATP channels. Arsenic also disrupts ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. These metabolic interferences lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. A post mortem reveals brick red colored mucosa, due to severe hemorrhage. Although arsenic causes toxicity, it can also play a protective role.^[15]

[edit] Diagnosis

There are tests available to diagnose poisoning by measuring arsenic in blood, urine, hair, and fingernails. The urine test is the most reliable test for arsenic exposure within the last few days. Urine testing needs to be done within 24–48 hours for an accurate analysis of an acute exposure. Tests on hair and fingernails can measure exposure to high levels of arsenic over the past 6–12 months. These tests can determine if one has been exposed to above-average levels of arsenic. They cannot predict, however, whether the arsenic levels in the body will affect health.^[16]

Hair is a potential bioindicator for arsenic exposure due to its ability to store trace elements from blood. Incorporated elements maintain their position during growth of hair. Thus for a temporal estimation of exposure, an assay of hair composition needs to be carried out with a single hair which is not possible with older techniques requiring homogenization and dissolution of several strands of hair. This type of biomonitoring has been achieved with newer microanalytical techniques like Synchroton radiation based X ray fluorescence (SXRF) spectroscopy and Microparticle induced X ray emission (PIXE).The highly focused and intense beams study small spots on biological samples allowing analysis to micro level along with the chemical speciation. In a study, this method has been used to follow arsenic level before, during and after treatment with Arsenious oxide in patients with Acute Promyelocytic Leukemia.^[17]

[edit] Treatment

Chemical and synthetic methods are now used to treat arsenic poisoning. Dimercaprol and dimercaptosuccinic acid are chelating agents which sequester the arsenic away from blood proteins and are used in treating acute arsenic poisoning. The most important side effect is hypertension. Dimercaprol is considerably more toxic than succimer.^[18]

In the journal Food and Chemical Toxicology, Keya Chaudhuri of the Indian Institute of Chemical Biology in Kolkata, and her colleagues reported giving rats daily doses of arsenic in their water, in levels equivalent to those found in groundwater in Bangladesh and West Bengal. Those rats which were also fed garlic extracts had 40 percent less arsenic in their blood and liver, and passed 45 percent more arsenic in their urine. The conclusion is that sulfur-containing substances in garlic scavenge arsenic from tissues and blood. The presentation concludes that people in areas at risk of arsenic contamination in the water supply should eat one to three cloves of garlic per day as a preventative.^[19][20][21]

Lead poisoning

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Lead poisoning
Classification and external resources
An X ray demonstrating the characteristic finding of lead poisoning, dense metaphyseal lines.
ICD–10	T56.0
ICD–9	984.9
DiseasesDB	7307
MedlinePlus	002473
eMedicine	article/815399
MeSH	D007855

Lead poisoning (also known as plumbism, colica Pictonum, saturnism, Devon colic, or painter’s colic) is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems. It interferes with the development of the nervous system and is therefore particularly toxic to children, causing potentially permanent learning and behavior disorders. Symptoms include abdominal pain, headache, anemia, irritability, and in severe cases seizures, coma, and death.

Routes of exposure to lead include contaminated air, water, soil, food, and consumer products. Occupational exposure is a common cause of lead poisoning in adults. One of the largest threats to children is lead paint that exists in many homes, especially older ones; thus children in older housing with chipping paint are at greater risk. Prevention of lead exposure can range from individual efforts (e.g. removing lead-containing items such as piping or blinds from the home) to nationwide policies (e.g. laws that ban lead in products or reduce allowable levels in water or soil).

Elevated lead in the body can be detected by the presence of changes in blood cells visible with a microscope and dense lines in the bones of children seen on X-ray. However, the main tool for diagnosis is measurement of the blood lead level; different treatments are used depending on this level. The major treatments are removal of the source of lead and chelation therapy (administration of agents that bind lead so it can be excreted).

Humans have been mining and using this heavy metal for thousands of years, poisoning themselves in the process. Although lead poisoning is one of the oldest known work and environmental hazards, the modern understanding of the small amount of lead necessary to cause harm did not come about until the latter half of the 20th century. No safe threshold for lead exposure has been discovered—that is, there is no known amount of lead that is too small to cause the body harm.

Contents [show] 1 Classification 2 Signs and symptoms 2.1 Acute poisoning 2.2 Chronic poisoning 3 Exposure routes 3.1 Occupational exposure 3.2 Paint 3.3 Soil 3.4 Water 3.5 Lead-containing products 4 Pathophysiology 4.1 Enzymes 4.2 Neurons 5 Complications 5.1 Renal system 5.2 Cardiovascular system 5.3 Reproductive system 5.4 Nervous system 6 Diagnosis 6.1 Reference values 7 Prevention 8 Treatment 9 Prognosis 10 Epidemiology 11 History 12 Notable cases 13 In other species 13.1 Wildlife 14 References 15 Cited texts 16 External links

[edit] Classification

Classically, “lead poisoning” or “lead intoxication” has been defined as exposure to high levels of lead typically associated with severe health effects.^[1] Poisoning is a pattern of symptoms that occur with toxic effects from mid to high levels of exposure; toxicity is a wider spectrum of effects, including subclinical ones (those that do not cause symptoms).^[2] However, professionals often use “lead poisoning” and “lead toxicity” interchangeably, and official sources do not always restrict the use of “lead poisoning” to refer only to symptomatic effects of lead.^[2]

The amount of lead in the blood and tissues, as well as the time course of exposure, determine toxicity.^[3][4] Diagnosis and treatment of lead exposure are based on blood lead level (the amount of lead in the blood), measured in micrograms of lead per deciliter of blood (μg/dL). The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 μg/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level.^[5][6] Authorities such as the American Academy of Pediatrics define lead poisoning as blood lead levels higher than 10 μg/dL.^[7] Lead poisoning may be acute (from intense exposure of short duration) or chronic (from repeat low-level exposure over a prolonged period), but the latter is much more common.

Lead forms a variety of compounds and exists in the environment in various forms.^[8] Features of poisoning differ depending on whether the agent is an organic compound (one that contains carbon), or an inorganic^[9] Organic lead poisoning is now very rare, because countries across the world have phased out the use of organic lead compounds as gasoline additives, but such compounds are still used in industrial settings.^[9]central nervous system^[9] one. Organic lead compounds, which cross the skin and respiratory tract easily, affect the predominantly.

[edit] Signs and symptoms

Lead poisoning can cause a variety of symptoms and signs which vary depending on the individual and the duration of lead exposure.^[10][11] Symptoms are nonspecific and may be subtle, and someone with elevated lead levels may have no symptoms.^[12] Symptoms usually develop over weeks to months as lead builds up in the body during a chronic exposure, but acute symptoms from brief, intense exposures also occur.^[13][14] Poisoning by organic lead compounds has symptoms predominantly in the central nervous system, such as insomnia, delirium, cognitive deficits, tremor, hallucinations, and convulsions.^[9] Symptoms from exposure to organic lead, which is probably more toxic than inorganic lead due to its lipid solubility, occur rapidly.

Symptoms may be different in adults and children; the main symptoms in adults are headache, abdominal pain, memory loss, kidney failure, male reproductive problems, and weakness, pain, or tingling in the extremities.^[15] The classic signs and symptoms in children are loss of appetite, abdominal pain, vomiting, weight loss, constipation, anemia, kidney failure, irritability, lethargy, learning disabilities, and behavior problems.^[15] Children may also experience hearing loss, delayed growth, drowsiness, clumsiness, or loss of new abilities, especially speech skills.^[12] Symptoms may appear in children at lower blood lead levels than in adults.^[16]

Early symptoms of lead poisoning in adults are commonly nonspecific and include depression, loss of appetite, intermittent abdominal pain, nausea, diarrhea, constipation, and muscle pain.^[17] Other early signs in adults include malaise, fatigue, decreased libido, and problems with sleep.^[10] An unusual taste in the mouth and personality changes are also early signs.^[18] In adults, symptoms can occur at levels above 40 μg/dL, but are more likely to occur only above 50–60 μg/dL.^[10] Symptoms begin to appear in children generally at around 60 μg/dL.^[19] However, the lead levels at which symptoms appear vary widely depending on unknown characteristics of each individual.^[20] At blood lead levels between 25 and 60 μg/dL, neuropsychiatric effects such as delayed reaction times, irritability, and difficulty concentrating, as well as slowed motor nerve^[21] Anemia may appear at blood lead levels higher than 50 μg/dL.^[17] In adults, Abdominal colic, involving paroxysms of pain, may appear at blood lead levels greater than 80 μg/dL.^[11] Signs that occur in adults at blood lead levels exceeding 100 μg/dL include wrist drop and foot drop, and signs of encephalopathy (a condition characterized by brain swelling), such as those that accompany increased pressure within the skull, delirium, coma, seizures, and headache.^[22] In children, signs of encephalopathy such as bizarre behavior, discoordination, and apathy occur at lead levels exceeding 70 μg/dL.^[22] For both adults and children, it is rare to be asymptomatic if blood lead levels exceed 100 μg/dL.^[11] conduction and headache can occur.

[edit] Acute poisoning

In acute poisoning, typical neurological signs are pain, muscle weakness, paraesthesia, and, rarely, symptoms associated with encephalitis.^[15] Abdominal pain, nausea, vomiting, diarrhea, and constipation are other acute symptoms.^[23] Lead’s effects on the mouth include astringency and a metallic taste.^[23] Gastrointestinalconstipation, diarrhea, poor appetite, or weight loss, are common in acute poisoning. Absorption of large amounts of lead over a short time can cause shock (insufficient fluid in the circulatory system) due to loss of water from the gastrointestinal tract.^[23] Hemolysis (the rupture of red blood cells) due to acute poisoning can cause anemia and hemoglobin in the urine.^[23] Damage to kidneys can cause changes in urination such as decreased urine output.^[23] People who survive acute poisoning often go on to display symptoms of chronic poisoning.^[23] problems, such as

[edit] Chronic poisoning

Chronic poisoning usually presents with symptoms affecting multiple systems,^[9] but is associated with three main types of symptoms: gastrointestinal, neuromuscular, and neurological.^[15] Central nervous system and neuromuscular symptoms usually result from intense exposure, while gastrointestinal symptoms usually result from exposure over longer periods.^[23] Signs of chronic exposure include loss of short-term memory or concentration, depression, nausea, abdominal pain, loss of coordination, and numbness and tingling in the extremities.^[18] Fatigue, problems with sleep, headaches, stupor, slurred speech, and anemia are also found in chronic lead poisoning.^[15] A “lead hue” of the skin with pallor is another feature.^[24] A blue line along the gum, with bluish black edging to the teeth is another indication of chronic lead poisoning.^[25] Children with chronic poisoning may refuse to play or may have hyperkinetic or aggressive behavior disorders.^[15]

[edit] Exposure routes

Lead is a common environmental pollutant.^[7] Causes of environmental contamination include industrial use of lead, such as is found in plants that process lead-acid batteries or produce lead wire or pipes, and metal recycling and foundries.^[26] Children living near facilities that process lead, such as smelters, have been found to have unusually high blood lead levels.^[27] In August 2009, parents rioted in China after lead poisoning was found in nearly 2000 children living near zinc and manganese smelters.^[28] Lead exposure can occur from contact with lead in air, household dust, soil, water, and commercial products.^[5]

Mercury poisoning [can also cause red, white blood and immune cell abnormalities]

Mercury poisoning

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Mercury poisoning
Classification and external resources
Elemental mercury
ICD–10	T56.1
ICD–9	985.0
DiseasesDB	8057
MedlinePlus	002476
eMedicine	emerg/813

Mercury poisoning (also known as hydrargyria or mercurialism) is a disease caused by exposure to mercury or its compounds. Mercury (chemical symbol Hg) is a heavy metal that occurs in several forms, all of which can produce toxic effects in high enough doses. Its zero oxidation state Hg⁰ exists as vapor or as liquid metal, its mercurous state Hg⁺ exists as inorganic salts, and its mercuric state Hg²⁺ may form either inorganic salts or organomercury compounds; the three groups vary in effects. Toxic effects include damage to the brain, kidney, and lungs.^[1] Mercury poisoning can result in several diseases, including acrodynia (pink disease), Hunter-Russell syndrome, and Minamata disease.^[2]

Symptoms typically include sensory impairment (vision, hearing, speech), disturbed sensation and a lack of coordination. The type and degree of symptoms exhibited depend upon the individual toxin, the dose, and the method and duration of exposure.

Contents [show] 1 Signs and symptoms 1.1 Causes 2 Mechanism 2.1 Elemental mercury 2.2 Inorganic mercury compounds 2.3 Organic mercury compounds 3 Diagnosis 4 Prevention 5 Treatment 6 Prognosis 6.1 Detection in biological fluids 7 History 7.1 Infantile Acrodynia 7.2 Medical procedures 7.2.1 Thiomersal 7.2.2 Dental amalgam 7.3 Cosmetics 7.4 Fluorescent lamps 8 See also 9 References 10 External links

[edit] Signs and symptoms

Common symptoms of mercury poisoning include peripheral neuropathy (presenting as paresthesia or itching, burning or pain), skin discoloration (pink cheeks, fingertips and toes), swelling, and desquamation (shedding of skin).

Because mercury blocks the degradation pathway of catecholamines, epinephrine excess causes profuse sweating, tachycardia (persistently faster-than-normal heart beat), increased salivation, and hypertension (high blood pressure). Mercury is thought to inactivate S-adenosyl-methionine, which is necessary for catecholamine catabolism by catechol-o-methyl transferase.

Affected children may show red cheeks, nose and lips, loss of hair, teeth, and nails, transient rashes, hypotonia (muscle weakness), and increased sensitivity to light. Other symptoms may include kidneyFanconi syndrome) or neuropsychiatric symptoms (Bradley Coyne Syndrome) such as emotional lability, memory impairment, or insomnia. disfunction (e.g.

Thus, the clinical presentation may resemble pheochromocytoma or Kawasaki disease.

An example of desquamation of the hand of a child with severe mercury poisoning acquired by handling elemental mercury is this photograph in Horowitz, et al. (2002).^[3]

[edit] Causes

The consumption of fish is by far the most significant source of ingestion-related mercury exposure in humans and animals, although plants and livestock also contain mercury due to bioaccumulation of mercury from soil, water and atmosphere, and due to biomagnification by ingesting other mercury-containing organisms.^[4]. Exposure to mercury can occur from breathing contaminated air;^[5] from eating foods containing mercury residues from processing, such as can occur with high-fructose corn syrup;^[6] from exposure to mercury vapor in mercury amalgam dental restorations;^[7] and from improper use or disposal of mercury and mercury-containing objects, for example, after spills of elemental mercury or improper disposal of fluorescent lamps.^[8]

Consumption of whale and dolphin meat, as is the practice in Japan, is a source of high-levels of mercury poisoning. Tetsuya Endo, a professor at the Health Sciences University of Hokkaido, has tested whale meat purchased in the whaling town of Taiji and found mercury levels that are more than 20 times acceptable Japanese standards. ^[9]

Human-generated sources such as coal plants emit approximately half of atmospheric mercury, with natural sources such as volcanoes responsible for the remainder. An estimated two-thirds of human-generated mercury comes from stationary combustion, mostly of coal. Other important human-generated sources include gold production, non-ferrous metal production, cement production, waste disposal, human crematoria, caustic soda production, pig iron and steel production, mercury production (mostly for batteries), and biomass burning.^[10]

Small independent gold mining operations employ workers who are exposed to more risk to mercury poisoning because of crude processing methods. Such is the danger for the galamsey in Ghana and similar workers known as orpailleurs in neighboring francophone countries. While there are no official government estimates of the labor force, observers believe twenty thousand to fifty thousand work as galamseys in Ghana, a figure that includes many women, who work as porters.

Mercury and many of its chemical compounds, especially organomercury compounds, can also be readily absorbed through direct contact with bare, or in some cases (such as dimethylmercury) insufficiently protected, skin. Mercury and its compounds are commonly used in chemical laboratories, hospitals, dental clinics, and facilities involved in the production of items such as fluorescent light bulbs, batteries, and explosives.^[11]

[edit] Mechanism

Mercury is such a highly reactive toxic agent that it is difficult to identify its specific mechanism of damage, and much remains unknown about the mechanism.^[12] It damages the central nervous system, endocrine system, kidneys, and other organs, and adversely affects the mouth, gums, and teeth. Exposure over long periods of time or heavy exposure to mercury vapor can result in brain damage and ultimately death. Mercury and its compounds are particularly toxic to fetuses and infants. Women who have been exposed to mercury in pregnancy have sometimes given birth to children with serious birth defects (see Minamata disease).

Mercury exposure in young children can have severe neurological consequences, preventing nerve sheaths from forming properly. Mercury inhibits the formation of myelin.

There is some evidence that mercury poisoning may predispose to Young’s syndrome (men with bronchiectasis and low sperm count).^[13]

Mercury poisoning’s effects partially depend on whether it has been caused by exposure to elemental mercury, inorganic mercury compounds (as salts), or organomercury compounds.

[edit] Elemental mercury

Quicksilver (liquid metallic mercury) is poorly absorbed by ingestion and skin contact. It is hazardous due to its potential to release mercury vapour. Animal data indicate that less than 0.01% of ingested mercury is absorbed through the intact gastrointestinal tract; though it may not be true for individuals suffering from ileus. Cases of systemic toxicity from accidental swallowing are rare, and attempted suicide via intravenous injection does not appear to result in systemic toxicity.^[12] Though not studied quantitatively, the physical properties of liquid elemental mercury limit its absorption through intact skin and in light of its very low absorption rate from the gastrointestinal tract, skin absorption would not be high.^[14] Some mercury vapour is absorbed dermally but uptake by this route is only approximately 1% of that by inhalation.^[15]

In humans, approximately 80% of inhaled mercury vapor is absorbed via the respiratory tract where it enters the circulatory system and is distributed throughout the body.^[16] Chronic exposure by inhalation, even at low concentrations in the range 0.7–42 μg/m³, has been shown in case control studies to cause effects such as tremors, impaired cognitive skills, and sleep disturbance in workers.^[17][18] Acute inhalation of high concentrations causes a wide variety of cognitive, personality, sensory, and motor disturbances. The most prominent symptoms include tremors (initially affecting the hands and sometimes spreading to other parts of the body), emotional lability (characterized by irritability, excessive shyness, confidence loss, and nervousness), insomnia, memory loss, neuromuscular changes (weakness, muscle atrophy, muscle twitching), headaches, polyneuropathy (paresthesia, stocking-glove sensory loss, hyperactive tendon reflexes, slowed sensory and motor nerve conduction velocities), and performance deficits in tests of cognitive function.^[14]

[edit] Inorganic mercury compounds

Mercury occurs inorganically as salts such as mercury(II) chloride. Mercury salts primarily affect the gastro-intestinal tract and the kidneys, and can cause severe kidney damage; however, as they can not cross the blood-brain barrier easily, mercury salts inflict little neurological damage without continuous or heavy exposure.^[19] As two oxidation states of mercury form salts (Hg⁺ and Hg²⁺), mercury salts occur in both mercury(I) (or mercurous) and mercury(II) (mercuric) forms. Mercury(II) salts are usually more toxic than their mercury(I) counterparts because their solubility in water is greater; thus, they are more readily absorbed from the gastrointestinal tract.^[19]

Hg(CN)₂ is a particularly toxic mercury compound. If ingested, both life-threatening mercury and cyanide poisoning can occur. Hg(CN)₂ can enter the body via inhalation, ingestion, or passage through the skin. Inhalation of mercuric cyanide irritates the throat and air passages. Heating or contact of Hg(CN)₂ with acid or acid mist releases toxic mercury and cyanide vapors that can cause bronchitis with cough and phlegm and/or lung tissue irritation. Contact with eyes can cause burns and brown stains in the eyes, and long time exposure can affect the peripheral vision. Contact with skin can cause skin allergy, irritation, and gray skin color.^[20]

Chronic exposure to trace amounts of the compound can lead to mercury buildup in the body over time; it may take months or even years for the body to eliminate excess mercury. Overexposure to mercuric cyanide can lead to kidney damage and/or mercury poisoning, leading to ‘shakes’ (ex: shaky handwriting), irritability, sore gums, increased saliva, metallic taste, loss of appetite, memory loss, personality changes, and brain damage. Exposure to large doses at one time can lead to sudden death.^[20]

Mercuric cyanide has not been tested on its ability to cause reproductive damage. Although inorganic mercury compounds (such as Hg(CN)₂) have not been shown to be human teratogens, they should be handled with care as they are known to damage developing embryos and decrease fertility in men and women.^[20]

According to one study, two people exhibited symptoms of cyanide poisoning within hours after ingesting mercuric cyanide or mercury oxycyanide, Hg(CN)₂•HgO, in suicide attempts. The toxicity of Hg(CN)₂ is commonly assumed to arise almost exclusively from mercury poisoning; however, the patient who ingested mercury oxycyanide died after 5 hours of cyanide poisoning before any mercury poisoning symptoms were observed. The patient who ingested Hg(CN)₂ initially showed symptoms of acute cyanide poisoning which were brought under control, and later showed signs of mercury poisoning before recovering. It is thought that the degree to which cyanide poisoning occurs is related to whether cyanide ions are released in the stomach, which depends on factors such as the amount ingested, stomach acidity, and volume of stomach contents.^[21]₂ molecules remain undissociated in pure water and in basic solutions,^[22] it makes sense that dissociation would increase with increasing acidity. High stomach acidity thus helps cyanide ions to become more bioavailable, increasing the likelihood of cyanide poisoning. Given that Hg(CN)

Mercury cyanide was used in two murders in New York in 1898. The perpetrator, Roland B. Molineux, sent poisoned medicines to his victims through the US mail. The first victim, Henry Barnett, died of mercury poisoning twelve days after taking the poison. The second victim, Catherine Adams, died of cyanide poisoning within 30 minutes of taking the poison. As in the suicide cases, the difference between the two cases may be attributed to differences in the acidities of the solutions containing the poison, or to differences in the acidities of the victims’ stomachs.^[23]

The drug NAP (n-acetyl penicillamine) has been used to treat mercury poisoning with limited success.^[20]

[edit] Organic mercury compounds

Compounds of mercury tend to be much more toxic than the element itself, and organic compounds of mercury are often extremely toxic and have been implicated in causing brain and liver damage. The most dangerous mercury compound, dimethylmercury, is so toxic that even a few microliters spilled on the skin, or even a latex glove, can cause death.^[24][25]

Methylmercury is the major source of organic mercury for all individuals.^[1] It works its way up the food chainbioaccumulation in the environment, reaching high concentrations among populations of some species. Larger species of fish, such as tuna or swordfish, are usually of greater concern than smaller species. The U.S. Food and Drug Administration (FDA) and the U.S. Environmental Protection Agency (EPA) advise women of child-bearing age, nursing mothers, and young children to completely avoid swordfish, shark, king mackereltilefish from the Gulf of Mexico, (Golden Tilefish from the Mid- and North-Atlantic present no risk), to limit consumption of albacore (“white”) tuna to no more than 6 oz (170 g) per week, and of all other fish and shellfish to no more than 12 oz (340 g) per week.^[26] A 2006 review, conducted by Dr. Dariush Mozaffarian and Dr. Eric B. Rimm, of the risks and benefits of fish consumption found that for adults the benefits of one to two servings of fish per week outweigh the risks, even (except for a few fish species) for women of childbearing age, and that avoidance of fish consumption could result in significant excess coronary heart disease deaths and suboptimal neural development in children.^[27] (Dr. Rimm has reported in the past that he has received payment or honoraria for presentations about food and diets from both the Culinary Institute of America and the International Chefs Association, among others.)^[27] through and

There is a long latent period between exposure to methylmercury and the appearance of symptoms in adult poisoning cases. The longest recorded latent period is five months after a single exposure, in the Dartmouth case (see History); other latent periods in the range of weeks to months have also been reported. No explanation for this long latent period is known. When the first symptom appears, typically paresthesia (a tingling or numbness in the skin), it is followed rapidly by more severe effects, sometimes ending in coma and death. The toxic damage appears to be determined by the peak value of mercury, not the length of the exposure.^[12]

Ethylmercury is a breakdown product of the antibacteriological agent ethylmercurithiosalicylate, which has been used as a topical antiseptic and a vaccine preservative (further discussed under Thiomersal below). Its characteristics have not been studied as extensively as those of methylmercury. It is cleared from the blood much more rapidly, with a half-life of 7 to 10 days, and it is metabolized much more quickly than methylmercury. It probably does not have methylmercury’s ability to cross the blood-brain barrier via a transporter, but instead relies on simple diffusion to enter the brain.^[1]

Other exposure sources of organic mercury include phenylmercuric acetate and phenylmercuric nitrate. These were used in indoor latex paints for their anti-mildew properties, but were removed in 1990 because of cases of toxicity.^[1]

[edit] Diagnosis

Diagnosis of elemental or inorganic mercury poisoning involves determining the history of exposure, physical findings, and an elevated body burden of mercury. Although whole blood mercury concentrations are typically less than 6 μg/L, diets rich in fish can result in blood mercury concentrations higher than 200 μg/L; it is not that useful to measure these levels for suspected cases of elemental or inorganic poisoning because of mercury’s short half-life in the blood. If the exposure is chronic, urine levels can be obtained; 24-hour collections are more reliable than spot collections. It is difficult or impossible to interpret urine samples of patients undergoing chelation therapy, as the therapy itself increases mercury levels in the samples.^[28]

Diagnosis of organic mercury poisoning differs in that whole-blood or hair analysis is more reliable than urinary mercury levels.^[28]

[edit] Prevention

Mercury poisoning can be prevented (or minimized) by eliminating or reducing exposure to mercury and mercury compounds. To that end, many governments and private groups have made efforts to regulate the use of mercury heavily, or to issue advisories about its use. For example, the export from the European Union^[29] The variability among regulations and advisories is at times confusing for the lay person as well as scientists. of mercury and some mercury compounds has been prohibited since 2010-03-15.

^[30]

Country	Regulating agency	Regulated activity	Medium	Type of mercury compound	Type of limit	Limit
US	Occupational Safety and Health Administration	occupational exposure	air	elemental mercury	Ceiling (not to exceed)	0.1 mg/m³
US	Occupational Safety and Health Administration	occupational exposure	air	organic mercury	Ceiling (not to exceed)	0.05 mg/m³
US	Food and Drug Administration	drinking	water	inorganic mercury	Maximum allowable concentration	2 ppb (0.002 mg/L)
US	Food and Drug Administration	eating	sea food	methylmercury	Maximum allowable concentration	1 ppm
US	Environmental Protection Agency	drinking	water	inorganic mercury	Maximum contaminant level	2 ppb (0.002 mg/L)

The United States Environmental Protection Agency‎ (EPA) issued recommendations in 2004 regarding exposure to mercury in fish and shellfish.^[31] The EPA also developed the “Fish Kids” awareness campaign for children and young adults ^[32] on account of the greater impact of mercury exposure to that population.

[edit] Treatment

Identifying and removing the source of the mercury is crucial. Decontamination requires removal of clothes, washing skin with soap and water, and flushing the eyes with saline solution as needed. Inorganic ingestion such as mercuric chloride should be approached as the ingestion of any other serious caustic. Immediate chelation therapy is the standard of care for a patient showing symptoms of severe mercury poisoning or the laboratory evidence of a large total mercury load.^[1]

Chelation therapy for acute inorganic mercury poisoning can be done with DMSA, 2,3-dimercapto-1-propanesulfonic acid (DMPS), D-penicillamine (DPCN), or dimercaprol (BAL).^[1] Only DMSA is FDA-approved for use in children for treating mercury poisoning. However, several studies found no clear clinical benefit from DMSA treatment for poisoning due to mercury vapor.^[33] No chelator for methylmercury or ethylmercury is approved by the FDA; DMSA is the most frequently used for severe methylmercury poisoning, as it is given orally, has fewer side effects, and has been found to be superior to BAL, DPCN, and DMPS.^[1] Alpha-lipoic acid (ALA) has been shown to be protective against acute mercury poisoning in several mammalian species when it is given soon after exposure; correct dosage is required, as inappropriate dosages increase toxicity. Although it has been hypothesized that frequent low dosages of ALA may have potential as a mercury chelator, studies in rats have been contradictory.^[34] Glutathione and N-acetylcysteine^[34] Experimental findings have demonstrated an interaction between selenium and methylmercury, but epidemiological studies have found little evidence that selenium helps to protect against the adverse effects of methylmercury.^[35] (NAC) are recommended by some physicians, but have been shown to increase mercury concentrations in the kidneys and the brain.

Even if the patient has no symptoms or documented history of mercury exposure, a minority of physicians (predominantly those in alternative medicine) use chelation to “rid” the body of mercury, which they believe to cause neurological and other disorders. A common practice is to challenge the patient’s body with a chelation agent, collect urine samples, and then use laboratory reports to diagnose the patient with toxic levels of mercury; often no pre-chelation urine sample is collected for comparison. The patient is then advised to undergo further chelation.^[33] No scientific data supports the claim that the mercury in vaccines causes autism^[36] or its symptoms,^[37] and there is no scientific support for chelation therapy as a treatment for autism.^[38]

Chelation therapy can be hazardous. In August 2005, an incorrect form of EDTA used for chelation therapy resulted in hypocalcemia, causing cardiac arrest that killed a five-year-old autistic boy.^[39]

[edit] Prognosis

Many of the toxic effects of mercury are partially or wholly reversible, either through specific therapy or through natural elimination of the metal after exposure has been discontinued.^[40] However, heavy or prolonged exposure can do irreversible damage, particularly in fetuses, infants, and young children. Young’s syndrome is believed to be a long term consequence of early childhood mercury poisoning.^[41] Mercuric Chloride may cause cancer as it has caused increases in several types of tumors in rats and mice, while methyl mercury has caused kidney tumors in male rats. The EPA has classified mercuric chloride and methyl mercury as possible human carcinogens (ATSDR, EPA)

[edit] Detection in biological fluids

Mercury may be measured in blood or urine to confirm a diagnosis of poisoning in hospitalized victims or to assist in the forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the metal. The concentrations in both fluids tend to reach high levels early after exposure to inorganic forms, while lower but very persistent levels are observed following exposure to elemental or organic mercury. Chelation therapy can cause a transient elevation of urine mercury levels.^[42]

[edit] History

• The first emperor of unified China, Qin Shi Huang, reportedly died of ingesting mercury pills that were intended to give him eternal life.^[43]
• The phrase mad as a hatter is likely a reference to mercury poisoning, as mercury-based compounds were once used in the manufacture of felt hats in the 18th and 19th century. (The Mad Hatter character of Alice in Wonderland was almost certainly inspired by an eccentric furniture dealer, not by a victim of mad hatter disease.)^[44]
• In 1810, two British ships, HMS Triumph and HMS Phipps, salvaged a large load of elemental mercury from a wrecked Spanish vessel near Cadiz, Spain. The bladders containing the mercury soon ruptured. The element spread about the ships in liquid and vapour forms. The sailors presented with neurologic compromises: tremor, paralysis, and excessive salivation as well as tooth loss, skin problems, and pulmonary complaints. In 1823 William Burnet, MD published a report on the effects of Mercurial vapour.^[45] The Triumph’s surgeon, Henry Plowman, had concluded that the ailments had arisen from inhaling the mercurialized atmosphere. His treatment was to order the lower deck gun ports to be opened, when it was safe to do so; sleeping on the orlop was forbidden; and no men slept in the lower deck if they were at all symptomatic. Windsails were set to channel fresh air into the lower decks day and night.^[46]
• For years, including the early part of his presidency, Abraham Lincoln took a common medicine of his time called “blue mass” which contained significant amounts of mercury.
• On September 5, 1920, silent movie actress Olive Thomas ingested mercury capsules dissolved in an alcoholic solution at the Hotel Ritz in Paris. There is still controversy over whether it was suicide, or whether she consumed the external preparation by mistake. Her husband, Jack Pickford (the brother of Mary Pickford), had syphilis, and the mercury was used as a treatment of the venereal disease at the time. She died a few days later at the American Hospital in Neuilly.
• An early scientific study of mercury poisoning was in 1923–6 by the German inorganic chemist, Alfred Stock, who himself became poisoned, together with his colleagues, by breathing mercury vapour that was being released by his laboratory equipment—diffusion pumps, float valves, and manometers—all of which contained mercury, and also from mercury that had been accidentally spilt and remained in cracks in the linoleum floor covering. He published a number of papers on mercury poisoning, founded a committee in Berlin to study cases of possible mercury poisoning, and introduced the term micromercurialism.^[47]
• The term Hunter-Russell syndrome derives from a study of mercury poisoning among workers in a seed packing factory in Norwich, England in the late 1930s who breathed methylmercury that was being used as a seed disinfectant and preservative.^[48]
• Outbreaks of methylmercury poisoning occurred in several places in Japan during the 1950s due to industrial discharges of mercury into rivers and coastal waters. The best-known instances were in Minamata and Niigata. In Minamata alone, more than 600 people died due to what became known as Minamata disease. More than 21,000 people filed claims with the Japanese government, of which almost 3000 became certified as having the disease. In 22 documented cases, pregnant women who consumed contaminated fish showed mild or no symptoms but gave birth to infants with severe developmental disabilities.^[2]
• Widespread mercury poisoning occurred in rural Iraq in 1971-1972, when grain treated with a methylmercury-based fungicide that was intended for planting only was used by the rural population to make bread, causing at least 6530 cases of mercury poisoning and at least 459 deaths (see Basra poison grain disaster).^[49]
• On August 14, 1996, Karen Wetterhahn, a chemistry professor working at Dartmouth College, spilled a small amount of dimethylmercury on her latex glove. She began experiencing the symptoms of mercury poisoning five months later and, despite aggressive chelation therapy, died a few months later from brain malfunction due to mercury intoxication.^[24][25]
• In April 2000, Alan Chmurny attempted to kill a former employee, Marta Bradley, by pouring mercury into the ventilation system of her car.^[50]
• On March 19, 2008, Tony Winnett, 55, inhaled mercury vapors while trying to extract gold from computer parts, and died ten days later. His Oklahoma residence became so contaminated that it had to be gutted.^[51][52]
• In December 2008, actor Jeremy Piven was diagnosed with hydrargyria resulting from eating sushi twice a day for twenty years.^[53]

[edit] Infantile Acrodynia

Infantile acrodynia (also known as “calomel disease”, “erythredemic polyneuropathy”, and “pink disease”) is a type of mercury poisoning in children characterized by pain and pink discoloration of the hands and feet.^[54]Greek, where άκρο means end (as in: upper extremity) and οδυνη means pain. Also known as pink disease, erythredema, Selter’s disease, or Swift-Feer disease, acrodynia was relatively commonplace amongst children in the first half of the 20th century.^[55] Initially, the cause of the acrodynia epidemic among infants and young children was unknown^[56]; however, mercury poisoning, primarily from calomel in teething powders, began to be widely accepted as its cause in the 1950s and 60s.^[55] The prevalence of acrodynia decreased greatly after calomel was excluded from most teething powders in 1954.^[55] The word is derived from the

Acrodynia is difficult to diagnose, “it is most often postulated that the etiology of this syndrome is an idiosyncratic hypersensitivity reaction to mercury because of the lack of correlation with mercury levels, many of the symptoms resemble recognized mercury poisoning.”^[57]

Bird flu

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Bird flu may refer to:

Biology and disease

• Avian influenza, influenza endemic to birds.
• Influenzavirus A, the causative agent for bird flu; the genus of the Orthomyxoviridae family. of viruses to which all viruses responsible for Avian influenza belongs to, but also includes viruses that are endemic to humans and other animals.
• H5N1, a subtype of Influenza A virus endemic to birds, currently perceived as a significant emerging pandemic threat.The bird flu can also be very deadly if not treated well

Reye’s syndrome

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  (Redirected from Reyes syndrome)

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Reye’s syndrome
Classification and external resources
ICD–10	G93.7
ICD–9	331.81
DiseasesDB	11463
MedlinePlus	001565
eMedicine	emerg/399
MeSH	D012202

Reye’s syndrome is a potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver, as well as causing hypoglycemia.^[1] The exact cause is unknown, and while it has been associated with aspirin consumption by children with viral illness, it also occurs in the absence of aspirin use.
The disease causes fatty liver with minimal inflammation and severe encephalopathy (with swelling of the brain). The liver may become slightly enlarged and firm, and there is a change in the appearance of the kidneys. Jaundice is not usually present.^[2]
Early diagnosis is vital; while most children recover with supportive therapy, severe brain injury or death are potential complications.

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Severe acute respiratory syndrome SARS

Severe acute respiratory syndrome

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“SARS” redirects here. For other uses, see SARS (disambiguation).

Severe Acute Respiratory Syndrome
Classification and external resources
SARS coronavirus (SARS-CoV), the causative agent of the syndrome.
ICD–10	U04.
ICD–9	079.82
DiseasesDB	32835
MedlinePlus	007192
eMedicine	med/3662
MeSH	D045169

Severe acute respiratory syndrome (SARS; pronounced /ˈsɑrz/ sarz) is a respiratory disease in humansSARS coronavirus (SARS-CoV).^[1] There has been one near pandemic to date, between the months of November 2002 and July 2003, with 8,096 known infected cases and 774 confirmed human deaths (a case-fatality rate of 9.6%) worldwide being listed in the World Health Organization‘s (WHO) 21 April 2004 concluding report.^[2] Within a matter of weeks in early 2003, SARS spread from the Guangdong province of China to rapidly infect individuals in some 37 countries around the world.^[3] which is caused by the

Mortality by age group as of 8 May 2003 is below 1% for people aged 24 or younger, 6% for those 25 to 44, 15% in those 45 to 64 and more than 50% for those over 65.^[4] For comparison, the case fatality rate for influenza is usually around 0.6% (primarily among the elderly) but can rise as high as 33% in locally severe epidemics of new strains. The mortality rate of the primary viral pneumonia form is about 70%.

As of May 2006, the spread of SARS has been fully contained, with the last infected human case seen in June 2003 (disregarding a laboratory induced infection case in 2004). However, SARS is not claimed to have been eradicated (unlike smallpox), as it may still be present in its natural host reservoirs (animal populations) and may potentially return into the human population in the future.^[update]

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