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Adrenochrome
Names
	IUPAC name 3-Hydroxy-1-methyl-2,3-dihydro-1H-indole-5,6-dione
	Other names Adraxone; Pink adrenaline
Identifiers
CAS Number	54-06-8 ;
3D model (JSmol)	Interactive image;
ChemSpider	5687 ;
ECHA InfoCard	100.000.176
PubChem CID	5898;
	InChI[show]
	SMILES[show]
Properties
Chemical formula	C9H9NO3
Molar mass	179.18 g·mol−1
Density	3.264 g/cm³
Boiling point	(decomposes, 115-120 °C)
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

CHEMISTRY[EDIT]

In vivo, adrenochrome is synthesized by the oxidation of epinephrine. In vitro, silver oxide (Ag₂O) is used as an oxidizing agent.^[1] Its presence is detected in solution by a pink color. The color turns brown upon polymerization.

EFFECT ON THE BRAIN[EDIT]

Several small-scale studies (involving 15 or fewer test subjects) conducted in the 1950s and 1960s reported that adrenochrome triggered psychotic reactions such as thought disorder, derealization, and euphoria.^[2] Researchers Abram Hoffer and Humphry Osmond claimed that adrenochrome is a neurotoxic, psychotomimetic substance and may play a role in schizophrenia and other mental illnesses.^[3] In what they called the “adrenochrome hypothesis”,^[4] they speculated that megadoses of vitamin C and niacin could cure schizophrenia by reducing brain adrenochrome.^[5]^[6] However, these hypotheses have never been scientifically accepted; adrenochrome is not currently believed to have any psychedelic properties.^[7]

LAW[EDIT]

Adrenochrome is unscheduled by the Controlled Substances Act in the United States, but if sold as a supplement, sales must conform to U.S. supplement laws. If sold for consumption as a food or drug, sales are regulated by the FDA.^[8]^{[unreliable source?]}

IN POPULAR CULTURE[EDIT]

Author Hunter S. Thompson mentions adrenochrome in his book Fear and Loathing in Las Vegas. The adrenochrome scene also appears in the novel’s film adaptation. In the DVD commentary, director Terry Gilliam admits that his and Thompson’s portrayal is a fictional exaggeration. In fact, Gilliam insists that the drug is entirely fictional and seems unaware of the existence of a substance with even a similar name.
The harvesting of an adrenal gland from a live victim to obtain adrenochrome for drug abuse is a plot feature in the second episode “Whom the Gods would Destroy”, of Series 1 of the British TV series Lewis (2008).^[9]
In Anthony Burgess‘ 1962 novel A Clockwork Orange, “drencrom” (presumably the Nadsat term for adrenochrome) is listed as one of the potential drugs that can be added to milk-plus (milk laced with a drug of the consumer’s choice).
British gothic rock band The Sisters of Mercy released a song with the title Adrenochrome on the B side of their 1982 single Body Electric. Both songs were subsequently re-released on the compilation album Some Girls Wander by Mistake in 1992. The song refers to the substance multiple times.

REFERENCES[EDIT]

Jump up^ MacCarthy, Chim, Ind. Paris 55,435(1946)
Jump up^ John Smythies (2002). “The adrenochrome hypothesis of schizophrenia revisited”. Neurotoxicity Research. 4 (2): 147–150. doi:10.1080/10298420290015827.
Jump up^ Hoffer, A. Osmond, H., Smithies, J.; Schizophrenia: a new approach. Journal of Mental Science #100 (January, 1954)
Jump up^ Hoffer, A (1990). “The Adrenochrome Hypothesis and Psychiatry”. Retrieved 2011-07-25.
Jump up^ Hoffer, A. and Osmond, H. The Hallucinogens (Academic Press, 1967).
Jump up^ Hoffer, A., Osmond, H., & Smythies, J. (1994). An Evolutionary Defense Against Severe Stress. Schizophrenia: A New Approach (pp. 205–221). Victoria, Canada: Journal of Orthomolecular Medicine
Jump up^ “The controversy that these reports created just sort of died away, and the adrenochrome family has never been accepted as being psychedelic. No one in the scientific community today is looking in and about the area, and at present this is considered as an interesting historical footnote.” As seen at: Alexander Shulgin and Ann Shulgin (1991). “#157 (TMA)”. PiHKAL – A Chemical Love Story. Transform Press.
Jump up^ Erowid. “Adrenochrome Law”. Retrieved 2013-01-14.
Jump up^ “Inspector Lewis Series Synopsis”. Archived from the original on 2008-06-26.

EXTERNAL LINKS[EDIT]

Adrenochrome Commentary at erowid.org
Adrenochrome deposits resulting from the use of epinephrine-containing eye drops used to treat glaucoma from the Iowa Eye Atlas (searched for diagnosis = adrenochrome)

Parabiosis

From Wikipedia, the free encyclopedia

For the Homeland episode of the same name, see Parabiosis (Homeland).

[Interesting to note there is an episode of “Homeland” named “Parabiosis”.]

Parabiosis, meaning “living beside”, is a technical term in various contexts in fields of study related to ecology and physiology. It accordingly has been defined independently in at least three disciplines, namely experimental or medical physiology, the ecology of inactive physiological states, and the ecology of certain classes of social species that share nests.

1ETYMOLOGY

ETYMOLOGY[EDIT]

Parabiosis derives most directly from new Latin,^[1] but the Latin in turn derives from two classical Greek roots. The first is παρά (para) for “beside” or “next to”. In modern etymology, this root appears in various senses, such as “close to”, “outside of”, and “different”.

In the physiological sense of “parabiosis”, “para” apparently was intended to mean “next to”.
In describing transiently inactive physiological states, “para” apparently meant “outside of”.
In ecological usage, the word was coined by the entomologist Auguste-Henri Forel as an analogue to “symbiosis“, also in the sense of “next to”. However, in this case, the emphasis was in contrast to “together” (“sym-“).

The second classical Greek root from which the Latin derives is βίος (bios), meaning “life”.

PARABIOTIC EXPERIMENTS[EDIT]

Left: A headless Cecropia Mothjoined with a pupa of the Polyphemus silkworm. Right: The abdomen of a Cecropia moth joined with a Cecropia pupa

In the field of experimental physiology, parabiosis is a class of techniques in which two living organisms are joined together surgically and develop single, shared physiological systems, such as a shared circulatory system.^[2]^[3] Through surgically connecting two animals, researchers can prove that the feedback system in one animal is circulated and affects the second animal via blood and plasma exchange. Total blood volume is exchanged approximately ten times per day in rat experiments using parabiosis. One limitation of the experiments is that outbred rats cannot be used because it can lead to a significant loss of pairs due to intoxication of the blood supply from a dissimilar rat.^[4]

In the mid-1800s, parabiotic experiments were pioneered by Paul Bert. He postulated that surgically connected animals could share a circulatory system. Bert was awarded the Prize of Experimental Physiology of the French Academy of Science in 1866 for his discoveries. Parabiotic experiments were scarcely revisited until the 20th century.^[5]

Many of the parabiotic experiments since 1950 involve research regarding metabolism. One of these experiments was published in 1959 by G. R. Hervey in the Journal of Physiology. This experiment was to support the theory that damage to the hypothalamus, particularly the ventromedial hypothalamus, leads to obesity caused by the overconsumption of food. This results from the ventromedial hypothalamus failing to respond to physiological signals that suppress appetite. The result is attributed to the feedback control system in the brain. Rats in the study were from the same litter, which had been a closed colony for multiple years. The two rats in each pair had no more than 3% difference in weight. Rats were paired at four weeks old. Unpaired rats were used as controls. The rats were conjoined in three ways. First, the peritoneal cavities were opened and connected between the two rats. Later, to avoid the risk of tangling the two rats’ intestines together, smaller cuts were made. After more refinement of the experimental procedure, the abdominal cavities were not opened and the rats were conjoined at the hip bone with minimal cutting. In order to prove that the two animals were sharing blood, researchers injected dye into the veins of one rat and the pigment would show up in the conjoined rat. It was necessary to verify the exchange of blood and plasma. The scientists refined the lesion placement by practicing the procedure on other rats. The rats were killed with ether and weighed at the conclusion of the experiment and the amount of fat in each animal was quantified.

Many of the parabiotic pairs died throughout the experiment before its conclusion. In each pair, one rat became obese and exhibited hyperphagia. The weight of the rat with the surgical lesion rose rapidly for a few months, then reached a plateau as a direct result of the surgical procedure. After the procedure, the rat with the impaired hypothalamus voraciously ate and the paired rat decreased their appetite. The paired rat became obviously thin throughout the experiment, even rejecting food when it was offered. Some of the paired rats starved to death. Lesions subsequently made in the hypothalamus of two paired rats resulted in hyperphagia and obesity. That result verifies that the paired rat decreased its eating in a direct response to the signals in the blood from the rat with the lesion. If its brain was similarly altered, it also ate voraciously and became obese. The control rats who were given surgical lesions in the hypothalamus became similarly obese to the parabiotic counterparts.^[6]

Later studies linked the effects of the previous parabiotic experiments about metabolism to the discovery of leptin. Many hormones and metabolites were proven to not be the satiety factor that caused one rat to starve in the experiments. Leptin seemed like a viable candidate. Starting in 1977, Ruth B.S. Harris, a graduate student under Hervey, repeated previous studies about parabiosis in rats and mice. Due to the discovery of leptin, she analyzed leptin concentrations of the mice in the parabiotic experiments. After injecting leptin into the obese mouse of each pair, she found that leptin circulated between the conjoined animals, but the circulation of leptin took some time to reach equilibrium. As a result of the injections, almost immediate weight loss resulted in the parabiotic pairs due to increased inhibition. Approximately 50–70% of fat was lost in the pairs. The obese mouse lost only fat. The lean mouse lost muscle mass and fat. Harris concluded that leptin levels are increased in the obese animal, but other factors could also affect the animals. Also, leptin was determined to decrease fat storage in both the obese and thin animals.^[4]

Parabiotic experiments have also been used to study diabetes. Douglas Coleman did further parabiotic experiments to determine diabetic chromosomal relationships. A major gene that causes obesity in mice was identified on chromosome 6. The obese gene (ob/ob) was determined from one mutant mouse, discovered in 1950. Coleman and researchers further identified a gene on chromosome 4 that led to hyperphagia and obesity in mice. The gene also correlated to the severe onset of diabetes (db/db gene). The experimenters used parabiosis to conjoin a db/db mouse to a normal mouse, and the normal mouse would starve to death after one week. The db/db mouse would still have a high blood sugar and food in its system. The db/db mouse was determined to have a satiety factor so potent that the other mouse would starve to death. A db/db mouse was conjoined with an ob/ob mouse and the result was the same as the first experiment. The obese mouse starved in 20–30 days, similar to the thin counterpart in the first experiment. The db/db mutant mouse overproduced a satiety factor but could not respond to it, perhaps due to a defective receptor, whereas the ob/ob mutant recognized and responded to the factor but could not reproduce it. Further studies with db/db mice with lesions in the arcuate nucleus of the hypothalamus suggested that the receptor for the satiety factor was found in these brain receptors.^[7]

Early parabiotic experiments also included cancer research. One study, published in 1966 by Friedell, studied the effects of radiation with X-rays on ovarian tumors. To study the tumors, two adult female rats were conjoined. The left rat was shielded and the right rat was exposed to high levels of radiation. The rats were given a controlled amount of food and water for the remainder of their natural lives. After death, the rats were autopsied and 149 of 328 pairs showed the presence of possible ovarian tumors in one or both of the two animals. This result matched previous studies of single rats. Since Friedell’s experiment, other parabiotic experiments have been useful in researching many types of cancer.^[8]

Chronic diseases of age have been saluted as prime candidates for parabiotic research because of the potential to conjoin an older animal with a younger animal. This process could be used to research cardiovascular disease, diabetes, osteoarthritis, and Alzheimer’s disease. As animals age, their oligodendrocytes reduce in efficiency, resulting in decreased myelination, causing negative effects on the central nervous system (CNS). Julia Ruckh and fellow researchers have used parabiosis to study remyelination from adult stem cells to see if conjoining young with older mice could reverse or delay this process. In the experiment, the two mice were conjoined and demyelination was induced via injection into the older mice. The experiment determined that factors from the younger mice reversed CNS demyelination in older mice by revitalizing the oligodendrocytes. The monocytes from the younger mice also enhanced the ability of the older mice to clear myelin debris because the young monocytes can clear lipids from myelin sheaths more effectively than older monocytes. The conjoining of the two animals reversed the effects of age on the myelination cells. The ability of the young mouse’s cells was unaffected. Enhanced immunity from the younger mouse also promoted the general health of the older mouse in each pair. The results of this experiment could lead to therapy processes for people with demyelinating diseases like multiple sclerosis.^[9]

Parabiotic research can be controversial. Due to accusations of animal cruelty, the practice is now shunned in many countries. Compared to other research techniques, there are relatively few parabiotic experiments. Some scientists argue for the benefits of parabiotic research. Eggel and Wyss-Coray argue that conjoining animals mimics naturally occurring parabiosis in nature due to the shared blood supply of conjoined twins. The experiments give insight into the way that bodily systems circulate, which has led to many advances in the study of a variety of diseases. Parabiotic experiments have been used to study obesity, chronic diseases of age, stem cell research, tissue regeneration, diabetes, transplants, tumor biology, and endocrinology.^[5]

HUMAN TRIALS[EDIT]

A two-year human trial to evaluate the beneficial effects of infusions of plasma from young donors (16–25 years of age) using blood biomarkers was started in June 2016 in Monterey, California. A panel of age-associated biomarkers will be measured before and after treatment, representing a spectrum of physiologic pathways with evidence-based connections to aging.^[10]

PARABIOSIS IN PHYSIOLOGY[EDIT]

Other than in experimental physiology, the term also is applicable to spontaneously occurring conditions such as in conjoined twins.^[1]

Logically the word parabiosis would be equally applicable to various forms of parasitism such as the obligate parasitic reproduction of Anglerfish of the family Ceratiidae, in which the circulatory systems of the males and females unite completely. Without the attachment of males to a female, the endocrine functions cannot mature, the individuals fail to develop properly and die young and without reproducing.^[11]

Similarly, in plants growing closely together roots or stems in intimate contact sometimes form natural grafts. More commonly, in parasitic plants such as mistletoe and dodder the haustoriaunite the circulatory systems of the host and the parasite so intimately that parasitic twiners such as Cassytha may act as vectors carrying disease organisms from one host plant to another.^[12]

Inactive physiological states[edit]

Parabiosis as a term also applies to the states assumed by many organisms in various kingdoms of life, such as some bacteria, the bear animalcules (Tardigrada), and Rotifera. At least some members of all these taxa can survive drying out, often for decades or longer. Some bacteria, such as those causing anthrax, produce inactive, resistant spores that survive underground for many years. The eggs of some animals, such as Anostraca, the brine shrimps and their close relatives, have resistant shells and can survive in seasonally dried-out pools. In such a state the organisms show no sign of life until suitable conditions return. In this sense the para root apparently refers to the state as being “outside” of life.^[1]

ECOLOGY OF SOCIAL ORGANISMS SHARING NESTS[EDIT]

Crematogaster modiglianii and Camponotus rufifemur ants sharing a nest

In the late 19th century the first examples were discovered, of colonies of ants that more or less routinely shared their nests with essentially unrelated species of ants. They did not obviously share anything beyond the upkeep of the nests, even segregating their brood, so these were a very surprising observations; most ants are radically intolerant of intruders, usually including even intruders of their own species.

In the early 20th century Auguste-Henri Forel coined the term “parabiosis” for such associations, and it was adopted by the likes of William Morton Wheeler.^[13] The term has remained in currency, for example: “Parabiosis is defined as a special symbiosis, so far known only from a few Neotropical ant species, in which two or more species occupy the same nest site and forage together while keeping brood separate”.^[14]

As is to be expected in matters concerning ethology and ecology however, such a class of behaviour patterns cannot be distinguished puristically from every other; there are exceptions and differences of kind and degree. Parabiosis ranges from the sharing of common trails to sharing common nests, and from effectively tolerating another species in general, to toleration only of the single colony of that species that shares the same nest. Furthermore, there is evidence for the partitioning of functions and unequal sharing of work between the two species in the nest.^[15] Early reports that parabiotic ant colonies forage and feed together peacefully also have been qualified by observations that revealed ants of one species in such an association aggressively displacing members of the other species from artificially provided food, while also profiting by following their recruitment trails to new food sources.^[14]

In practice parabiosis hardly could be a purely neutral interaction. There can be consequent benefits from shared nest defence and maintenance even when there is neither direct cooperation nor inimical interaction between the two associated populations in a nest.^[16]