127-473: An eyebrow is an area of short hairs above each eye that follows the shape of the lower margin of the brow ridges of some mammals . In humans , eyebrows serve two main functions: first, communication through facial expression , and second, prevention of sweat, water, and other debris from falling down into the eye socket. It is common for people to modify their eyebrows by means of hair removal and makeup. A number of theories have been proposed to explain
254-566: A diaphragm , focuses it through an adjustable assembly of lenses to form an image , converts this image into a set of electrical signals, and transmits these signals to the brain through neural pathways that connect the eye via the optic nerve to the visual cortex and other areas of the brain. Eyes with resolving power have come in ten fundamentally different forms, classified into compound eyes and non-compound eyes. Compound eyes are made up of multiple small visual units, and are common on insects and crustaceans . Non-compound eyes have
381-455: A fovea area which gives acute vision. In the acute zone, the eyes are flattened and the facets larger. The flattening allows more ommatidia to receive light from a spot and therefore higher resolution. The black spot that can be seen on the compound eyes of such insects, which always seems to look directly at the observer, is called a pseudopupil . This occurs because the ommatidia which one observes "head-on" (along their optical axes ) absorb
508-408: A 50-kDa light chain polypeptide. The heavy chain contains domains with several functions; it has the domain responsible for binding specifically to presynaptic nerve terminals, as well as the domain responsible for mediating translocation of the light chain into the cell cytoplasm as the vacuole acidifies. The light chain is a M27-family zinc metalloprotease and is the active part of the toxin. It
635-620: A center at the Hooper Foundation in San Francisco, where he developed techniques for growing the organism and extracting the toxin, and conversely, for preventing organism growth and toxin production, and inactivating the toxin by heating. The California canning industry was thereby preserved. With the outbreak of World War II, weaponization of botulinum toxin was investigated at Fort Detrick in Maryland. Carl Lamanna and James Duff developed
762-460: A central point. The nature of these eyes means that if one were to peer into the pupil of an eye, one would see the same image that the organism would see, reflected back out. Many small organisms such as rotifers , copepods and flatworms use such organs, but these are too small to produce usable images. Some larger organisms, such as scallops , also use reflector eyes. The scallop Pecten has up to 100 millimetre-scale reflector eyes fringing
889-428: A cluster of numerous ommatidia on each side of the head, organised in a way that resembles a true compound eye. The body of Ophiocoma wendtii , a type of brittle star , is covered with ommatidia, turning its whole skin into a compound eye. The same is true of many chitons . The tube feet of sea urchins contain photoreceptor proteins, which together act as a compound eye; they lack screening pigments, but can detect
1016-642: A cosmetic complication of a cosmetic surgery was the first report on the specific treatment of wrinkles and was published in the journal Plastic and Reconstructive Surgery in 1989. Editors of the journal of the American Society of Plastic Surgeons have clearly stated "the first described use of the toxin in aesthetic circumstances was by Clark and Berris in 1989." Also in 1987, Jean and Alastair Carruthers, both doctors in Vancouver, British Columbia , observed that blepharospasm patients who received injections around
1143-482: A diagnostic technique for evaluating an individual muscle's contribution to an eye movement. Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by Daniel B. Drachman 's work with chicks at Johns Hopkins, Alan B. Scott and colleagues injected botulinum toxin into monkey extraocular muscles. The result
1270-427: A factor of 1,000 or more. Ocelli , some of the simplest eyes, are found in animals such as some of the snails . They have photosensitive cells but no lens or other means of projecting an image onto those cells. They can distinguish between light and dark but no more, enabling them to avoid direct sunlight . In organisms dwelling near deep-sea vents , compound eyes are adapted to see the infra-red light produced by
1397-641: A few facets, each with a retina capable of creating an image. With each eye producing a different image, a fused, high-resolution image is produced in the brain. The mantis shrimp has the world's most complex colour vision system. It has detailed hyperspectral colour vision. Trilobites , now extinct, had unique compound eyes. Clear calcite crystals formed the lenses of their eyes. They differ in this from most other arthropods, which have soft eyes. The number of lenses in such an eye varied widely; some trilobites had only one while others had thousands of lenses per eye. In contrast to compound eyes, simple eyes have
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#17330854663571524-407: A focusing lens , and often an iris . Muscles around the iris change the size of the pupil , regulating the amount of light that enters the eye and reducing aberrations when there is enough light. The eyes of most cephalopods , fish , amphibians and snakes have fixed lens shapes, and focusing is achieved by telescoping the lens in a similar manner to that of a camera . The compound eyes of
1651-407: A fuller look, eyebrows can be cloned in an eyebrow transplant . Individual strands of the eyebrow are created to mimic a natural-looking eyebrow of the desired shape. The process of eyebrow transplant is quite similar to the process of hair transplant. In this process as well, follicles from an active area are transferred to the area where there are no hairs. Follicles are mostly taken from the back of
1778-402: A group of anaerobic microorganisms. In 1919, Georgina Burke used toxin-antitoxin reactions to identify two strains of Clostridium botulinum , which she designated A and B. Over the next three decades, 1895–1925, as food canning was approaching a billion-dollar-a-year industry, botulism was becoming a public health hazard. Karl Friedrich Meyer , a Swiss-American veterinary scientist, created
1905-612: A high refractive index, decreasing to the edges; this decreases the focal length and thus allows a sharp image to form on the retina. This also allows a larger aperture for a given sharpness of image, allowing more light to enter the lens; and a flatter lens, reducing spherical aberration . Such a non-homogeneous lens is necessary for the focal length to drop from about 4 times the lens radius, to 2.5 radii. So-called under-focused lens eyes, found in gastropods and polychaete worms, have eyes that are intermediate between lens-less cup eyes and real camera eyes. Also box jellyfish have eyes with
2032-403: A lens focusing light from one direction on the rhabdom, while light from other directions is absorbed by the dark wall of the ommatidium . The second type is named the superposition eye. The superposition eye is divided into three types: The refracting superposition eye has a gap between the lens and the rhabdom, and no side wall. Each lens takes light at an angle to its axis and reflects it to
2159-447: A limit on the possible resolution that can be obtained (assuming that they do not function as phased arrays ). This can only be countered by increasing lens size and number. To see with a resolution comparable to our simple eyes, humans would require very large compound eyes, around 11 metres (36 ft) in radius. Compound eyes fall into two groups: apposition eyes, which form multiple inverted images, and superposition eyes, which form
2286-454: A longer duration of effect of up to six months or longer. Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin. Smoothing of wrinkles is usually visible three to five days after injection, with maximum effect typically a week following injection. Muscles can be treated repeatedly to maintain the smoothed appearance. DaxibotulinumtoxinA (Daxxify)
2413-417: A muscle that pulls too strongly, or pulls against one that has been weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so injection might seem to need to be repeated, but muscles adapt to the lengths at which they are chronically held, so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding
2540-450: A number of months, paralysis side effects can have the same durations. At least in some cases, these effects are reported to dissipate in the weeks after treatment. Bruising at the site of injection is not a side effect of the toxin, but rather of the mode of administration, and is reported as preventable if the clinician applies pressure to the injection site; when it occurs, it is reported in specific cases to last 7–11 days. When injecting
2667-451: A parabolic mirror to focus the image; it combines features of superposition and apposition eyes. Another kind of compound eye, found in males of Order Strepsiptera , employs a series of simple eyes—eyes having one opening that provides light for an entire image-forming retina. Several of these eyelets together form the strepsipteran compound eye, which is similar to the 'schizochroal' compound eyes of some trilobites . Because each eyelet
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#17330854663572794-512: A permanent effect. In January 2014, botulinum toxin was approved by UK's Medicines and Healthcare products Regulatory Agency for treatment of restricted ankle motion due to lower-limb spasticity associated with stroke in adults. In July 2016, the US Food and Drug Administration (FDA) approved abobotulinumtoxinA (Dysport) for injection for the treatment of lower-limb spasticity in pediatric patients two years of age and older. AbobotulinumtoxinA
2921-420: A pit to reduce the angles of light that enters and affects the eye-spot, to allow the organism to deduce the angle of incoming light. Found in about 85% of phyla, these basic forms were probably the precursors to more advanced types of "simple eyes". They are small, comprising up to about 100 cells covering about 100 μm. The directionality can be improved by reducing the size of the aperture, by incorporating
3048-497: A plastic surgeon from Sacramento, California. In 1987 Clark was challenged with eliminating the disfigurement caused by only the right side of the forehead muscles functioning after the left side of the forehead was paralyzed during a facelift procedure. This patient had desired to look better from her facelift, but was experiencing bizarre unilateral right forehead eyebrow elevation while the left eyebrow drooped, and she constantly demonstrated deep expressive right forehead wrinkles while
3175-498: A reflective layer behind the receptor cells, or by filling the pit with a refractile material. Pit vipers have developed pits that function as eyes by sensing thermal infra-red radiation, in addition to their optical wavelength eyes like those of other vertebrates (see infrared sensing in snakes ). However, pit organs are fitted with receptors rather different from photoreceptors, namely a specific transient receptor potential channel (TRP channels) called TRPV1 . The main difference
3302-466: A refractive cornea: these have a negative lens, enlarging the observed image by up to 50% over the receptor cells, thus increasing their optical resolution. In the eyes of most mammals , birds , reptiles, and most other terrestrial vertebrates (along with spiders and some insect larvae) the vitreous fluid has a higher refractive index than the air. In general, the lens is not spherical. Spherical lenses produce spherical aberration. In refractive corneas,
3429-612: A resolution better than 1°. Also, superposition eyes can achieve greater sensitivity than apposition eyes , so are better suited to dark-dwelling creatures. Eyes also fall into two groups on the basis of their photoreceptor's cellular construction, with the photoreceptor cells either being ciliated (as in the vertebrates) or rhabdomeric . These two groups are not monophyletic; the Cnidaria also possess ciliated cells, and some gastropods and annelids possess both. Some organisms have photosensitive cells that do nothing but detect whether
3556-405: A sharp image. Ocelli (pit-type eyes of arthropods) blur the image across the whole retina, and are consequently excellent at responding to rapid changes in light intensity across the whole visual field; this fast response is further accelerated by the large nerve bundles which rush the information to the brain. Focusing the image would also cause the sun's image to be focused on a few receptors, with
3683-499: A single erect image. Compound eyes are common in arthropods, annelids and some bivalved molluscs. Compound eyes in arthropods grow at their margins by the addition of new ommatidia. Apposition eyes are the most common form of eyes and are presumably the ancestral form of compound eyes. They are found in all arthropod groups, although they may have evolved more than once within this phylum. Some annelids and bivalves also have apposition eyes. They are also possessed by Limulus ,
3810-517: A single lens and focus light onto the retina to form a single image. This type of eye is common in mammals, including humans. The simplest eyes are pit eyes. They are eye-spots which may be set into a pit to reduce the angle of light that enters and affects the eye-spot, to allow the organism to deduce the angle of incoming light. Eyes enable several photo response functions that are independent of vision. In an organism that has more complex eyes, retinal photosensitive ganglion cells send signals along
3937-454: A single lens. Jumping spiders have one pair of large simple eyes with a narrow field of view , augmented by an array of smaller eyes for peripheral vision . Some insect larvae , like caterpillars , have a type of simple eye ( stemmata ) which usually provides only a rough image, but (as in sawfly larvae) can possess resolving powers of 4 degrees of arc, be polarization-sensitive, and capable of increasing its absolute sensitivity at night by
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4064-408: A spherical lens, cornea and retina, but the vision is blurry. Heterogeneous eyes have evolved at least nine times: four or more times in gastropods , once in the copepods , once in the annelids , once in the cephalopods , and once in the chitons , which have aragonite lenses. No extant aquatic organisms possess homogeneous lenses; presumably the evolutionary pressure for a heterogeneous lens
4191-587: A toxin produced by the bacteria causes botulism. On 14 December 1895, there was a large outbreak of botulism in the Belgian village of Ellezelles that occurred at a funeral where people ate pickled and smoked ham; three of them died. By examining the contaminated ham and performing autopsies on the people who died after eating it, van Ermengem isolated an anaerobic microorganism that he called Bacillus botulinus . He also performed experiments on animals with ham extracts, isolated bacterial cultures, and toxins extracts from
4318-415: A transparent humour that optimised colour filtering, blocked harmful radiation, improved the eye's refractive index , and allowed functionality outside of water. The transparent protective cells eventually split into two layers, with circulatory fluid in between that allowed wider viewing angles and greater imaging resolution, and the thickness of the transparent layer gradually increased, in most species with
4445-532: A variety of diseases caused by an overactive nervous system, making him the first to suggest that it could be used therapeutically. In 1870, the German physician Müller coined the term botulism to describe the disease caused by sausage poisoning, from the Latin word botulus , meaning 'sausage'. In 1895 Émile van Ermengem , a Belgian microbiologist, discovered what is now called Clostridium botulinum and confirmed that
4572-412: Is a cosmetic surgery to raise the eyebrow, usually to create a more feminine or youthful appearance. It is not a new phenomenon, with the earliest description of brow lifting published in medical literature in 1919 by French surgeon Raymond Passot. Brows can be affected during a face lift or an eye lift. In the 1970s, doctors started injecting patients' eyebrows with botox or similar toxins to paralyse
4699-400: Is a combination of inputs from the numerous ommatidia (individual "eye units"), which are located on a convex surface, thus pointing in slightly different directions. Compared with simple eyes, compound eyes possess a very large view angle, and can detect fast movement and, in some cases, the polarisation of light. Because the individual lenses are so small, the effects of diffraction impose
4826-412: Is a simple eye, it produces an inverted image; those images are combined in the brain to form one unified image. Because the aperture of an eyelet is larger than the facets of a compound eye, this arrangement allows vision under low light levels. Good fliers such as flies or honey bees, or prey-catching insects such as praying mantis or dragonflies , have specialised zones of ommatidia organised into
4953-404: Is advantageous to have a convex eye-spot, which gathers more light than a flat or concave one. This would have led to a somewhat different evolutionary trajectory for the vertebrate eye than for other animal eyes. The thin overgrowth of transparent cells over the eye's aperture, originally formed to prevent damage to the eyespot, allowed the segregated contents of the eye chamber to specialise into
5080-430: Is also used to treat disorders of hyperactive nerves including excessive sweating, neuropathic pain , and some allergy symptoms. In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain . Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion. The use of botulinum toxin A in children with cerebral palsy
5207-542: Is considered a key factor in this. The majority of the advancements in early eyes are believed to have taken only a few million years to develop, since the first predator to gain true imaging would have touched off an "arms race" among all species that did not flee the photopic environment. Prey animals and competing predators alike would be at a distinct disadvantage without such capabilities and would be less likely to survive and reproduce. Hence multiple eye types and subtypes developed in parallel (except those of groups, such as
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5334-417: Is effective against all main strains of botulism. Botulinum toxin exerts its effect by cleaving key proteins required for nerve activation. First, the toxin binds specifically to presynaptic surface of neurons that use the neurotransmitter acetylcholine . Once bound to the nerve terminal, the neuron takes up the toxin into a vesicle by receptor-mediated endocytosis . As the vesicle moves farther into
5461-401: Is great enough for this stage to be quickly "outgrown". This eye creates an image that is sharp enough that motion of the eye can cause significant blurring. To minimise the effect of eye motion while the animal moves, most such eyes have stabilising eye muscles. The ocelli of insects bear a simple lens, but their focal point usually lies behind the retina; consequently, those can not form
5588-449: Is less hair. Several options exist for removing hair to achieve a thinner or smaller eyebrow, or to "correct" a unibrow , including manual and electronic tweezing , waxing , and threading . The most common method is to use tweezers to thin out and shape the eyebrow. Waxing is becoming more popular. Lastly, there is threading eyebrows, where a cotton thread is rolled over hair to pull it out. Small scissors are sometimes used to trim
5715-410: Is little difference in refractive index between the vitreous fluid and the surrounding water. Hence creatures that have returned to the water—penguins and seals, for example—lose their highly curved cornea and return to lens-based vision. An alternative solution, borne by some divers, is to have a very strongly focusing cornea. A unique feature of most mammal eyes is the presence of eyelids which wipe
5842-690: Is safe in the upper and lower limb muscles. While botulinum toxin is generally considered safe in a clinical setting, serious side effects from its use can occur. Most commonly, botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing temporary paralysis of unintended muscles. Side effects from cosmetic use generally result from unintended paralysis of facial muscles. These include partial facial paralysis, muscle weakness, and trouble swallowing . Side effects are not limited to direct paralysis, however, and can also include headaches, flu-like symptoms, and allergic reactions. Just as cosmetic treatments only last
5969-465: Is sold under the brand names Jeuveau, Botox, and Xeomin. Botulinum toxin B is sold under the brand name Myobloc. In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A US supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around
6096-472: Is that photoreceptors are G-protein coupled receptors but TRP are ion channels . The resolution of pit eyes can be greatly improved by incorporating a material with a higher refractive index to form a lens, which may greatly reduce the blur radius encountered—hence increasing the resolution obtainable. The most basic form, seen in some gastropods and annelids, consists of a lens of one refractive index. A far sharper image can be obtained using materials with
6223-609: Is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the US, the FDA approves the text of the labels of prescription medicines and for which medical conditions the drug manufacturer may sell the drug. However, prescribers may freely prescribe them for any condition they wish, also known as off-label use . Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia . AbobotulinumtoxinA has been approved for
6350-434: Is their primary function. Humans developed a smooth forehead with visible, hairy eyebrows capable of a wide range of movement. Such eyebrows can express a wide range of subtle emotions – including recognition and sympathy. Fashion in eyebrow shape has changed throughout the ages and eyebrows have always featured heavily in female fashion, often as part of cultural demands made on women about body hair . Cosmetic methods over
6477-540: Is translocated into the host cell cytoplasm where it cleaves the host protein SNAP-25 , a member of the SNARE protein family, which is responsible for fusion . The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane, thus preventing the release of the neurotransmitter acetylcholine from axon endings. This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by
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#17330854663576604-453: Is used to relax the clenching of muscles, including those of the esophagus , jaw , lower urinary tract and bladder , or clenching of the anus which can exacerbate anal fissure . Botulinum toxin appears to be effective for refractory overactive bladder . Strabismus , otherwise known as improper eye alignment, is caused by imbalances in the actions of muscles that rotate the eyes. This condition can sometimes be relieved by weakening
6731-418: Is used to treat a number of therapeutic indications, many of which are not part of the approved drug label. Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including cerebral palsy , post-stroke spasticity , post-spinal cord injury spasticity, spasms of the head and neck, eyelid , vagina , limbs, jaw, and vocal cords . Similarly, botulinum toxin
6858-442: The arthropods are composed of many simple facets which, depending on anatomical detail, may give either a single pixelated image or multiple images per eye. Each sensor has its own lens and photosensitive cell(s). Some eyes have up to 28,000 such sensors arranged hexagonally, which can give a full 360° field of vision. Compound eyes are very sensitive to motion. Some arthropods, including many Strepsiptera , have compound eyes of only
6985-440: The copepod Pontella has three. The outer has a parabolic surface, countering the effects of spherical aberration while allowing a sharp image to be formed. Another copepod, Copilia , has two lenses in each eye, arranged like those in a telescope. Such arrangements are rare and poorly understood, but represent an alternative construction. Multiple lenses are seen in some hunters such as eagles and jumping spiders, which have
7112-420: The incident light , while those to one side reflect it. There are some exceptions from the types mentioned above. Some insects have a so-called single lens compound eye, a transitional type which is something between a superposition type of the multi-lens compound eye and the single lens eye found in animals with simple eyes. Then there is the mysid shrimp, Dioptromysis paucispinosa . The shrimp has an eye of
7239-414: The retinohypothalamic tract to the suprachiasmatic nuclei to effect circadian adjustment and to the pretectal area to control the pupillary light reflex . Complex eyes distinguish shapes and colours . The visual fields of many organisms, especially predators, involve large areas of binocular vision for depth perception . In other organisms, particularly prey animals, eyes are located to maximise
7366-459: The 1920s and 1930s. In the 21st century, tattooing became popular as a way to achieve and maintain an eyebrow shape, using a coil machine, rotary machine or a manual tool containing a row of needles. This process, also called cosmetic tattooing or microblading involves an eyebrow artist implanting pigments in small, precise cuts that mimic the look of hair. Shaving lines in eyebrows is another cosmetic alteration, popular among some younger people in
7493-409: The 1990s and 2000s. Eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system . In higher organisms, the eye is a complex optical system that collects light from the surrounding environment, regulates its intensity through
7620-453: The FDA issued a communication to health care professionals reiterating the new drug names and the approved uses for each. A similar warning was issued by Health Canada in 2009, warning that botulinum toxin products can spread to other parts of the body. Botulinum toxin produced by Clostridium botulinum (an anaerobic, gram-positive bacterium) is the cause of botulism. Humans most commonly ingest
7747-481: The German microbiologist J. Leuchs published a paper showing that the outbreaks in Ellezelles and Darmstadt were caused by different strains of Bacillus botulinus and that the toxins were serologically distinct. In 1917, Bacillus botulinus was renamed Clostridium botulinum , as it was decided that term Bacillus should only refer to a group of aerobic microorganisms, while Clostridium would be only used to describe
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#17330854663577874-416: The German physician Justinus Kerner published the first complete description of the symptoms of botulism, based on extensive clinical observations and animal experiments. He concluded that the toxin develops in bad sausages under anaerobic conditions, is a biological substance, acts on the nervous system, and is lethal even in small amounts. Kerner hypothesized that this "sausage toxin" could be used to treat
8001-502: The ICAM) will not indicate a "positive" when samples containing botulinum toxin are tested. To confirm a diagnosis of botulinum toxin poisoning, therapeutically or to provide evidence in death investigations, botulinum toxin may be quantitated by immunoassay of human biological fluids; serum levels of 12–24 mouse LD 50 units per milliliter have been detected in poisoned people. During the early 1980s, German and French newspapers reported that
8128-418: The United States and Canada. Both trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines. Participants received a single intramuscular injection of daxibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of daxibotulinumtoxinA are headache, drooping eyelids, and weakness of facial muscles. LetibotulinumtoxinA (Letybo)
8255-515: The United States and the European Union. All three trials enrolled participants 18 to 75 years old with moderate to severe glabellar lines (wrinkles between the eyebrows). Participants received a single intramuscular injection of letibotulinumtoxinA or placebo at five sites within the muscles between the eyebrows. The most common side effects of letibotulinumtoxinA are headache, drooping of eyelid and brow, and twitching of eyelid. Botulinum toxin
8382-461: The acetylcholine vesicles cannot bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter. This stops nerve signaling, leading to flaccid paralysis . The toxin itself is released from the bacterium as a single chain, then becomes activated when cleaved by its own proteases. The active form consists of a two-chain protein composed of a 100- kDa heavy chain polypeptide joined via disulfide bond to
8509-584: The affected cell. The seven toxin serotypes (A–G) are traditionally separated by their antigenicity. They have different tertiary structures and sequence differences. While the different toxin types all target members of the SNARE family, different toxin types target different SNARE family members. The A, B, and E serotypes cause human botulism, with the activities of types A and B enduring longest in vivo (from several weeks to months). Existing toxin types can recombine to create "hybrid" (mosaic, chimeric) types. Examples include BoNT/CD, BoNT/DC, and BoNT/FA, with
8636-495: The area ($ 200–1000) and depends on expertise of a physician, clinic location, number of units, and treatment complexity. In the US, botox for medical purposes is usually covered by insurance if deemed medically necessary by a doctor and covers a plethora of medical problems including overactive bladder (OAB), urinary incontinence due to neurologic conditions, headaches and migraines, TMJ, spasticity in adults, cervical dystonia in adults, severe axillary hyperhidrosis (or other areas of
8763-479: The bacteria. From these he concluded that the bacteria themselves do not cause foodborne botulism, but rather produce a toxin that causes the disease after it is ingested. As a result of Kerner's and van Ermengem's research, it was thought that only contaminated meat or fish could cause botulism. This idea was refuted in 1904 when a botulism outbreak occurred in Darmstadt , Germany, because of canned white beans. In 1910,
8890-432: The body), blepharospasm, upper or lower limb spasticity. Botox for excessive sweating is FDA approved. Standard areas for aesthetics botox injections include facial and other areas that can form fine lines and wrinkles due to every day muscle contractions and/or facial expressions such as smiling, frowning, squinting, and raising eyebrows. These areas include the glabellar region between the eyebrows, horizontal lines on
9017-403: The brows or mimic hairs where there are sparse areas. Brow gels are also used in creating a thicker brow; they allow for the hairs to be more textured, which gives the appearance of thicker, fuller brows. Lastly, brow powders or even eyeshadows are used for those who want a fuller and more natural look, by placing the brow powder or eyeshadow (closest to the natural hair colour) in areas where there
9144-464: The case fatality rate for botulinum poisoning can be greatly reduced. Two preparations of botulinum antitoxins are available for treatment of botulism. Trivalent (serotypes A, B, E) botulinum antitoxin is derived from equine sources using whole antibodies . The second antitoxin is heptavalent botulinum antitoxin (serotypes A, B, C, D, E, F, G), which is derived from equine antibodies that have been altered to make them less immunogenic. This antitoxin
9271-426: The cell, it acidifies, activating a portion of the toxin that triggers it to push across the vesicle membrane and into the cell cytoplasm . Botulinum neurotoxins recognize distinct classes of receptors simultaneously ( gangliosides , synaptotagmin and SV2 ). Once inside the cytoplasm, the toxin cleaves SNARE proteins (proteins that mediate vesicle fusion, with their target membrane bound compartments) meaning that
9398-399: The cells of the dilator muscle. The vitreous is the transparent, colourless, gelatinous mass that fills the space between the lens of the eye and the retina lining the back of the eye. It is produced by certain retinal cells. It is of rather similar composition to the cornea, but contains very few cells (mostly phagocytes which remove unwanted cellular debris in the visual field, as well as
9525-455: The centuries have been developed to alter the appearance of eyebrows by adding or removing hair, changing the color, or changing the position to meet the aesthetic ideal of the time, for example, by tinting the eyebrow with permanent dye, similar to hair colour, often in order to darken them. Cosmetics tools such as eyebrow brushes, shaders, and pencils are often used to define the eyebrow or make it appear fuller. These can create an outline for
9652-602: The concentration and crystallization techniques that Edward J. Schantz used to create the first clinical product. When the Army's Chemical Corps was disbanded, Schantz moved to the Food Research Institute in Wisconsin, where he manufactured toxin for experimental use and provided it to the academic community. The mechanism of botulinum toxin action – blocking the release of the neurotransmitter acetylcholine from nerve endings –
9779-399: The directionality of light by the shadow cast by its opaque body. The ciliary body is triangular in horizontal section and is coated by a double layer, the ciliary epithelium. The inner layer is transparent and covers the vitreous body, and is continuous from the neural tissue of the retina. The outer layer is highly pigmented, continuous with the retinal pigment epithelium, and constitutes
9906-504: The disease botulism . The toxin is also used commercially for medical and cosmetic purposes. Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent. The seven main types of botulinum toxin are named types A to G (A, B, C1, C2, D, E, F and G). New types are occasionally found. Types A and B are capable of causing disease in humans, and are also used commercially and medically. Types C–G are less common; types E and F can cause disease in humans, while
10033-588: The edge of its shell. It detects moving objects as they pass successive lenses. There is at least one vertebrate, the spookfish , whose eyes include reflective optics for focusing of light. Each of the two eyes of a spookfish collects light from both above and below; the light coming from above is focused by a lens, while that coming from below, by a curved mirror composed of many layers of small reflective plates made of guanine crystals . A compound eye may consist of thousands of individual photoreceptor units or ommatidia ( ommatidium , singular). The image perceived
10160-422: The eye allows light to enter and project onto a light-sensitive layer of cells known as the retina . The cone cells (for colour) and the rod cells (for low-light contrasts) in the retina detect and convert light into neural signals which are transmitted to the brain via the optic nerve to produce vision. Such eyes are typically spheroid, filled with the transparent gel-like vitreous humour , possess
10287-412: The eye and spread tears across the cornea to prevent dehydration. These eyelids are also supplemented by the presence of eyelashes , multiple rows of highly innervated and sensitive hairs which grow from the eyelid margins to protect the eye from fine particles and small irritants such as insects. An alternative to a lens is to line the inside of the eye with "mirrors", and reflect the image to focus at
10414-446: The eye. Photoreception is phylogenetically very old, with various theories of phylogenesis. The common origin ( monophyly ) of all animal eyes is now widely accepted as fact. This is based upon the shared genetic features of all eyes; that is, all modern eyes, varied as they are, have their origins in a proto-eye believed to have evolved some 650-600 million years ago, and the PAX6 gene
10541-545: The eyebrows, either with another method of hair removal or alone. All of these methods can be painful for seconds or minutes due to the sensitivity of the area around the eye but, often, this pain decreases over time as the individual becomes used to it. In time, hair that has been plucked will stop growing back. Some people wax or shave off their eyebrows and leave them bare, stencil or draw them in with eye liner or tattoo them on. In Western societies, it has become more common for men to pluck part of their eyebrows. To create
10668-510: The eyes and upper face also enjoyed diminished facial glabellar lines ("frown lines" between the eyebrows). Alastair Carruthers reported that others at the time also noticed these effects and discussed the cosmetic potential of botulinum toxin. Unlike other investigators, the Carruthers did more than just talk about the possibility of using botulinum toxin cosmetically. They conducted a clinical study on otherwise normal individuals whose only concern
10795-485: The field of view, such as in rabbits and horses , which have monocular vision . The first proto-eyes evolved among animals 600 million years ago about the time of the Cambrian explosion . The last common ancestor of animals possessed the biochemical toolkit necessary for vision, and more advanced eyes have evolved in 96% of animal species in six of the ~35 main phyla . In most vertebrates and some molluscs ,
10922-466: The first letter indicating the light chain type and the latter indicating the heavy chain type. BoNT/FA received considerable attention under the name "BoNT/H", as it was mistakenly thought it could not be neutralized by any existing antitoxin. Botulinum toxins are closely related to tetanus toxin . The two are collectively known as Clostridium neurotoxins and the light chain is classified by MEROPS as family M27. Clostridium neurotoxins belong in
11049-758: The first strabismus patients in 1977, reported its clinical utility in 1980, and had soon trained hundreds of ophthalmologists in EMG-guided injection of the drug he named Oculinum ("eye aligner"). In 1986, Oculinum Inc, Scott's micromanufacturer and distributor of botulinum toxin, was unable to obtain product liability insurance, and could no longer supply the drug. As supplies became exhausted, people who had come to rely on periodic injections became desperate. For four months, as liability issues were resolved, American blepharospasm patients traveled to Canadian eye centers for their injections. Based on data from thousands of people collected by 240 investigators, Oculinum Inc (which
11176-797: The forehead, crow's feet around the eyes, and even circular bands that form around the neck secondary to platysmal hyperactivity. Botulinum toxin has been recognized as a potential agent for use in bioterrorism . It can be absorbed through the eyes, mucous membranes, respiratory tract, and non-intact skin. The effects of botulinum toxin are different from those of nerve agents involved insofar in that botulism symptoms develop relatively slowly (over several days), while nerve agent effects are generally much more rapid. Evidence suggests that nerve exposure (simulated by injection of atropine and pralidoxime ) will increase mortality by enhancing botulinum toxin's mechanism of toxicity. With regard to detection, protocols using NBC detection equipment (such as M-8 paper or
11303-402: The function of the eyebrow in humans. One approach suggests its main function is to prevent moisture (mostly sweat and rain) from flowing into the eye. Another theory holds that clearly visible eyebrows provided safety from predators when early hominid groups started sleeping on the ground. Recent research, however, suggests eyebrows in humans developed as a means of communication and that this
11430-481: The geometry of cephalopod and most vertebrate eyes creates the impression that the vertebrate eye evolved from an imaging cephalopod eye , but this is not the case, as the reversed roles of their respective ciliary and rhabdomeric opsin classes and different lens crystallins show. The very earliest "eyes", called eye-spots, were simple patches of photoreceptor protein in unicellular animals. In multicellular beings, multicellular eyespots evolved, physically similar to
11557-441: The gut, enemas or induced vomiting may be used. For wound infections, infected material may be removed surgically. Botulinum antitoxin is available and may be used to prevent the worsening of symptoms, though it will not reverse existing nerve damage. In severe cases, mechanical respiration may be used to support people with respiratory failure. The nerve damage heals over time, generally over weeks to months. With proper treatment,
11684-413: The head because it is the best harvesting site when it comes to hairs. The follicles are then injected into the skin. The healing process after an eyebrow transplant is similar to the process of tattoo. In this process, patients may experience light bruising and crusting of the skin. People who have genetically thin eyebrows or who have over-tweezed are considered ideal for the transplant. An eyebrow lift
11811-449: The horseshoe crab, and there are suggestions that other chelicerates developed their simple eyes by reduction from a compound starting point. (Some caterpillars appear to have evolved compound eyes from simple eyes in the opposite fashion.) Apposition eyes work by gathering a number of images, one from each eye, and combining them in the brain, with each eye typically contributing a single point of information. The typical apposition eye has
11938-561: The hot vents, allowing the creatures to avoid being boiled alive. There are ten different eye layouts. Eye types can be categorised into "simple eyes", with one concave photoreceptive surface, and "compound eyes", which comprise a number of individual lenses laid out on a convex surface. "Simple" does not imply a reduced level of complexity or acuity. Indeed, any eye type can be adapted for almost any behaviour or environment. The only limitations specific to eye types are that of resolution—the physics of compound eyes prevents them from achieving
12065-425: The hyalocytes of Balazs of the surface of the vitreous, which reprocess the hyaluronic acid ), no blood vessels, and 98–99% of its volume is water (as opposed to 75% in the cornea) with salts, sugars, vitrosin (a type of collagen), a network of collagen type II fibres with the mucopolysaccharide hyaluronic acid, and also a wide array of proteins in micro amounts. Amazingly, with so little solid matter, it tautly holds
12192-531: The injection site. However, the clinical use of botulinum toxin A in cerebral palsy children has been proven to be safe with minimal side effects. Additionally, the FDA announced name changes to several botulinum toxin products, to emphasize that the products are not interchangeable and require different doses for proper use. Botox and Botox Cosmetic were given the generic name of onabotulinumtoxinA, Myobloc as rimabotulinumtoxinB, and Dysport retained its generic name of abobotulinumtoxinA. In conjunction with this,
12319-434: The left side was perfectly smooth due to the paralysis. Clark was aware that Botulinum toxin was safely being used to treat babies with strabismus and he requested and was granted FDA approval to experiment with Botulinum toxin to paralyze the moving and wrinkling normal functioning right forehead muscles to make both sides of the forehead appear the same. This study and case report of the cosmetic use of Botulinum toxin to treat
12446-424: The lens tissue is corrected with inhomogeneous lens material (see Luneburg lens ), or with an aspheric shape. Flattening the lens has a disadvantage; the quality of vision is diminished away from the main line of focus. Thus, animals that have evolved with a wide field-of-view often have eyes that make use of an inhomogeneous lens. As mentioned above, a refractive cornea is only useful out of water. In water, there
12573-861: The masseter muscle of the jaw, loss of muscle function can result in a loss or reduction of power to chew solid foods. With continued high doses, the muscles can atrophy or lose strength; research has shown that those muscles rebuild after a break from Botox. Side effects from therapeutic use can be much more varied depending on the location of injection and the dose of toxin injected. In general, side effects from therapeutic use can be more serious than those that arise during cosmetic use. These can arise from paralysis of critical muscle groups and can include arrhythmia , heart attack , and in some cases, seizures, respiratory arrest, and death. Additionally, side effects common in cosmetic use are also common in therapeutic use, including trouble swallowing, muscle weakness, allergic reactions, and flu-like syndromes. In response to
12700-503: The muscles temporarily, causing the brow to raise. Japanese women and men from the 8th century practiced hikimayu : shaving or plucking the eyebrow hair and painting smudge-like ones higher on the forehead or pencilling in thin ones in a different place. This practice is comparable to that in the Elizabethan era when high-status women would remove eyebrows altogether. Thin eyebrows, achieved by rigorous plucking, were again fashionable in
12827-486: The occurrence of these side effects, in 2008, the FDA notified the public of the potential dangers of the botulinum toxin as a therapeutic. Namely, the toxin can spread to areas distant from the site of injection and paralyze unintended muscle groups, especially when used for treating muscle spasticity in children treated for cerebral palsy. In 2009, the FDA announced that boxed warnings would be added to available botulinum toxin products, warning of their ability to spread from
12954-458: The other types cause disease in other animals. Botulinum toxins are among the most potent toxins known to science. Intoxication can occur naturally as a result of either wound or intestinal infection or by ingesting formed toxin in food. The estimated human median lethal dose of type A toxin is 1.3–2.1 ng /kg intravenously or intramuscularly , 10–13 ng/kg when inhaled, or 1000 ng/kg when taken by mouth. Botulinum toxin
13081-459: The parabolic superposition compound eye type, seen in arthropods such as mayflies , the parabolic surfaces of the inside of each facet focus light from a reflector to a sensor array. Long-bodied decapod crustaceans such as shrimp , prawns , crayfish and lobsters are alone in having reflecting superposition eyes, which also have a transparent gap but use corner mirrors instead of lenses. This eye type functions by refracting light, then using
13208-602: The police had raided a Baader-Meinhof gang safe house in Paris and had found a makeshift laboratory that contained flasks full of Clostridium botulinum , which makes botulinum toxin. Their reports were later found to be incorrect; no such lab was ever found. Commercial forms are marketed under the brand names Botox (onabotulinumtoxinA), Dysport/Azzalure (abobotulinumtoxinA), Letybo (letibotulinumtoxinA), Myobloc (rimabotulinumtoxinB), Xeomin/Bocouture (incobotulinumtoxinA), and Jeuveau (prabotulinumtoxinA). Botulinum toxin A
13335-461: The possibility of damage under the intense light; shielding the receptors would block out some light and thus reduce their sensitivity. This fast response has led to suggestions that the ocelli of insects are used mainly in flight, because they can be used to detect sudden changes in which way is up (because light, especially UV light which is absorbed by vegetation, usually comes from above). Some marine organisms bear more than one lens; for instance
13462-438: The receptor patches for taste and smell. These eyespots could only sense ambient brightness: they could distinguish light and dark, but not the direction of the light source. Through gradual change, the eye-spots of species living in well-lit environments depressed into a shallow "cup" shape. The ability to slightly discriminate directional brightness was achieved by using the angle at which the light hit certain cells to identify
13589-509: The refracting superposition type, in the rear behind this in each eye there is a single large facet that is three times in diameter the others in the eye and behind this is an enlarged crystalline cone. This projects an upright image on a specialised retina. The resulting eye is a mixture of a simple eye within a compound eye. Another version is a compound eye often referred to as "pseudofaceted", as seen in Scutigera . This type of eye consists of
13716-416: The same angle on the other side. The result is an image at half the radius of the eye, which is where the tips of the rhabdoms are. This type of compound eye, for which a minimal size exists below which effective superposition cannot occur, is normally found in nocturnal insects, because it can create images up to 1000 times brighter than equivalent apposition eyes, though at the cost of reduced resolution. In
13843-404: The source. The pit deepened over time, the opening diminished in size, and the number of photoreceptor cells increased, forming an effective pinhole camera that was capable of dimly distinguishing shapes. However, the ancestors of modern hagfish , thought to be the protovertebrate, were evidently pushed to very deep, dark waters, where they were less vulnerable to sighted predators, and where it
13970-622: The surroundings are light or dark , which is sufficient for the entrainment of circadian rhythms . These are not considered eyes because they lack enough structure to be considered an organ, and do not produce an image. Every technological method of capturing an optical image that humans commonly use occurs in nature, with the exception of zoom and Fresnel lenses . Simple eyes are rather ubiquitous, and lens-bearing eyes have evolved at least seven times in vertebrates , cephalopods , annelids , crustaceans and Cubozoa . Pit eyes, also known as stemmata , are eye-spots which may be set into
14097-483: The toxin can block nerves controlling the respiratory system or heart, resulting in death. Botulism can be difficult to diagnose, as it may appear similar to diseases such as Guillain–Barré syndrome , myasthenia gravis , and stroke . Other tests, such as brain scan and spinal fluid examination, may help to rule out other causes. If the symptoms of botulism are diagnosed early, various treatments can be administered. In an effort to remove contaminated food that remains in
14224-420: The toxin from eating improperly canned foods in which C. botulinum has grown. However, the toxin can also be introduced through an infected wound. In infants, the bacteria can sometimes grow in the intestines and produce botulinum toxin within the intestine and can cause a condition known as floppy baby syndrome . In all cases, the toxin can then spread, blocking nerves and muscle function. In severe cases,
14351-510: The toxin is now known to inhibit release of peripheral nociceptive neurotransmitters, suppressing the central pain processing systems responsible for migraine headache. As of 2018 , botulinum toxin injections are the most common cosmetic operation, with 7.4 million procedures in the United States, according to the American Society of Plastic Surgeons . The global market for botulinum toxin products, driven by their cosmetic applications,
14478-402: The transparent crystallin protein. Botox Botulinum toxin , or botulinum neurotoxin (commonly called botox ), is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction , thus causing flaccid paralysis . The toxin causes
14605-469: The treatment of axillary hyperhidrosis , which cannot be managed by topical agents. In 2010, the FDA approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache . However, the use of botulinum toxin injections for episodic migraine has not been approved by the FDA. In cosmetic applications, botulinum toxin is considered relatively safe and effective for reduction of facial wrinkles , especially in
14732-527: The uppermost third of the face. Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan , Dysport/Azzalure from Galderma and Ipsen , Xeomin/Bocouture from Merz, Jeuveau/Nuceiva from Evolus, manufactured by Daewoong in South Korea. The effects of botulinum toxin injections for glabellar lines ('11's lines' between the eyes) typically last two to four months and in some cases, product-dependent, with some patients experiencing
14859-469: The vertebrates, that were only forced into the photopic environment at a late stage). Eyes in various animals show adaptation to their requirements. For example, the eye of a bird of prey has much greater visual acuity than a human eye , and in some cases can detect ultraviolet radiation. The different forms of eye in, for example, vertebrates and molluscs are examples of parallel evolution , despite their distant common ancestry. Phenotypic convergence of
14986-464: The village of Wildbad in what is now Baden-Württemberg , Germany. Thirteen people became sick and six died after eating pork stomach filled with blood sausage , a local delicacy. Additional cases of fatal food poisoning in Württemberg led the authorities to issue a public warning against consuming smoked blood sausages in 1802 and to collect case reports of "sausage poisoning". Between 1817 and 1822,
15113-413: The wider family of AB toxins , which also includes Anthrax toxin and Diphtheria toxin . Nonclassical types include BoNT/X ( P0DPK1 ), which is toxic in mice and possibly in humans; a BoNT/J ( A0A242DI27 ) found in cow Enterococcus ; and a BoNT/Wo ( A0A069CUU9 ) found in the rice-colonizing Weissella oryzae . One of the earliest recorded outbreaks of foodborne botulism occurred in 1793 in
15240-494: The world" with less than one gram of raw botulinum toxin. Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the US and other countries. LetibotulinumtoxinA (Letybo)
15367-530: Was approved for medical use in the United States in February 2024. It is indicated to temporarily improve the appearance of moderate-to-severe glabellar lines. The FDA approved letibotulinumtoxinA based on evidence from three clinical trials (BLESS I [NCT02677298], BLESS II [NCT02677805], and BLESS III [NCT03985982]) of 1,271 participants with moderate to severe wrinkles between the eyebrows for efficacy and safety assessment. These trials were conducted at 31 sites in
15494-555: Was approved for medical use in the United States in September 2022. It is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines (wrinkles between the eyebrows). DaxibotulinumtoxinA is an acetylcholine release inhibitor and neuromuscular blocking agent. The FDA approved daxibotulinumtoxinA based on evidence from two clinical trials (Studies GL-1 and GL-2), of 609 adults with moderate to severe glabellar lines. The trials were conducted at 30 sites in
15621-400: Was elucidated in the mid-20th century, and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues. Ophthalmologists specializing in eye muscle disorders ( strabismus ) had developed the method of EMG-guided injection (using the electromyogram , the electrical signal from an activated muscle, to guide injection) of local anesthetics as
15748-513: Was forecast to reach $ 2.9 billion by 2018. The facial aesthetics market, of which they are a component, was forecast to reach $ 4.7 billion ($ 2 billion in the US) in the same timeframe. In 2020, 4,401,536 botulinum toxin Type A procedures were administered. In 2019 the botulinum toxin market made US$ 3.19 billion. Botox cost is generally determined by the number of units administered (avg. $ 10–30 per unit) or by
15875-399: Was remarkable; a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side effects. After working out techniques for freeze-drying, buffering with albumin , and assuring sterility, potency, and safety, Scott applied to the FDA for investigational drug use, and began manufacturing botulinum type A neurotoxin in his San Francisco lab. He injected
16002-426: Was soon acquired by Allergan) received FDA approval in 1989 to market Oculinum for clinical use in the United States to treat adult strabismus and blepharospasm . Allergan then began using the trademark Botox. This original approval was granted under the 1983 US Orphan Drug Act . The effect of botulinum toxin type-A on reducing and eliminating forehead wrinkles was first described and published by Richard Clark, MD,
16129-450: Was their eyebrow furrow. They performed their study between 1987 and 1989 and presented their results at the 1990 annual meeting of the American Society for Dermatologic Surgery. Their findings were subsequently published in 1992. William J. Binder reported in 2000 that people who had cosmetic injections around the face reported relief from chronic headache. This was initially thought to be an indirect effect of reduced muscle tension, but
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