Ergotamine is an ergopeptine and part of the ergot family of alkaloids. It possesses structural similarity to several neurotransmitters, has biological activity as a vasoconstrictor, it is used medicinally for treatment of acute migraine attacks. Medicinal usage of ergot fungus began in the 16th century to induce childbirth, yet dosage uncertainties discouraged the use, it has been used to prevent post-partum hemorrhage. It was first isolated from the ergot fungus by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921; the mechanism of action of ergotamine is complex. The molecule shares structural similarity with neurotransmitters such as serotonin and epinephrine and can thus bind to several receptors acting as an agonist; the anti-migraine effect is due to constriction of the intracranial extracerebral blood vessels through the 5-HT1B receptor, by inhibiting trigeminal neurotransmission by 5-HT1D receptors. Ergotamine has effects on the dopamine and norepinephrine receptors. Ergotamine is a secondary metabolite and the principal alkaloid produced by the ergot fungus, Claviceps purpurea, related fungi in the family Clavicipitaceae.
Its biosynthesis in these fungi requires the amino acid dimethylallyl diphosphate. These precursor compounds are the substrates for the enzyme, tryptophan dimethylallyltransferase, catalyzing the first step in ergot alkaloid biosynthesis, i.e. the prenylation of L-tryptophan. Further reactions, involving methyltransferase and oxygenase enzymes, yield the ergoline, lysergic acid. Lysergic acid is the substrate of lysergyl peptide synthetase, a nonribosomal peptide synthetase, which covalently links LA to the amino acids, L-alanine, L-proline, L-phenylalanine. Enzyme-catalyzed or spontaneous cyclizations, oxygenations/oxidations, isomerizations at selected residues precede, give rise to, formation of ergotamine. Ergotamine both produces damages the peripheral epithelium. In high doses, ergotamine is conducive to vascular stasis and gangrene, it can increase uterine contractivity and is used therapeutically post-partum to decrease uterine bleeding. See ergometrine. Ergotamine continues to be prescribed for migraines.
The common form of prescription is Cafergot, a combination of caffeine and ergotamine. Contraindications include: atherosclerosis, Buerger's syndrome, coronary artery disease, hepatic disease, pruritus, Raynaud's syndrome, renal disease. It's contraindicated if patient is taking macrolide antibiotics, certain HIV protease inhibitors, certain azole antifungals delavirdine, efavirenz or a 5-HT1 agonist. In the United States, ergotamine is available as a suppository, a sublingual tablet, a tablet, sometimes in combination with caffeine; the suppository is available under the brand name Migergot, which contains 2 mg of ergotamine with 100 mg caffeine. The sublingual tablet contains 2 mg of ergotamine; the combination tablet in combination with caffeine called Cafergot contains 1 mg of ergotamine and 100 mg of caffeine.</ref> This preparation may be used following the aura/onset of pain to abort the migraine. For the best results, dosage should start at the first sign of an attack. Side effects of ergotamine include vomiting.
At higher doses, it can cause raised arterial blood pressure and bradycardia or tachycardia. Severe vasoconstriction may cause symptoms of intermittent claudication. Ergotamine is a controlled substance in the United States as it is a used precursor for the production of LSD. Dihydroergotamine, a semi-synthetic form used as an abortive migraine treatment Ergotism Ergometrine
The Times of Northwest Indiana is a daily newspaper headquartered in Munster, Indiana. It is the second-largest newspaper in Indiana, behind only The Indianapolis Star; the paper was founded on June 1906, as The Lake County Times. Its founder, Simon McHie, was a native of a small town along the Niagara River in Canada. In 1933, the name was changed to The Hammond Times, it became an afternoon paper serving Hammond and East Chicago. In May 1962, the McHie family sold the publication to Robert S. Howard; the paper expanded to all of northwest Indiana in 1967 and dropped Hammond from its masthead to become The Times. Offices were moved to Munster in 1989, the paper began morning delivery and began printing different editions based on distribution region; the Howard papers were bought in April 2002 by Lee Enterprises. The Times prints different editions based on delivery region; the three major news regions are: Munster Crown Point Valparaiso The Times’ main office is located in Munster. There are bureau offices in Indianapolis.
Blood and High Heels is a 2012 Hungarian short film and written by Dávid Géczy. It's official selected at Cannes Film Festival Short Film Corner; the film was included in the France and Los Angeles Film Market list. It starred Iván Kamarás and Sonia Couling; the film is about workplace sexual harassment, the worse relationship between one feminist secretary & one chauvinistic boss in the current world economic crisis. Rose Red got a new job as a secretary during the economic crisis and a new boss Ivan Milkov, who thinks "the world in crises, caused by women". Sonia Couling - Rose Red Iván Kamarás - Ivan Milkov Alexis Latham - director The Same Wind Blows - Marton Vojnits
Marmaduke Gwynne was a descendant of the Gwynne family of Glanbrân near Llandovery and an early and influential Methodist convert. He employed Theophilus Evans as an Anglican private chaplain, he was converted to Methodism by Howell Harris. He served as a legal adviser and financial supporter to the Methodists and his daughter Sarah married Charles Wesley. Gwynne was born in Breconshire, to Howell and Mary Gwynne, he was baptised on 1 January 1692. He was the eldest of seven children and his name was the same as his maternal grandfather who had built up the family fortune in a life of public service driven by self-interest, his grandfather had lost his position as a judge in Anglesey due to allegations of corruption and Jacobitism. Gwynne attended Jesus College, Oxford before joining Gray's Inn in 1711, he seemed to get his interest in the law from his namesake and his interest in religion from his father and Sackville Gwynne, the squire at Glanbrân near Llandovery. By the time Gwynne had reached his majority he had returned from London to take up a substantial inheritance of Garth and Llanelwedd from his grandfather.
When Gwynne married Sarah Evans of Peterwell at Lampeter it was a combination of two fortunes as Evans brought a lump sum of £30,000 and her own income of £600 for year. Gwynne became a magistrate and High Sheriff of Radnorshire in 1718. In 1726 Sarah, Gwynne's fifth child was born. Gwynne became a firm friend of the clergyman Theophilus Evans and from 1727 Evans was employed as a private chaplain at the Gwynne residence in Garth where he would preach sometimes more than once a day; this Gwynne was converted to Methodism and became an active supporter of the evangelist Howell Harris in 1737. The family story is, he took along a copy of the Riot Act, the reading of, a necessary preliminary to dispersing an assembly thought contrary to public order, but with the need to presume innocence he first listened to one of his sermons. Gwynne was invited Harris back to his house to eat that evening; when Gwynne returned his wife refused to eat with the stranger. His eleven-year-old daughter, was intrigued but Theophilus Evans was unimpressed and within two years he had moved away from his erstwhile benefactor.
In 1738 Gwynne was offering Harris the use of valuable books in Welsh and he was seen as amongst the first members of the gentry in Wales to declare their support for this religious revolution. Meanwhile, only his daughter shared his spiritual confidence in his household. Harris was arrested in January 1741 when it was claimed that he and his followers had broken into a celebration by force of arms and one of Harris's men had assaulted a Justice of the Peace when he had arrived to arrest him; when the case came to court, Harris refused a lawyer and this obliged Gwynne to appear on his behalf. However, when Harris walked from the court he was seized by a mob intent on murder. Gwynne and his brother, Roderick Gwynne of Glanbrân, were able to avert a lynching. Gwynne was able to use his skill and influence to avoid a custodial sentence, but Harris had to take a fine for a reduced charge of "behaving in a riotous manner". Gwynne continued to correspond with Harris. Despite his wife's objections he made his house welcome to passing travellers of similar beliefs including the Reverend Edward Godwin, George Whitefield, the Reverend Benjamin Dutton and his wife, Ann Dutton.
Ann Dutton was to become an influential Baptist writer. His house guests included John and Charles Wesley; the Gwynne family had twenty servants who looked after them and a minimum of ten house guests and more. Gwynne attended the 1745 Methodist conference in Bristol and he was the only non-preacher at the conference. On 8 April 1749 his daughter, married Charles Wesley at Llanllywenfel parish church near Garth, Powys. Sarah had met Charles two years before and it was said to be "love at first sight" and a rare happy marriage in the Wesley family. Sarah's mother is said to have brought a sixth share of £30,000 and £600 per year to the marriage whereas Charles had to get his brother to underwrite a potential income of £100 per year from book sales to reassure Sarah's family. Gwynne's enthusiasm for the Wesleys cooled his relationship with Harris. Gwynne stepped back from his active support for Methodism but he remained on good terms with the Wesleys and Howell Harris. Gwynne lived in Ludlow for several years after 1745 but returned to Breconshire.
Marmaduke Gwynne died in 1769, aged 77, was buried at Llanlleonfel parish church near the Garth estate. He had six daughters and three sons Howell and Marmaduke. In time it was the descendants of his second son Marmaduke who inherited the family's wealth and lived at Llanelwedd Hall until the early 20th century
A poikilotherm is an animal whose internal temperature varies considerably. It is the opposite of an animal which maintains thermal homeostasis. While the term in principle can apply to all organisms, it is only applied to animals, to vertebrates; the fluctuations are consequence of variation in the ambient environmental temperature. Many terrestrial ectotherms are poikilothermic; however some ectotherms remain in temperature-constant environments to the point that they are able to maintain a constant internal temperature. It is this distinction that makes the term "poikilotherm" more useful than the vernacular "cold-blooded", sometimes used to refer to ectotherms more generally. Poikilothermic animals include types of vertebrate animals some fish and reptiles, as well as many invertebrate animals; the naked mole-rat and sloth are some of the rare mammals. The term derives from Greek poikilos, meaning "varied," from a root meaning "dappled" or “painted,” and thermos, meaning "heat". Poikilotherm animals must be able to function over a wider range of temperatures than homeotherms.
The speed of most chemical reactions vary with temperature, in order to function poikilotherms may have four to ten enzyme systems that operate at different temperatures for an important chemical reaction. As a result, poikilotherms have larger, more complex genomes than homeotherms in the same ecological niche. Frogs are a notable example of this effect, though their complex development is an important factor in their large genome; because their metabolism is variable and below that of homeothermic animals, sustained high-energy activities like powered flight in large animals or maintaining a large brain is beyond poikilotherm animals. The metabolism of poikilotherms favors strategies such as sit-and-wait hunting over chasing prey for larger animals with high movement cost; as they do not use their metabolisms to heat or cool themselves, total energy requirement over time is low. For the same body weight, poikilotherms need only 5 to 10% of the energy of homeotherms; some adaptations are behavioral.
Lizards and snakes bask in the sun in the early morning and late evening, seek shelter around noon. The eggs of the yellow-faced bumblebee are unable to regulate heat. A behavioral adaptation to combat this is incubation, where to maintain the internal temperatures of eggs, the queen and her workers will incubate the brood constantly, by warming their abdomens and touching them to the eggs; the bumblebee generates heat by shivering flight muscles though they are not flying. Termite mounds are oriented in a north–south direction so that they absorb as much heat as possible around dawn and dusk and minimise heat absorption around noon. Tuna are able to warm their entire bodies through a heat exchange mechanism called the rete mirabile, which helps keep heat inside the body, minimises the loss of heat through the gills, they have their swimming muscles near the center of their bodies instead of near the surface, which minimises heat loss. Gigantothermy means using a low ratio of surface area to volume to minimise heat loss, such as in sea turtles.
Camels, although they are homeotherms, thermoregulate using a method termed "temperature cycling" to conserve energy. In hot deserts, they allow their body temperature to rise during the day and fall during the night, adjusting their body temperature to cycle over 6 °C, it is comparatively easy for a poikilotherm to accumulate enough energy to reproduce. Poikilotherms at the same trophic level have much shorter generations than homeotherms: weeks rather than years; such applies to animals with similar ecological roles such as cats and snakes. This difference in energy requirement means that a given food source can support a greater density of poikilothermic animals than homeothermic animals; this is reflected in the predator-prey ratio, higher in poikilothermic fauna compared to homeothermic ones. However, when homeotherms and poikilotherms have similar niches, compete, the homeotherm can drive poikilothermic competitors to extinction, because homeotherms can gather food for a greater fraction of each day.
In medicine, loss of normal thermoregulation in humans is referred to as "poikilothermia". This is seen with sedative and hypnotic drugs or in'compartment syndrome'. For example, barbiturates and chloral hydrate may precipitate this effect. REM sleep is considered a poikilothermic state in humans; the dictionary definition of poikilotherm at Wiktionary
DuckTales: Remastered is a Metroidvania-style platform video game developed by WayForward Technologies and published by Capcom. The game is a high-definition remake of DuckTales, a game released on the Nintendo Entertainment System in 1989, it was released for multiple gaming platforms, including Microsoft Windows, the PlayStation 3, the Xbox 360, the Wii U, over a three-month period between August and November 2013, expanded to iOS, Windows Phone in April 2015. The game was delisted from sale on August 8, 2019; the game features a 2.5 D presentation with 3D modeled levels. Like the original version, the game focuses on Scrooge McDuck traveling across the world in search of five treasures to further increase his fortune. Remastered took one and a half years to make, being developed in late 2011, features vast enhancements to the original graphics and audio, an expanded storyline, a full voice cast that includes the original animated series' then-surviving voice actors and actresses. Remastered received positive reviews.
Reviewers praised the game for its gameplay and presentation while criticizing the overabundance of story content. DuckTales: Remastered features a 2.5D presentation, with 2D hand-drawn character sprites and 3D modeled levels. The gameplay of Remastered remains identical to the original DuckTales game, with players taking the role of Scrooge McDuck as he travels across the world in search of five treasures to further increase his fortune. Scrooge can swing his cane to strike or break objects, can bounce on it like a pogo stick to attack enemies from above; this allows him to reach higher areas, as well as bounce across hazardous areas that would hurt him on foot. Along the way, Scrooge can find various diamonds, found in treasure chests or appearing in certain areas, to increase his fortune and ice cream or cakes that can restore his health. Various characters from the series appear throughout the stages with differing roles, aiding or hindering the player's progress; some gameplay tweaks are introduced, such as a map screen on easier difficulties and an easier pogo jump, which can be toggled on and off.
DuckTales: Remastered features a new tutorial level set in Scrooge's money bin, which includes a boss fight against Big Time Beagle, as well as a new final level in Mount Vesuvius where both the final boss fight and race to the top take place. Money gathered in levels can now be used to unlock various gallery items such as concept art and pieces of music, fill up Scrooge's money bin; the original game's five levels are featured, all of which have been expanded, can be played in any order. Each one includes new objectives that must be met to complete the stage, all of the bosses have new patterns; the game features a full story plot, explaining the motives and reasoning behind each stage, including how Scrooge is able to breathe on the Moon. Characters featured in the original game, such as Magica De Spell, Flintheart Glomgold and the Beagle Boys play a greater role in the game's plot; the original game's hidden treasures are now found only on higher difficulties, the game consists of only one ending.
The Beagle Boys attempt another raid on Scrooge's money bin, with Baggy and Bouncer Beagle capturing Huey and Louie. After Scrooge rescues them, he finds Big Time Beagle in his office with a painting in his hands. With the help of Duckworth, Big Time is retreats; the painting reveals the locations of five treasures, Scrooge wastes no time to set out for them. Scrooge and Launchpad visit the Amazon to find the Sceptre of the Incan King. Using eight golden coins, they uncover the hidden temple of Manco Capquack, but the sceptre is lost and the temple is destroyed by its guardian statue; the chief of the natives approaches Scrooge and Launchpad and thanks them for returning their city to them, gives Scrooge the recovered sceptre in return, just the king's back scratcher. Scrooge, the nephews and Webby visit the castle of Drake Von Vladstone known as Dracula Duck, the heir to the Coin of the Lost Realm; the boys fall into a trap door and are spread throughout the Transylvanian mansion, but Scrooge saves them from the Beagle Boys, disguised as ghosts.
Each of the beagle boys were carrying a torn sheet of paper which contained part of a riddle. They uncover a mirror where Scrooge solves the riddle, Magica De Spell reveals herself, after the coin. Scrooge and Magica face off for it, the sorceress is defeated and retreats empty-handed. Scrooge and the nephews travel to the African Mines to find the Giant Diamond of the Inner Earth, but they find the workers are being scared off by voices and earthquakes, claiming the mine is haunted. Deep underground, Scrooge discovers that the Terra-Firmians and their games are the cause, after interfering he is attacked by their king. Defeated, the king makes an agreement with Scrooge to stop the games in exchange for the mining operations to continue, as it will rid them of the diamonds they consider to be "garbage rocks", he gives Scrooge the Giant Diamond of the Inner Earth to start with. Seeking the Crown of Genghis Khan in the Himalayas, Launchpad crashes into a mountain far from their destination and loses a spare fuel regulator, further spread throughout the level by rabbits.
While recovering them, Scrooge stumbles upon Bubba the Caveduck, frozen in ice, after freeing him and brings him back to the plane, Scrooge discovers that Webby snuck along for the ride. After getting the plane airborne, they are all ambushed by the Beagle Boys. After dealing with them, Scrooge confronts an angry Yeti, but Webby interferes and reveals that it was angry because it stepped on a thorn; as Scrooge