Niacin known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It belongs to the group of the pyridinecarboxylic acid. Niacin is obtained in the diet from a variety of whole and processed foods, with highest contents in fortified packaged foods, salmon, some vegetable and other animal sources; some countries require its addition to grains. Supplemental niacin is used to treat high blood cholesterol and pellagra. Insufficient amounts of niacin can cause nausea and mouth lesions, anemia and tiredness; this lack of niacin may be observed in pandemic deficiency diseases, which are caused by a lack of five crucial vitamins and are found in areas of widespread poverty and malnutrition. Niacin supplementation has not been found useful for decreasing the risk of cardiovascular disease in those on a statin, but appears to be effective in those not taking a statin. Although niacin and nicotinamide are identical in their vitamin activity, nicotinamide does not have the same pharmacological effects as niacin.
When niacin takes on the - amide group, it does not reduce cause flushing. As the precursor for NAD and NADP, niacin is involved in DNA repair. In 2016 it was the 277th most prescribed medication in the United States with more than a million prescriptions, it has the European food additive series E number of E375. Niacin and niacinamide are used for treatment of pellagra. Niacin has sometimes been used in addition to other lipid-lowering medications. Systematic reviews found no effect of niacin on cardiovascular disease or death, in spite of raising HDL cholesterol, reported side effects including an increased risk of diabetes. Niacin is contraindicated with active liver disease, persistent elevated serum transaminases, active peptic ulcer disease, or arterial bleeding; the most common adverse effects of niacin at low doses are flushing, abdominal pain, dyspepsia, vomiting, rhinitis and rash. These can be minimized by initiating therapy at low dosages, increasing dosage and avoiding administration on an empty stomach.
The acute adverse effects of high-dose niacin therapy –, used in the treatment of hyperlipidemias – further include hypotension, glucose intolerance and insulin resistance, blurred or impaired vision, macular edema. With long-term use, the adverse effects of high-dose niacin therapy include hepatic dysfunction and acute liver failure; the long-term use of niacin at high doses significantly increases the risk of cerebral hemorrhage, ischemic stroke, gastrointestinal ulceration and bleeding, diabetes and diarrhea. Flushing lasts for about 15 to 30 minutes, though it can sometimes last up to two hours, it is sometimes accompanied by a prickly or itching sensation, in particular, in areas covered by clothing. Flushing can be blocked by taking 300 mg of aspirin half an hour before taking niacin, by taking one tablet of ibuprofen per day or by co-administering the prostaglandin receptor antagonist laropiprant. Taking niacin with meals helps reduce this side effect. Acquired tolerance will help reduce flushing.
Reduction of flushing focuses on blocking the prostaglandin-mediated pathway. Slow- or "sustained"-release forms of niacin have been developed to lessen these side effects. Prostaglandin is the primary cause of the flushing reaction, with serotonin appearing to have a secondary role in this reaction; the effect is mediated by prostaglandin E2 and D2 due to GPR109A activation of epidermal Langerhans cells and keratinocytes. Langerhans cells use cyclooxygenase type 1 for PGE2 production and are more responsible for acute flushing, while keratinocytes are COX-2 dependent and are in active continued vasodilation. Flushing was thought to involve histamine, but histamine has been shown not to be involved in the reaction. Hepatotoxicity is related to metabolism via amidation resulting in NAD production; the time-release form has a lower therapeutic index for lowering serum lipids relative to this form of toxicity. The high doses of niacin used to improve the lipid profile have been shown to elevate blood sugar by 5-10%, thereby worsening existing diabetes mellitus.
One review found that niacin therapy was associated with an increase in the risk of new-onset diabetes over 3.6 years from 4.9% to 5.5%. Side effects of heart arrhythmias have been reported. Increased prothrombin time and decreased platelet count have been reported; the time-release variety, at high doses, can cause acute toxic reactions. High doses of niacin can cause niacin maculopathy, a thickening of the macula and retina, which leads to blurred vision and blindness; this maculopathy is reversible. Niacin in doses used to lower cholesterol levels has been associated with birth defects in laboratory animals, with possible consequences for infant development in pregnant women. Between 1906 and 1940 more than 3 million Americans were affected by pellagra, with more than 100,000 deaths. Joseph Goldberger was assigned to study pellagra by the Surgeon General of the United State
Democracy is a play by Michael Frayn which premiered in London at the Royal National Theatre on September 9, 2003. Directed by Michael Blakemore, starring Roger Allam as Willy Brandt and Conleth Hill as Günter Guillaume, it won the Evening Standard and Critics' Circle awards for Best Play. Democracy premiered on Broadway at the Brooks Atkinson Theatre on November 18, 2004, ran for 173 performances, it was nominated for the Tony Drama Desk Award as Best Play. It has been staged in Copenhagen, Stockholm, Wellington, Vancouver and Moscow. A revival of the play, directed by Paul Miller at Sheffield's Crucible Theatre, transferred to London's Old Vic Theatre in 2012; the play, based on actual events, deals with the decision West German chancellor Willy Brandt had to make about exposing the Communist spy Günter Guillaume who worked as his secretary and had heard some of the state's most important secrets. Willy Brandt – Roger Allam Hans-Dietrich Genscher – Nicholas Blane Ulrich Bauhaus – Paul Broughton Horst Ehmke – Jonathan Coy Günther Nollau – Christopher Ettridge Helmut Schmidt – Glyn Grain Reinhard Wilke – Paul Gregory Günter Guillaume – Conleth Hill Arno Kretschmann – Steven Pacey Herbert Wehner – David Ryall Willy Brandt – James Naughton Günter Guillaume – Richard Thomas Arno Kretschmann – Michael Cumpsty Herbert Wehner – Robert Prosky Reinhard Wilke – Terry Beaver Helmut Schmidt – John Dossett Internet Broadway Database listing Interview with Michael Frayn September 19, 2003 broadwaycom.com summary of critics
Marianne Mendt is an Austrian jazz singer and actress, best known for her participation in the 1971 Eurovision Song Contest. Mendt trained as a jazz singer and toured as a singer and bass player, with group the Internationals, around Europe. Back in Vienna she was noticed by talent-spotter Gerhard Bronner, who wrote for her the song "A Glock'n", used as the theme tune for a television drama and reached No. 12 when released as a single in 1970. Marianne Mendt published several'Austrian versions' of well-known jazz and pop songs like Mercy, Mercy, Spinning Wheel and Aquarius/Let the Sunshine In. In 1971, Mendt was chosen by broadcaster ORF to represent Austria with the song "Musik" in the 16th Eurovision Song Contest, held in Dublin on 3 April, it marked Austria's return to Eurovision following a two-year absence. "Musik" – the only song performed at Eurovision to date in the Viennese German dialect – was drawn as the show's opening song, at the end of voting could only manage 16th place of the 18 entries, after a somewhat nervous and hesitant performance from Mendt.
Mendt combined her singing career with acting in productions at the large Vienna theatres. In the 1990s, Mendt's acting career came to the fore, notably in the role of Gitti Schimek in TV drama Kaisermühlen Blues which ran from 1992 until 2000. Mendt remains an active performer appearing at concerts and jazz festivals in Austria. Marianne Mendt website