Gly-His-Lys raises a handful of sensible questions. This page answers them in order, starting with the fundamentals and moving to applications.
Reviewed 2026-08-01. Anything still debated is marked as such rather than presented as settled.
Laboratory studies describe GHK-Cu as a source of copper that cells can take up, with reported effects on collagen, elastin, and glycosaminoglycan synthesis in cultured fibroblasts. The peptide also appears in wound-repair research, where it is linked to the activity of matrix metalloproteinases and their inhibitors. These observations come largely from cell and animal models. How directly the complex controls any single pathway in intact human skin remains an open question, and reported effects depend on concentration, vehicle, and exposure time.
Copper takes part in redox chemistry, and the same property that makes it useful in enzymes can generate reactive oxygen species when the ion is loosely bound. GHK chelates copper through imidazole, amino, and amide nitrogen donors, which reduces the amount of free copper in solution. Whether that chelation is protective, neutral, or harmful in a given tissue is not settled. Laboratory assays report both antioxidant and pro-oxidant behavior, depending on the conditions and the readout used.
The peptide was first isolated from human albumin in 1973 by Loren Pickart, who later described its copper-binding behavior. Early work linked the complex to wound healing and tissue remodeling. Plasma levels of GHK decline with age, a pattern that stimulated interest in topical and supplemental applications. Researchers have reported that the tripeptide influences collagen synthesis, antioxidant defense, and inflammatory signaling in cell and animal models. Human clinical evidence remains limited and often relies on small studies.
Commercial products list GHK-Cu as copper tripeptide-1, a cosmetic ingredient. Formulators value its blue color and water solubility, which allow incorporation into serums, creams, and masks. Regulatory treatment varies: in the United States it appears in cosmetics, while some jurisdictions classify certain claims as drug-like. The compound is not an approved drug for any indication. Studies continue to examine its effects on skin, hair, and wound repair, but dosage, delivery, and long-term safety questions remain open.
GHK-Cu is a coordination complex formed between the tripeptide glycyl-L-histidyl-L-lysine and copper(II). The peptide sequence consists of glycine, histidine, and lysine, and its imidazole and amino groups provide binding sites for the metal ion. In the complex, copper is held through nitrogen donors from the histidine side chain, the N-terminal amine, and deprotonated amide nitrogens. The resulting compound is intensely blue and water-soluble. It occurs naturally in human plasma, saliva, and urine at low concentrations.
| Property | Value | Notes |
|---|---|---|
| Copper binding sites | Imidazole, amino, and amide nitrogens | Form chelate rings with Cu(II) |
| Conditional binding constant | Reported near 10^16 at neutral pH | Value depends on method and medium |
| Visible absorption | Broad band in the blue-violet region | Source of the characteristic color |
| Common analytical methods | LC-MS, HPLC, UV-Vis, ICP-OES | Used for identity and copper content |
| Main degradation routes | Oxidation, photolysis, hydrolysis | Accelerated by light, heat, and pH extremes |
Laboratory characterization of GHK-Cu typically combines separation, spectroscopic, and elemental techniques. Reverse-phase high-performance liquid chromatography is widely used to assess peptide purity, often with ultraviolet detection near the copper-related absorption band or with mass spectrometry for identity confirmation. Because the molecule contains copper, elemental methods such as inductively coupled plasma mass spectrometry or atomic absorption spectroscopy are used to quantify metal content and confirm stoichiometry. No single universal pharmacopeial monograph exists for GHK-Cu. Laboratories therefore validate their own methods, and reported purity values depend on the chosen assay and calibration standards.
Stability of GHK-Cu is influenced by light, oxygen, moisture, pH, and temperature. Solid material is generally kept desiccated and frozen to reduce hydrolysis and oxidation, while aqueous solutions are best prepared fresh or stored cold in aliquots. Repeated freeze-thaw cycles can promote aggregation, precipitation, or peptide degradation. Copper coordination may change under strongly acidic or alkaline conditions, potentially altering the complex's spectroscopic properties. Published long-term stability data for specific matrices, such as cosmetic emulsions or biological buffers, are limited, so shelf-life claims should be treated as formulation-specific rather than universal.
Quality control for GHK-Cu relies on documentation and independent testing rather than a single accepted standard. A certificate of analysis may report peptide purity, copper content, residual solvents, water content, and microbial limits, but the underlying methods and acceptance criteria vary by supplier. Verification can include mass confirmation, amino acid analysis, and comparison with a reference standard when one is available. Open questions include how different copper-binding modes or peptide isomers affect measured activity and whether conventional purity assays capture those differences. Buyers of research-grade material typically need to request raw data rather than rely solely on a summary certificate.
GHK-Cu is the copper complex of the tripeptide glycyl-L-histidyl-L-lysine, a short sequence found naturally in human plasma, saliva and urine. Loren Pickart reported the isolation of the free peptide in 1973 while studying factors that influenced the growth of aged liver cells in culture. The peptide was later shown to bind copper(II) with high affinity, and the metal-bound form became the focus of most subsequent research. Its concentration in circulation declines markedly with age, a pattern that is well documented, though the physiological consequences of that decline remain debated.
The peptide portion consists of three amino acids: glycine, histidine and lysine. Copper(II) coordinates through the imidazole nitrogen of histidine, the alpha-amino group of glycine and a deprotonated amide nitrogen of the backbone, producing a roughly square-planar geometry. This arrangement gives the complex its characteristic blue-to-violet colour and helps it resist dissociation in water. Reported stability constants are high, although values differ between studies because of differences in ionic strength and measurement method.
The International Nomenclature of Cosmetic Ingredients lists the substance as copper tripeptide-1, the name that appears on most topical product labels. Related designations include copper peptide and GHK-Cu, and the hyphenated form is common in research literature. In cosmetics the material is regulated as an ingredient rather than as a drug, so products may reach the market without evidence of the effects claimed for them. Whether those effects are clinically meaningful is an open question, since most supportive data come from laboratory work and small trials.
Solutions of GHK-Cu respond strongly to pH, redox conditions, and the presence of competing chelators such as EDTA. Below roughly pH 4 the copper tends to dissociate, because the amide nitrogen donors become protonated and can no longer coordinate. Strongly alkaline conditions instead favour hydrolysis and precipitation of copper hydroxide. Dissolved oxygen and light accelerate breakdown of the peptide backbone, and the copper released during that process can catalyse further oxidation, so dry, cold, dark storage is the usual recommendation.
Routine characterisation relies on reversed-phase high-performance liquid chromatography for peptide purity, paired with mass spectrometry for identity confirmation. Ultraviolet-visible spectroscopy detects the metal centre through its absorption band in the visible region, and inductively coupled plasma mass spectrometry quantifies total copper so that a metal-to-peptide ratio can be calculated. Amino acid analysis confirms the expected residue composition. Together these techniques establish concentration, identity, and stoichiometry, but none of them directly reports biological activity.
Aqueous GHK-Cu solutions are less stable than the dry powder. Light, dissolved oxygen and elevated temperature all accelerate loss of the intact complex, and the main observable changes are fading of the blue colour and the appearance of peptide fragments. Acidic conditions protonate the histidine imidazole and weaken copper binding, while strongly alkaline conditions promote hydrolysis of the peptide backbone. Because several degradation routes operate at once, a single shelf-life figure does not describe all storage conditions.
Solid material is typically kept as a lyophilised powder in a sealed, light-protected container at minus 20 degrees Celsius, with desiccant where humidity is high. Working solutions are often prepared fresh, aliquoted and frozen to avoid repeated freeze-thaw cycles. Glassware and buffers are checked for trace metal contamination, since other transition metals can displace copper. Records of lot number, reconstitution date and storage temperature help trace unexpected colour changes. Blue colour itself is not a reliable purity test, because partly degraded solutions can remain visibly coloured.
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Mutations result from errors during replication, mitosis, meiosis, or damage to DNA, which then may trigger error-prone repair or cause an error during replication (translesion synthesis). Mutations may also result from substitution, insertion or deletion of segments of DNA due to mobile genetic elements.
Accounts of exactly what happened vary but it seems likely that he was mockingly offering it to the Labour benches, not, as some alleged, "brandishing" it – an illusion caused by Prior pulling his other arm down. Thatcher was furious. Speaker Thomas suspended the sitting and made Heseltine wait until next day to apologise so that tempers could cool. Heseltine was faced with calls for his resignation from the Shadow Cabinet; he thought it would play well with the public, but in Crick's view it helped to cement a reputation for impulsiveness and poor judgement. In autumn 1976 Heseltine was reshuffled, against his will, to the job of Shadow Environment Secretary. He was particularly cross at having to give up the job of Shadow Industry Secretary to John Biffen. He accepted on condition that he would not have to take the Environment job when the Conservatives returned to office. As Benn had given way to Eric Varley there was no longer such a need for aggressive campaigning on Industry, and Thatcher, who had herself been Shadow Environment Secretary in 1974, wanted him to campaign on council house sales (Heseltine offered up to 50% discounts for tenants who bought their homes) and reform of the rates, as she thought his predecessor Timothy Raison ineffective.
It was not until he [Trask] had exercised for some time that he could perform any labor ... [H]is neck and back have continued to curve drawing his head downward on his breast. The account of Trask became the first documented case of AS in the United States, owing to its indisputable description of inflammatory disease characteristics of AS and the hallmark of deforming injury in AS. In the late nineteenth century, the neurophysiologist Vladimir Bekhterev of Russia in 1893, Adolf Strümpell of Germany in 1897, and Pierre Marie of France in 1898 were the first to give adequate descriptions which permitted an accurate diagnosis of AS prior to severe spinal deformity. For this reason, AS is also known as Bekhterev disease, Bechterew's disease or Marie–Strümpell disease. The word is from Greek ankylos meaning crooked, curved or rounded, spondylos meaning vertebra, and -itis meaning inflammation.
The Greater Manchester Integrated Transport Authority (GMITA) was a local government institution responsible for the strategic direction of passenger transport in Greater Manchester. It existed from 1969 to 1974 as the SELNEC Passenger Transport Authority and was then replaced by Greater Manchester County Council. It was created again in 1986 as the Greater Manchester Passenger Transport Authority. It was renamed in 2008 as the Greater Manchester Integrated Transport Authority. Policy of the authority was delivered by the Greater Manchester Passenger Transport Executive. It was replaced by the Greater Manchester Combined Authority in 2011.
Sources: en.wikipedia.org
Protactinium(V) bromide has two similar monoclinic forms: one is obtained by sublimation at 400–410 °C, and another by sublimation at a slightly lower temperature of 390–400 °C. Protactinium iodides can be produced by reacting protactinium metal with elemental iodine at 600 °C, and by reacting Pa2O5 with AlI3 at elevated temperatures. Protactinium(III) iodide can be obtained by heating protactinium(V) iodide in vacuum. As with oxides, protactinium forms mixed halides with alkali metals. The most remarkable among these is Na3PaF8, where the protactinium ion is symmetrically surrounded by 8 F− ions, forming a nearly perfect cube. More complex protactinium fluorides are also known, such as Pa2F9 and ternary fluorides of the types MPaF6 (M = Li, Na, K, Rb, Cs or NH4), M2PaF7 (M = K, Rb, Cs or NH4), and M3PaF8 (M = Li, Na, Rb, Cs), all of which are white crystalline solids. The MPaF6 formula can be represented as a combination of MF and PaF5. These compounds can be obtained by evaporating a hydrofluoric acid solution containing both complexes. For the small alkali cations like Na, the crystal structure is tetragonal, whereas it becomes orthorhombic for larger cations K+, Rb+, Cs+ or NH4+. A similar variation was observed for the M2PaF7 fluorides: namely, the crystal symmetry was dependent on the cation and differed for Cs2PaF7 and M2PaF7 (M = K, Rb or NH4).
After oral administration, zopiclone is rapidly absorbed, with a bioavailability around 75–80%. Time to peak plasma concentration is 1–2 hours. A high-fat meal preceding zopiclone administration does not change absorption (as measured by AUC), but reduces peak plasma levels and delays its occurrence, thus may delay the onset of therapeutic effects. The plasma protein-binding of zopiclone has been reported to be weak, between 45 and 80% (mean 52–59%). It is rapidly and widely distributed to body tissues, including the brain, and is excreted in urine, saliva, and breast milk. Zopiclone is partly extensively metabolized in the liver to form an active N-demethylated derivative (N-desmethylzopiclone) and an inactive zopiclone-N-oxide. Hepatic enzymes playing the most significant role in zopiclone metabolism are CYP3A4 and CYP2E1. In addition, about 50% of the administered dose is decarboxylated and excreted via the lungs. In urine, the N-demethyl and N-oxide metabolites account for 30% of the initial dose. Between 7 and 10% of zopiclone is recovered from the urine, indicating extensive metabolism of the drug before excretion. The terminal elimination half-life of zopiclone ranges from 3.5 to 6.5 hours (5 hours on average). The pharmacokinetics of zopiclone in humans are stereoselective.
Anshel Pfeffer(Hebrew: אנשיל פפר, born 22 June 1973); British -Israeli journalist; a senior correspondent and columnist for Haaretz, covering military, Jewish and international affairs, and Israel correspondent for The Economist.; has also written for The Guardian, The New York Times, The Washington Post and The Times; received the B'nai B'rith award for "Recognizing Excellence in Diaspora Reportage" Melanie Phillips,(born 4 June 1951) Neoconservative, and right wing hawkish pro Zionist journalist; began her career writing for The Guardian and New Statesman; during the 1990s, she came to identify with ideas more associated with the right and currently writes for The Times, The Jerusalem Post, and The Jewish Chronicle, covering political and social issues from a social conservative perspective.Irving Kristol, defines her as a liberal who has "been mugged by reality";was panellist on BBC Radio 4 programme The Moral Maze and BBC One's Question Time; was awarded the Orwell Prize for Journalism Hella Pick CBE (24 April 1929 – 4 April 2024); in 1960, was UN correspondent of The Guardian newspaper, tutored by chief US correspondent Alistair Cooke; awarded CBE in 2000; was Arts & Culture Programme Director at Institute for Strategic Dialogue, an independent think-tank based in London; author ofSimon Wiesenthal: A Life in Search of Justice, Weidenfeld & Nicolson, 1996; Guilty Victim – Austria from the Holocaust to Haider, I B Tauris & Co Ltd, 2000 and Invisible Walls, Weidenfeld & Nicolson, 2021 Gabriel Pogrund (born 1993 or 1994) is a journalist who has worked for the New Statesman, Shortlist, Ha'aretz and Jewish News and is currently Whitehall editor at The Sunday Times; won 2017 Young Journalist of the Year at the British Press Awards and in 2018 was a Stern Fellow at The Washington Post. In 2020 Pogrund and Patrick Maguire published Left Out: The Inside Story of Labour Under Corbyn, which in part, addresses charges of, and assumptions about 'the new anti-Semitism' in the Labour Party. Eve Pollard Evelyn, Lady Lloyd, (née Pollard, formerly Winkleman, born 25 December 1943); has been the editor of several tabloid newspapers; was fashion editor at Honey magazine; also worked for Daily Mirror; was launch editor-in-chief of Elle magazine in the US and edited Sunday magazine for the News of the World and You magazine for the Mail on Sunday; also worked in television as features editor of TV-am (1982–1983) and devised Frocks on the Box for ITV contractor TVS.; often appeared on radio and TV; was regular participant in Through the Keyhole; was a guest panellist on the talk show Loose Women; in 2016, was appointed the first Chair of Reporters without Borders in the UK. In June 2019, was awarded the prestigious Journalist Laureate prize by the London Press Club. 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Karen Pollock journalist, writer, activist chief executive of Holocaust Educational Trust (HET); was Director of the All-Party Parliamentary Group against Antisemitism; later joined Holocaust Educational Trust (HET); is involved with the anti-fascist organisation Searchlight and London Jewish Forum, as well as the Holocaust Memorial Day Trust. She has written for The Guardian, Jewish News, The Jewish Chronicle, and The Huffington Post; gave TED talk entitled 'The search for humanity in the Holocaust' for TEDxDurhamUniversity 2016. She represented British Jews at United Nations World Conference against Racism. She is a vice-president of the Jewish Leadership Council. She was appointed Member of the Order of the British Empire (MBE) in the 2012 New Year Honours for services to education, specifically about the Holocaust, and Commander of the Order of the British Empire (CBE) in the 2020 Birthday Honours for services to Holocaust education. 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Joshua Rozenberg KC (hon) (born 1950), British solicitor, legal affairs commentator, journalist; husband of Melanie Phillips, began career in journalism in 1975 at the BBC where he launched Law in Action on BBC Radio 4 in 1984. At BBC he worked as producer, reporter and legal correspondent; in 2000 left to join The Daily Telegraph as legal affairs editor, where he remained until 2008. After leaving the Telegraph wrote for Evening Standard ; writes for Law Society Gazette and The Critic; wrote for The Guardian's online law page from 2010 to 2016; returned to the BBC to present Law in Action, nearly 25 years after leaving the radio programme. He continues to be seen on BBC Television News as a legal affairs analyst. In January 2016, was made an honorary QC. 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Setright, motoring journalist Rachel Shabi; British journalist and author; contributing writer to The Guardian and the author of Not the Enemy, Israel's Jews from Arab Lands, which argued that Israel has discriminated against and culturally stripped its population of Jews from Arab and Muslim countries. The book received a National Jewish Book Award.Born in Israel to Iraqi Jewish parents in Ramat Gan, Shabi grew up in the UK. Jonathan Shalit (born 17 April 1962), journalist writing for Jewish Chronicle, The Sun, The Telegraph, Daily Express, Royal Television; talent manager and chairman of the InterTalent Rights Group; advises government on the UK's entertainment and creative industries; has guided and managed Charlotte Church, Mel B, Baroness Brady, Kelly Brook, Cher, Dame Joan Collins, Rebecca Ferguson, Katherine Jenkins, Sir Elton John, Vinnie Jones, Kelly Hoppen, Lorraine Kelly, Myleene Klass, N-Dubz, Arlene Phillips, Sir George Martin (the Beatles' producer), Pixie Lott, Sting, Tulisa, Gregg Wallace, Simon Cowell, and the winners of the ITV television talent show Britain's Got Talent. Shalit is chair of trustees and Chief Barker of Variety, the Children's Charity and a leading figure behind the return to London of the Variety Club Showbusiness Awards in 2022. He is also Chairman of the MOBO Charity Foundation (Music of Black Origin), a Trustee of both ChickenShed (Theatre Changing Lives), Patron of the Royal Television Society and co-chairman of the Classic BRITS, and a supporter of Norwood. He gave evidence to Leveson Inquiry into practices and ethics of British Press and was awarded the OBE in 2014 for services to entertainment industry. He also holds an honorary professorship, awarded in 2012, and honorary doctorate at Henley Business School of Reading University in recognition of his contribution to the arts, music and broadcasting. Miriam Shaviv (born 24 August 1976), columnist for "The Jewish Chronicle", "Haaretz", "The Times of Israel", "The Forward"; former literary editor of The Jerusalem Post; Features Editor of the "Times Higher Education" magazine. David Shukman (born 30 May 1958) journalist, and the former science editor of BBC News. Alexandra Shulman (born 13 November 1957); daughter of the critic Milton Shulman and the writer Drusilla Beyfus; previously worked at Arista Records; columnist for The Daily Telegraph and Daily Mail; first novel, Can We Still Be Friends?, published in 2012; was assessed as one of the 100 most powerful women in the United Kingdom by Woman's Hour on BBC Radio 4. Shulman was appointed Officer of the Order of the British Empire in the 2005 New Year Honours for services to the magazine industry. She was later promoted to Commander of the Order of the British Empire in the 2018 New Year Honours for services to fashion journalism; was formerly a trustee of the National Portrait Gallery. Brother Jason Shulman worked as graphic designer for The Sunday Telegraph and art director for Harpers & Queen and Harvey Nichols' magazines. Jake Wallis Simons; Editor of the Jewish Chronicle, writer for The Jerusalem Post, The Times of Israel, Haaretz, the Spectator, the Telegraph, a commentator for Sky News and a broadcaster for BBC Radio 4 and the World Service; was Associate Global Editor for the Daily Mail Online, and features writer for the Sunday Telegraph; also worked for the Times, The Guardian, CNN, POLITICO, Newsweek and La Repubblica; author of Israelophobia: The Newest Version of the Oldest Hatred and What To Do About It, published by Little, Brown and Company Samantha Simmonds (born 1972 or 1973); newsreader, television presenter and journalist; was a news anchor for Sky News until July 2016; returned to presenting for BBC News in March 2017; has also written for Jewish News, MSN (US), Daily Mail, Daily Mirror, The Sun, The Telegraph, Yahoo News Australia, Evening Standard, Times of Israel, Good Housekeeping (UK), HuffPost UK, Women's Health, Women's Health (UK), TV Times, Glamour (UK), Celebs Now, The Jewish Chronicle, Woman Magazine. Ruth Smeeth (née Anderson; born 29 June 1979);Labour Party politician;became director of public affairs and campaigns at the Britain Israel Communications and Research Centre (BICOM) in November 2005; writes for Index on Censorship, The Guardian, Daily Mail, The Independent, The Telegraph, Daily Express, The Sunday Times, The Times, Times of Israel, HuffPost UK, New Statesman;was a deputy director of anti-racist organisation, Hope not Hate. She has also been employed by the Community Security Trust and has worked for the Board of Deputies of British Jews and she is a member of Labour Friends of Israel.; became chief executive of Index on Censorship, an organisation which campaigns for freedom of speech. 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Ed Vaizey (born June 1968) Baron Vaizey of Didcot; of Polish Jewish ancestry; commentator for Conservative Party in broadcast and news media; wrote for The Guardian, The Sunday Times, The Times and The Daily Telegraph; briefly wrote editorials for the Evening Standard; also a regular broadcaster, having appeared on Fi Glover's and Edwina Currie's shows on BBC Radio 5 Live, as regular panelist on Channel 5's The Wright Stuff, BBC Radio 4's Despatch Box and Westminster Hour, and occasionally presented People and Politics on the BBC World Service; in 2010, was named tenth in the 2010 Guardian Film Power 100 list. He played a cameo role as an Oxfordshire MP in the 2012 film Tortoise in Love. Adam Wagner; journalist and op-ed writer for The Jewish Chronicle, Times of Israel, Haaretz, The Guardian, Forbes, Daily Mirror, HuffPostUK, New Statesman; barrister, a member of the Equality and Human Rights Commission's panel of counsel. In 2019 he represented Campaign Against Antisemitism (CAA) in its case a formal investigation under section 20 of the Equality Act 2006 into whether Labour Party had "unlawfully discriminated against, harassed or victimised people because they are Jewish"; specialist in human rights and public law, including COVID-19 lockdown rules. George Weidenfeld, Baron Weidenfeld, (13 September 1919 – 20 January 2016) was a British publisher, philanthropist, and newspaper columnist. He was also a lifelong Zionist and renowned as a master networker. He was on good terms with popes, prime ministers and presidents and put his connections to good use for diplomatic and philanthropic ends; founder of Institute for Strategic Dialogue Victor Weisz, Vicky, cartoonist Claudia Winkleman (born 15 January 1972); television presenter, radio personality, film critic and journalist; has written for The Sunday Times, The Independent, London paper Metro and has written opinion-led lifestyle journalism for Cosmopolitan, Tatler and The Independent; has also written for BBC, Daily Mail, The Mirror UK, The Sun, The Telegraph, Daily Express, The Times, and Radio Times Jonathan Wittenberg (born 17 September 1957 in Glasgow, Scotland); Masorti rabbi, the Senior Rabbi of Masorti Judaism UK; leading writer and thinker on Judaism; has written for The Guardian, Daily Mirror, HuffPost, Times of Israel, Haaretz, and The Jewish Chronicle. He is Rabbi of the New North London Synagogue,; member of the Elijah Interfaith Institute Board of World Religious Leaders.; has featured on Thought for the Day on the BBC Radio Four Today programme. Martin Wolf (born 16 August 1946 in London) journalist; chief economics commentator at the Financial Times; widely regarded as one of the most influential economics journalists in the world. Lawrence H. Summers called him "the world's preeminent financial journalist." Mohamed A. El-Erian, former CEO of the PIMCO, said Wolf is "by far, the most influential economic columnist out there".Prospect magazine described him as "the Anglosphere's most influential finance journalist",; Kenneth Rogoff said, "He really is the premier financial and economics writer in the world". In 2012, he received the Ischia International Journalism Award.In 2019, Wolf received the Gerald Loeb Lifetime Achievement Award from the UCLA Anderson School of Management. Donald Zec (12 March 1919 – 6 September 2021); author of over ten books, newspaper journalist and biographer; worked for the Daily Mirror for 40 years.
Sources: en.wikipedia.org
==== GABAA receptor positive modulation ==== All of the NSAAs approved for the treatment of prostate cancer have been found to possess an off-target action of acting as weak non-competitive inhibitors of human GABAA receptor currents in vitro to varying extents. The IC50 values are 44 μM for flutamide (as hydroxyflutamide), 21 μM for nilutamide, 5.2 μM for bicalutamide, and 3.6 μM for enzalutamide. In addition, flutamide, nilutamide, and enzalutamide have been found to cause convulsions and/or death in mice at sufficiently high doses. Bicalutamide was notably not found to do this, but this was likely simply due to the limited central nervous system penetration of bicalutamide in this species. In any case, enzalutamide is the only approved NSAA that has been found to be associated with a significantly increased incidence of seizures and other associated side effects clinically, so the relevance of the aforementioned findings with regard to bicalutamide and the other NSAAs is unclear.
=== Addiction remission === The term fen-phen was created in 1994 when Pietr Hitzig and Richard B. Rothman reported that this combination could presumptively remit alcohol and cocaine craving. The authors suggested that other combined dopamine and serotonin agonists or precursors might share this therapeutic potential. Subsequent experiments in rats supported these preliminary reports. In 2006 it was confirmed that the combination of phentermine and the serotonin precursor 5-hydroxytryptophan (5-HTP), in place of fenfluramine, significantly decreased alcohol withdrawal seizures in rats. Intramural National Institutes of Health (NIH) double-blind protocols to demonstrate the efficacy of fen-phen in alcohol and cocaine addiction were designed, but never performed.
At pH > 8, silica itself may dissolve. When solutions at extreme pH are needed, the stationary phase can be made of silica polymerized with organic substances, or hydrophobic organic polymers. With such stationary phases, retention time is longer for nonpolar molecules, whereas polar molecules elute more readily (emerge early in the analysis). A chromatographer can increase retention times by adding more water to the mobile phase. Since water is highly polar, it makes the nonpolar analyte interact more strongly with nonpolar stationary phase. Similarly, an investigator can decrease retention time by adding more organic nonpolar solvent to the mobile phase. RP-HPLC operates on the principle of hydrophobic interactions, which originates from the high symmetry in the dipolar water structure and plays the most important role in all processes in life science. RP-HPLC allows the measurement of these interactive forces. The binding of the analyte to the stationary phase is proportional to the contact surface area around the non-polar segment of the analyte molecule upon association with the ligand on the stationary phase. This solvophobic effect is dominated by the force of water for "cavity-reduction" around the analyte and the C18-chain versus the complex of both. The energy released in this process is proportional to the surface tension of the eluent (water: 7.3×10−6 J/cm2, methanol: 2.2×10−6 J/cm2) and to the hydrophobic surface of the analyte and the ligand respectively.
Sources: en.wikipedia.org
It is not approved as a pharmaceutical in major markets and is used mainly as a cosmetic ingredient and a laboratory reagent. Regulatory status varies by country and by the product category in which it appears. Claims about therapeutic effects should be treated separately from permitted cosmetic labeling.
Reversed-phase high-performance liquid chromatography and mass spectrometry are common for the peptide portion. Copper content is usually determined by inductively coupled plasma techniques or by spectrophotometry. Ultraviolet-visible spectroscopy takes advantage of the visible absorption band of the copper complex.
Light, oxygen, and elevated temperature promote degradation of the peptide, and strongly acidic or alkaline conditions accelerate hydrolysis. The copper complex is generally more resistant to oxidation than the free peptide. Storage in a dry, dark, cold environment limits loss over time.
GHK is the free tripeptide, while GHK-Cu includes a bound copper(II) ion. The copper complex is the form most often studied for skin and wound-related activity. The two names are sometimes used interchangeably in product labeling, but they refer to distinct chemical species.