http://roma.corriere.it/notizie/cronaca/10_luglio_12/diabete-molecola-scoperta-cattolica-roma-1703365435737.shtml
per Marlin e Julien, parere
- Thread starter juliensorel
- Start date
http://users.unimi.it/minucci/BARB_2009-2010/Invecchiamento.pdf(su p66shc) da pag. 72 nel Power Point.
Ne avevamo parlato a suo tempo (ma ci dovrebbe anche essere in Ending Aging...) del ruolo del P66. Comunque la dispensa da te postata è un bel riepilogo sulle varie questioni. Per quanto riguarda il P66 parrebbe rilanciato alla grande il ruolo dell'ossidazione nell'invecchiamento, ma parrebbe anche che alla fine si l'H2O2 il nemico da abbattere e quindi che l'incremento della catalasi sia quanto di meglio si possa fare ora.
Ciao
MA - r l i n
Ciao
MA - r l i n
Marlin, Ma si può contare quante moli di H2O2 vengono prodotte in ogni cellula ogni 24 ore (credo che i conti siano già stati svolti) considerando le moli di O2 prodotte durante la respiraizone cellulare. E quante molti sfuggono all'azione della catalasi? perché Questo delta dovrebbe farci carpire circa il tenore ottimale in grammi di antiox esogeni da introdurre.
Più cachi, più a lungo vivi 
Protective effect of persimmon (Diospyros kaki) peel proanthocyanidin against oxidative damage under H2O2-induced cellular senescence.
http://www.ncbi.nlm.nih.gov/pubmed/18520066
Persimmon oligomeric proanthocyanidins extend life span of senescence-accelerated mice.
http://www.ncbi.nlm.nih.gov/pubmed/20041772
Protective effect of persimmon (Diospyros kaki) peel proanthocyanidin against oxidative damage under H2O2-induced cellular senescence.
http://www.ncbi.nlm.nih.gov/pubmed/18520066
Persimmon oligomeric proanthocyanidins extend life span of senescence-accelerated mice.
http://www.ncbi.nlm.nih.gov/pubmed/20041772
Interessanti gli studi sull'effetto anti-age dei cachi, Kasper, mi chiedo però cosa abbiano di diverso le proantocianidine di questo frutto rispetto a quelle di altri frutti come mirtilli, uva (semi), cranberry etc.
Julien, il perossido di idrogeno ha anche delle funzioni positive, non è un bene provare a eliminarlo completamente:
http://www.herbs2000.com/h_menu/hydrogen_peroxide.htm
In particolare:
Hydrogen peroxide must be present for our immune system to function properly. The cells in the body that fight infection (the class of white blood cells known as granulocytes) produce hydrogen peroxide as a first line of defense against harmful parasites, bacteria, viruses, and fungi. Hydrogen peroxide is also needed for the metabolism of protein, carbohydrates, fats, vitamins, and minerals. It is a by-product of cell metabolism (that is actively broken down by peroxidase), a hormonal regulator, and a necessary part of the body's production of estrogen, progesterone, and thyroxin. If that weren't enough, hydrogen peroxide is involved in the regulation of blood sugar and the production of energy in body cells
Comunque si tratta di di una produzione variabile nei tempi tra i diversi organismi e in uno stesso organismo. Si potrebbe procedere con un overkill di catalasi, ma ammesso che la reazione avvenga in tempo reale per sopprimere tutte le molecole di H2O2 ci sarebbero le controindicazioni di cui sopra...
A mio avviso continua a non essere sbagliato l'approccio tipo Protandim, ossia quella produzione endogena di catalasi e glutatione perossidasi stimolata da alcune sostanze che agiscono sui nostri organi e in particolare sul fegato (lo stesso approccio che ho emulato con l'Anti-Age).
Ciao
MA - r l i n
Julien, il perossido di idrogeno ha anche delle funzioni positive, non è un bene provare a eliminarlo completamente:
http://www.herbs2000.com/h_menu/hydrogen_peroxide.htm
In particolare:
Hydrogen peroxide must be present for our immune system to function properly. The cells in the body that fight infection (the class of white blood cells known as granulocytes) produce hydrogen peroxide as a first line of defense against harmful parasites, bacteria, viruses, and fungi. Hydrogen peroxide is also needed for the metabolism of protein, carbohydrates, fats, vitamins, and minerals. It is a by-product of cell metabolism (that is actively broken down by peroxidase), a hormonal regulator, and a necessary part of the body's production of estrogen, progesterone, and thyroxin. If that weren't enough, hydrogen peroxide is involved in the regulation of blood sugar and the production of energy in body cells
Comunque si tratta di di una produzione variabile nei tempi tra i diversi organismi e in uno stesso organismo. Si potrebbe procedere con un overkill di catalasi, ma ammesso che la reazione avvenga in tempo reale per sopprimere tutte le molecole di H2O2 ci sarebbero le controindicazioni di cui sopra...
A mio avviso continua a non essere sbagliato l'approccio tipo Protandim, ossia quella produzione endogena di catalasi e glutatione perossidasi stimolata da alcune sostanze che agiscono sui nostri organi e in particolare sul fegato (lo stesso approccio che ho emulato con l'Anti-Age).
Ciao
MA - r l i n
>>non è un bene provare a eliminarlo completamente:
non voglio eliminarlo, voglio avere il tasso di un H202 di un neonato.
non voglio eliminarlo, voglio avere il tasso di un H202 di un neonato.
http://www.impactaging.com/papers/v2/n7/pdf/100169.pdf
http://www.impactaging.com/papers/v2/n7/pdf/100168.pdf
http://en.wikipedia.org/wiki/Lithocholic_acid
Chenodeoxycholic acid (also known as chenodesoxycholic acid and chenocholic acid) is a bile acid. It occurs as a white crystalline substance insoluble in water but soluble in alcohol and acetic acid, with melting point at 165-167 °C. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the 4 main organic acids produced by the liver. Chenodeoxycholic acid is synthesized in the liver from cholesterol. It was first isolated in the domestic goose, hence the 'cheno' portion of its name (Greek: ÷Þíá = goose) [1] This compound, when altered by bacteria in the colon, will result in conversion to its secondary bile acid known as lithocholic acid. Chissa gli effetti combinati di un coleretico (tipo il ginger) e di un probiotico (Probiotici del kefir). Cmq è strano sembra che LCA sia tossico e correlato con il cancro al colon.
scientists in the us claim to have hit upon a key clue in tracing the connection between high-fat diets and increased colon-cancer risk. researchers from the ut southwestern medical center report that the body's natural mechanisms are not built to handle lithocholic acid, a toxic byproduct of dietary fat, in the volume generated by high-fat diets. their findings are published in a recent edition of science. dr. david mangelsdorf, professor of pharmacology and investigator in the howard hughes medical institute (hhmi) at ut southwestern, said observational evidence established a strong association between high-fat diets and colorectal cancer, but scientists could not explain the biological and biochemical mechanisms that formed the link. the rate of colorectal cancer is much higher in the united states - where a high-fat diet is common - than in japan, where people don't eat a lot of fat and colorectal cancer is almost nonexistent. but no one has understood why that is, he said. the new findings show that at least part of the answer lies in the body's inability to cope with large amounts of lithocholic acid, produced when the body processes cholesterol. the body produces bile acids when it breaks down cholesterol, part and parcel of dietary fat. those bile acids go to the small intestine and are broken down into secondary bile acids, one of which is lithocholic acid. most secondary bile acids circulate to the liver, but only a little bit of lithocholic acid does so. much of it remains in the small intestine, then moves into the colon, or large intestine. lithocholic acid is highly toxic, and it builds up in a high-fat diet, mangelsdorf said. we don't know how it causes cancer; but it is known to cause cancer in mice, and people with colon cancer have high concentrations of it. scientists knew that a certain receptor controlled the small amount of lithocholic acid in the liver. receptors are proteins that bind to certain substances to help the body absorb or get rid of them. the lithocholic acid-controlling receptor also is present in the colon. but there isn't enough of it to cope with large volumes of lithocholic acid. however, the lithocholic acid-controlling receptor is similar in structure to another receptor, which binds to vitamin d to help the body absorb calcium. mangelsdorf's team wondered if the vitamin d receptor might also help eliminate lithocholic acid. the researchers discovered that the vitamin d receptor actually plays a major role in eliminating lithocholic acid. like the receptor that works in the liver, the vitamin d receptor binds to lithocholic acid, then binds to a specific gene, called cyp3a. this triggers the production of an enzyme that breaks down the toxic acid. those findings were made using assays, which are small, flat panels used to study genetic activity outside living organisms. the researchers then used tissue cultures to show that the process is replicated in living cells. the team fed vitamin d and lithocholic acid to mouse models. the lithocholic acid activated the animals' cyp3a genes, as well as other genes that the vitamin d receptor is known to bind to after binding with vitamin d. it turned out that in vivo, the vitamin d receptor appeared to play a large role in breaking down lithocholic acid, mangelsdorf said. while the research identifies a possible target for helping the body eliminate excess lithocholic acid, exploiting the research might not be so simple. taking extra vitamin d would stimulate more activity in the vitamin d receptors, but that also would cause the body to absorb more calcium. ingesting too much vitamin d can lead to hypercalcemia, a toxic condition that occurs with excessive calcium buildup. mangelsdorf said the body's natural lithocholic acid-response mechanism simply wasn't built to handle the amount of fat in the modern american diet. our bodies can handle slight changes in lithocholic acid that come from a normal diet, but not a high-fat diet, he said. the current american diet can provide more fat on a daily basis than a human being was ever meant to handle. the study was supported by the howard hughes medical institute, the national institutes of health, the robert a. welch foundation and the human frontier science program.
fonte: http://colon-cancer.chikaworldfood.com/T_11490_____link-between-high-fat-diet-and-colorectal-cancer--new-evidence.htm
http://www.impactaging.com/papers/v2/n7/pdf/100168.pdf
http://en.wikipedia.org/wiki/Lithocholic_acid
Chenodeoxycholic acid (also known as chenodesoxycholic acid and chenocholic acid) is a bile acid. It occurs as a white crystalline substance insoluble in water but soluble in alcohol and acetic acid, with melting point at 165-167 °C. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the 4 main organic acids produced by the liver. Chenodeoxycholic acid is synthesized in the liver from cholesterol. It was first isolated in the domestic goose, hence the 'cheno' portion of its name (Greek: ÷Þíá = goose) [1] This compound, when altered by bacteria in the colon, will result in conversion to its secondary bile acid known as lithocholic acid. Chissa gli effetti combinati di un coleretico (tipo il ginger) e di un probiotico (Probiotici del kefir). Cmq è strano sembra che LCA sia tossico e correlato con il cancro al colon.
scientists in the us claim to have hit upon a key clue in tracing the connection between high-fat diets and increased colon-cancer risk. researchers from the ut southwestern medical center report that the body's natural mechanisms are not built to handle lithocholic acid, a toxic byproduct of dietary fat, in the volume generated by high-fat diets. their findings are published in a recent edition of science. dr. david mangelsdorf, professor of pharmacology and investigator in the howard hughes medical institute (hhmi) at ut southwestern, said observational evidence established a strong association between high-fat diets and colorectal cancer, but scientists could not explain the biological and biochemical mechanisms that formed the link. the rate of colorectal cancer is much higher in the united states - where a high-fat diet is common - than in japan, where people don't eat a lot of fat and colorectal cancer is almost nonexistent. but no one has understood why that is, he said. the new findings show that at least part of the answer lies in the body's inability to cope with large amounts of lithocholic acid, produced when the body processes cholesterol. the body produces bile acids when it breaks down cholesterol, part and parcel of dietary fat. those bile acids go to the small intestine and are broken down into secondary bile acids, one of which is lithocholic acid. most secondary bile acids circulate to the liver, but only a little bit of lithocholic acid does so. much of it remains in the small intestine, then moves into the colon, or large intestine. lithocholic acid is highly toxic, and it builds up in a high-fat diet, mangelsdorf said. we don't know how it causes cancer; but it is known to cause cancer in mice, and people with colon cancer have high concentrations of it. scientists knew that a certain receptor controlled the small amount of lithocholic acid in the liver. receptors are proteins that bind to certain substances to help the body absorb or get rid of them. the lithocholic acid-controlling receptor also is present in the colon. but there isn't enough of it to cope with large volumes of lithocholic acid. however, the lithocholic acid-controlling receptor is similar in structure to another receptor, which binds to vitamin d to help the body absorb calcium. mangelsdorf's team wondered if the vitamin d receptor might also help eliminate lithocholic acid. the researchers discovered that the vitamin d receptor actually plays a major role in eliminating lithocholic acid. like the receptor that works in the liver, the vitamin d receptor binds to lithocholic acid, then binds to a specific gene, called cyp3a. this triggers the production of an enzyme that breaks down the toxic acid. those findings were made using assays, which are small, flat panels used to study genetic activity outside living organisms. the researchers then used tissue cultures to show that the process is replicated in living cells. the team fed vitamin d and lithocholic acid to mouse models. the lithocholic acid activated the animals' cyp3a genes, as well as other genes that the vitamin d receptor is known to bind to after binding with vitamin d. it turned out that in vivo, the vitamin d receptor appeared to play a large role in breaking down lithocholic acid, mangelsdorf said. while the research identifies a possible target for helping the body eliminate excess lithocholic acid, exploiting the research might not be so simple. taking extra vitamin d would stimulate more activity in the vitamin d receptors, but that also would cause the body to absorb more calcium. ingesting too much vitamin d can lead to hypercalcemia, a toxic condition that occurs with excessive calcium buildup. mangelsdorf said the body's natural lithocholic acid-response mechanism simply wasn't built to handle the amount of fat in the modern american diet. our bodies can handle slight changes in lithocholic acid that come from a normal diet, but not a high-fat diet, he said. the current american diet can provide more fat on a daily basis than a human being was ever meant to handle. the study was supported by the howard hughes medical institute, the national institutes of health, the robert a. welch foundation and the human frontier science program.
fonte: http://colon-cancer.chikaworldfood.com/T_11490_____link-between-high-fat-diet-and-colorectal-cancer--new-evidence.htm
E così anche gli high-fat diet addicts sono serviti...[]
Beh il legame era abbastanza noto, però il fatto che si sia trovato il colpevole in questo LCA o, meglio nel meccanismo messo in atto, è un passo avanti. Forse può spiegare bene anche il paradosso francese dove i grassi abbondano e le malattie cardiovascolari no, ma bisognerebbe vedere come stanno messi con i tumori al colon...magari per scoprire che vino (e magari anche birra, ne bevono non poca in Francia) possono compensare questo squilibrio (al contrario, chessò di Coca e Pepsi che fanno strage in USA[]...)
Interessante anche il legame col solito VDR, il recettore della vit.D3, parrebbe la soluzione, ma qui si sventola il timore dell'ipercalcemia, che i fans della D3 negano recisamente...[] (io la sto usando topicamente - come calcitriolo peraltro, la forma attiva, mica bruscolini []- e non so se preoccuparmi, occorrerebbe apposito esame, ma sono abbastanza tranquillo, anche perché non esagero con latte e latticini, a parte il grana che dovrebbe essere la mia fonte anche per il calcio).
Quindi riepilogando l'LCA potrebbe far bene un sacco di cose, ma male al colon, forse preso insieme alla vitamina D3 e tenendo sotto controllo la calcemia ci potrebbe essere la quadratura del cerchio (che poi è più o meno quello che vanno predicando, anche qui, i nostri fautori della high fat diet...[], ma non oso pensare di cosa pensano della frase: the current american diet can provide more fat on a daily basis than a human being was ever meant to handle...nemmeno nel mitico paleolitico ?[] ).
Ciao
MA - r l i n
]Beh il legame era abbastanza noto, però il fatto che si sia trovato il colpevole in questo LCA o, meglio nel meccanismo messo in atto, è un passo avanti. Forse può spiegare bene anche il paradosso francese dove i grassi abbondano e le malattie cardiovascolari no, ma bisognerebbe vedere come stanno messi con i tumori al colon...magari per scoprire che vino (e magari anche birra, ne bevono non poca in Francia) possono compensare questo squilibrio (al contrario, chessò di Coca e Pepsi che fanno strage in USA[
]...)Interessante anche il legame col solito VDR, il recettore della vit.D3, parrebbe la soluzione, ma qui si sventola il timore dell'ipercalcemia, che i fans della D3 negano recisamente...[
] (io la sto usando topicamente - come calcitriolo peraltro, la forma attiva, mica bruscolini []- e non so se preoccuparmi, occorrerebbe apposito esame, ma sono abbastanza tranquillo, anche perché non esagero con latte e latticini, a parte il grana che dovrebbe essere la mia fonte anche per il calcio).Quindi riepilogando l'LCA potrebbe far bene un sacco di cose, ma male al colon, forse preso insieme alla vitamina D3 e tenendo sotto controllo la calcemia ci potrebbe essere la quadratura del cerchio (che poi è più o meno quello che vanno predicando, anche qui, i nostri fautori della high fat diet...[
], ma non oso pensare di cosa pensano della frase: the current american diet can provide more fat on a daily basis than a human being was ever meant to handle...nemmeno nel mitico paleolitico ?[] ).Ciao
MA - r l i n
http://dx.doi.org/10.1016/S0024-3205(03)00166-8
The polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules?
A. Gugliucci, and T. Menini
Biochemistry Laboratory, Division of Basic Medical Sciences, Touro University, College of Osteopathic Medicine, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, USA
Received 9 September 2002; accepted 2 December 2002. ; Available online 8 March 2003.
Abstract
Due to the importance of glycation in the genesis of diabetic complications, an intense search for synthetic new antiglycation agents is ongoing. However, a somewhat neglected avenue is the search for endogenous compounds that may inhibit the process and be a source of protodrugs. Based on their ubiquity, their polycationic nature, their essential role in growth, their relatively high concentrations in tissues, and their high concentrations in sperm, we hypothesized that polyamines inhibit glycation and that might be one of their so far elusive functions. In this study we demonstrate a potent antiglycation effect of physiological concentrations of the polyamines spermine and spermidine. We employed two approaches: in the first, we monitored structural changes on histones and ubiquitin in which polyamines inhibit glycation-induced dimer and polymer formation. In the second we monitored functional impairment of catalytic activity of antithrombin III and plasminogen. Protection is afforded against glycation by hexoses, trioses and dicarbonyls AGE precursors and is comparable to those of aminoguanidine and carnosine.
The polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules?
A. Gugliucci, and T. Menini
Biochemistry Laboratory, Division of Basic Medical Sciences, Touro University, College of Osteopathic Medicine, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, USA
Received 9 September 2002; accepted 2 December 2002. ; Available online 8 March 2003.
Abstract
Due to the importance of glycation in the genesis of diabetic complications, an intense search for synthetic new antiglycation agents is ongoing. However, a somewhat neglected avenue is the search for endogenous compounds that may inhibit the process and be a source of protodrugs. Based on their ubiquity, their polycationic nature, their essential role in growth, their relatively high concentrations in tissues, and their high concentrations in sperm, we hypothesized that polyamines inhibit glycation and that might be one of their so far elusive functions. In this study we demonstrate a potent antiglycation effect of physiological concentrations of the polyamines spermine and spermidine. We employed two approaches: in the first, we monitored structural changes on histones and ubiquitin in which polyamines inhibit glycation-induced dimer and polymer formation. In the second we monitored functional impairment of catalytic activity of antithrombin III and plasminogen. Protection is afforded against glycation by hexoses, trioses and dicarbonyls AGE precursors and is comparable to those of aminoguanidine and carnosine.
> E così anche gli high-fat diet addicts sono serviti...
> Beh il legame era abbastanza noto, però il fatto che si sia trovato il colpevole in questo LCA o, meglio nel meccanismo > messo in atto, è un passo avanti.
Un passo avanti lo facevi se ti fossi letto i pdf di Julien:
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.
Ma pre-giudizio arriva appunto prima ... prima ancora di leggere.
Peccato.
> Beh il legame era abbastanza noto, però il fatto che si sia trovato il colpevole in questo LCA o, meglio nel meccanismo > messo in atto, è un passo avanti.
Un passo avanti lo facevi se ti fossi letto i pdf di Julien:
Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes.
Ma pre-giudizio arriva appunto prima ... prima ancora di leggere.
Peccato.
Peccato... che me lo sono proprio letto tutto, forse tu non hai letto il mio commento attentamente perché da quello lo si capiva subito, considerando che appunto cercavo soluzioni per evitare gli effetti negativi dell'LCA e sfruttare appunto quelli positivi anti-age...
Rileggi quindi quanto ho scritto sopra anche perché alla fine davo atto che l'abbinamento con vit.D3 poteva essere la soluzione ideale e che questo era appunto stato proposto qui sul forum da qualcuno che la pensa più o meno come te...[]
Ciao
MA - r l i n
Rileggi quindi quanto ho scritto sopra anche perché alla fine davo atto che l'abbinamento con vit.D3 poteva essere la soluzione ideale e che questo era appunto stato proposto qui sul forum da qualcuno che la pensa più o meno come te...[
]Ciao
MA - r l i n
>>Quindi...Agaricus bisporus (detto fungo champignon...)
Certo. E' più di un mese che li mangio trifolati freschi.
L'unica perplessità proveniva dalla lettura di Wiki:
Potential medicinal value
Results of an enzyme assay conducted with Agaricus bisporus and the enzyme aromatase.[20][21]Agaricus bisporus also contains sodium, potassium, and phosphorus,[22] conjugated linoleic acid[23] and antioxidants.[24]
A clinical trial is scheduled to take place at the City of Hope National Medical Center due to earlier research indicating that the common mushroom can inhibit aromatase, and therefore may be able to lower estrogen levels in the human body[21], which might reduce breast cancer susceptibility.[20] [25] In 2009, a case control study of over 2000 women, correlated a large decrease of breast cancer incidence in women who consumed mushrooms. Women in the study who consumed fresh mushrooms daily, were 64% less likely to develop breast cancer, while those that combined a mushroom diet with regular green tea consumption, reduced their risk of breast cancer by nearly 90%.[26]
The table mushroom has also been shown to possess possible immune system enhancing properties. An in vitro study demonstrated the mushroom enhanced dendritic cell function.[27][28]
Health Risks
Some studies have revealed that raw A. bisporus - along with some other edible mushrooms - contain small amounts of carcinogenic hydrazine derivatives, including agaritine and gyromitrin.[29][30] However, this research also noted when cooked, these compounds were reduced significantly.[31]
http://en.wikipedia.org/wiki/Agaritine
Tutavia studi recenti smentiscono e addirittua ribaltano le assunzioni citate su wikipedia.
http://www.ncbi.nlm.nih.gov/pubmed/20347942
L'agaricus inoltre è una vera e propria farmacia ambulante (beta glucani, erotienina, poliammine, vitamine, minerali CLA ecc...) a basso costo. E inoltre i funghi mi sono sempre piaciuti. []
Certo. E' più di un mese che li mangio trifolati freschi.
L'unica perplessità proveniva dalla lettura di Wiki:
Potential medicinal value
Results of an enzyme assay conducted with Agaricus bisporus and the enzyme aromatase.[20][21]Agaricus bisporus also contains sodium, potassium, and phosphorus,[22] conjugated linoleic acid[23] and antioxidants.[24]
A clinical trial is scheduled to take place at the City of Hope National Medical Center due to earlier research indicating that the common mushroom can inhibit aromatase, and therefore may be able to lower estrogen levels in the human body[21], which might reduce breast cancer susceptibility.[20] [25] In 2009, a case control study of over 2000 women, correlated a large decrease of breast cancer incidence in women who consumed mushrooms. Women in the study who consumed fresh mushrooms daily, were 64% less likely to develop breast cancer, while those that combined a mushroom diet with regular green tea consumption, reduced their risk of breast cancer by nearly 90%.[26]
The table mushroom has also been shown to possess possible immune system enhancing properties. An in vitro study demonstrated the mushroom enhanced dendritic cell function.[27][28]
Health Risks
Some studies have revealed that raw A. bisporus - along with some other edible mushrooms - contain small amounts of carcinogenic hydrazine derivatives, including agaritine and gyromitrin.[29][30] However, this research also noted when cooked, these compounds were reduced significantly.[31]
http://en.wikipedia.org/wiki/Agaritine
Tutavia studi recenti smentiscono e addirittua ribaltano le assunzioni citate su wikipedia.
http://www.ncbi.nlm.nih.gov/pubmed/20347942
L'agaricus inoltre è una vera e propria farmacia ambulante (beta glucani, erotienina, poliammine, vitamine, minerali CLA ecc...) a basso costo. E inoltre i funghi mi sono sempre piaciuti. [
]Julien, sei sicuro che l'MTOR sia il nemico numero 1?
http://www.sciencedaily.com/releases/2010/07/100719124402.htm
Impaired Activity of the Protein MTOR a Strain on the Heart
ScienceDaily (July 19, 2010)
A team of researchers, led by Gianluigi
Condorelli, at the University of California San Diego, La Jolla, has
generated data in mice that suggest that drugs that inhibit the protein
MTOR, which are used to treat several forms of cancer, might have
adverse effects on heart function in patients with ongoing heart
dysfunction.
In the study, it was found that adult mice lacking MTOR in their heart
muscle cells developed a fatal heart condition. Disease was associated
with accumulation of the protein 4E-BP1, which is an inhibitor of
protein generation that is normally held in check by a protein complex
containing MTOR. Further analysis indicated that in a model of high
blood pressure the mice lacking MTOR in their heart muscle cells
developed heart failure more quickly than did normal mice. Importantly,
deletion of 4E-BP1 under these conditions improved heart function and
survival.
Thus, decreased MTOR activity impairs the protective heart response to
stress, by enhancing 4E-BP1 activity, providing a potential new
therapeutic strategy for improving heart function in patients with heart
failure and a warning to clinicians using MTOR inhibitors.
The research appears in the Journal of Clinical Investigation.
------------------------------------------------------------------------
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by Journal of Clinical Investigation, via
EurekAlert!, a service of AAAS.
------------------------------------------------------------------------
Journal Reference:
1. Zhang et al. MTORC1 regulates cardiac function and myocyte survival
through 4E-BP1 inhibition in mice. Journal of Clinical Investigation,
2010; DOI: 10.1172/JCI43008
http://www.sciencedaily.com/releases/2010/07/100719124402.htm
Impaired Activity of the Protein MTOR a Strain on the Heart
ScienceDaily (July 19, 2010)
A team of researchers, led by Gianluigi
Condorelli, at the University of California San Diego, La Jolla, has
generated data in mice that suggest that drugs that inhibit the protein
MTOR, which are used to treat several forms of cancer, might have
adverse effects on heart function in patients with ongoing heart
dysfunction.
In the study, it was found that adult mice lacking MTOR in their heart
muscle cells developed a fatal heart condition. Disease was associated
with accumulation of the protein 4E-BP1, which is an inhibitor of
protein generation that is normally held in check by a protein complex
containing MTOR. Further analysis indicated that in a model of high
blood pressure the mice lacking MTOR in their heart muscle cells
developed heart failure more quickly than did normal mice. Importantly,
deletion of 4E-BP1 under these conditions improved heart function and
survival.
Thus, decreased MTOR activity impairs the protective heart response to
stress, by enhancing 4E-BP1 activity, providing a potential new
therapeutic strategy for improving heart function in patients with heart
failure and a warning to clinicians using MTOR inhibitors.
The research appears in the Journal of Clinical Investigation.
------------------------------------------------------------------------
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily
staff) from materials provided by Journal of Clinical Investigation, via
EurekAlert!, a service of AAAS.
------------------------------------------------------------------------
Journal Reference:
1. Zhang et al. MTORC1 regulates cardiac function and myocyte survival
through 4E-BP1 inhibition in mice. Journal of Clinical Investigation,
2010; DOI: 10.1172/JCI43008
Il fatto che mTOR sia legato ai processi anabolici rende abbastanza logiche simili conseguenze la proteina in questione è in un inibitore della generazione di (altre) proteine...
E' un difficile equilibrio quello da trovare tra processi di crescita e processi di conservazione e probabilmente anche se si dovesse trovare questo equilibrio a livello personale non condurrebbe a incrementi dell'esistenza apprezzabili dagli immortalisti e comunque vi sarebbe sempre il trade off tra un'esistenza con caratteristiche più giovanili (anabolismo dei vari tessuti) più breve e un'esistenza più lunga, ma in uno stato catabolico e conservativo con un aspetto senile (vedi i vari centenari che quando va bene sembrano degli 80enni conservati a lungo...)
Temo che un analogo e collegato trade off ci possa essere peraltro tra cancro e malattie cardiovascolari, ossia che mentre l'anabolismo possa più facilmente portare a sviluppare tumori, il catabolismo possa correre il rischio di indebolire l'apparato cardiocircolatorio e in particolare il cuore, come pare dimostrare, sebbene sugli animali questo studio.
Non per riportare sempre l'acqua al mio mulino, ma io sto appunto facendo un tentativo di mediare tra questi due estremi (chiamiamoli CR contro GH[]), per esempio integrando attivatori della telomerasi con inibitori usati a giorni alterni. Non penso che questo porti di per sè a un esistenza lunghissima, ma forse evita di ridurre i rischi di entrambi gli approcci estremi e quindi di ottimizzare i benefici di entrambi.
Ciao
MA - r l i n
E' un difficile equilibrio quello da trovare tra processi di crescita e processi di conservazione e probabilmente anche se si dovesse trovare questo equilibrio a livello personale non condurrebbe a incrementi dell'esistenza apprezzabili dagli immortalisti e comunque vi sarebbe sempre il trade off tra un'esistenza con caratteristiche più giovanili (anabolismo dei vari tessuti) più breve e un'esistenza più lunga, ma in uno stato catabolico e conservativo con un aspetto senile (vedi i vari centenari che quando va bene sembrano degli 80enni conservati a lungo...)
Temo che un analogo e collegato trade off ci possa essere peraltro tra cancro e malattie cardiovascolari, ossia che mentre l'anabolismo possa più facilmente portare a sviluppare tumori, il catabolismo possa correre il rischio di indebolire l'apparato cardiocircolatorio e in particolare il cuore, come pare dimostrare, sebbene sugli animali questo studio.
Non per riportare sempre l'acqua al mio mulino, ma io sto appunto facendo un tentativo di mediare tra questi due estremi (chiamiamoli CR contro GH[
]), per esempio integrando attivatori della telomerasi con inibitori usati a giorni alterni. Non penso che questo porti di per sè a un esistenza lunghissima, ma forse evita di ridurre i rischi di entrambi gli approcci estremi e quindi di ottimizzare i benefici di entrambi.Ciao
MA - r l i n
Il pesticida (resveratrolo) colpisce ancora.
E dire che l'illustrissimo (e ricchissimo) dott. Sinclair - la peste colga chi ne mette in dubbio i risultati - ci aveva promesso la vita eterna.
O era l'eterna dialisi?
http://www.myelomabeacon.com/news/2010/05/06/suspended-resveratrol-clinical-trial-more-details-emerge/
Representatives from Sirtris Pharmaceuticals, developer of a proprietary formulation of resveratrol called SRT501, confirmed yesterday that a clinical trial of the drug in multiple myeloma patients was suspended because several patients developed kidney failure. The Myeloma Beacon reported the trial’s suspension in an article earlier this week.
Sirtris representatives also have told the Beacon that all patients who experienced kidney failure during the trial were being treated with only SRT501 when their kidney problems developed.
However, it is still uncertain whether the kidney failures were simply a manifestation of the underlying myeloma, or if they were related to the resveratrol treatment.
“We still are investigating. We do not know all the details, and we have a lot of data to review,” said Dr. Eric Jacobson, Chief Medical Officer of Sirtris, in an interview with The Beacon. “But we think it likely that the drug itself is not directly toxic to the kidneys.”
“This was most likely a manifestation of the underlying myeloma.” Dr. Jacobson noted that SRT501 has not caused a single case of kidney failure in any of the previous trials of the drug, which involved some 340 healthy persons, colon cancer patients, and diabetes patients. “We have never seen another case of [kidney] failure except in this myeloma study.”
Sirtris is a subsidiary of the pharmaceutical company GlaxoSmithKline.
SRT501 is a formulation of resveratrol, a molecule found in small quantities in the skin of red grapes and in red wine. Resveratrol is thought to be the source of red wine’s reported health benefits.
According to Sirtris representatives, the resveratrol in SRT501 is from a plant-based source and is micronized, or milled into very small uniform particles, to maximize uptake into the body.
Previous studies have indicated that resveratrol may be effective at killing cancer cells, including multiple myeloma cells. Research has also shown that it may make other chemotherapy drugs, like Velcade (bortezomib) and thalidomide (Thalomid), more effective.
Scientific evidence for these claims has been controversial and confined mostly to the laboratory. The SRT501 trial was the first attempt to determine the effectiveness of resveratrol in treating multiple myeloma patients.
Participants in the SRT501 trial received five grams of the drug once per day on 20 days of a 21-day cycle. Testing for disease progression was scheduled after every two cycles.
Patients with stable results after two cycles continued with the SRT501 treatment alone, while those who experienced disease progression received supplemental treatment with Velcade.
The study was suspended before recruitment was complete due to safety concerns. More specifically, five of the 24 patients (21 percent) developed cast nephropathy, or “myeloma kidney.” In all cases, the cast nephropathy developed while the patients were only receiving SRT501.
According to Dr. Nelson Leung, a kidney specialist at the Mayo Xxxxxx in Rochester, Minnesota, cast nephropathy is a common complication of multiple myeloma. It occurs when excess protein blocks the kidney, resulting in kidney failure, and it affects 15 to 30 percent of myeloma patients.
The exact cause of cast nepropathy is not known, but free light chains — molecules in the blood overproduced by people with myeloma — are thought to play a key role. “Dehydration and high calcium levels have also been associated with cast nephropathy,” said Dr. Leung.
Patients in the SRT501 trial were required to have normal kidney function prior to the trial in order to participate in it. Due to the relatively high dose of SRT501 used in the study, however, some participants experienced nausea and vomiting, which could have led to dehydration. Sirtris believes this may have been a factor in the kidney failure seen in the clinical trial.
“In a patient who was prone to the renal failure from their high light chains, ” said Dr. Jacobson, “dehydration could have tipped the balance. That could have been an indirect precipitating cause of the kidney problems.”
Dr. Jacobson also noted that all of the patients in the trial had experienced at least one treatment failure for multiple myeloma, and the majority of participants had failed several treatments.
Nonetheless, there is some concern that the dose of resveratrol used in the study could have contributed to the safety issues. Dr. Bharat Aggarwal, Professor of Cancer Research at the University of Texas M. D. Anderson Cancer Center, expressed surprise at the amount of SRT501 given to the patients.
“I am not surprised that they had toxicity. It is too high a dose,” said Prof. Aggarwal, who has studied resveratrol in myeloma cells but is not involved in the SRT501 study.
“Phase 1 clinical trials with resveratrol showed that even when tested in high doses, it was safe,” Prof. Aggarwal added. “Whether SRT501 has a different profile of toxicity, is not clear.”
Sirtris, however, believes that the high dose is necessary. “We are using an extraordinary amount of resveratrol because of what we know about the amounts that are probably required to show a biological effect,” said George Vlasuk, CEO of Sirtris, in an interview yesterday with The Beacon. The daily five gram dose of SRT501 used in the suspended trial also was a common dose used in other SRT501 trials.
Representatives from Sirtris emphasized in their discussions with the Beacon that the SRT501 myeloma trial has not been stopped. Although new participants are not being recruited at this time, evaluation of SRT501 and its efficacy will continue.
“The trial was not stopped. The trial remains active,” said Vlasuk. “We are simply, out of an abundance of caution, trying to understand if SRT501 is actually providing a benefit to these patients.”
“If we determine that’s the case, or at least that it doesn’t have an adverse safety finding, we will continue with this trial.”
Company representatives also emphasized that, despite news reports to the contrary, Sirtris has not made a decision to halt overall development of SRT501.
It is not clear what implications, if any, the safety issues during the SRT501 trial may have for the use of dietary supplements containing resveratrol. SRT501 is a very pure form of the compound, and the five gram dosage is higher than the amounts contained in most supplements.
When Dr. Aggarwal was asked whether he would recommend that certain myeloma patients take resveratrol supplements, he said, “We have no data in patients to suggest that resveratrol helps.”
E dire che l'illustrissimo (e ricchissimo) dott. Sinclair - la peste colga chi ne mette in dubbio i risultati - ci aveva promesso la vita eterna.
O era l'eterna dialisi?
http://www.myelomabeacon.com/news/2010/05/06/suspended-resveratrol-clinical-trial-more-details-emerge/
Representatives from Sirtris Pharmaceuticals, developer of a proprietary formulation of resveratrol called SRT501, confirmed yesterday that a clinical trial of the drug in multiple myeloma patients was suspended because several patients developed kidney failure. The Myeloma Beacon reported the trial’s suspension in an article earlier this week.
Sirtris representatives also have told the Beacon that all patients who experienced kidney failure during the trial were being treated with only SRT501 when their kidney problems developed.
However, it is still uncertain whether the kidney failures were simply a manifestation of the underlying myeloma, or if they were related to the resveratrol treatment.
“We still are investigating. We do not know all the details, and we have a lot of data to review,” said Dr. Eric Jacobson, Chief Medical Officer of Sirtris, in an interview with The Beacon. “But we think it likely that the drug itself is not directly toxic to the kidneys.”
“This was most likely a manifestation of the underlying myeloma.” Dr. Jacobson noted that SRT501 has not caused a single case of kidney failure in any of the previous trials of the drug, which involved some 340 healthy persons, colon cancer patients, and diabetes patients. “We have never seen another case of [kidney] failure except in this myeloma study.”
Sirtris is a subsidiary of the pharmaceutical company GlaxoSmithKline.
SRT501 is a formulation of resveratrol, a molecule found in small quantities in the skin of red grapes and in red wine. Resveratrol is thought to be the source of red wine’s reported health benefits.
According to Sirtris representatives, the resveratrol in SRT501 is from a plant-based source and is micronized, or milled into very small uniform particles, to maximize uptake into the body.
Previous studies have indicated that resveratrol may be effective at killing cancer cells, including multiple myeloma cells. Research has also shown that it may make other chemotherapy drugs, like Velcade (bortezomib) and thalidomide (Thalomid), more effective.
Scientific evidence for these claims has been controversial and confined mostly to the laboratory. The SRT501 trial was the first attempt to determine the effectiveness of resveratrol in treating multiple myeloma patients.
Participants in the SRT501 trial received five grams of the drug once per day on 20 days of a 21-day cycle. Testing for disease progression was scheduled after every two cycles.
Patients with stable results after two cycles continued with the SRT501 treatment alone, while those who experienced disease progression received supplemental treatment with Velcade.
The study was suspended before recruitment was complete due to safety concerns. More specifically, five of the 24 patients (21 percent) developed cast nephropathy, or “myeloma kidney.” In all cases, the cast nephropathy developed while the patients were only receiving SRT501.
According to Dr. Nelson Leung, a kidney specialist at the Mayo Xxxxxx in Rochester, Minnesota, cast nephropathy is a common complication of multiple myeloma. It occurs when excess protein blocks the kidney, resulting in kidney failure, and it affects 15 to 30 percent of myeloma patients.
The exact cause of cast nepropathy is not known, but free light chains — molecules in the blood overproduced by people with myeloma — are thought to play a key role. “Dehydration and high calcium levels have also been associated with cast nephropathy,” said Dr. Leung.
Patients in the SRT501 trial were required to have normal kidney function prior to the trial in order to participate in it. Due to the relatively high dose of SRT501 used in the study, however, some participants experienced nausea and vomiting, which could have led to dehydration. Sirtris believes this may have been a factor in the kidney failure seen in the clinical trial.
“In a patient who was prone to the renal failure from their high light chains, ” said Dr. Jacobson, “dehydration could have tipped the balance. That could have been an indirect precipitating cause of the kidney problems.”
Dr. Jacobson also noted that all of the patients in the trial had experienced at least one treatment failure for multiple myeloma, and the majority of participants had failed several treatments.
Nonetheless, there is some concern that the dose of resveratrol used in the study could have contributed to the safety issues. Dr. Bharat Aggarwal, Professor of Cancer Research at the University of Texas M. D. Anderson Cancer Center, expressed surprise at the amount of SRT501 given to the patients.
“I am not surprised that they had toxicity. It is too high a dose,” said Prof. Aggarwal, who has studied resveratrol in myeloma cells but is not involved in the SRT501 study.
“Phase 1 clinical trials with resveratrol showed that even when tested in high doses, it was safe,” Prof. Aggarwal added. “Whether SRT501 has a different profile of toxicity, is not clear.”
Sirtris, however, believes that the high dose is necessary. “We are using an extraordinary amount of resveratrol because of what we know about the amounts that are probably required to show a biological effect,” said George Vlasuk, CEO of Sirtris, in an interview yesterday with The Beacon. The daily five gram dose of SRT501 used in the suspended trial also was a common dose used in other SRT501 trials.
Representatives from Sirtris emphasized in their discussions with the Beacon that the SRT501 myeloma trial has not been stopped. Although new participants are not being recruited at this time, evaluation of SRT501 and its efficacy will continue.
“The trial was not stopped. The trial remains active,” said Vlasuk. “We are simply, out of an abundance of caution, trying to understand if SRT501 is actually providing a benefit to these patients.”
“If we determine that’s the case, or at least that it doesn’t have an adverse safety finding, we will continue with this trial.”
Company representatives also emphasized that, despite news reports to the contrary, Sirtris has not made a decision to halt overall development of SRT501.
It is not clear what implications, if any, the safety issues during the SRT501 trial may have for the use of dietary supplements containing resveratrol. SRT501 is a very pure form of the compound, and the five gram dosage is higher than the amounts contained in most supplements.
When Dr. Aggarwal was asked whether he would recommend that certain myeloma patients take resveratrol supplements, he said, “We have no data in patients to suggest that resveratrol helps.”
Qui si è sempre detto che è la dose che fa....il pesticida[]
I am not surprised that they had toxicity. It is too high a dose,”
In USA hanno sempre esagerato....
Comunque in parte il caso mi ricorda quella sperimentazione di un farmaco contro l'Alzheimer che stava andando benissimo e che è stata bloccata agli inizi del presente decennio per alcune morti sospette...solo di recente si è capito che il responsabile di quei casi era l'additivo....e si sta cercando un'altra cura che funzioni così bene contro l'Alzheimer....(si è nel frattempo perso circa un decennio...)
Ad ogni modo si tratta pur sempre dei test della Glaxo, che resta una big pharma mooolto interessata a questo pesticida, magari loro masticano biochimica un po' più di noi ....[], anche se questo non li mette al riparo dal poter essere battuti sul tempo dagli asiatici (che nella loro millenaria saggezza sanno usare le dosi giuste[]):
http://www.ncbi.nlm.nih.gov/pubmed/20644332
Ciao
MA - r l i n
]I am not surprised that they had toxicity. It is too high a dose,”
In USA hanno sempre esagerato....
Comunque in parte il caso mi ricorda quella sperimentazione di un farmaco contro l'Alzheimer che stava andando benissimo e che è stata bloccata agli inizi del presente decennio per alcune morti sospette...solo di recente si è capito che il responsabile di quei casi era l'additivo....e si sta cercando un'altra cura che funzioni così bene contro l'Alzheimer....(si è nel frattempo perso circa un decennio...)
Ad ogni modo si tratta pur sempre dei test della Glaxo, che resta una big pharma mooolto interessata a questo pesticida, magari loro masticano biochimica un po' più di noi ....[
], anche se questo non li mette al riparo dal poter essere battuti sul tempo dagli asiatici (che nella loro millenaria saggezza sanno usare le dosi giuste[]):http://www.ncbi.nlm.nih.gov/pubmed/20644332
Ciao
MA - r l i n
Mi aspettavo questa tua risposta []
E avevo già pronta la replica, per bocca della Sirtris: Sirtris, however, believes that the high dose is necessary. “We are using an extraordinary amount of resveratrol because of what we know about the amounts that are probably required to show a biological effect,” said George Vlasuk, CEO of Sirtris, in an interview yesterday with The Beacon. The daily five gram dose of SRT501 used in the suspended trial also was a common dose used in other SRT501 trials.
Ciao
]E avevo già pronta la replica, per bocca della Sirtris: Sirtris, however, believes that the high dose is necessary. “We are using an extraordinary amount of resveratrol because of what we know about the amounts that are probably required to show a biological effect,” said George Vlasuk, CEO of Sirtris, in an interview yesterday with The Beacon. The daily five gram dose of SRT501 used in the suspended trial also was a common dose used in other SRT501 trials.
Ciao
Si può anche perseverare nei propri errori e magari lasciare una porta aperta alla correzione con quel probably che tu ti sei guardato bene dal mettere in grassetto rispetto al resto della frase[]
Si prendono patologie gravi e si tenta di curarle con questa sostanza, siamo lontani dagli scopi per cui parliamo di resveratrolo in questa sezione. E comunque si tratta di una patologia, non di tutte le altre....
Nel frattempo gli studi sul pesticida si susseguono e volendo postare i penultimi rispetto a quello postato sopra c'è solo l'imbarazzo della scelta:
http://www.ncbi.nlm.nih.gov/pubmed/20642113
http://www.ncbi.nlm.nih.gov/pubmed/20637737
http://www.ncbi.nlm.nih.gov/pubmed/20637373
http://www.ncbi.nlm.nih.gov/pubmed/20631324
....per fermarsi al mese ancora in corso....
Ciao
MA - r l i n
]Si prendono patologie gravi e si tenta di curarle con questa sostanza, siamo lontani dagli scopi per cui parliamo di resveratrolo in questa sezione. E comunque si tratta di una patologia, non di tutte le altre....
Nel frattempo gli studi sul pesticida si susseguono e volendo postare i penultimi rispetto a quello postato sopra c'è solo l'imbarazzo della scelta:
http://www.ncbi.nlm.nih.gov/pubmed/20642113
http://www.ncbi.nlm.nih.gov/pubmed/20637737
http://www.ncbi.nlm.nih.gov/pubmed/20637373
http://www.ncbi.nlm.nih.gov/pubmed/20631324
....per fermarsi al mese ancora in corso....
Ciao
MA - r l i n