Tratto dal sito della SISA (vedi articolo originale)
Il ruolo della lipoproteina (a) [Lp(a)] nella stima del rischio cardiovascolare è stato e continua ad essere oggetto di dibattito.
La Lp(a) è una particella simile alle LDL, se ne differenzia solo per la presenza di una glicoproteina denominata apo(a) che è legata covalentemente all'apo B.
A differenza delle altre lipoproteine che hanno una funzione biologica chiara come molecole di trasporto dei lipidi nel plasma, la funzione della Lp(a) è praticamente sconosciuta.
In vitro, è stato osservato che è in grado di oltrepassare l'intima arteriosa umana e, negli studi compiuti su animali, è stata riportata la capacità di Lp(a) di promuovere trombosi, infiammazione e formazione di cellule schiumose, effetti questi che interessano i momenti salienti dell'aterosclerosi: genesi, progressione ed evento clinico finale.
Nella maggior parte dei numerosi studi epidemiologici degli ultimi anni, l'associazione tra concentrazione ematica di Lp(a) e rischio cardiovascolare è confermata, ma l'associazione rimane modesta e l'aggiunta della Lp(a) ai tradizionali marcatori lipidici e non lipidici del rischio cardiovascolare ha un impatto solo marginale sulla classificazione dei pazienti nelle classi di rischio (1).
Il livello plasmatico di Lp(a) è estremamente variabile: da valori molto bassi, quasi indosabili (<0,2 mg/dL) a livelli molto elevati (>200 mg/dL), cioè 1.000 volte di più.
La variabilità dipende essenzialmente dalle isoforme dell'apo(a) che si differenziano tra loro per la dimensione della molecola che è determinata dal numero di ripetizioni delle tipiche strutture ad ansa, i kringle, in particolare dal numero di kringle 4 tipo 2 (2).
Più la molecola di apo(a) è piccola, più la concentrazione plasmatica di Lp(a) è elevata, probabilmente perché è più efficientemente secreta dagli epatociti di quanto non lo siano le isoforme di dimensioni maggiori.
Il polimorfismo del gene che codifica per le dimensioni dell'apo(a) è dunque il maggior predittore della concentrazione plasmatica di Lp(a) e rende conto del 40-70% della variazione dei livelli plasmatici della lipoproteina, cui contribuiscono comunque anche altre varianti genetiche (3).
Il forte ruolo della genetica nel determinare il livello della Lp(a) è responsabile della sua particolare distribuzione nella popolazione che, a differenza di quanto si osserva in generale per altri analiti, tra cui il colesterolo, non è normale, ma è fortemente asimmetrica e questo può essere causa delle difficoltà nell'accertare il peso di Lp(a) nella stima del rischio di aterosclerosi.
Recentemente sono state trovate due varianti genetiche caratterizzate da livelli particolarmente alti di Lp(a) di piccole dimensioni ed ambedue le varianti erano associate ad un elevato rischio cardiovascolare (4).
La prevalenza di queste varianti genetiche non è nota e dipende in gran parte dall'etnia della popolazione studiata.
Nello studio PROCARDIS (Precocious Coronary Artery Disease), condotto su oltre 6.000 soggetti, di cui circa la metà con malattia coronarica, reclutati in Gran Bretagna, Italia, Svezia e Germania, una persona su sei è risultata portatrice di una di queste due varianti e aveva di conseguenza livelli più elevati di Lp(a) e un rischio di infarto doppio rispetto ai soggetti con genotipo diverso.
I soggetti portatori di entrambe le varianti avevano un rischio elevato di più di quattro volte (4).
La Lp(a) si conferma quindi come un fattore di rischio cardiovascolare indipendente da quelli tradizionali quali colesterolo totale, colesterolo LDL, apoproteina B, ipertensione, diabete, obesità e fumo, ma il suo peso prognostico è rilevante solo quando i suoi livelli sono elevati.
Mancherebbe, cioè, una relazione continua tra livello di Lp(a) e rischio e questo, insieme a problemi di standardizzazione della metodica di misura, potrebbe spiegare i risultati spesso contrastanti degli studi epidemiologici.
La stima del rischio è basata sullo studio di popolazioni che per la maggior parte hanno bassi valori di Lp(a) e questo comporta che il peso della Lp(a) nella stima sia così diluito da diventare poco significativo.
La Kamstrup ed i suoi collaboratori hanno riclassificato nelle classi di rischio i pazienti che avevano un livello di Lp(a) maggiore di 47 mg/dL, corrispondente ad un valore superiore all'80esimo percentile della distribuzione nel loro campione di 8.720 pazienti ed hanno osservato che nel 23% di essi il rischio di infarto veniva riclassificato più correttamente ad un livello superiore se si aggiungeva al pannello dei fattori di rischio anche la Lp(a). Nessun miglioramento nella stima del rischio si è invece osservato nell'intera popolazione, a conferma del fatto che solo nei soggetti con valori elevati di Lp(a), la sua misura ha un impatto significativo sulla stima del rischio.
Da questo studio e da altri risulterebbe quindi inutile la misura della Lp(a) nella popolazione generale per una più precisa valutazione del rischio cardiovascolare, come del resto era già stato sottolineato da più parti e anche nelle recenti linee guida congiunte delle Società europee di cardiologia e dell'arteriosclerosi (5) che suggeriscono la determinazione della Lp(a) solo nei soggetti con un alto rischio cardiovascolare o con una forte familiarità per malattie aterosclerotiche precoci.
Rimane però il problema di cosa fare se il rischio cardiovascolare è elevato a causa dell'alta concentrazione di Lp(a).
Solo l'acido nicotinico aveva dimostrato una buona azione di riduzione di questa lipoproteina, ma il farmaco non è più disponibile. Non rimane altro che intervenire con più energia sugli altri fattori di rischio modificabili.
mercoledì 27 agosto 2014
domenica 24 agosto 2014
Segnali di gas fra cellule
Tratto dal sito Galileo (vedi articolo originale)
Il monossido di azoto, noto per essere un pericoloso inquinante derivato dagli scarichi delle macchine, è in realtà prodotto anche dalle cellule degli animali superiori, le quali se ne servono per comunicare fra loro.
Questa in sintesi l’importantissima scoperta che è stata premiata quest’anno con il Nobel per la medicina, assegnato a Robert F. Furchgott della State University a New York, Luiss J. Ignarro, della University of California a Los Angeles e Ferid Murad, della Texas Medical School a Houston.
“L’aspetto rivoluzionario degli studi appena premiati con il Nobel, sta nel fatto che essi hanno aperto nuovi orizzonti sui mezzi utilizzati dalle cellule per trasmettersi messaggi, un’attività che è alla base dello sviluppo e della sopravvivenza di ogni animale”, spiega Pietro Calissano, direttore dell’Istituto di Neurobiologia del CNR, a Roma.
Fino a pochi anni fa infatti, si riteneva che le cellule potessero comunicare fra loro solo tramite ormoni, prodotti dalle ghiandole endocrine, o neurotrasmettitori, prodotti dalle cellule nervose.
Gli ormoni sono messaggeri che diffondono in tutto l’organismo, anche se vengono recepiti solo da quelle cellule che hanno sulla loro membrana le molecole adatte per legarli.
Possiamo immaginare che gli ormoni trasmettano messaggi in maniera simile ai giornali, che sono disponibili per moltissime persone ma vengono letti solo da coloro che hanno i mezzi per riceverli (ad esempio perché hanno denaro per comprarli o sanno leggere).
I neurotrasmettitori invece sono generalmente utilizzati da una cellula nervosa per trasmettere un messaggio a un’altra cellula, di solito vicina.
In questo senso il loro modo di comunicare è simile a quello ottenuto con una telefonata, che stabilisce un contatto diretto tra due interlocutori.
“Quello che nessuno si aspettava, almeno fino alle scoperte dei tre scienziati appena premiati”, continua Calissano, “è che esistesse un’altra possibile via di comunicazione fra cellule e che utilizzasse molecole insospettabili come dei gas, quali appunto il monossido di azoto”.
Quest’ultimo viene emesso da alcune cellule, fra cui cellule nervose o cellule dell’epitelio che riveste i vasi, e raggiunge le cellule vicine, senza però essere specifico per una sola “interlocutrice”, come i neurotrasmettitori, e senza diffondersi per lunghe distanze, come gli ormoni.
Il primo passo verso la scoperta dell’uso del monossido di azoto da parte delle cellule è stato compiuto nel 1977 da Ferid Murad.
In quel periodo lo scienziato studiava il meccanismo di azione della nitroglicerina, impiegata da più di un secolo come cura per l’angina pectoris, in quanto causa la dilatazione delle arterie.
Inaspettatamente Murad scoprì che la nitroglicerina provoca il rilassamento della muscolatura dei vasi sanguigni perché rilascia monossido di azoto.
Sebbene l’idea fosse affascinante, all’epoca non vi erano dati scientifici per approfondire questa tesi.
Alla svolta si è giunti nel 1986, quando a una conferenza scientifica Ignarro e Furchgott annunciarono di aver scoperto che il monossido di azoto viene utilizzato nel corpo umano per trasmettere segnali.
Era la prima volta che si ipotizzava una funzione del genere per un gas.
Secondo l’ipotesi degli scienziati, alcune molecole segnale, come ormoni e neurotrasmettitori, circolano nell’epitelio che riveste un vaso sanguigno parzialmente occluso da placche di colesterolo.
In risposta a tali segnali le cellule epiteliali producono monossido di azoto il quale, diffondendosi come una nuvoletta di gas, raggiunge le vicine cellule della muscolatura liscia che governano la contrazione e il rilascio del vaso.
Penetrando in queste cellule il monossido di azoto attiva una serie di reazioni chimiche che determinano il rilassamento dei muscoli, e quindi la dilatazione dell’arteria.
“Dal 1986 ad oggi le scoperte sull’azione del monossido di azoto si sono moltiplicate” dice Calissano, “infatti, come spesso avviene, anche il meccanismo di comunicazione tramite gas è utilizzato in diversi distretti dell’organismo per funzioni diverse.
Particolarmente interessante è stata ad esempio la scoperta che esso viene utilizzato dalle cellule nervose come via di comunicazione, in sinergia con i neurotrasmettitori classici.”
Oltre alle cellule dei vasi sanguigni e a quelle nervose si è recentemente scoperto che il monossido di azoto viene prodotto anche dalle cellule del sistema immunitario, che se ne servono come arma chimica, per intossicare i batteri e i parassiti.
Altrettanto interessanti sono gli sviluppi clinici, in breve tempo si spera di poter utilizzare il gas per curare più efficacemente l’aterosclerosi e buoni risultati sono stati ottenuti nella cura dell’alta pressione sanguigna nei polmoni dei bambini.
Inoltre lo studio del monossido di azoto come vasodilatatore ha permesso la messa a punto di farmaci contro l’impotenza, fra cui il Viagra.
“Molto promettenti sono gli studi sull’azione di questo gas nel cervello”, conclude Calissano, “ad esempio sembra che abbia un ruolo fondamentale nel determinare la morte delle cellule cerebrali in seguito a un’ischemia.
Inoltre è stata accertata la capacità del monossido di azoto di spingere alcune cellule verso l’apoptosi, ovvero verso una forma di suicidio programmato. Per questo motivo i ricercatori sperano di poterlo presto utilizzare per indurre alla morte le cellule tumorali.
Non bisogna poi dimenticare le interessanti prospettive aperte dalla successiva scoperta di altri gas con la medesima funzione di comunicare, quali ad esempio l’ossido di carbonio”.
domenica 29 giugno 2014
Lombalgia
Psoas
Il muscolo psoas ha il compito di sollevare la gamba verso il busto e o ruotarla all’esterno, compiendo azione a partire dalla parte interna della testa del femore (trocantere minore) arrivando fino all’articolazione tra le vertebre lombari e toraciche.
Questo muscolo, quando per diverse cause “si accorcia “, provoca forti dolori alla parte lombare della schiena.
Piriforme
Il muscolo piriforme è il muscolo posto tra l’osso sacro e la testa del femore (gran trocantere) deputato alla rotazione esterna della coscia, si può affermare che possieda il gran pregio di “avvolgere” il nervo sciatico in uscita dal bacino e diretto verso la coscia.
Questa caratteristica fa sì che, quando il “piriforme” si irriti, faccia infiammare il detto nervo causando i classici episodi di “sciatica”, dolore ramificato alla coscia ed al polpaccio.
Esercizi allungamento
Questo esercizio di stretching aiuta ad allungare il muscolo ileo-psoas.
Questo muscolo, quando per diverse cause “si accorcia “, provoca forti dolori alla parte lombare della schiena.
Piriforme
Questa caratteristica fa sì che, quando il “piriforme” si irriti, faccia infiammare il detto nervo causando i classici episodi di “sciatica”, dolore ramificato alla coscia ed al polpaccio.
Esercizi allungamento
sabato 7 giugno 2014
Prostate cancer biomarkers identified in seminal fluid
From ScienceDaily website (see original article)
Improved diagnosis and management of one of the most common cancers in men -- prostate cancer -- could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study now published in the journal Endocrine-Related Cancer have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men's Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
"While the PSA test is very sensitive, it is not highly specific for prostate cancer," Dr Selth says. "This results in many unnecessary biopsies of non-malignant disease.
More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
"Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumors are urgently needed to improve patient care.
Identification of such biomarkers is a major focus of our research," he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men's Health at the University of Adelaide and is based in the University's Dame Roma Mitchell Cancer Research Laboratories.
Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumors.
The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
"The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn't, compared with a standard PSA test," Dr Selth says.
"We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumors.
This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required."
This research builds on previous work by Dr Selth's team, published in the British Journal of Cancer, which demonstrated that microRNAs in the blood can predict men who are likely to relapse after surgical removal of their prostate cancer.
"We are excited by the potential clinical application of microRNAs in a range of body fluids," he says.
Improved diagnosis and management of one of the most common cancers in men -- prostate cancer -- could result from research at the University of Adelaide, which has discovered that seminal fluid (semen) contains biomarkers for the disease.
Results of a study now published in the journal Endocrine-Related Cancer have shown that the presence of certain molecules in seminal fluid indicates not only whether a man has prostate cancer, but also the severity of the cancer.
Speaking in the lead-up to Men's Health Week (9-15 June), University of Adelaide research fellow and lead author Dr Luke Selth says the commonly used PSA (prostate specific antigen) test is by itself not ideal to test for the cancer.
"While the PSA test is very sensitive, it is not highly specific for prostate cancer," Dr Selth says. "This results in many unnecessary biopsies of non-malignant disease.
More problematically, PSA testing has resulted in substantial over-diagnosis and over-treatment of slow growing, non-lethal prostate cancers that could have been safely left alone.
"Biomarkers that can accurately detect prostate cancer at an early stage and identify aggressive tumors are urgently needed to improve patient care.
Identification of such biomarkers is a major focus of our research," he says.
Dr Selth, a Young Investigator of the Prostate Cancer Foundation (USA), is a member of the Freemasons Foundation Centre for Men's Health at the University of Adelaide and is based in the University's Dame Roma Mitchell Cancer Research Laboratories.
Using samples from 60 men, Dr Selth and colleagues discovered a number of small ribonucleic acid (RNA) molecules called microRNAs in seminal fluid that are known to be increased in prostate tumors.
The study showed that some of these microRNAs were surprisingly accurate in detecting cancer.
"The presence of these microRNAs enabled us to more accurately discriminate between patients who had cancer and those who didn't, compared with a standard PSA test," Dr Selth says.
"We also found that the one specific microRNA, miR-200b, could distinguish between men with low grade and higher grade tumors.
This is important because, as a potential prognostic tool, it will help to indicate the urgency and type of treatment required."
This research builds on previous work by Dr Selth's team, published in the British Journal of Cancer, which demonstrated that microRNAs in the blood can predict men who are likely to relapse after surgical removal of their prostate cancer.
"We are excited by the potential clinical application of microRNAs in a range of body fluids," he says.
venerdì 27 dicembre 2013
How 'Good Cholesterol' Stops Inflammation
From ScienceDaily website (see original article)
Dec. 9, 2013 — High cholesterol levels are seen as a cause of dangerous deposits in the bloodstream, which lead to hardening of the arteries (atherosclerosis).
As a consequence, thrombosis, strokes, and heart attacks can develop, which are among the leading causes of death in Western society.
Low-density lipoprotein (LDL) is commonly referred to as the "bad cholesterol," because it promotes atherosclerosis.
In contrast, the "good cholesterol," high-density lipoprotein (HDL), helps transport excess cholesterol out of the bloodstream and can counteract an inflammatory reaction in damaged vessel walls.
"It has long been known that HDL has a protective function in cardiovascular diseases that are based on atherosclerosis," reports Prof. Eicke Latz, Director of the Institute of Innate Immunity at the University of Bonn and who is further affiliated with the German Center for Neurodegenerative Diseases (DZNE) and the University of Massachusetts Medical School in the USA.
"The molecular causes to which this protective effect of HDL can be attributed were unclear until now."
For instance, studies had shown that therapies that simply increase HDL levels in the blood of patients are not sufficient to reduce the incidence of atherosclerosis.
HDL has anti-inflammatory effects on immune cells -- however the mechanisms have remained unclear until now.
The research group has now investigated how HDL acts upon inflammatory processes.
Bioinformatics approach revealed a candidate gene
Principle investigators Dr. Dominic De Nardo and Larisa I. Labzin are both Australians currently training in the lab of Prof. Eicke Latz.
In collaboration with other working groups of the University of Bonn, an international research team from Japan, Australia, China, the USA, and Germany has identified how HDL acts to prevent chronic inflammation.
In a very extensive study over a period of about three years, the group performed experiments in human and mouse cells, to determine which genes are regulated by high HDL levels.
"At first, we were really just feeling around in the dark," reports Prof. Latz.
Close cooperation with the working group of Prof. Joachim L. Schultze of the Life and Medical Sciences (LIMES) Institute of the University of Bonn finally got the scientists on the right track.
"With the aid of genomic and bioinformatics approaches, we were able to filter out a candidate gene from the wealth of regulated genes," adds Prof. Schultze.
This gene is found in phagocytes, which act in the body like police on the beat and, as part of the innate immune defense system, arrest intruders.
These patrolmen are supported by a kind of "criminal file," the so-called Toll-like receptors (TLR).
With their help, the phagocytes can distinguish between "good" and "bad."
If it is a dangerous intruder, the TLR can also trigger the release of inflammatory substances via biochemical signaling pathways.
The transcriptional regulator, ATF3, plays a key role in this process.
"It reduces the transcription of the inflammatory genes and prevents further stimulation of inflammatory processes via the Toll-like receptors," explains Dr. Dominic De Nardo.
Sustained inflammatory reactions can lead to organ failure
The immune system uses inflammatory processes to keep pathogens in check, to detect damaged tissue, and then repair it.
In sustained inflammatory reactions, however, there are dangerous consequences -including blood poisoning or organ failure.
"The transcriptional regulator ATF3 acts to reduce these inflammatory reactions by suppressing the activation of inflammatory genes following excessive stimulation of immunoreceptors," reports Dr. De Nardo.
In the end, high-density lipoprotein (HDL) is responsible for down regulating the inflammatory reactions, via the activation of ATF3.
"To put it simply, high HDL levels in blood are an important protective factor against sustained inflammation," summarizes Prof. Latz.
"Our studies also indicate that the amount of HDL in blood alone is not decisive for the protective function of HDL, but that the anti-inflammatory function is probably more important.
These results also suggest a molecular approach for treating inflammation in other widespread diseases, such as diabetes," sums up Prof. Latz.
Dec. 9, 2013 — High cholesterol levels are seen as a cause of dangerous deposits in the bloodstream, which lead to hardening of the arteries (atherosclerosis).
As a consequence, thrombosis, strokes, and heart attacks can develop, which are among the leading causes of death in Western society.
Low-density lipoprotein (LDL) is commonly referred to as the "bad cholesterol," because it promotes atherosclerosis.
In contrast, the "good cholesterol," high-density lipoprotein (HDL), helps transport excess cholesterol out of the bloodstream and can counteract an inflammatory reaction in damaged vessel walls.
"It has long been known that HDL has a protective function in cardiovascular diseases that are based on atherosclerosis," reports Prof. Eicke Latz, Director of the Institute of Innate Immunity at the University of Bonn and who is further affiliated with the German Center for Neurodegenerative Diseases (DZNE) and the University of Massachusetts Medical School in the USA.
"The molecular causes to which this protective effect of HDL can be attributed were unclear until now."
For instance, studies had shown that therapies that simply increase HDL levels in the blood of patients are not sufficient to reduce the incidence of atherosclerosis.
HDL has anti-inflammatory effects on immune cells -- however the mechanisms have remained unclear until now.
The research group has now investigated how HDL acts upon inflammatory processes.
Bioinformatics approach revealed a candidate gene
Principle investigators Dr. Dominic De Nardo and Larisa I. Labzin are both Australians currently training in the lab of Prof. Eicke Latz.
In collaboration with other working groups of the University of Bonn, an international research team from Japan, Australia, China, the USA, and Germany has identified how HDL acts to prevent chronic inflammation.
In a very extensive study over a period of about three years, the group performed experiments in human and mouse cells, to determine which genes are regulated by high HDL levels.
"At first, we were really just feeling around in the dark," reports Prof. Latz.
Close cooperation with the working group of Prof. Joachim L. Schultze of the Life and Medical Sciences (LIMES) Institute of the University of Bonn finally got the scientists on the right track.
"With the aid of genomic and bioinformatics approaches, we were able to filter out a candidate gene from the wealth of regulated genes," adds Prof. Schultze.
This gene is found in phagocytes, which act in the body like police on the beat and, as part of the innate immune defense system, arrest intruders.
These patrolmen are supported by a kind of "criminal file," the so-called Toll-like receptors (TLR).
With their help, the phagocytes can distinguish between "good" and "bad."
If it is a dangerous intruder, the TLR can also trigger the release of inflammatory substances via biochemical signaling pathways.
The transcriptional regulator, ATF3, plays a key role in this process.
"It reduces the transcription of the inflammatory genes and prevents further stimulation of inflammatory processes via the Toll-like receptors," explains Dr. Dominic De Nardo.
Sustained inflammatory reactions can lead to organ failure
The immune system uses inflammatory processes to keep pathogens in check, to detect damaged tissue, and then repair it.
In sustained inflammatory reactions, however, there are dangerous consequences -including blood poisoning or organ failure.
"The transcriptional regulator ATF3 acts to reduce these inflammatory reactions by suppressing the activation of inflammatory genes following excessive stimulation of immunoreceptors," reports Dr. De Nardo.
In the end, high-density lipoprotein (HDL) is responsible for down regulating the inflammatory reactions, via the activation of ATF3.
"To put it simply, high HDL levels in blood are an important protective factor against sustained inflammation," summarizes Prof. Latz.
"Our studies also indicate that the amount of HDL in blood alone is not decisive for the protective function of HDL, but that the anti-inflammatory function is probably more important.
These results also suggest a molecular approach for treating inflammation in other widespread diseases, such as diabetes," sums up Prof. Latz.
venerdì 13 dicembre 2013
Study Reveals Gene Expression Changes With Meditation
From ScienceDaily website (see original article)
Dec. 8, 2013 — With evidence growing that meditation can have beneficial health effects, scientists have sought to understand how these practices physically affect the body.
A new study by researchers in Wisconsin, Spain, and France reports the first evidence of specific molecular changes in the body following a period of mindfulness meditation.
The study investigated the effects of a day of intensive mindfulness practice in a group of experienced meditators, compared to a group of untrained control subjects who engaged in quiet non-meditative activities.
After eight hours of mindfulness practice, the meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which in turn correlated with faster physical recovery from a stressful situation.
"To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice," says study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison.
"Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs," says Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.
The study was published in the journal Psychoneuroendocrinology.
Mindfulness-based trainings have shown beneficial effects on inflammatory disorders in prior clinical studies. The new results provide a possible biological mechanism for therapeutic effects.
The results show a down-regulation of genes that have been implicated in inflammation.
The affected genes include the pro-inflammatory genes RIPK2 and COX2 as well as several histone deacetylase (HDAC) genes, which regulate the activity of other genes epigenetically by removing a type of chemical tag.
What's more, the extent to which some of those genes were downregulated was associated with faster cortisol recovery to a social stress test involving an impromptu speech and tasks requiring mental calculations performed in front of an audience and video camera.
Perhaps surprisingly, the researchers say, there was no difference in the tested genes between the two groups of people at the start of the study.
The observed effects were seen only in the meditators following mindfulness practice.
In addition, several other DNA-modifying genes showed no differences between groups, suggesting that the mindfulness practice specifically affected certain regulatory pathways.
However, it is important to note that the study was not designed to distinguish any effects of long-term meditation training from those of a single day of practice.
Instead, the key result is that meditators experienced genetic changes following mindfulness practice that were not seen in the non-meditating group after other quiet activities -- an outcome providing proof of principle that mindfulness practice can lead to epigenetic alterations of the genome.
Previous studies in rodents and in people have shown dynamic epigenetic responses to physical stimuli such as stress, diet, or exercise within just a few hours.
"Our genes are quite dynamic in their expression and these results suggest that the calmness of our mind can actually have a potential influence on their expression," Davidson says.
"The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions," Kaliman says.
"Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions."
Dec. 8, 2013 — With evidence growing that meditation can have beneficial health effects, scientists have sought to understand how these practices physically affect the body.
A new study by researchers in Wisconsin, Spain, and France reports the first evidence of specific molecular changes in the body following a period of mindfulness meditation.
The study investigated the effects of a day of intensive mindfulness practice in a group of experienced meditators, compared to a group of untrained control subjects who engaged in quiet non-meditative activities.
After eight hours of mindfulness practice, the meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which in turn correlated with faster physical recovery from a stressful situation.
"To the best of our knowledge, this is the first paper that shows rapid alterations in gene expression within subjects associated with mindfulness meditation practice," says study author Richard J. Davidson, founder of the Center for Investigating Healthy Minds and the William James and Vilas Professor of Psychology and Psychiatry at the University of Wisconsin-Madison.
"Most interestingly, the changes were observed in genes that are the current targets of anti-inflammatory and analgesic drugs," says Perla Kaliman, first author of the article and a researcher at the Institute of Biomedical Research of Barcelona, Spain (IIBB-CSIC-IDIBAPS), where the molecular analyses were conducted.
The study was published in the journal Psychoneuroendocrinology.
Mindfulness-based trainings have shown beneficial effects on inflammatory disorders in prior clinical studies. The new results provide a possible biological mechanism for therapeutic effects.
The results show a down-regulation of genes that have been implicated in inflammation.
The affected genes include the pro-inflammatory genes RIPK2 and COX2 as well as several histone deacetylase (HDAC) genes, which regulate the activity of other genes epigenetically by removing a type of chemical tag.
What's more, the extent to which some of those genes were downregulated was associated with faster cortisol recovery to a social stress test involving an impromptu speech and tasks requiring mental calculations performed in front of an audience and video camera.
Perhaps surprisingly, the researchers say, there was no difference in the tested genes between the two groups of people at the start of the study.
The observed effects were seen only in the meditators following mindfulness practice.
In addition, several other DNA-modifying genes showed no differences between groups, suggesting that the mindfulness practice specifically affected certain regulatory pathways.
However, it is important to note that the study was not designed to distinguish any effects of long-term meditation training from those of a single day of practice.
Instead, the key result is that meditators experienced genetic changes following mindfulness practice that were not seen in the non-meditating group after other quiet activities -- an outcome providing proof of principle that mindfulness practice can lead to epigenetic alterations of the genome.
Previous studies in rodents and in people have shown dynamic epigenetic responses to physical stimuli such as stress, diet, or exercise within just a few hours.
"Our genes are quite dynamic in their expression and these results suggest that the calmness of our mind can actually have a potential influence on their expression," Davidson says.
"The regulation of HDACs and inflammatory pathways may represent some of the mechanisms underlying the therapeutic potential of mindfulness-based interventions," Kaliman says.
"Our findings set the foundation for future studies to further assess meditation strategies for the treatment of chronic inflammatory conditions."
sabato 2 novembre 2013
Bacteria and Fat: A 'Perfect Storm' for Inflammation
From ScienceDaily website (see original article)
Oct. 30, 2013 — Making fat cells immortal might seem like a bad idea to most people, but for a team of University of Iowa scientists it was the ideal way to study how the interaction between bacteria and fat cells might contribute to diabetes.
The connection between fat, bacteria, and diabetes is inflammation, which is the body's normal reaction to infection or injury.
Inflammation is beneficial in small, controlled doses but can be extremely harmful when it persists and becomes chronic.
"The idea is that when fat cells (adipocytes) interact with environmental agents -- in this case, bacterial toxins -- they then trigger a chronic inflammatory process," says Patrick Schlievert, Ph.D., UI professor and head of microbiology and co-senior author of a new study published in the journal PLOS ONE.
"We know that chronic inflammation leads to insulin resistance, which can then lead to diabetes.
So people are very interested in the underlying causes of chronic inflammation."
The UI researchers used immortalized fat cells to show that bacterial toxins stimulate fat cells to release molecules called cytokines, which promote inflammation.
By immortalizing fat cells the UI team created a stockpile of continuously dividing, identical cells that are necessary for repeat experiments to validate results, explains Al Klingelhutz, Ph.D., UI microbiologist and co-senior author of the study.
Previous studies have shown that a toxin called lipopolysaccharide (LPS) produced by E. coli bacteria that reside in the human gut, triggers fat cells to produce pro-inflammatory cytokines, and this interaction has been proposed to contribute to the development of diabetes.
The UI team focused on a different bacterium, Staphylococcus aureus (staph), which appears to be important in the context of diabetes for two reasons. First, as people become obese and then progress into diabetes they become very heavily colonized with staph bacteria.
Secondly, staph is the most common microbe isolated from diabetic foot ulcers, one of the most common and health-threatening complications of diabetes.
All staph bacteria make toxins called superantigens -- molecules that disrupt the immune system.
Schlievert's research has previously shown that superantigens cause the deadly effects of various staph infections, such as toxic shock syndrome, sepsis, and endocarditis.
The new UI study shows that superantigens from staph bacteria trigger fat cells to produce pro-inflammatory molecules.
Moreover, the study found that superantigens synergized with LPS from E. coli to magnify fat cells' cytokine responses, amplifying the inflammation, which could potentially boost the likelihood of developing diabetes.
"The E. coli that resides in our gut produces LPS and every day a small amount of this toxin gets into our circulation, but it is generally cleared from the circulation by the liver.
However, people colonized by staph bacteria are also chronically exposed to superantigens, which shut down the LPS detoxification pathway," Schlievert explains.
"That creates a synergy between the 'uncleared' LPS and the superantigen.
All these two molecules do is cause inflammation and cytokine production. So in essence, their presence together creates a perfect storm for inflammation."
The findings suggest that by promoting chronic inflammation through their effect on fat cells, staph superantigens may play a role in the development of diabetes.
In addition, the chronic inflammation caused by the superantigens may also hinder wound healing in diabetic foot ulcers.
The ulcers, which affect 15 to 25 percent of people with diabetes, are notoriously difficult to heal and can often lead to amputation.
Why immortalize fat cells?
The UI team created immortalized fat cells for their research because primary fat cells (taken directly from fat tissue) are not very useful for lab experiments.
Once the primary cells are grown in a dish, they quickly stop dividing and can't be used for repeated experiments.
In contrast, the immortalized fat cells allow experiments to be repeated multiple times on identical cells ensuring consistent, reproducible results.
Klingelhutz and his team immortalized immature precursor fat cells by adding in two genes from HPV (the virus that causes cervical cancer) along with a gene for part of an enzyme that controls the length of cells' telomeres -- the pieces of DNA that protect chromosome tips from deterioration.
These immortal precursor cells could then be "grown up" in petri dishes and differentiated into normal fat cells.
"The immortal fat cells are a great experimental tool that will allow us to investigate the mechanisms of the inflammation and allow us to test ways to potentially inhibit the response," says Klingelhutz. "That would be a goal in the future."
Oct. 30, 2013 — Making fat cells immortal might seem like a bad idea to most people, but for a team of University of Iowa scientists it was the ideal way to study how the interaction between bacteria and fat cells might contribute to diabetes.
The connection between fat, bacteria, and diabetes is inflammation, which is the body's normal reaction to infection or injury.
Inflammation is beneficial in small, controlled doses but can be extremely harmful when it persists and becomes chronic.
"The idea is that when fat cells (adipocytes) interact with environmental agents -- in this case, bacterial toxins -- they then trigger a chronic inflammatory process," says Patrick Schlievert, Ph.D., UI professor and head of microbiology and co-senior author of a new study published in the journal PLOS ONE.
"We know that chronic inflammation leads to insulin resistance, which can then lead to diabetes.
So people are very interested in the underlying causes of chronic inflammation."
The UI researchers used immortalized fat cells to show that bacterial toxins stimulate fat cells to release molecules called cytokines, which promote inflammation.
By immortalizing fat cells the UI team created a stockpile of continuously dividing, identical cells that are necessary for repeat experiments to validate results, explains Al Klingelhutz, Ph.D., UI microbiologist and co-senior author of the study.
Previous studies have shown that a toxin called lipopolysaccharide (LPS) produced by E. coli bacteria that reside in the human gut, triggers fat cells to produce pro-inflammatory cytokines, and this interaction has been proposed to contribute to the development of diabetes.
The UI team focused on a different bacterium, Staphylococcus aureus (staph), which appears to be important in the context of diabetes for two reasons. First, as people become obese and then progress into diabetes they become very heavily colonized with staph bacteria.
Secondly, staph is the most common microbe isolated from diabetic foot ulcers, one of the most common and health-threatening complications of diabetes.
All staph bacteria make toxins called superantigens -- molecules that disrupt the immune system.
Schlievert's research has previously shown that superantigens cause the deadly effects of various staph infections, such as toxic shock syndrome, sepsis, and endocarditis.
The new UI study shows that superantigens from staph bacteria trigger fat cells to produce pro-inflammatory molecules.
Moreover, the study found that superantigens synergized with LPS from E. coli to magnify fat cells' cytokine responses, amplifying the inflammation, which could potentially boost the likelihood of developing diabetes.
"The E. coli that resides in our gut produces LPS and every day a small amount of this toxin gets into our circulation, but it is generally cleared from the circulation by the liver.
However, people colonized by staph bacteria are also chronically exposed to superantigens, which shut down the LPS detoxification pathway," Schlievert explains.
"That creates a synergy between the 'uncleared' LPS and the superantigen.
All these two molecules do is cause inflammation and cytokine production. So in essence, their presence together creates a perfect storm for inflammation."
The findings suggest that by promoting chronic inflammation through their effect on fat cells, staph superantigens may play a role in the development of diabetes.
In addition, the chronic inflammation caused by the superantigens may also hinder wound healing in diabetic foot ulcers.
The ulcers, which affect 15 to 25 percent of people with diabetes, are notoriously difficult to heal and can often lead to amputation.
Why immortalize fat cells?
The UI team created immortalized fat cells for their research because primary fat cells (taken directly from fat tissue) are not very useful for lab experiments.
Once the primary cells are grown in a dish, they quickly stop dividing and can't be used for repeated experiments.
In contrast, the immortalized fat cells allow experiments to be repeated multiple times on identical cells ensuring consistent, reproducible results.
Klingelhutz and his team immortalized immature precursor fat cells by adding in two genes from HPV (the virus that causes cervical cancer) along with a gene for part of an enzyme that controls the length of cells' telomeres -- the pieces of DNA that protect chromosome tips from deterioration.
These immortal precursor cells could then be "grown up" in petri dishes and differentiated into normal fat cells.
"The immortal fat cells are a great experimental tool that will allow us to investigate the mechanisms of the inflammation and allow us to test ways to potentially inhibit the response," says Klingelhutz. "That would be a goal in the future."
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