Tratto da "Salute 24" (vedi articolo originale)
Leggi articolo originale su European Heart Journal
Niente di meglio di un quotidiano e vigoroso esercizio fisico per favorire la riabilitazione dopo un attacco di cuore: secondo uno studio pubblicato sull'European Heart Journal dai ricercatori della Liverpool John Moores University (Regno Unito), il movimento fisico non blando aiuterebbe le cellule staminali cardiache «dormienti» ad attivarsi, stimolando la crescita di nuovo tessuto cardiaco e favorendo, quindi, il recupero post-insufficienza cardiaca.
Lo studio, per ora condotto su un gruppo di topi, ha dimostrato che lo sport - mezz'ora di tapis roulant 4 volte a settimana, per 4 settimane - rende attive più del 60% delle cellule staminali cardiache che solitamente, negli adulti, rimangono dormienti, oltre a migliorare la capacità aerobica e l'irrorazione sanguigna.
Dopo solo due settimane di esercizio aerobico i topi avevano infatti aumentato il numero di cardiomiociti - le cellule battenti del tessuto cardiaco - del 7%.
Questo studio è il primo del suo genere a suggerire che la riabilitazione basata sul movimento fisico potrebbe avere lo stesso effetto sulle cellule dormienti delle iniezioni di apposite sostanze chimiche che stimolino le staminali stesse a produrre nuovo tessuto, e aggiunge nuove evidenze scientifiche che confermano che il cuore può essere in grado di rigenerarsi autonomamente.
Altri studi dovranno però essere condotti per comprendere se gli stessi effetti possono essere sortiti sugli uomini.
sabato 29 dicembre 2012
Un ormone “stonato” alimenta il tumore
Tratto da "Salute 24" (vedi articolo originale)
Tumori e metastasi, colpa di una danza stonata.
Quella di un meccanismo utile allo sviluppo embrionale, che per un “cortocircuito” va in tilt e accende il gene della staminalità tumorale.
Grazie a gruppo di ricercatori dell’Università degli Studi di Padova, guidati da Stefano Piccolo – Piccolo ha appena ricevuto il premio scientifico FIRC “Guido Venosta” - è più chiaro il rapporto tra l'eccesso dell’ormone Wnt, normalmente coinvolto nella costruzione degli organi e nei processi rigenerativi, e il gene TAZ che “invia” staminali a supporto del tumore. Lo studio è pubblicato su Cell.
In condizioni normali lo sviluppo di un nuovo organo avviene solo durante lo sviluppo embrionale, e solo pochi organi, come il fegato, sono capaci di rigenerarsi dopo aver subito un danno.
Il cancro è un "organo" che ha scoperto il segreto di come riprodurre se stesso, ed è grazie alle sue cellule staminali che si possono sviluppare le metastasi, con ricadute dopo la chemioterapia.
Le cellule tumorali da sole però non riuscirebbero a fare molto e anche il più aggressivo dei tumori ha bisogno di ricevere parecchi segnali dall’ambiente che lo circonda.
Uno di questi segnali viene da un ormone che si chiama Wnt: un fattore attivo durante lo sviluppo embrionale e nei normali processi rigenerativi.
Lo studio di Stefano Piccolo, che porta la firma di Luca Azzolin e Michelangelo Cordenonsi, spiega come l'eccesso di Wnt attivi nella cellula un gene maestro della staminalità tumorale, chiamato TAZ.
TAZ era già noto ai ricercatori: è un gene che durante lo sviluppo di un organo controlla le sue dimensioni e animali che per difetti genetici nascono con troppo TAZ sviluppano organi giganteschi.
Lo stesso meccanismo viziato che può portare al processo di crescita di un tumore e la proliferazione delle metastasi, versione stonata di quella danza armoniosa che guida invece lo sviluppo embrionale.
La scoperta apre nuove prospettive terapeutiche: in futuro, grazie a farmaci mirati e anticorpi monoclonali sarà possibile colpire con un unico vettore sia Wnt che TAZ e arrestare, quindi, lo sviluppo della malattia.
Tumori e metastasi, colpa di una danza stonata.
Quella di un meccanismo utile allo sviluppo embrionale, che per un “cortocircuito” va in tilt e accende il gene della staminalità tumorale.
Grazie a gruppo di ricercatori dell’Università degli Studi di Padova, guidati da Stefano Piccolo – Piccolo ha appena ricevuto il premio scientifico FIRC “Guido Venosta” - è più chiaro il rapporto tra l'eccesso dell’ormone Wnt, normalmente coinvolto nella costruzione degli organi e nei processi rigenerativi, e il gene TAZ che “invia” staminali a supporto del tumore. Lo studio è pubblicato su Cell.
In condizioni normali lo sviluppo di un nuovo organo avviene solo durante lo sviluppo embrionale, e solo pochi organi, come il fegato, sono capaci di rigenerarsi dopo aver subito un danno.
Il cancro è un "organo" che ha scoperto il segreto di come riprodurre se stesso, ed è grazie alle sue cellule staminali che si possono sviluppare le metastasi, con ricadute dopo la chemioterapia.
Le cellule tumorali da sole però non riuscirebbero a fare molto e anche il più aggressivo dei tumori ha bisogno di ricevere parecchi segnali dall’ambiente che lo circonda.
Uno di questi segnali viene da un ormone che si chiama Wnt: un fattore attivo durante lo sviluppo embrionale e nei normali processi rigenerativi.
Lo studio di Stefano Piccolo, che porta la firma di Luca Azzolin e Michelangelo Cordenonsi, spiega come l'eccesso di Wnt attivi nella cellula un gene maestro della staminalità tumorale, chiamato TAZ.
TAZ era già noto ai ricercatori: è un gene che durante lo sviluppo di un organo controlla le sue dimensioni e animali che per difetti genetici nascono con troppo TAZ sviluppano organi giganteschi.
Lo stesso meccanismo viziato che può portare al processo di crescita di un tumore e la proliferazione delle metastasi, versione stonata di quella danza armoniosa che guida invece lo sviluppo embrionale.
La scoperta apre nuove prospettive terapeutiche: in futuro, grazie a farmaci mirati e anticorpi monoclonali sarà possibile colpire con un unico vettore sia Wnt che TAZ e arrestare, quindi, lo sviluppo della malattia.
venerdì 21 dicembre 2012
Cancer Study Overturns Current Thinking About Gene Activation
From Science Daily website (see original article).
Dec. 13, 2012 — A new Australian study led by Professor Susan Clark from Sydney's Garvan Institute of Medical Research shows that large regions of the genome -- amounting to roughly 2% -- are epigenetically activated in prostate cancer.
Regions activated contain many prostate cancer-specific genes, including PSA (prostate specific antigen) and PCA3, the most common prostate cancer markers.
Until now, these genes were not known to be regulated epigenetically.
A previous study from Professor Clark's lab showed that similarly large regions of the prostate cancer genome are also epigenetically silenced, demonstrating a structured rearrangement of the cancer epigenome.
Epigenetics looks at biochemical changes that affect how the genome is organised in the cell nucleus, which in turn controls how genes are expressed.
Attachment or detachment of certain molecules can literally open or close DNA's structure, allowing a gene to be expressed if the structure is opened, and silenced if the structure is closed.
Among other aspects of epigenetic activation, the new study shows that the epigenetic process known as 'methylation' can activate genes, often by changing the gene start site, overturning the prevailing dogma that DNA methylation can only silence genes.
The findings as a whole have extensive ramifications for cancer diagnosis and treatment, including epigenetic-based gene therapies, as they require the targeting of domains of genes, as opposed to single genes.
PhD student Saul Bert and Professor Clark used gene expression profiling data and genome-wide sequencing technology from prostate tumour cells to determine which parts of the genome were epigenetically activated in prostate cancer.
They then examined the mechanisms behind activation, publishing their findings in the international journal Cancer Cell.
DNA is made up of building blocks of nucleic acid known as 'base pairs', specifically guanine-cytosine (GC) and adenine-thymine (AT). Unlike other parts of the genome, there are dense clusters of CG pairs very close to gene start sites.
These CG clusters, known as 'CpG islands', are where methylation occurs.
"When I started my PhD, we were looking to see if there was loss of methylation at CpG islands, causing gene activation in cancer," said Saul Bert.
"We took a whole genome approach, looking at all the gene transcription start sites that included CpG islands.
What we saw surprised us, because we saw gene activation at hypermethylated sites -- that went against current thinking.
"We went on to show in the lab that if you methylate CpG islands that are very close to transcription start sites, but not exactly on top of them, then it's possible to turn genes on.
"While the realisation that methylation can trigger gene activation represents a paradigm shift in thinking, our other finding -- that the prostate cancer genome contains domains that harbour multiple gene families, tumour related genes, microRNAs and cancer biomarkers -- is equally important.
These domains are simultaneously switched on through significant epigenetic remodelling.
"In this study, we identified 35 domains including 251 genes. While the genes may seem to be functionally unrelated, their coordinated regulation in the cancer genome suggests the presence of epigenetic 'master controllers' that can switch on or off very large regions of DNA."
Project leader Professor Clark believes the study will have a significant impact on our understanding of diagnostic tests and on chemotherapy treatment.
"What we are seeing in prostate cancer would apply to other cancers.
The big new finding is about the ways in which neighbouring genes are being co-ordinately activated in cancer," said Professor Clark.
"The increased expression is not just due to genetic amplification -- but we now show is also due to unraveling of the cancer genome.
"We need to understand this process more deeply to determine the impact of current epigenetic therapies that are aimed at promoting gene activation rather than suppressing oncogene expression."
Dec. 13, 2012 — A new Australian study led by Professor Susan Clark from Sydney's Garvan Institute of Medical Research shows that large regions of the genome -- amounting to roughly 2% -- are epigenetically activated in prostate cancer.
Regions activated contain many prostate cancer-specific genes, including PSA (prostate specific antigen) and PCA3, the most common prostate cancer markers.
Until now, these genes were not known to be regulated epigenetically.
A previous study from Professor Clark's lab showed that similarly large regions of the prostate cancer genome are also epigenetically silenced, demonstrating a structured rearrangement of the cancer epigenome.
Epigenetics looks at biochemical changes that affect how the genome is organised in the cell nucleus, which in turn controls how genes are expressed.
Attachment or detachment of certain molecules can literally open or close DNA's structure, allowing a gene to be expressed if the structure is opened, and silenced if the structure is closed.
Among other aspects of epigenetic activation, the new study shows that the epigenetic process known as 'methylation' can activate genes, often by changing the gene start site, overturning the prevailing dogma that DNA methylation can only silence genes.
The findings as a whole have extensive ramifications for cancer diagnosis and treatment, including epigenetic-based gene therapies, as they require the targeting of domains of genes, as opposed to single genes.
PhD student Saul Bert and Professor Clark used gene expression profiling data and genome-wide sequencing technology from prostate tumour cells to determine which parts of the genome were epigenetically activated in prostate cancer.
They then examined the mechanisms behind activation, publishing their findings in the international journal Cancer Cell.
DNA is made up of building blocks of nucleic acid known as 'base pairs', specifically guanine-cytosine (GC) and adenine-thymine (AT). Unlike other parts of the genome, there are dense clusters of CG pairs very close to gene start sites.
These CG clusters, known as 'CpG islands', are where methylation occurs.
"When I started my PhD, we were looking to see if there was loss of methylation at CpG islands, causing gene activation in cancer," said Saul Bert.
"We took a whole genome approach, looking at all the gene transcription start sites that included CpG islands.
What we saw surprised us, because we saw gene activation at hypermethylated sites -- that went against current thinking.
"We went on to show in the lab that if you methylate CpG islands that are very close to transcription start sites, but not exactly on top of them, then it's possible to turn genes on.
"While the realisation that methylation can trigger gene activation represents a paradigm shift in thinking, our other finding -- that the prostate cancer genome contains domains that harbour multiple gene families, tumour related genes, microRNAs and cancer biomarkers -- is equally important.
These domains are simultaneously switched on through significant epigenetic remodelling.
"In this study, we identified 35 domains including 251 genes. While the genes may seem to be functionally unrelated, their coordinated regulation in the cancer genome suggests the presence of epigenetic 'master controllers' that can switch on or off very large regions of DNA."
Project leader Professor Clark believes the study will have a significant impact on our understanding of diagnostic tests and on chemotherapy treatment.
"What we are seeing in prostate cancer would apply to other cancers.
The big new finding is about the ways in which neighbouring genes are being co-ordinately activated in cancer," said Professor Clark.
"The increased expression is not just due to genetic amplification -- but we now show is also due to unraveling of the cancer genome.
"We need to understand this process more deeply to determine the impact of current epigenetic therapies that are aimed at promoting gene activation rather than suppressing oncogene expression."
giovedì 6 dicembre 2012
Il sistema nervoso parasimpatico
Il sistema nervoso parasimpatico si distingue in due sezioni: craniale e sacrale.
La sezione craniale è costituita da neuroni pregangliari situati nel tronco dell’encefalo, i cui cilindrassi raggiungono la periferia attraverso il III, VII, IX, X e XI paio di n. cranici.
Provvede, così, all’innervazione per la secrezione delle ghiandole lacrimali, sottolinguali e sottomascellari (n. intermediario di Wrisberg) e per la vasodilatazione; all’innervazione secretoria della ghiandola parotide (IX paio) e delle ghiandole faringee; all’innervazione delle fibre muscolari lisce dell’esofago (plesso faringeo), dei bronchi e dei polmoni (plesso bronchiale), del muscolo cardiaco (plesso cardiaco), dello stomaco (plesso gastrico), del fegato e della cistifellea (plesso epatico), di duodeno, pancreas, intestino fino al colon trasverso (plesso celiaco), con associata funzione vasoattiva.
La sezione sacrale è costituita da neuroni pregangliari posti alla base delle corna anteriori del midollo sacrale, i cui cilindrassi escono attraverso le radici anteriori II, III e IV sacrali. I neuroni postgangliari sono i gangli del plesso ipogastrico; le fibre postgangliari sono i nervi pelvici.
In particolare, le fibre postgangliari portano impulsi motori per il colon discendente, il retto, l’ano, la vescica e alcuni muscoli genitali esterni; impulsi inibitori per gli sfinteri interni dell’ano, della vescica e dell’uretra; impulsi secretori per la prostata, le ghiandole di Bartolini e Cowper; impulsi vasodilatatori per il retto, l’ano e i genitali esterni. Il sistema parasimpatico utilizza per la trasmissione sinaptica nei gangli, nelle fibre pregangliari e nelle fibre postgangliari, l’acetilcolina. I recettori per l’acetilcolina sono indicati come muscarinici e nicotinici, a seconda che mimino rispettivamente l’azione della muscarina o della nicotina.
I recettori postgangliari sono muscarinici; a livello gangliare e a livello muscolare i recettori sono di tipo nicotinico.
La sezione craniale è costituita da neuroni pregangliari situati nel tronco dell’encefalo, i cui cilindrassi raggiungono la periferia attraverso il III, VII, IX, X e XI paio di n. cranici.
Provvede, così, all’innervazione per la secrezione delle ghiandole lacrimali, sottolinguali e sottomascellari (n. intermediario di Wrisberg) e per la vasodilatazione; all’innervazione secretoria della ghiandola parotide (IX paio) e delle ghiandole faringee; all’innervazione delle fibre muscolari lisce dell’esofago (plesso faringeo), dei bronchi e dei polmoni (plesso bronchiale), del muscolo cardiaco (plesso cardiaco), dello stomaco (plesso gastrico), del fegato e della cistifellea (plesso epatico), di duodeno, pancreas, intestino fino al colon trasverso (plesso celiaco), con associata funzione vasoattiva.
La sezione sacrale è costituita da neuroni pregangliari posti alla base delle corna anteriori del midollo sacrale, i cui cilindrassi escono attraverso le radici anteriori II, III e IV sacrali. I neuroni postgangliari sono i gangli del plesso ipogastrico; le fibre postgangliari sono i nervi pelvici.
In particolare, le fibre postgangliari portano impulsi motori per il colon discendente, il retto, l’ano, la vescica e alcuni muscoli genitali esterni; impulsi inibitori per gli sfinteri interni dell’ano, della vescica e dell’uretra; impulsi secretori per la prostata, le ghiandole di Bartolini e Cowper; impulsi vasodilatatori per il retto, l’ano e i genitali esterni. Il sistema parasimpatico utilizza per la trasmissione sinaptica nei gangli, nelle fibre pregangliari e nelle fibre postgangliari, l’acetilcolina. I recettori per l’acetilcolina sono indicati come muscarinici e nicotinici, a seconda che mimino rispettivamente l’azione della muscarina o della nicotina.
I recettori postgangliari sono muscarinici; a livello gangliare e a livello muscolare i recettori sono di tipo nicotinico.
Il nervo vago e il cuore
In caso di mancata innervazione del ramo destro del nervo vago parasimpatico al nodo sino-atriale provoca delle tachicardie, mentre se viene a mancare quello sinistro, manca l’innervazione al nodo atrio-ventricolare e di conseguenza crea aritmie.
Riparabili i danni dell'infarto
La rigenerazione del cuore dopo un infarto è una prospettiva possibile e concreta grazie alla scoperta di un gruppo di ricercatori del Centro internazionale di ingegneria genetica e biotecnologie dell’Unido a Trieste e guidato dal professor Mauro Giacca.
La scoperta pubblicata su Nature (leggi articolo) riguarda l’identificazione di quaranta piccole molecole di Rna, le quali iniettate nel cuore sono in grado di risvegliare e attivare le cellule dormienti di una parte danneggiata da un infarto del miocardio, ad esempio, rigenerandole, e guarendo quindi senza lasciare cicatrice alcuna.
PROSSIMO FARMACO
Il gruppo di Giacca stava lavorando da una decina d’anni a questo obiettivo e da un paio d’anni era iniziata l’identificazione dei microRna codificati dal genoma umano.
Una volta trovati sono iniziate le sperimentazioni su topi, ratti e cellule umane in provetta dimostrando di funzionare come previsto.
«Ora continueremo le ricerche - precisa Giacca -, per arrivare come obiettivo alla generazione di un farmaco che, iniettato nel cuore danneggiato, possa facilmente innescare la ricostruzione.
Ed è un obiettivo concreto e può essere anche molto vicino».
Nel mondo ogni anno vi sono 17 milioni di vittime per malattie cardiache, l’80 per cento delle quali nei Paesi in via sviluppo.
La prospettiva dunque offerta dal risultato triestino è tremendamente importante.
mercoledì 5 dicembre 2012
Brain Inflammation Likely Key Initiator to Prion and Parkinson's Disease
From Science Daily website (see original article).
ScienceDaily (Nov. 29, 2012) — In a recent publication, researchers of the Computational Biology group at the Luxembourg Centre for Systems Biomedicine showed that neuro-inflammation plays a crucial role in initiating prion disease.
Prion diseases represent a family of neurodegenerative disorders associated with the loss of brain cells and caused by proteins called prions (derived from ‘protein’ and ‘infection’).
The diseases are found in both humans and animals, such as Creutzfeld-Jakob disease and mad cow disease respectively.
Although mostly harmless, prions can transform into infectious agents, which accumulate in the brain and destroy the nervous tissue.
But how exactly does the accumulation of prions cause destruction of the brain? “Understanding the process by which prions destroy neurons is critical for finding a cure for prion disease”, says Isaac Crespo, first author of the publication.
He and his colleagues tackled this question with a computational approach: they ran their own computer programmes on experimental data generated by other research groups, and identified a set of 16 proteins that seems to control the onset of the disease.
Interestingly, almost all of these proteins have known functions in neuro-inflammation.
“What we consider remarkable and constitutes our main finding, is the key role that neuro-inflammation plays in initiating prion disease.
This finding is not only relevant for prion diseases, but also for other ‘protein misfolding diseases’ such as Parkinson’s and Alzheimer diseases” says Prof. Dr. Antonio del Sol, group leader of the Computational Biology group.
Since its publication on October 15th, Crespo’s paper was accessed so frequently, that it received the mark ‘Highly Accessed’, only awarded to articles that are downloaded very frequently.
The strong interest that scientists are showing for these research findings reflects the urgency with which researchers are trying to understand prion diseases for which there is no cure until today.
ScienceDaily (Nov. 29, 2012) — In a recent publication, researchers of the Computational Biology group at the Luxembourg Centre for Systems Biomedicine showed that neuro-inflammation plays a crucial role in initiating prion disease.
Prion diseases represent a family of neurodegenerative disorders associated with the loss of brain cells and caused by proteins called prions (derived from ‘protein’ and ‘infection’).
The diseases are found in both humans and animals, such as Creutzfeld-Jakob disease and mad cow disease respectively.
Although mostly harmless, prions can transform into infectious agents, which accumulate in the brain and destroy the nervous tissue.
But how exactly does the accumulation of prions cause destruction of the brain? “Understanding the process by which prions destroy neurons is critical for finding a cure for prion disease”, says Isaac Crespo, first author of the publication.
He and his colleagues tackled this question with a computational approach: they ran their own computer programmes on experimental data generated by other research groups, and identified a set of 16 proteins that seems to control the onset of the disease.
Interestingly, almost all of these proteins have known functions in neuro-inflammation.
“What we consider remarkable and constitutes our main finding, is the key role that neuro-inflammation plays in initiating prion disease.
This finding is not only relevant for prion diseases, but also for other ‘protein misfolding diseases’ such as Parkinson’s and Alzheimer diseases” says Prof. Dr. Antonio del Sol, group leader of the Computational Biology group.
Since its publication on October 15th, Crespo’s paper was accessed so frequently, that it received the mark ‘Highly Accessed’, only awarded to articles that are downloaded very frequently.
The strong interest that scientists are showing for these research findings reflects the urgency with which researchers are trying to understand prion diseases for which there is no cure until today.
martedì 4 dicembre 2012
Metabolic Protein Launches Sugar Feast That Nurtures Brain Tumors
From Science Daily website (see original article).
ScienceDaily (Nov. 26, 2012) — Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein's pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which brain tumors thrive.
They also found a vital spot along the protein's journey that can be attacked with a type of drug not yet deployed against glioblastoma multiforme, the most common and lethal form of brain cancer. Published online by Nature Cell Biology, the paper further illuminates the importance of pyruvate kinase M2 (PKM2) in cancer development and progression.
"PKM2 is very active during infancy, when you want rapid cell growth, and eventually it turns off. Tumor cells turn PKM2 back on -- it's overexpressed in many types of cancer," said Zhimin Lu, M.D., Ph.D., the paper's senior author and an associate professor in MD Anderson's Department of Neuro-Oncology.
Lu and colleagues showed earlier this year that PKM2 in the nucleus also activates a variety of genes involved in cell division. The latest paper shows how it triggers aerobic glycolysis, processing glucose into energy, also known as the Warburg effect, upon which many types of solid tumors rely to survive and grow.
"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Lu said. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles' heel for cancer."
By pinpointing the complicated steps necessary for PKM2 to penetrate the nucleus, Lu and colleagues found a potentially druggable target that could keep the protein locked in the cell's cytoplasm.
MEK, ERK emerge as targets
The process begins when the epidermal growth factor connects to its receptor on the cell surface.
This leads to:
* Activation of the MEK protein, which in turn activates ERK.
* ERK sticking a phosphate group to a specific spot on PKM2.
* Phosphorylation priming PKM2 for a series of steps that culminate in its binding to the protein importin, which lives up to its name by taking PKM2 through the nuclear membrane.
Once in the nucleus, the team showed that PKM2 activates two genes crucial to aerobic glycolysis and another that splices PKM RNA to make even more PKM2.
An experiment applying several kinase-inhibiting drugs to human glioblastoma cell lines showed that only a MEK/ERK inhibitor prevented EGF-induced smuggling of PKM2 into the nucleus. ERK activation then is mandatory for PKM2 to get into the nucleus.
"MEK/ERK inhibitors have not been tried yet in glioblastoma multiforme," Lu said. Phosporylated PKM2 is a potential biomarker to identify patients who are candidates for MEK/ERK inhibitors once those drugs are developed.
MEK inhibitor blocks tumor growth
The researchers also found that the two glycolysis genes activated by PKM2, called GLUT1 and LDHA, are required for glucose consumption and conversion of pyruvate to lactate, crucial factors in the Warburg Effect. Depleting PKM2 in tumor cell lines reduced glucose consumption and lactate production.
In mice, depleting PKM2 blocked the growth of brain tumors. Re-expressing the wild type protein caused tumors to grow. However, re-expression of a PKM2 mutant protein that lost its ability to get into the nucleus failed to promote tumor formation. Experiments in human glioblastoma cell lines showed the same effect.
Injecting the MEK inhibitor selumetinib into tumors inhibited tumor growth, reduced ERK phosphorylation, PKM2 expression and lactate production in mice. In 48 human tumor samples, the team found that activity of EGFR, ERK1/2 and PKM2 were strongly correlated.
Cause of PKM2 overexpression
Lu and colleagues also published a paper in Molecular Cell that revealed a mechanism for overexpression of PKM2 in glioblastoma. They found that EGF receptor activation turns on NF-KB, which leads to a series of events culminating in PKM2 gene activation.
PKM2 levels were measured in tumor samples from 55 glioblastoma patients treated with standard of care surgery, radiation and chemotherapy. The 20 with low PKM2 expression had a median survival of 34.5 months, compared to 13.6 months for the 35 patients with high levels of PKM2.
Level of PKM2 expression in 27 low-grade astrocytomas was about half of the expression found in higher grade glioblastomas.
"In these two papers, we show how PKM2 is overexpressed in tumors, how it gets into the nucleus, that nuclear entry is essential to tumor development, and identified potential drugs and a biomarker that could usefully treat people," Lu said.
Co-authors of the Nature Cell Biology paper are first author Weiwei Yang, Ph.D., Yanhua Zheng, Ph.D., Yan Xia, Ph.D., and Haitao Ji, Ph.D., of MD Anderson's Department of Neuro-Oncology and Brain Tumor Center; Xiaomin Chen, Ph.D., of MD Anderson's Department of Biochemistry and Molecular Biology; Ken Aldape, M.D., MD Anderson's Department of Pathology; Fang Guo, Ph.D., Nanomedicine Center, Shanghai Research Institute, China Academy of Science; Costas Lyssiotis, Ph.D., and Lewis Cantley, Ph.D., Beth Israel Deaconess Medical Center, Harvard Medical School.
This research was funded by grants from the National Institutes of Health (numbers 2RO1CA109035, RO1GM068566 and RO1GM56302), MD Anderson's Cancer Center Support Grant (CA16672) from the National Cancer Institute; and a research grant from the Cancer Prevention and Research Institute of Texas.
ScienceDaily (Nov. 26, 2012) — Researchers at The University of Texas MD Anderson Cancer Center have tracked down a cancer-promoting protein's pathway into the cell nucleus and discovered how, once there, it fires up a glucose metabolism pathway on which brain tumors thrive.
They also found a vital spot along the protein's journey that can be attacked with a type of drug not yet deployed against glioblastoma multiforme, the most common and lethal form of brain cancer. Published online by Nature Cell Biology, the paper further illuminates the importance of pyruvate kinase M2 (PKM2) in cancer development and progression.
"PKM2 is very active during infancy, when you want rapid cell growth, and eventually it turns off. Tumor cells turn PKM2 back on -- it's overexpressed in many types of cancer," said Zhimin Lu, M.D., Ph.D., the paper's senior author and an associate professor in MD Anderson's Department of Neuro-Oncology.
Lu and colleagues showed earlier this year that PKM2 in the nucleus also activates a variety of genes involved in cell division. The latest paper shows how it triggers aerobic glycolysis, processing glucose into energy, also known as the Warburg effect, upon which many types of solid tumors rely to survive and grow.
"PKM2 must get to the nucleus to activate genes involved in cell proliferation and the Warburg effect," Lu said. "If we can keep it out of the nucleus, we can block both of those cancer-promoting pathways. PKM2 could be an Achilles' heel for cancer."
By pinpointing the complicated steps necessary for PKM2 to penetrate the nucleus, Lu and colleagues found a potentially druggable target that could keep the protein locked in the cell's cytoplasm.
MEK, ERK emerge as targets
The process begins when the epidermal growth factor connects to its receptor on the cell surface.
This leads to:
* Activation of the MEK protein, which in turn activates ERK.
* ERK sticking a phosphate group to a specific spot on PKM2.
* Phosphorylation priming PKM2 for a series of steps that culminate in its binding to the protein importin, which lives up to its name by taking PKM2 through the nuclear membrane.
Once in the nucleus, the team showed that PKM2 activates two genes crucial to aerobic glycolysis and another that splices PKM RNA to make even more PKM2.
An experiment applying several kinase-inhibiting drugs to human glioblastoma cell lines showed that only a MEK/ERK inhibitor prevented EGF-induced smuggling of PKM2 into the nucleus. ERK activation then is mandatory for PKM2 to get into the nucleus.
"MEK/ERK inhibitors have not been tried yet in glioblastoma multiforme," Lu said. Phosporylated PKM2 is a potential biomarker to identify patients who are candidates for MEK/ERK inhibitors once those drugs are developed.
MEK inhibitor blocks tumor growth
The researchers also found that the two glycolysis genes activated by PKM2, called GLUT1 and LDHA, are required for glucose consumption and conversion of pyruvate to lactate, crucial factors in the Warburg Effect. Depleting PKM2 in tumor cell lines reduced glucose consumption and lactate production.
In mice, depleting PKM2 blocked the growth of brain tumors. Re-expressing the wild type protein caused tumors to grow. However, re-expression of a PKM2 mutant protein that lost its ability to get into the nucleus failed to promote tumor formation. Experiments in human glioblastoma cell lines showed the same effect.
Injecting the MEK inhibitor selumetinib into tumors inhibited tumor growth, reduced ERK phosphorylation, PKM2 expression and lactate production in mice. In 48 human tumor samples, the team found that activity of EGFR, ERK1/2 and PKM2 were strongly correlated.
Cause of PKM2 overexpression
Lu and colleagues also published a paper in Molecular Cell that revealed a mechanism for overexpression of PKM2 in glioblastoma. They found that EGF receptor activation turns on NF-KB, which leads to a series of events culminating in PKM2 gene activation.
PKM2 levels were measured in tumor samples from 55 glioblastoma patients treated with standard of care surgery, radiation and chemotherapy. The 20 with low PKM2 expression had a median survival of 34.5 months, compared to 13.6 months for the 35 patients with high levels of PKM2.
Level of PKM2 expression in 27 low-grade astrocytomas was about half of the expression found in higher grade glioblastomas.
"In these two papers, we show how PKM2 is overexpressed in tumors, how it gets into the nucleus, that nuclear entry is essential to tumor development, and identified potential drugs and a biomarker that could usefully treat people," Lu said.
Co-authors of the Nature Cell Biology paper are first author Weiwei Yang, Ph.D., Yanhua Zheng, Ph.D., Yan Xia, Ph.D., and Haitao Ji, Ph.D., of MD Anderson's Department of Neuro-Oncology and Brain Tumor Center; Xiaomin Chen, Ph.D., of MD Anderson's Department of Biochemistry and Molecular Biology; Ken Aldape, M.D., MD Anderson's Department of Pathology; Fang Guo, Ph.D., Nanomedicine Center, Shanghai Research Institute, China Academy of Science; Costas Lyssiotis, Ph.D., and Lewis Cantley, Ph.D., Beth Israel Deaconess Medical Center, Harvard Medical School.
This research was funded by grants from the National Institutes of Health (numbers 2RO1CA109035, RO1GM068566 and RO1GM56302), MD Anderson's Cancer Center Support Grant (CA16672) from the National Cancer Institute; and a research grant from the Cancer Prevention and Research Institute of Texas.
giovedì 15 novembre 2012
Bone Marrow Holds Secrets for Treating Colitis and Crohn's
From Science Daily website (see original article)
ScienceDaily (Sep. 24, 2012) — Michigan State University researchers have unlocked secrets in bone marrow that could lead to improved treatments for colitis and Crohn's disease.
The results, featured in the current issue of Proceedings of the National Academy of the Sciences, show that the havoc inflammatory bowel diseases wreaks on the digestive tract is mirrored in bone marrow. Early indications also show that the disorders of the gut could potentially be treated through the bone marrow, said Pam Fraker, MSU University Distinguished Professor of biochemistry and molecular biology.
"It's possible that if we could reduce bone marrow's ability to produce inflammatory cells that we could reduce the severity of colitis and Crohn's disease," said Fraker, who co-authored the study with MSU colleagues Laura McCabe, professor of physiology and radiology, and Mark Trottier, research specialist. "This could limit the damage that the disease causes and reduce the number of patients needing surgery."
Colitis and Crohn's affect more than a million people in the United States, including a growing number of children. There are no preventive treatments; however, steroids are often prescribed to reduce the diseases' pain and inflammation. The side effect of this course is tissue damage, which could lead to surgery and additional complications.
Watching a young patient suffer through the pain of severe colitis bolstered Fraker's need to research this devastating disease.
"She was very frail, sick, addicted to narcotics to numb her pain and had several intestinal surgeries to no avail," Fraker said. "This became a huge motivator for me as it drove home how little real help is available to these patients."
Fraker focused on bone marrow, which is a large, highly active and responsive tissue. When colitis was induced in mice, she was surprised by the significant and swift changes that occurred in their bone marrow.
The symptoms of colitis, such as swelling, anemia and unhealthy increases in monocytes and neutrophils, (cells that fight infection but exacerbate the excessive swelling in intestines) were reflected in the bone marrow.
The bone marrow's reactions actually fan the flames of the inflammatory bowel diseases rather than help cure it. When bone marrow amps up production of monocytes and neutrophils, it does it at the expense of making lymphocytes and red blood cells, keys to immune defense.
The research was funded in part by the Crohn's and Colitis Foundation.
ScienceDaily (Sep. 24, 2012) — Michigan State University researchers have unlocked secrets in bone marrow that could lead to improved treatments for colitis and Crohn's disease.
The results, featured in the current issue of Proceedings of the National Academy of the Sciences, show that the havoc inflammatory bowel diseases wreaks on the digestive tract is mirrored in bone marrow. Early indications also show that the disorders of the gut could potentially be treated through the bone marrow, said Pam Fraker, MSU University Distinguished Professor of biochemistry and molecular biology.
"It's possible that if we could reduce bone marrow's ability to produce inflammatory cells that we could reduce the severity of colitis and Crohn's disease," said Fraker, who co-authored the study with MSU colleagues Laura McCabe, professor of physiology and radiology, and Mark Trottier, research specialist. "This could limit the damage that the disease causes and reduce the number of patients needing surgery."
Colitis and Crohn's affect more than a million people in the United States, including a growing number of children. There are no preventive treatments; however, steroids are often prescribed to reduce the diseases' pain and inflammation. The side effect of this course is tissue damage, which could lead to surgery and additional complications.
Watching a young patient suffer through the pain of severe colitis bolstered Fraker's need to research this devastating disease.
"She was very frail, sick, addicted to narcotics to numb her pain and had several intestinal surgeries to no avail," Fraker said. "This became a huge motivator for me as it drove home how little real help is available to these patients."
Fraker focused on bone marrow, which is a large, highly active and responsive tissue. When colitis was induced in mice, she was surprised by the significant and swift changes that occurred in their bone marrow.
The symptoms of colitis, such as swelling, anemia and unhealthy increases in monocytes and neutrophils, (cells that fight infection but exacerbate the excessive swelling in intestines) were reflected in the bone marrow.
The bone marrow's reactions actually fan the flames of the inflammatory bowel diseases rather than help cure it. When bone marrow amps up production of monocytes and neutrophils, it does it at the expense of making lymphocytes and red blood cells, keys to immune defense.
The research was funded in part by the Crohn's and Colitis Foundation.
How Chronic Inflammation Can Cause Cancer
From Science Daily website (see original article)
ScienceDaily (Nov. 12, 2012) - A hormone-like substance produced by the body to promote inflammation can cause an aggressive form of leukemia when present at high levels, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).
The study shows that high levels of interleukin-15 (IL-15) alone can cause large granular lymphocytic (LGL) leukemia, a rare and usually fatal form of cancer, in an animal model. The researchers also developed a treatment for the leukemia that showed no discernible side effects in the animal model.
Published in the journal Cancer Cell, the findings show that IL-15 is also overexpressed in patients with LGL leukemia and that it causes similar cellular changes, suggesting that the treatment should also benefit people with the malignancy.
"We know that inflammation can cause cancer, but we don't know the exact mechanism," says principal investigator Dr. Michael A. Caligiuri, CEO of The James Cancer Hospital and Solove Research Institute, and director of Ohio State's Comprehensive Cancer Center.
"Here, we show one way it can happen, and we used that information to potentially cure the cancer."
Normally, the body releases IL-15 to stimulate the development, survival and proliferation of natural-killer cells, which are immune cells that destroy cancer and virus-infected cells. This research shows that when IL-15 is present in high amounts in the body for prolonged periods, such as during chronic inflammation, it can cause certain immune cells called large granular lymphocytes, or LGLs, to become cancerous.
This malignant transformation begins when IL-15 attaches to receptors on the surface of normal LGLs, an event that boosts levels of a cancer-causing protein called Myc (pronounced "mick") inside the cells. The high Myc levels, in turn, bring changes that cause chromosome instability and additional gene mutations. The high Myc levels also activate a process called DNA methylation, which turns off a variety of genes, including important genes that normally suppress cancer growth.
"We stand the best chance of curing cancer when we understand its causes," says first author Anjali Mishra, a postdoctoral researcher in Caligiuri's laboratory. "Once we understood how this inflammatory hormone causes this leukemia, we used that information to develop a treatment by interfering with the process."
Caligiuri and Mishra were joined in this study by Dr. Guido Marcucci, associate director for Translational Research at the OSUCCC -- James, Dr. Robert Lee, professor of pharmaceutics and pharmaceutical chemistry in Ohio State's College of Pharmacy and a group of collaborators. The investigators conducted the research using cells isolated from patients with LGL leukemia and a mouse model of the disease. Key findings include:
- Exposing normal, human, large granular lymphocytes to IL-15 caused cell proliferation, chromosomal instability and global DNA hypermethylation;
- Excessive IL-15 activated the cancer-causing Myc oncogene in large granular lymphocytes, leading to genetic instability, DNA hypermethylation and malignant transformation;
- Details of how Myc upregulation causes the genetic instability and hypermethylation.
"We now plan to develop this drug for clinical use," says Marcucci, who holds the John B. and Jane T. McCoy Chair in Cancer Research in Cancer Research.
martedì 30 ottobre 2012
Cause of High Cholesterol Discovered
From Science Daily website (see original article)
ScienceDaily (Oct. 28, 2012) — Canadian scientists have discovered that a protein called resistin, secreted by fat tissue, causes high levels of "bad" cholesterol (low-density lipoprotein or LDL), increasing the risk of heart disease.
The research, presented October 28 at the Canadian Cardiovascular Congress, proves that resistin increases the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear "bad" cholesterol from the body. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease.
The research also shows that resistin adversely impacts the effects of statins, the main cholesterol-reducing drug used in the treatment and prevention of cardiovascular disease.
Dr. Shirya Rashid -- senior author of the study and assistant professor in the department of medicine at McMaster University -- notes that a staggering 40 per cent of people taking statins are resistant to their impact on lowering blood LDL.
"The bigger implication of our results is that high blood resistin levels may be the cause of the inability of statins to lower patients' LDL cholesterol," says Dr. Rashid.
She believes the discovery could lead to revolutionary new therapeutic drugs, especially those that target and inhibit resistin and thereby increase the effectiveness of statins.
"The possibilities for improved therapy for the causes of cardiovascular disease are very important," says Heart and Stroke Foundation spokesperson Dr. Beth Abramson. "About 40 per cent of Canadians have high blood cholesterol levels: it's a significant health concern in Canada."
Dr. Abramson notes that the research reconfirms the importance of maintaining a healthy weight and cholesterol level, two critical factors in the prevention of heart disease.
High blood cholesterol is a major risk factor for heart disease and stroke. It can lead to a buildup of plaque in the artery walls and narrowing of the arteries, causing a condition called atherosclerosis which can make it more difficult for blood to flow through the heart and body.
Being overweight also increases the likelihood of high blood pressure and diabetes, compounding the risks of heart disease and stroke.
"Fortunately, we know a great deal about heart disease prevention and how to reverse some of the risks," says Dr. Abramson. She urges Canadians to maintain their heart health through regular visits to their doctor, monitoring their weight and waist size, eating a variety of nutritious, low-fat foods and being physically active. "It's equally important to take your medications as directed by your physician to help further reduce risks."
ScienceDaily (Oct. 28, 2012) — Canadian scientists have discovered that a protein called resistin, secreted by fat tissue, causes high levels of "bad" cholesterol (low-density lipoprotein or LDL), increasing the risk of heart disease.
The research, presented October 28 at the Canadian Cardiovascular Congress, proves that resistin increases the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear "bad" cholesterol from the body. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease.
The research also shows that resistin adversely impacts the effects of statins, the main cholesterol-reducing drug used in the treatment and prevention of cardiovascular disease.
Dr. Shirya Rashid -- senior author of the study and assistant professor in the department of medicine at McMaster University -- notes that a staggering 40 per cent of people taking statins are resistant to their impact on lowering blood LDL.
"The bigger implication of our results is that high blood resistin levels may be the cause of the inability of statins to lower patients' LDL cholesterol," says Dr. Rashid.
She believes the discovery could lead to revolutionary new therapeutic drugs, especially those that target and inhibit resistin and thereby increase the effectiveness of statins.
"The possibilities for improved therapy for the causes of cardiovascular disease are very important," says Heart and Stroke Foundation spokesperson Dr. Beth Abramson. "About 40 per cent of Canadians have high blood cholesterol levels: it's a significant health concern in Canada."
Dr. Abramson notes that the research reconfirms the importance of maintaining a healthy weight and cholesterol level, two critical factors in the prevention of heart disease.
High blood cholesterol is a major risk factor for heart disease and stroke. It can lead to a buildup of plaque in the artery walls and narrowing of the arteries, causing a condition called atherosclerosis which can make it more difficult for blood to flow through the heart and body.
Being overweight also increases the likelihood of high blood pressure and diabetes, compounding the risks of heart disease and stroke.
"Fortunately, we know a great deal about heart disease prevention and how to reverse some of the risks," says Dr. Abramson. She urges Canadians to maintain their heart health through regular visits to their doctor, monitoring their weight and waist size, eating a variety of nutritious, low-fat foods and being physically active. "It's equally important to take your medications as directed by your physician to help further reduce risks."
giovedì 18 ottobre 2012
Prostate Cancer: Curcumin Curbs Metastases, Study Shows
From Science Daily website (see original article)
ScienceDaily (Oct. 12, 2012) — Powdered turmeric has been used for centuries to treat osteoarthritis and other illnesses. Its active ingredient, curcumin, inhibits inflammatory reactions. A new study led by a research team at Ludwig-Maximilians-Universität (LMU) in Munich now shows that it can also inhibit formation of metastases.
Prostate cancer is one of the most prevalent malignancies in the Western world, and is often diagnosed only after metastatic tumors have formed in other organs. In three percent of cases, these metastases are lethal. A research team led by PD Dr. Beatrice Bachmeier at LMU Munich has been studying the mode of action of a natural product that inhibits the formation of metastases. The compound is found in turmeric, a plant that has been used for medicinal purposes for thousands of years, and is a major ingredient of curry.
Bachmeier's research centers on curcumin, the polyphenol responsible for the characteristic color of curry. Curcumin is well tolerated and is therefore, in principle, suitable both for prophylactic use (primary prevention) and also for the suppression of metastases in cases where an established tumor is already present (secondary prevention). In a previous study Bachmeier and her colleagues had demonstrated that the substance reduces statistically significantly the formation of lung metastases in an animal model of advanced breast cancer.
The new study was designed to investigate the efficacy of curcumin in the prevention of prostate cancer metastases, and to determine the agent's mechanism of action. The researchers first examined the molecular processes that are abnormally regulated in prostate carcinoma cells. Breast and prostate cancers are often associated with latent or chronic inflammatory reactions, and in both cases, the tumor cells were found to produce pro-inflammatory immunomodulators including the cytokines CXCL1 und CXCL2.
The researchers went on to show that curcumin specifically decreases the expression of these two proteins, and in a mouse model, this effect correlated with a decline in the incidence of metastases. "Due to the action of curcumin, the tumor cells synthesize smaller amounts of cytokines that promote metastasis," says Bachmeier. "As a consequence, the frequency of metastasis formation in the lungs is significantly reduced, in animals with breast cancer, as we showed previously, or carcinoma of the prostate, as demonstrated in our new study."
Curcumin and chemoprevention Bachmeier therefore believes that curcumin may be useful in the prevention of breast and prostate cancers -- which are both linked to inflammation -- and in reducing their metastatic potential. "This does not mean that the compound should be seen as a replacement for conventional therapies. However, it could play a positive role in primary prevention -- before a full-blown tumor arises -- or help to avert formation of metastases. In this context the fact that the substance is well tolerated is very important, because one can safely recommend it to individuals who have an increased tumor risk."
A daily intake of up to 8g of curcumin is regarded as safe, and its anti-inflammatory properties have long been exploited in traditional oriental medicine. Men with benign hyperplasia of the prostate (BHP) are one possible target group for prophylaxis, as are women who have a family history of breast cancer. The agent might also be valuable as a supplement to certain cancer therapies. At all events, curcumin's beneficial effects must first be confirmed in controlled clinical tests. Bachmeier is now planning such a trial in patients who suffer from therapy-resistant carcinoma of the prostate.
ScienceDaily (Oct. 12, 2012) — Powdered turmeric has been used for centuries to treat osteoarthritis and other illnesses. Its active ingredient, curcumin, inhibits inflammatory reactions. A new study led by a research team at Ludwig-Maximilians-Universität (LMU) in Munich now shows that it can also inhibit formation of metastases.
Prostate cancer is one of the most prevalent malignancies in the Western world, and is often diagnosed only after metastatic tumors have formed in other organs. In three percent of cases, these metastases are lethal. A research team led by PD Dr. Beatrice Bachmeier at LMU Munich has been studying the mode of action of a natural product that inhibits the formation of metastases. The compound is found in turmeric, a plant that has been used for medicinal purposes for thousands of years, and is a major ingredient of curry.
Bachmeier's research centers on curcumin, the polyphenol responsible for the characteristic color of curry. Curcumin is well tolerated and is therefore, in principle, suitable both for prophylactic use (primary prevention) and also for the suppression of metastases in cases where an established tumor is already present (secondary prevention). In a previous study Bachmeier and her colleagues had demonstrated that the substance reduces statistically significantly the formation of lung metastases in an animal model of advanced breast cancer.
The new study was designed to investigate the efficacy of curcumin in the prevention of prostate cancer metastases, and to determine the agent's mechanism of action. The researchers first examined the molecular processes that are abnormally regulated in prostate carcinoma cells. Breast and prostate cancers are often associated with latent or chronic inflammatory reactions, and in both cases, the tumor cells were found to produce pro-inflammatory immunomodulators including the cytokines CXCL1 und CXCL2.
The researchers went on to show that curcumin specifically decreases the expression of these two proteins, and in a mouse model, this effect correlated with a decline in the incidence of metastases. "Due to the action of curcumin, the tumor cells synthesize smaller amounts of cytokines that promote metastasis," says Bachmeier. "As a consequence, the frequency of metastasis formation in the lungs is significantly reduced, in animals with breast cancer, as we showed previously, or carcinoma of the prostate, as demonstrated in our new study."
Curcumin and chemoprevention Bachmeier therefore believes that curcumin may be useful in the prevention of breast and prostate cancers -- which are both linked to inflammation -- and in reducing their metastatic potential. "This does not mean that the compound should be seen as a replacement for conventional therapies. However, it could play a positive role in primary prevention -- before a full-blown tumor arises -- or help to avert formation of metastases. In this context the fact that the substance is well tolerated is very important, because one can safely recommend it to individuals who have an increased tumor risk."
A daily intake of up to 8g of curcumin is regarded as safe, and its anti-inflammatory properties have long been exploited in traditional oriental medicine. Men with benign hyperplasia of the prostate (BHP) are one possible target group for prophylaxis, as are women who have a family history of breast cancer. The agent might also be valuable as a supplement to certain cancer therapies. At all events, curcumin's beneficial effects must first be confirmed in controlled clinical tests. Bachmeier is now planning such a trial in patients who suffer from therapy-resistant carcinoma of the prostate.
lunedì 2 luglio 2012
Cuore - Patologia - Aritmie
L'aritmia è l'alterazione del normale ritmo cardiaco causata dall'anormale attività elettrica del cuore.
Patogenesi
Le aritmie sono dovute a:
Classificazione
Possiamo avere:
1) Alterazioni a livello del nodo senoatriale
2) Alterazioni di origine sopraventricolare
Tachiaritmie atriali
Tachiaritmie
Extrasistole
Patogenesi
Le aritmie sono dovute a:
- una normale o a un'anomala formazione dell'impulso,
- un'anomala conduzione dell'impulso,
- una combinazione di queste.
Classificazione
Possiamo avere:
- tachiaritmia o tachicardia se il battito aumenta in modo anomalo al di sopra di 100 al min
- bradiaritmia o bradicardia se il battito rallenta al di sotto di 40-50 per min.
1) Alterazioni a livello del nodo senoatriale
2) Alterazioni di origine sopraventricolare
Tachiaritmie atriali
- Fibrillazione atriale
Nella fibrillazione atriale, gli impulsi elettrici che danno luogo alla contrazione degli atri si attivano in maniera totalmente caotica e frammentaria dando origine a contrazioni disorganizzate e frammentarie.
Queste contrazioni degli atri sono spesso inefficaci dal punto di vista emodinamico, per cui la funzione di pompa del cuore, esercitata principalmente dalle contrazioni ventricolari, perde il piccolo contributo della contrazione atriale (circa il 5%).
Quindi durante la fibrillazione atriale, senza altre patologie del cuore, il miocardio perde solo una piccola parte (come detto sopra, mediamente il 5%) della sua funzione di pompa.
Può presentarsi in soggetti normali, particolarmente quando questi sono sottoposti a stress emotivi, interventi chirurgici, abuso acuto di alcol, stati febbrili.
Può comparire in soggetti sofferenti di cardiopatia, come la stenosi mitralica o altre cardiopatie valvolari, la cardiopatia ipertensiva e ischemica.
Una delle cause extracardiache più frequenti di fibrillazione atriale è l'ipertiroidismo.
Il sintomo classico della FA è la palpitazione: il paziente avverte un senso soggettivo di battito irregolare, che si può accompagnare a mancanza d'aria o svenimenti quando la frequenza del battito ventricolare diventa particolarmente elevata.
L'astenia, cioè la stanchezza fisica, è un altro sintomo sempre presente nella FA.
Tachiaritmie
- Tachicardia parossistica sopraventricolare
Extrasistole
- Extrasistole ventricolare
E' un battito prematuro, ossia una contrazione del muscolo cardiaco che avviene prima del previsto.
Talvolta sono espressione di stress, stanchezza, sforzi fisici, deprivazione di sonno, tabagismo, abuso di caffeina. In alcuni casi possono comparire dopo un pasto abbondante, legate a distensione del fondo gastrico, o legate alla presenza di un'ernia iatale.
Più di rado possono essere espressione di una malattia cardiaca, di un disturbo elettrolitico, (ad es. carenza di potassio) o di una malattia della tiroide.
- Tachicardia ventricolare
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