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.
giovedì 15 novembre 2012
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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