News Article | February 28, 2017
RenalGuard Therapy® holds the potential to provide a new standard-of care for preventing cardiac contrast-agent induced acute kidney injury (CI-AKI) in high-risk patients undergoing percutaneous coronary interventions or transcatheter aortic valve replacement, according to a newly published report and companion editorial in JACC: Cardiovascular Interventions. The report, an independent systematic review and meta-analysis of four previously published randomized controlled clinical trials, found that RenalGuard Therapy was associated with a highly significant reduction of CI-AKI (7.76% vs. 21.43%; p<0.00001), a significantly lower need for patient dialysis (0.58% vs. 3.45%; p = 0.02), and a consistent positive trend towards lower rates of mortality, post-procedural acute coronary syndrome, stroke, and acute pulmonary edema. Moreover, the analysis found that most of the patients treated with RenalGuard reached a high urine output despite severely depressed kidney function without significant changes in electrolyte balance or any adverse reactions. The meta-analysis, entitled "Prevention of Contrast-Induced Acute Kidney Injury by Furosemide with Matched Hydration in Patients Undergoing Interventional Procedures," was performed and published by researchers from Cardiocentro Ticino, Lugano, Switzerland and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy. The editorial, entitled "High Urine Output with Matched Hydration for CI-AKI Prevention: 'Saus Per Aquam' (Health through Water)," was authored by Antonio L Bartorelli, MD, Centro Cardiologico Monzino, Istituto IRCCS, Milan, Italy and Giancarlo Marenzi, MD, Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan, Milan, Italy. "We are grateful to the authors, whose detailed analysis shows that RenalGuard not only lowers the incidence of CI-AKI, but offers a real benefit for patients and health care payers by significantly reducing the need for dialysis," said Andrew Halpert, President, RenalGuard Solutions™. "This detailed review adds strongly to the growing body of clinical evidence that RenalGuard can significantly lower health care risks arising from the use of medically valuable but potentially toxic contrast agents used today in a variety of diagnostic and interventional coronary procedures. We expect these findings to continue to drive adoption of RenalGuard Therapy in Europe and other areas where it currently available, and we look forward to further adding to these findings through our ongoing U.S. pivotal trial, which we expect to complete around the end of this year." Mr. Halpert noted that RenalGuard System is currently marketed for use in the cardiac catheterization laboratory in Europe, the Middle East, and South Africa, and that the company expects to file for pre-marketing approval with the U.S. Food and Drug Administration in 2018. The meta-analysis authors noted that lowering the incidence of CI-AKI, which would also lead to an associated significant reduction in the need for dialysis, could have a strong positive economic impact on health care costs. According to the United Kingdom's National Health Service Kidney Care program, the annual cost of AKI in the UK is estimated at US $700 million to $1 billion per year -- more than the yearly national expenditures related to either breast cancer or lung and skin cancer combined. CI-AKI is associated with higher in-hospital and long-term morbidity and mortality, persistent loss of kidney function, and risk of progression to end-stage renal disease. There are currently no therapies approved in the United States for the reduction of CI-AKI associated with coronary interventional procedures. RenalGuard measures a patient's urine output and automatically infuses hydration fluid based on that urine output. The system is designed to induce high urine rates, which have been shown to protect the kidney from a range of insults. A number of studies have demonstrated RenalGuard's ability to protect patients from AKI following catheterization procedures when compared to the standard of care, including: MYTHOS, which found RenalGuard to be superior to overnight hydration; REMEDIAL II, which found RenalGuard to be superior to sodium bicarbonate hydration; Protect-TAVI, which reported a significant reduction in post-procedural acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) when using RenalGuard during the procedure, compared to standard therapy; and AKIGUARD, which showed significant improvement in long-term outcomes when using RenalGuard vs. standard therapy. RenalGuard Solutions, Inc. is a medical device company focused on innovative technologies for the cardiac and vascular markets. The company's lead product, RenalGuard, is designed to protect patients from acute kidney injury (AKI), including contrast-induced AKI. Two investigator-sponsored studies in Europe have demonstrated RenalGuard's effectiveness at preventing CI-AKI in at-risk patients. RenalGuard is CE-marked and is sold in Europe and certain countries around the world via a network of distributors. The CIN-RG RenalGuard pivotal study is underway in the United States to support a planned Premarket Approval filing with the U.S. Food and Drug Administration. For further information, please visit the website at http://www.renalguard.com.
News Article | November 13, 2015
With outposts in nearly every organ and a direct line into the brain stem, the vagus nerve is the nervous system’s superhighway. About 80 percent of its nerve fibers — or four of its five “lanes” — drive information from the body to the brain. Its fifth lane runs in the opposite direction, shuttling signals from the brain throughout the body. Doctors have long exploited the nerve’s influence on the brain to combat epilepsy and depression. Electrical stimulation of the vagus through a surgically implanted device has already been approved by the U.S. Food and Drug Administration as a therapy for patients who don’t get relief from existing treatments. Now, researchers are taking a closer look at the nerve to see if stimulating its fibers can improve treatments for rheumatoid arthritis, heart failure, diabetes and even intractable hiccups. In one recent study, vagus stimulation made damaged hearts beat more regularly and pump blood more efficiently. Researchers are now testing new tools to replace implants with external zappers that stimulate the nerve through the skin. But there’s a lot left to learn. While studies continue to explore its broad potential, much about the vagus remains a mystery. In some cases, it’s not yet clear exactly how the nerve exerts its influence. And researchers are still figuring out where and how to best apply electricity. “The vagus has far-reaching effects,” says electrophysiologist Douglas Zipes of Indiana University in Indianapolis. “We’re only beginning to understand them.” Anchored in the brain stem, the vagus travels through the neck and into the chest, splitting into the left vagus and the right vagus. Each of these roads is composed of tens of thousands of nerve fibers that branch into the heart, lungs, stomach, pancreas and nearly every other organ in the abdomen. This broad meandering earned the nerve its name — vagus means “wandering” in Latin — and enables its diverse influence. The nerve plays a role in a vast range of the body’s functions. It controls heart rate and blood pressure as well as digestion, inflammation and immunity. It’s even responsible for sweating and the gag reflex. “The vagus is a huge communicator between the brain and the rest of the body,” says cardiologist Brian Olshansky of the University of Iowa in Iowa City. “There really isn’t any other nerve like that.” The FDA approved the first surgically implanted vagus nerve stimulator for epilepsy in 1997. Data from 15 years of vagus nerve stimulation in 59 patients at one hospital suggest that the implant is a safe, effective approach for combating epilepsy in some people, researchers in Spain reported in Clinical Neurology and Neurosurgery in October. Twenty of the patients experienced at least 50 percent fewer seizures; two of those had a 90 percent drop in seizures. The most common side effects were hoarseness, neck pain and coughing. In other research, those effects often subsided when stimulation was stopped. Early on, researchers studying the effects of vagus stimulation on epilepsy noticed that patients experienced a benefit unrelated to seizure reduction: Their moods improved. Subsequent studies in adults without epilepsy found similar effects. In 2005, the FDA approved vagus nerve stimulation to treat drug-resistant depression. The vagus nerve detects inflammation or infection in the body and relays signals from the brain stem along its southbound fibers. This signal prompts other nerves to release norepinephrine, which makes immune T cells in the spleen release the chemical acetylcholine to depress inflammation via macrophages. Although many details about how stimulation affects the brain remain unclear, studies suggest that vagus stimulation increases levels of the neurotransmitter norepinephrine, which carries messages between nerve cells in parts of the brain implicated in mood disorders. Some antidepressant drugs work by boosting levels of norepinephrine. Silencing norepinephrine-producing brain cells in rats erased the antidepressant effect of vagus nerve stimulation, scientists reported in the Journal of Psychiatric Research in September. Vagus stimulation for epilepsy and depression attempts to target the nerve fibers that shuttle information from body to brain. But its fifth lane, which carries signals from brain to body, is a major conductor of messages controlling the body’s involuntary functions, including heart rhythms and gut activity. The nerve’s southbound fibers can also be a valuable target for stimulation. Around 15 years ago, scientists determined that the brain-to-body lane of the vagus plays a crucial role in controlling inflammation. While testing the effects of an anti-inflammatory drug in rats, neurosurgeon Kevin Tracey and his colleagues found that a tiny amount of the drug in the rats’ brains blocked the production of an inflammatory molecule in the liver and spleen. The researchers began cutting nerves one at a time to find the ones responsible for transmitting the anti-inflammatory signal from brain to body. “When we cut the vagus nerve, which runs from the brain stem down to the spleen, the effect was gone,” says Tracey, president and CEO of the Feinstein Institute for Medical Research in Manhasset, N.Y. Later research indicated that stimulating undamaged vagus fibers also had anti-inflammatory effects in animals. Vagus stimulation prompts release of acetylcholine, Tracey and colleagues reported in 2000. Acetylcholine, a neurotransmitter like norepinephrine, can prevent inflammation. In 2011, rheumatologist Paul-Peter Tak, of the University of Amsterdam, and his colleagues implanted vagus nerve stimulators into four men and four women who had rheumatoid arthritis, an autoimmune inflammatory condition that causes swollen, tender joints. After 42 days of vagus stimulation — one to four minutes per day — six of the eight arthritis patients experienced at least a 20 percent improvement in their pain and swelling. Two of the six had complete remission, the researchers reported at an American College of Rheumatology conference in 2012. “From a scientific perspective, it’s an extremely exciting result,” says Tak, who is also a senior vice president at GlaxoSmithKline pharmaceuticals based in Stevenage, England. Despite advances in treatments over the last two decades, rheumatoid arthritis patients need better options, he says. In 2014, Tak and his colleagues reported that vagus stimulation reduced inflammation and joint damage in rats with arthritis. After a week of once-daily, minute-long stimulation sessions, swelling in the rats’ ankles shrank by more than 50 percent, the scientists reported in PLOS ONE. If these results hold up in future studies, Tak hopes to see the procedure tested in a range of other chronic inflammatory illnesses, including inflammatory bowel disorders such as Crohn’s disease. Studies in animals have shown promise in this area: In 2011, researchers reported in Autonomic Neuroscience: Basic and Clinical that vagus stimulation prevented weight loss in rats with inflamed colons. Treating inflammatory conditions with vagus stimulation is fundamentally different from treating epilepsy or depression, Tak says. More research with patients will be necessary to develop the technique. “We are entering a completely unknown area, because it’s such a new approach,” he says. There could be financial hurdles as well, he says. But GlaxoSmithKline, which Tak joined after initiating the arthritis study, has purchased shares of SetPoint Medical, a company in Valencia, Calif., that produces implantable vagus nerve stimulators, Tak says. As he and others put stimulation to the test for inflammation, some scientists are attempting to see if manipulating the nerve can help heal the heart. The vagus nerve has profound control over heart rate and blood pressure. Patients with heart failure, in which the heart fails to pump enough blood through the body, tend to have less active vagus nerves. Trying to correct the problem with electrical stimulation makes sense, says Michael Lauer, director of the cardiovascular sciences division at the National Heart, Lung and Blood Institute in Bethesda, Md. “It’s a great idea.” Yet so far, results from studies on the effects of vagus stimulation on heart failure have been inconsistent. In 2011, researchers reported in the European Heart Journal that repeated vagus nerve stimulation improved quality of life and the heart’s blood-pumping efficiency in heart failure patients. A vagus stimulation trial of heart failure patients in India published in the Journal of Cardiac Failure in 2014 echoed these results. After six months of therapy, the patients’ left ventricles pumped an average of 4.5 percent more blood per beat. Last August, however, researchers reported that a six-month clinical trial of vagus stimulation failed to improve heart function in heart failure patients in Europe. This study had the most participants — 87 — but used the lowest average level of electrical stimulation. “All the results thus far are preliminary. The studies that have been finished to date are relatively small,” Lauer says. “But there certainly are promising findings that [suggest] we may be barking up the right tree.” Another group of scientists is testing more intense vagus stimulation for patients with heart failure. The trial, called INOVATE-HF, is funded by the Israeli medical device company BioControl Medical and uses a higher level of electrical current than the European study that showed no measurable improvements. “If you try to lower blood pressure and you take a quarter of a pill instead of one pill, blood pressure won’t change,” says cardiologist Peter Schwartz of the IRCCS Istituto Auxologico Italiano in Milan. It’s equally important to use the right dose of vagus stimulation, he says. The new trial is also much larger than earlier studies, with more than 700 patients enrolled internationally. Results are expected by the end of 2016. Vagus manipulation isn’t limited to heart failure research. It’s also being tried in atrial fibrillation, in which the heart flutters erratically. “When it flutters, it doesn’t really push blood very efficiently,” says clinical electrophysiologist Benjamin Scherlag of the University of Oklahoma in Oklahoma City. Atrial fibrillation is common in people over age 60, Scherlag says, and can ultimately lead to blood clots and strokes. Treatments include drugs that alter heart rhythm or thin the blood, but they don’t work for all patients and some have nasty side effects, Scherlag says. In the lab, scientists can use high-intensity vagus stimulation to alter heart rhythm and induce atrial fibrillation in animals. But milder stimulation that alters heart rate only slightly, if at all, can actually quell atrial fibrillation, animal studies and one human study show. Vagus stimulation for atrial fibrillation is still in its infancy, and clinical applications haven’t been adequately tested, says Indiana’s Zipes. “Nevertheless, the concept bears looking into.” In patients with atrial fibrillation (AF), stimulating the vagus through the right ear (blue) decreased the length of heart fluttering episodes. With no stimulation (red), episodes did not shorten. At intensities so low they didn’t cause any perceptible change in heart rate, vagus stimulation controlled atrial fibrillation in dogs, Scherlag and colleagues reported in 2011. In 20 people receiving surgery for atrial fibrillation, low-level vagus stimulation reduced the duration of heart fluttering episodes from an average of 16.7 minutes to an average of 10.4 minutes, Scherlag and his colleagues reported in the Journal of the American College of Cardiology in March. In their study, Scherlag and his colleagues didn’t implant a nerve stimulator. In fact, they didn’t directly contact the nerve at all. They accessed tendrils of the vagus through the skin of their patients’ ears. Other researchers are also testing devices that stimulate the nerve without surgery. “Vagal nerve stimulation is very nice, but in order to get to the vagus nerve … you have to cut down surgically,” Scherlag says. “This is not the kind of thing you want to do, except under extreme situations.” But in the ear, tiny fingers of the vagus’s fibers run close to the surface of the skin, primarily under the small flap of flesh, the tragus, that covers the ear’s opening. Studies have explored using stimulation of those fibers through the skin of the ear to treat heart failure, epilepsy and depression, as well as memory loss, headaches and even diabetes — a reflection of the nerve’s control over a variety of hormones in addition to acetylcholine and norepinephrine. Stimulating the vagus nerve through the ear of diabetic rats lowered and controlled blood sugar concentrations, researchers from China and Boston reported in PLOS ONE in April. The stimulation prompted the rats’ bodies to release the hormone melatonin, which controls other hormones that regulate blood sugar. Ear-based vagus stimulation appeared to improve memory slightly in 30 older adults in the Netherlands. After stimulation, study subjects were better able to recall whether they had been shown a particular face before, says study coauthor Heidi Jacobs, a clinical neuroscientist at Maastricht University in the Netherlands. The researchers, who reported the work in the May Neurobiology of Aging, plan to investigate whether these effects last over time and exactly how the stimulation affects the brain, Jacobs says. The ear isn’t the only nonsurgical target. The company electroCore, based in Basking Ridge, N.J., manufactures a small, handheld device that can stimulate the vagus when placed on the throat. The company initially tested the devices to reduce asthma symptoms — relying on the nerve’s anti-inflammatory action. But during testing, patients reported that their headaches were disappearing, says J.P. Errico, CEO of electroCore. Now, the company is investigating the use of an electroCore device to treat chronic cluster headaches, severe headache attacks that can come and go for over a year. People suffering from an average of 67.3 cluster headaches each month experienced around four fewer attacks per week on average when using the device along with standard treatments like drugs, researchers reported in Cephalalgia in September. Several researchers have reservations about skin-deep stimulation. “The advantages of the handheld devices are that there’s no surgery required,” says Feinstein Institute’s Tracey, who is a founder and consultant for implant maker SetPoint Medical. But patient compliance becomes an issue. “Patient compliance with anything, whether it’s swallowing a pill or holding a device, is notoriously difficult,” he says. If a stimulator is implanted, a patient can forget about it, Tak agrees. He and Tracey both predict that implants will soon become smaller and safer. Even for depression and epilepsy, Tak says, researchers still need to figure out the best ways of stimulating the vagus — exactly where to place a device, and how much of a shock to deliver. The nerve’s multitasking, two-way nature makes it a challenge to fully understand and control. It’s hard to know exactly what you’re zapping when you stimulate the vagus nerve, says physiologist Gareth Ackland of University College London. He compares vagus stimulation to flipping on a light switch in one room of a house and discovering that this endows other rooms in the house with magical powers. “I’m not sure which room it’s going to happen in, I’m not sure for how long and I’m not sure if, after a while, it’s going to work or not,” he says. The intensity of electrical current, duration of stimulation and each patient’s health status could all affect the results of a vagus stimulation trial, Ackland says. And it’s possible that a widespread effect, such as suppressing inflammation caused by the immune system, could even be harmful to some patients. Ackland says that he and his colleagues agree that the vagus nerve is important. And he’s not ready to discount vagus stimulation as a potential therapy for conditions such as heart failure. But he warns that there’s a good deal of biology left to understand. “There’s an awful lot of basic science and basic clinical research that is needed before launching into a variety of potential interventions,” he says. For Tracey, it’s about way more than the vagus. “Nobody should overpromise that the vagus nerve is the secret to everything,” he says. But with a better map of the body’s nerves and their functions, the lessons learned by studying the vagus could inform future therapies that use nerve stimulation, he says. If researchers can understand and manipulate a particular circuit in a nerve that controls a specific molecule — for example, a protein involved in pain or even cell division — they could zero in on crucial targets. “The promise,” he says, “is for tremendous precision.” This article appears in the November 28, 2015, issue of Science News with the headline, "Waking the Vagus."
News Article | February 15, 2017
New study indicates that sugar intake and uric acid concentration independently contribute to the incidence and progression of liver disease, reports the Journal of Hepatology Amsterdam, The Netherlands, February 14, 2017 - Recent research suggests that dietary fructose intake may increase serum uric acid concentrations and that both uric acid concentration and fructose consumption may be increased in individuals with non-alcoholic fatty liver disease (NAFLD). Investigators have now established that both dietary fructose consumption and serum uric acid concentrations are independently associated with non-alcoholic steatohepatitis (NASH). Their conclusions are published in the Journal of Hepatology. NAFLD, the accumulation of extra fat in liver cells in people who drink little or no alcohol, is recognized as the fastest growing cause of liver disease in both Western and developing countries. It is estimated to affect up to 30% of the general population in Western countries and up to 9.6% of all children and 38% of obese children across a spectrum of liver disease, including NASH (defined as steatosis, hepatocyte ballooning and inflammation). Although NASH is a less aggressive form of NAFLD, it can progress to severe fibrosis and cirrhosis, with development of hepatocellular carcinoma in adults. "It is plausible that dietary fructose intake and uric acid concentrations are potential risk factors for liver disease progression in NAFLD. Numerous studies have shown that high uric acid levels are associated with metabolic syndrome and NAFLD, but to date, to the best of our knowledge, no studies have tested the independence of associations among uric acid concentrations, fructose consumption, and NASH confirmed by biopsy," explained senior investigator Valerio Nobili, MD, Chief of the Hepatometabolic Unit Liver Diseases Laboratory, Bambino Gesù Hospital, IRCCS, Rome, Italy. A team of researchers in Italy and the UK studied 271 obese children and adolescents with NAFLD (155 males, mean age 12.5 years) who underwent liver biopsy. All patients completed a food frequency questionnaire, indicating when specific foods were consumed (breakfast, morning snack, lunch, afternoon snack, dinner, etc.), how often (every day of the week, sometimes, or never), and portion size. Major sources of dietary fructose among children and adolescents are soda and other sweetened beverages. Nearly 90% reported drinking sodas and soft drinks one or more times a week. Almost 95% of patients regularly consumed morning and afternoon snacks consisting of crackers, pizza and salty food, biscuits, yogurt, or other snacks. In the group of patients studied, 37.6% of patients had NASH and 47% of patients with NASH had high uric acid compared with 29.7% of patients who did not have NASH. Fructose consumption was independently associated with high uric acid, which occurred more frequently in patients with NASH than in not-NASH patients. "In this study, we show for the first time that uric acid concentrations and dietary fructose consumption are independently and positively associated with NASH. The development of NASH may markedly affect life expectancy and quality of life in affected individuals and therefore it is crucial to understand the risk factors for NASH in children and adolescents in order to design effective interventions which can be used safely to treat this young group of patients," Dr. Nobili concluded. Efforts geared towards behavior modification, nutrition education, and limiting access to soda and other sweetened beverages could potentially reduce fructose consumption in this particular population. Several countries have already launched campaigns to ban soda vending machines in schools.
Campello S.,IRCCS |
Strappazzon F.,IRCCS |
Strappazzon F.,University of Rome Tor Vergata |
Cecconi F.,IRCCS |
And 2 more authors.
Biochimica et Biophysica Acta - Bioenergetics | Year: 2014
Mitochondria are double-membraned highly dynamic organelles; the shape, location and function of which are determined by a constant balance between opposing fusion and fission events. A fine modulation of mitochondrial structure is crucial for their correct functionality and for many physiological cell processes, the status of these organelles, being thus a key aspect in a cell's fate. Indeed, the homeostasis of mitochondria needs to be highly regulated for the above mentioned reasons, and since a) they are the major source of energy; b) they participate in various signaling pathways; albeit at the same time c) they are also the major source of reactive oxygen species (ROS, the main damaging detrimental players for all cell components). Elaborate mechanisms of mitochondrial quality control have evolved for maintaining a functional mitochondrial network and avoiding cell damage. The first mechanism is the removal of damaged mitochondrial proteins within the organelle via chaperones and protease; the second is the cytosolic ubiquitin-proteasome system (UPS), able to eliminate proteins embedded in the outer mitochondrial membrane; the third is the removal of the entire mitochondria through mitophagy, in the case of extensive organelle damage and dysfunction. In this review, we provide an overview of these mitochondria stability and quality control mechanisms, highlighting mitophagy, and emphasizing the central role of mitochondrial dynamics in this context. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components. © 2013 The Authors.
Angelini C.,IRCCS |
Nascimbeni A.C.,University of Padua |
Semplicini C.,University of Padua
Therapeutic Advances in Neurological Disorders | Year: 2013
The world of metabolic myopathies has been dramatically modified by the advent of enzyme replacement therapy (ERT), the first causative treatment for glycogenosis type II (GSDII) or Pompe disease, which has given new impetus to research into that disease and also other pathologies. This article reviews new advances in the treatment of GSDII, the consensus about ERT, and its limitations. In addition, the most recent knowledge regarding the pathophysiology, phenotype, and genotype of the disease is discussed. Pharmacological, immunotherapy, nutritional, and physical/rehabilitative treatments for late-onset Pompe disease and other metabolic myopathies are covered, including treatments for defects in glycogen metabolism, such as glycogenosis type V (McArdle disease), and glycogenosis type III (debrancher enzyme deficiency), and defects in lipid metabolism, such as carnitine palmitoyltransferase II deficiency and electron transferring flavoprotein dehydrogenase deficiency, or riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. © 2013 The Author(s).
Fuxe K.,Karolinska Institutet |
Borroto-Escuela D.O.,Karolinska Institutet |
Romero-Fernandez W.,Karolinska Institutet |
Palkovits M.,Hungarian Academy of Sciences |
And 3 more authors.
Neuropsychopharmacology | Year: 2014
There is serious interest in understanding the dynamics of the receptor-receptor and receptor-protein interactions in space and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor-receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor-receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology. © 2014 American College of Neuropsychopharmacology.
Castelvecchio S.,I.R.C.C.S. |
Multimedia manual of cardiothoracic surgery : MMCTS / European Association for Cardio-Thoracic Surgery | Year: 2013
The increase in left ventricular (LV) volume after a myocardial infarction (MI) is a component of the remodelling process and is associated with a poor clinical outcome. Hence, the current management strategy for ischaemic LV dysfunction has been aimed at reversing the remodelling process. Surgical LV reconstruction (LVR) has been introduced as an optional therapeutic strategy aimed at reducing LV volumes through the exclusion of the scar tissue, thereby restoring the physiological volume and shape and improving LV function and clinical status. Until recently, several studies have shown that surgical LVR is effective and relatively safe, with a favourable 5-year outcome. However, in spite of the large amount of reports drawn on various data sets, the additional benefit of LVR to CABG remains debated. We briefly discuss the rationale for surgically reversing LV remodelling through LVR, and, more extensively, the technique and the indications to the best of our knowledge.
Pazzaglia M.,University of Rome La Sapienza |
Galli G.,University of Rome La Sapienza |
Scivoletto G.,IRCCS |
PLoS ONE | Year: 2013
A tool such as a prosthetic device that extends or restores movement may become part of the identity of the person to whom it belongs. For example, some individuals with spinal cord injury (SCI) adapt their body and action representation to incorporate their wheelchairs. However, it remains unclear whether the bodily assimilation of a relevant external tool develops as a consequence of altered sensory and motor inputs from the body or of prolonged confinement sitting or lying in the wheelchair. To explore such relationships, we used a principal component analysis (PCA) on collected structured reports detailing introspective experiences of wheelchair use in 55 wheelchair-bound individuals with SCI. Among all patients, the regular use of a wheelchair induced the perception that the body's edges are not fixed, but are instead plastic and flexible to include the wheelchair. The PCA revealed the presence of three major components. In particular, the functional aspect of the sense of embodiment concerning the wheelchair appeared to be modulated by disconnected body segments. Neither an effect of time since injury nor an effect of exposure to/experience of was detected. Patients with lesions in the lower spinal cord and with loss of movement and sensation in the legs but who retained upper body movement showed a higher degree of functional embodiment than those with lesions in the upper spinal cord and impairment in the entire body. In essence, the tool did not become an extension of the immobile limbs; rather, it became an actual tangible substitution of the functionality of the affected body part. These findings suggest that the brain can incorporate relevant artificial tools into the body schema via the natural process of continuously updating bodily signals. The ability to embody new essential objects extends the potentiality of physically impaired persons and can be used for their rehabilitation. © 2013 Pazzaglia et al.
Rivista Italiana della Medicina di Laboratorio | Year: 2013
Summary: The Editorial summarizes some critical points of the economic theory of innovation, from its definition and general characteristics to sources, generation models, diffusion and cycle of life. In Medicine, the epitome of innovation theory is Translational Medicine. Its interpretative models (T models and process models) and generation, synthesis and diffusion of evidence (Evidence-based Medicine, Comparative Effectiveness Research and Health Technology Assessment) are briefly revised. The goals and methodology of Knowledge Translation, a tool for overcoming the barriers to spread of innovation and evidence, are described, with attention to the criticism derived from the concept of "wisdom translation". In conclusion, two examples of innovation in Laboratory Medicine (biomarkers cycle of life; instrumental miniaturization and information technology) are examined to highlight the indissoluble integration of innovation, evidence generation and synthesis, knowledge translation and clinical diagnostic in Laboratory Medicine. © 2013 Springer-Verlag Italia. Parole chiave: InnovazioneEvidence-based medicineComparative effectiveness researchHealth technology assessmentKnowledge translationMedicina di Laboratorio.
News Article | February 14, 2017
Recent research suggests that dietary fructose intake may increase serum uric acid concentrations and that both uric acid concentration and fructose consumption may be increased in individuals with non-alcoholic fatty liver disease (NAFLD). Investigators have now established that both dietary fructose consumption and serum uric acid concentrations are independently associated with non-alcoholic steatohepatitis (NASH). Their conclusions are published in the Journal of Hepatology. NAFLD, the accumulation of extra fat in liver cells in people who drink little or no alcohol, is recognized as the fastest growing cause of liver disease in both Western and developing countries. It is estimated to affect up to 30% of the general population in Western countries and up to 9.6% of all children and 38% of obese children across a spectrum of liver disease, including NASH (defined as steatosis, hepatocyte ballooning and inflammation). Although NASH is a less aggressive form of NAFLD, it can progress to severe fibrosis and cirrhosis, with development of hepatocellular carcinoma in adults. "It is plausible that dietary fructose intake and uric acid concentrations are potential risk factors for liver disease progression in NAFLD. Numerous studies have shown that high uric acid levels are associated with metabolic syndrome and NAFLD, but to date, to the best of our knowledge, no studies have tested the independence of associations among uric acid concentrations, fructose consumption, and NASH confirmed by biopsy," explained senior investigator Valerio Nobili, MD, Chief of the Hepatometabolic Unit Liver Diseases Laboratory, Bambino Gesù Hospital, IRCCS, Rome, Italy. A team of researchers in Italy and the UK studied 271 obese children and adolescents with NAFLD (155 males, mean age 12.5 years) who underwent liver biopsy. All patients completed a food frequency questionnaire, indicating when specific foods were consumed (breakfast, morning snack, lunch, afternoon snack, dinner, etc.), how often (every day of the week, sometimes, or never), and portion size. Major sources of dietary fructose among children and adolescents are soda and other sweetened beverages. Nearly 90% reported drinking sodas and soft drinks one or more times a week. Almost 95% of patients regularly consumed morning and afternoon snacks consisting of crackers, pizza and salty food, biscuits, yogurt, or other snacks. In the group of patients studied, 37.6% of patients had NASH and 47% of patients with NASH had high uric acid compared with 29.7% of patients who did not have NASH. Fructose consumption was independently associated with high uric acid, which occurred more frequently in patients with NASH than in not-NASH patients. "In this study, we show for the first time that uric acid concentrations and dietary fructose consumption are independently and positively associated with NASH. The development of NASH may markedly affect life expectancy and quality of life in affected individuals and therefore it is crucial to understand the risk factors for NASH in children and adolescents in order to design effective interventions which can be used safely to treat this young group of patients," Dr. Nobili concluded. Efforts geared toward behavior modification, nutrition education, and limiting access to soda and other sweetened beverages could potentially reduce fructose consumption in this particular population. Several countries have already launched campaigns to ban soda vending machines in schools.