Blood Institute

Framingham, MA, United States

Blood Institute

Framingham, MA, United States

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News Article | May 8, 2017
Site: www.prnewswire.com

Dr. Phillip Chan, Chief Executive Officer of CytoSorbents stated, "After a strong 2016 finish, we began 2017 with continued solid year-over-year growth and healthy 68% product gross margins, while adding new catalysts that are expected to accelerate sales through the remainder of 2017 and beyond. Our trailing 12 month revenue is now $9.2 million, up from $8.2 million at the end of 2016.  We continue to target operating profitability before the end of 2018, based upon increased visibility and key factors outlined in our recent annual shareholder letter. These include 1) Continued direct and distributor sales momentum of CytoSorb in key international markets 2) Significantly enhanced reimbursement in our largest market of Germany and reimbursement progress in other major markets 3) The ramp of our co-marketing agreement with Fresenius Medical Care (FMC) 4) Continued progress by our strategic partners, including FMC, Terumo Cardiovascular, Biocon, and Dr. Reddy's in their exclusive sales territories, and 5) New clinical data driving the use of CytoSorb in different applications." "In particular, we are pleased that many hospitals in Germany, following first quarter negotiations of their 2017 operating budgets with the government, have reported solid increases in reimbursement for CytoSorb under the new dedicated reimbursement code that includes the full cost of the device as well as the procedure.  Our sales force and customers in Germany have been eagerly awaiting the finalization of these rates, as these data are very important to purchasing decisions. We expect many more hospitals to post similar reimbursement rates soon." "Meanwhile, we continue numerous initiatives throughout our business that are expected to help us meet the growing demand for CytoSorb.  These include our recently announced financing that gives us the capital for commercial expansion and to fund our clinical strategy; our ongoing buildout of a new manufacturing facility at less than 20% of our previously budgeted cost by remaining on-site and leveraging our existing manufacturing infrastructure; strengthening our U.S. clinical team with the planned start of our REFRESH 2 trial later this year, pending FDA approval; and the pending launch of our new therapeutic extracorporeal membrane oxygenation (ECMO) kit that is designed to accelerate this field beyond the 1,000+ treatments already performed." "Please join us on our previously announced earnings call today at 4:45PM EST where we will cover our progress.  We will also respond to questions from the audience during our live Q&A session.  The investor presentation and a written transcript of the conference call will be available within a week of the webcast." It is recommended that participants dial in approximately 10 minutes prior to the start of the call.  There will also be a simultaneous live webcast of the conference call that can be accessed through the following audio feed link: http://public.viavid.com/index.php?id=124222 An archived recording of the conference call will be available within a week under the Investor Relations section of the Company's website at Comparison for the three months ended March 31, 2017 and 2016: Revenue from product sales was approximately $2,596,000 in the three months ended March 31, 2017, as compared to approximately $1,597,000 in the three months ended March 31, 2016, an increase of approximately $999,000, or 63%. This increase was largely driven by an increase in direct sales from both new customers and repeat orders from existing customers, along with an increase in distributor sales. Grant income was approximately $517,000 for the three months ended March 31, 2017 as compared to approximately $213,000 for the three months ended March 31, 2016, an increase of approximately $304,000.  This increase was a result of revenue recognized from new grants and billable milestones achieved on existing grants. As a result of the increases in both product sales and grant income, for the three months ended March 31, 2017, we generated total revenue of approximately $3,114,000, as compared to revenues of approximately $1,810,000, for the three months ended March 31, 2016, an increase of approximately $1,304,000 or 72%. For the three months ended March 31, 2017 and 2016, cost of revenue was approximately $1,254,000 and $819,000, respectively, an increase of approximately $435,000. Product cost of revenues increased approximately $228,000 during the three months ended March 31, 2017 as compared to the three months ended March 31, 2016 due to increased sales.  Product gross margins were approximately 68% for the three months ended March 31, 2017, as compared to approximately 62% for the three months ended March 31, 2016.   This increase in gross margin was due to a favorable mix of sales prices. For the three months ended March 31, 2017, research and development expenses were approximately $470,000 as compared to research and development expenses of approximately $856,000 for the three months ended March 31, 2016.  The decrease of approximately $386,000 was due to a decrease in costs related to our various clinical studies and trials of approximately $208,000, a decrease in salaries related to non-clinical research and development activities of approximately $26,000, and an increase in direct labor and other costs being deployed toward grant-funded activities of approximately $205,000, which had the effect of decreasing the amount of our non-reimbursable research and development costs.  These decreases were offset by an increase in our non-clinical research and development activities of approximately $53,000. Legal, Financial and Other Consulting Expense: Legal, financial and other consulting expenses were approximately $280,000 for the three months ended March 31, 2017, as compared to approximately $255,000 for the three months ended March 31, 2016.  The increase of approximately $25,000 was due to an increase in employment agency fees of approximately $31,000 related to the recruitment of senior level personnel and an increase in legal fees of approximately $22,000 related to certain corporate initiatives.  These increases were offset by decreases in auditing and other consulting fees of approximately $28,000 due to fees incurred related to the audit of our internal controls as required by The Sarbanes-Oxley Act of 2002 in 2016 that did not recur. Selling, general and administrative expenses were approximately $2,667,000 for the three months ended March 31, 2017, as compared to approximately $1,970,000 for the three months ending March 31, 2016.  The increase of $697,000 was due to increase in salaries, commissions and related costs of approximately $320,000 due to headcount additions and personnel related costs, an increase in royalty expenses of approximately $94,000 due to the increase in product sales, additional sales and marketing costs, which include advertising and conferences of approximately $69,000, an increase in travel and entertainment and other costs of approximately $56,000, an increase in stock-based compensation of approximately $89,000 related to restricted stock units awarded to the Company's executive staff during the year ended December 31, 2016, an increase in rent expense of approximately $17,000 related to the new expanded office facility in Germany, an increase in office supplies and related expenses of approximately $15,000 and other general and administrative cost increases of approximately $37,000. For the three ended March 31, 2017, interest expense was approximately $120,000, as compared to interest income of approximately $4,000 for the three ended March 31, 2016. This increase in interest expense of approximately $124,000 is directly related to interest expense incurred and amortization of loan acquisition costs related to the Company's financing facility with Bridge Bank on which $5,000,000 was drawn on June 30, 2016. For the three months ended March 31, 2017, the gain on foreign currency transactions was approximately $153,000 as compared to approximately $232,000 for the three months ended March 31, 2016. The 2017 first quarter gain is directly related to the increase in the exchange rate of the Euro at March 31, 2017 as compared to December 31, 2016.  The exchange rate of the Euro to the U.S. dollar was $1.07 per Euro at March 31, 2017 as compared to $1.05 per Euro at December 31, 2016. We recognize warrants as liabilities at their fair value on the date of the grant because of price adjustment provisions in the warrants, then measure the fair value of the warrants on each reporting date, and record a change to the warrant liability as appropriate. The change in warrant liability resulted in other income of approximately $147,000 for the three months ended March 31, 2017 as compared to approximately $18,000 for the three months ended March 31, 2016. The change in warrant liability was a result of the change in the fair value of the warrant liability from December 31, 2016 to March 31, 2017 and from December 31, 2015 to March 31, 2016.   See Note 4 to the consolidated financial statements for details related to the calculation of the fair value of the warrant liability. Since inception, our operations have been primarily financed through the private placement of debt and equity securities. At March 31, 2017, we had current assets of approximately $6,281,000 including cash on hand of approximately $3,240,000 and current liabilities of approximately $6,183,000. On June 30, 2016, the Company and its wholly-owned subsidiary, CytoSorbents Medical, Inc., entered into a Loan and Security Agreement (the "Loan and Security Agreement") with Bridge Bank, a division of Western Alliance Bank, (the "Bank"), pursuant to which the Bank agreed to loan up to an aggregate of $10 million to the Company, to be disbursed in two equal tranches of $5 million. We received the proceeds from the first tranche on June 30, 2016. In addition, on April 5, 2017, the Company closed on the sale of an aggregate of 2,222,222 shares of Common Stock pursuant to the Company's existing shelf registration statement (File No. 333-205806) on Form S-3. The Company received gross proceeds of approximately $10 million, based on a public offering price of $4.50 per share. On April 11, 2017, the Company closed the sale of an additional 333,333 shares of the Company's Common Stock, pursuant to the underwriters' full exercise of an over-allotment option. The Company received gross proceeds of approximately $1.5 million as a result of the exercise of the option. As a result, the Company received total gross proceeds of $11.5 million, and, after deducting the underwriting discounts and commissions and estimated expenses related to the offering, the Company received total net proceeds of approximately $10.3 million. CytoSorbents has not historically given financial guidance on quarterly results until the quarter has been completed. However, we continue to expect our second quarter 2017 product sales to exceed sales reported in the second quarter of 2016. For additional information please see the Company's Quarterly Report on Form 10-Q for the quarter ending March 31, 2017 filed on May 8, 2017 on http://www.sec.gov. CytoSorbents Corporation is a leader in critical care immunotherapy, specializing in blood purification. Its flagship product, CytoSorb® is approved in the European Union with distribution in 43 countries around the world, as a safe and effective extracorporeal cytokine adsorber, designed to reduce the "cytokine storm" or "cytokine release syndrome" that could otherwise cause massive inflammation, organ failure and death in common critical illnesses such as sepsis, burn injury, trauma, lung injury and pancreatitis, as well as in cancer immunotherapy. These are conditions where the risk of death is extremely high, yet no effective treatments exist. CytoSorb® is also being used during and after cardiac surgery to remove inflammatory mediators, such as cytokines and free hemoglobin, which can lead to post-operative complications, including multiple organ failure. CytoSorbents has completed its REFRESH (REduction in FREe Hemoglobin) 1 trial – a multi-center, randomized controlled study that has demonstrated the safety of intra-operative CytoSorb® use in a heart-lung machine during complex cardiac surgery.  In 2017, the company plans to initiate a pivotal REFRESH 2 trial intended to support U.S. FDA approval.  CytoSorb® has been used safely in more than 23,000 human treatments to date. CytoSorbents' purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Its technologies have received non-dilutive grant, contract, and other funding in excess of $18 million from DARPA, the U.S. Army, the U.S. Department of Health and Human Services, the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), U.S. Special Operations Command (SOCOM) and others. The Company has numerous products under development based upon this unique blood purification technology, protected by 32 issued U.S. patents and multiple applications pending, including CytoSorb-XL, HemoDefend™, VetResQ™, ContrastSorb, DrugSorb, and others.  For more information, please visit the Company's websites at www.cytosorbents.com and www.cytosorb.com or follow us on Facebook and Twitter This press release includes forward-looking statements intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, statements about our plans, objectives, representations and contentions and are not historical facts and typically are identified by use of terms such as "may," "should," "could," "expect," "plan," "anticipate," "believe," "estimate," "predict," "potential," "continue" and similar words, although some forward-looking statements are expressed differently. You should be aware that the forward-looking statements in this press release represent management's current judgment and expectations, but our actual results, events and performance could differ materially from those in the forward-looking statements. Factors which could cause or contribute to such differences include, but are not limited to, the risks discussed in our Annual Report on Form 10-K, filed with the SEC on March 3, 2017, as updated by the risks reported in our Quarterly Reports on Form 10-Q, and in the press releases and other communications to shareholders issued by us from time to time which attempt to advise interested parties of the risks and factors which may affect our business. We caution you not to place undue reliance upon any such forward-looking statements. We undertake no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, other than as required under the Federal securities laws. Please Click to Follow Us on Facebook Twitter To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/cytosorbents-reports-first-quarter-2017-financial-results-300453507.html


News Article | May 9, 2017
Site: www.eurekalert.org

Childhood bullying may lead to long-lasting health consequences, impacting psychosocial risk factors for cardiovascular health well into adulthood, according to a study published in Psychological Science, a journal of the Association for Psychological Science. The unique study tracked a diverse group of over 300 American men from first grade through their early thirties and the findings indicate that being a victim of bullying and being a bully were both linked to negative outcomes in adulthood. The study, led by psychology researcher Karen A. Matthews of the University of Pittsburgh, showed that men who were bullies during childhood were more likely to smoke cigarettes and use marijuana, to experience stressful circumstances, and to be aggressive and hostile at follow-up more than 20 years later. Men who were bullied as children, on the other hand, tended to have more financial difficulties, felt more unfairly treated by others, and were less optimistic about their future two decades later. These outcomes are especially critical, the researchers note, because they put the men at higher risk for poor health, including serious cardiovascular issues, later in life. "The long term effects of bullying involvement are important to establish," says Matthews. "Most research on bullying is based on addressing mental health outcomes, but we wished to examine the potential impact of involvement in bullying on physical health and psychosocial risk factors for poor physical health." Previous research has linked psychosocial risk factors like stress, anger, and hostility to increased risk of health problems such as heart attacks, stroke, and high blood pressure. Because bullying leads to stressful interpersonal interactions for both the perpetrators and targets, Matthews and colleagues hypothesized that both bullies and bullying victims might be at higher risk of negative health outcomes related to stress. The research team recruited participants from the Pittsburgh Youth Study, a longitudinal study of 500 boys enrolled in Pittsburgh public schools in 1987 and 1988, when the boys were in the first grade. More than half of the boys in the original study were Black and nearly 60% of the boys' families received public financial assistance such as food stamps. Along with regular assessments on psychosocial, behavioral, and biological risk factors for poor health, researchers collected data from children, parents, and teachers on bullying behavior when the participants were 10 to 12 years old. Matthews and colleagues successfully recruited over 300 of the original study participants to complete questionnaires on psychosocial health factors such as stress levels, health history, diet and exercise, and socioeconomic status. Around 260 of the men came into the lab for blood draws, cardiovascular and inflammation assessments, and height and weight measurements. Unexpectedly, neither bullying nor being bullied in childhood was related to inflammation or metabolic syndrome in adulthood. However, both childhood bullies and bullying victims had increased psychosocial risk factors for poor physical health. The boys who engaged in more bullying in childhood tended to be more aggressive and were more likely to smoke in adulthood, risk factors for cardiovascular disease and other life-threatening diseases. The boys with higher scores for being bullied tended to have lower incomes, more financial difficulties, and more stressful life experiences. They also perceived more unfair treatment relative to their peers. These outcomes are also related to risk for cardiovascular disease. "The childhood bullies were still aggressive as adults and victims of bullies were still feeling like they were treated unfairly as adults," Matthews explained. "Both groups had a lot of stress in their adult lives - so the impact of childhood bullying lasts a long time!" The effects of bullying were fairly similar for both Black and White men, as well as those participants who came from low socioeconomic status families. Matthews and colleagues anticipate that both bullies and their victims may be at greater risk for poor physical health, including cardiovascular-disease events, over the long term. But they caution that many participants in the original study could not participate in this follow-up study because they were either deceased or incarcerated, which may have affected the results in unknown ways. The findings suggest that identifying children who are at risk for involvement in bullying and intervening early on may yield long-term psychosocial and even physical health benefits that last into adulthood. Co-authors on the research include J. Richard Jennings and Laisze Lee of the University of Pittsburgh and Dustin A. Pardini of Arizona State University. This research was supported by National Heart, Lung, and Blood Institute Grant R01-HL111802. Data collection for the Pittsburgh Youth Study was funded by National Institute on Drug Abuse Grant DA411018, National Institute of Mental Health Grants MH48890 and MH50778, the Pew Charitable Trusts, and Office of Juvenile Justice and Delinquency Prevention Grant 96-MU-FX-0012. For more information about this study, please contact: Karen A. Matthews at matthewska@upmc.edu. The article abstract is available online: http://journals. The APS journal Psychological Science is the highest ranked empirical journal in psychology. For a copy of the article "Bullying and Being Bullied in Childhood Are Associated With Different Psychosocial Risk Factors for Poor Physical Health in Men" and access to other Psychological Science research findings, please contact Anna Mikulak at 202-293-9300 or amikulak@psychologicalscience.org.


News Article | April 19, 2017
Site: www.rdmag.com

Blood transfusions can save the lives of patients who have suffered major blood loss, but hospitals don't always have enough or the right type on hand. In search of a solution, researchers have developed a promising substitute using blood's oxygen-carrying component, hemoglobin. The in vitro study, reported in ACS' journal Biomacromolecules, found that the modified hemoglobin was an effective oxygen carrier and also scavenged for potentially damaging free radicals. Red blood cells are the most commonly transfused component of blood, according to the U.S. National Heart, Lung, and Blood Institute. These cells carry the protein hemoglobin, which performs the essential function of delivering oxygen to the body's tissues. Scientists have tried developing chemically modified hemoglobin -- which by itself is toxic -- as a blood substitute but have found that it forms methemoglobin. This form of the protein doesn't bind oxygen and thus decreases the amount of oxygen that blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage. Hong Zhou, Lian Zhao, Yan Wu and colleagues wanted to see if packaging hemoglobin in a benign envelope could get around these problems. The researchers developed a one-step method for wrapping hemoglobin in polydopamine, or PDA, which has been widely studied for biomedical applications. A battery of lab tests showed that the PDA-coated hemoglobin effectively carried oxygen, while preventing the formation of methemoglobin and hydrogen peroxide. In addition, it caused minimal cell damage, and acted as an effective antioxidant, scavenging for potentially damaging free radicals and reactive oxygen species.


News Article | April 19, 2017
Site: www.eurekalert.org

Blood transfusions can save the lives of patients who have suffered major blood loss, but hospitals don't always have enough or the right type on hand. In search of a solution, researchers have developed a promising substitute using blood's oxygen-carrying component, hemoglobin. The in vitro study, reported in ACS' journal Biomacromolecules, found that the modified hemoglobin was an effective oxygen carrier and also scavenged for potentially damaging free radicals. Red blood cells are the most commonly transfused component of blood, according to the U.S. National Heart, Lung, and Blood Institute. These cells carry the protein hemoglobin, which performs the essential function of delivering oxygen to the body's tissues. Scientists have tried developing chemically modified hemoglobin -- which by itself is toxic -- as a blood substitute but have found that it forms methemoglobin. This form of the protein doesn't bind oxygen and thus decreases the amount of oxygen that blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage. Hong Zhou, Lian Zhao, Yan Wu and colleagues wanted to see if packaging hemoglobin in a benign envelope could get around these problems. The researchers developed a one-step method for wrapping hemoglobin in polydopamine, or PDA, which has been widely studied for biomedical applications. A battery of lab tests showed that the PDA-coated hemoglobin effectively carried oxygen, while preventing the formation of methemoglobin and hydrogen peroxide. In addition, it caused minimal cell damage, and acted as an effective antioxidant, scavenging for potentially damaging free radicals and reactive oxygen species. The authors acknowledge funding from the National Natural Science Foundation of China and the Beijing Natural Science Foundation. The abstract that accompanies this study is available here. The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With nearly 157,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio. To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.


News Article | May 2, 2017
Site: www.eurekalert.org

Mission Viejo, Calif. (May 2, 2017) - A new analysis of the National Health and Nutrition Examination Survey (NHANES) data, compared avocado consumers to non-consumers and found that consuming avocados may be associated with an overall better diet, higher intake of essential nutrients, lower body weight, lower Body Mass Index (BMI) and smaller waist circumference. Insulin and homocysteine levels were lower in the avocado group, as well as a significantly reduced incidence of metabolic syndrome. Homocysteine, when elevated, has been associated with an increased risk of cardiovascular disease.i Metabolic syndrome is the name for a group of risk factors that raises the risk for heart disease and other health problems, such as diabetes and stroke.ii The analysis, "Avocado consumption by adults is associated with better nutrient Intake, diet quality, and some measures of adiposity: National Health and Nutrition Examination Survey, 2001-2012," was published in the journal Internal Medicine Review. * Avocado consumers have improved diet quality, as measured by the Healthy Eating Index 2010. The findings are based on avocado consumption and its association with nutrient and food group intake, diet quality, and health biomarkers assessed using a nationally representative sample of 29,684 adults (ages 19 years and older) participating in the 2001-2012 NHANES. Fresh avocado intake averaged a consumption of 76 grams per day (a little more than half of a medium Hass avocado) and was assessed by 24-hour dietary recalls. Diet quality was measured using the Healthy Eating Index-2010 (HEI-2010), which measured adherence to the 2010 Dietary Guidelines for Americans. The analysis was supported by the U.S. Department of Agriculture Children's Nutrition Research Center and the Hass Avocado Board (HAB). "These findings indicate incorporating avocados could be one way for Americans to meet the recommended fruit and vegetable intake and potentially improve physiologic measures," said Nikki Ford, Hass Avocado Board Director of Nutrition. "As we fund additional clinical studies investigating the relationship between fresh avocado consumption and weight management and risk factors for cardiovascular disease and diabetes, we continue to encourage healthcare professionals to remain committed to recommending avocados as part of an overall healthy diet." For more information on avocado nutrition research, please visit LoveOneToday.com/Research The Hass Avocado Board (HAB) is an agriculture promotion group established in 2002 to promote the consumption of Hass Avocados in the United States. A 12-member board representing domestic producers and importers of Hass Avocados directs HAB's promotion, research and information programs under supervision of the United States Department of Agriculture. Funding for HAB comes from Hass avocado producers and importers in the United States. iiWhat is Metabolic Syndrome? National Heart, Lung, and Blood Institute. Available at: https:/ . Accessed March 23, 2017/


DALLAS, May 1, 2017 -- People with no major heart disease risk factors in middle age live longer and stay healthy far longer than others, according to a 40-year study reported in the American Heart Association's journal Circulation. "Good cardiovascular health in middle age delays the onset of many types of disease so that people live longer and spend a much smaller proportion of their lives with chronic illness," said Norrina Allen, Ph.D., M.P.H., assistant professor of preventive medicine at Northwestern University Feinberg School of Medicine in Chicago. In the first study to analyze the impact of cardiovascular health in middle age on the duration of illness later in life, researchers examined data from the Chicago Health Association study, which did initial health assessments in the late 1960s/early 1970s and has followed participants on an ongoing basis using Medicare health records. Researchers determined how many participants had favorable factors: non-smokers, free of diabetes and normal weight, blood pressure, and cholesterol levels; versus those with elevated risk factors or high risk factors. Comparing those who had two or more high-risk factors in middle age among the 17,939 participants who reached age 65 without a chronic illness, researchers found that those with all favorable factors: "Health professionals need to let young adults know that maintaining or adopting a heart-healthy lifestyle makes it more likely that you'll live longer and still be healthy enough to do the things you love to do when you're older," Allen said. Looking solely at heart disease in 18,714 participants who reached age 65 without having a heart attack, stroke or congestive heart failure, those with all favorable risk factors: Allen noted that at the start of the study, when their average age was 44, only 5.6 percent of participants had all favorable factors. That data is even more grim than a 2011-2012 national survey suggesting only 8.9 percent of U.S. adults age 40-59 had five or more "ideal" health factors, according to The American Heart Association's Heart Disease and Stroke Statistics -- 2017 Update. "We need to think about cardiovascular health at all stages of life," she said. "The small proportion of participants with favorable levels in their 40s is a call for all of us to maintain or adopt healthy lifestyles earlier in life. But risk factors and their effects accumulate over time, so even if you have risks it's never too late to reduce their impact on your later health by exercising, eating right, and treating your high blood pressure, cholesterol and diabetes." The American Heart Association created My Life Check ® to educate the public on improving health by aiming to achieve seven health measures called Life's Simple 7. It's a composite measure of seven modifiable heart-healthy factors: cigarette smoking, physical activity, diet, body mass index, blood pressure, cholesterol and glucose levels. The study recruited people from Chicago worksites in 1967-1972 and lacks information on how chronic illnesses affected the quality of life of participants. Co-authors are Lihui Zhao, Ph.D.; Lei Liu, Ph.D.; Martha Daviglus, M.D., Ph.D.; Kiang Liu, Ph.D.; James Fries, M.D.; Tina Shih, Ph.D.; Daniel Garside, M.S.; Thanh Huyen Vu, M.D.; Jeremiah Stamler, M.D.; and Donald M. Lloyd-Jones, M.D., Sc.M. Author disclosures are on the manuscript. The National Heart, Lung, and Blood Institute funded the study. Statements and conclusions of study authors published in American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations and health insurance providers are available at http://www. .


News Article | April 19, 2017
Site: phys.org

Blood transfusions can save the lives of patients who have suffered major blood loss, but hospitals don't always have enough or the right type on hand. In search of a solution, researchers have developed a promising substitute using blood's oxygen-carrying component, hemoglobin. The in vitro study, reported in ACS' journal Biomacromolecules, found that the modified hemoglobin was an effective oxygen carrier and also scavenged for potentially damaging free radicals. Red blood cells are the most commonly transfused component of blood, according to the U.S. National Heart, Lung, and Blood Institute. These cells carry the protein hemoglobin, which performs the essential function of delivering oxygen to the body's tissues. Scientists have tried developing chemically modified hemoglobin—which by itself is toxic—as a blood substitute but have found that it forms methemoglobin. This form of the protein doesn't bind oxygen and thus decreases the amount of oxygen that blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage. Hong Zhou, Lian Zhao, Yan Wu and colleagues wanted to see if packaging hemoglobin in a benign envelope could get around these problems. The researchers developed a one-step method for wrapping hemoglobin in polydopamine, or PDA, which has been widely studied for biomedical applications. A battery of lab tests showed that the PDA-coated hemoglobin effectively carried oxygen, while preventing the formation of methemoglobin and hydrogen peroxide. In addition, it caused minimal cell damage, and acted as an effective antioxidant, scavenging for potentially damaging free radicals and reactive oxygen species. Explore further: How stress controls hemoglobin levels in blood More information: Quan Wang et al. Bioinspired Polydopamine-Coated Hemoglobin as Potential Oxygen Carrier with Antioxidant Properties, Biomacromolecules (2017). DOI: 10.1021/acs.biomac.7b00077 Abstract Oxidative side reaction is one of the major factors hindering the development of hemoglobin-based oxygen carriers (HBOCs). To avoid the oxidative toxicity, we designed and synthesized polydopamine-coated hemoglobin (Hb-PDA) nanoparticles via simple one-step assemblage without any toxic reagent. Hb-PDA nanoparticles showed oxidative protection of Hb by inhibiting the generation of methemoglobin (MetHb) and ferryl (Fe IV) Hb, as well as excellent antioxidant properties by scavenging free radicals and reactive oxygen species (ROS). Interestingly, the scavenging rate of Hb-PDA nanoparticles for ABTS+ radical is at most 89%, while for DPPH radical it reaches 49%. In addition, Hb-PDA efficiently reduced the intracellular H2O2-induced ROS generation. Moreover, Hb-PDA nanoparticles exhibited high oxygen affinity, low effect on blood constituents, and low cytotoxicity. The results indicate that polydopamine-coated hemoglobin might be a promising approach for constructing novel oxygen carriers with the capacity to reduce oxidative side reaction.


News Article | May 2, 2017
Site: www.medicalnewstoday.com

Billions of people struggle with weight gain and obesity in the United States and across the globe. The Centers for Disease Control and Prevention (CDC) report that over a third of the U.S. population are obese, and the World Health Organization (WHO) estimate that almost 2 billion adults are overweight worldwide. Obesity can generally be prevented with a healthful diet and plenty of exercise, but sometimes we continue to gain weight despite our best efforts. For instance, people tend to gain weight as they age - particularly around the belly - and can subsequently become overweight, in a phenomenon commonly known as midlife weight gain. In fact, it is estimated that the average U.S. adult gains 30 pounds between the ages of 20 and 50, despite the fact that people tend to eat less during this period. This paradox sparked the interest of a team of researchers from the National Institutes of Health (NIH), who set out to investigate the mechanism behind midlife weight gain. The researchers were led by Dr. Jay H. Chung, Ph.D., head of the Laboratory of Obesity and Aging Research at the National Heart, Lung, and Blood Institute, which is a part of the NIH. The findings were published in the journal Cell Metabolism. Chung and team investigated the biochemical transformations that take place in animals in their middle age. Looking at animals that were the equivalent of 45 human years old, Chung and team found that an enzyme - called DNA-dependent protein kinase (DNA-PK) - becomes more active with age. Furthermore, the researchers found that DNA-PK turns nutrients into fat and lowers the number of mitochondria. Mitochondria are the so-called powerhouses of the cells. They are small compartments inside the cell that turn food into energy and break down waste products. Mitochondria are responsible for producing as much as 90 percent of the energy that cells need to grow, and they also play a crucial role in the death of other cells. The younger we are, the more mitochondria we have in our bodies. From midlife onward, however, the number of mitochondria starts to decrease. It is known that a lower number of mitochondria can lead to obesity, and mitochondrial dysfunction has been associated with a decrease in one's ability to exercise. To further understand the role of the DNA-PK enzyme, Chung and team tested its effect on two groups of mice. Both groups were fed a high-fat diet, but one group received an inhibitor that blocked the DNA-PK enzyme, while the other group did not. The group that received the DNA-PK-inhibiting drug gained 40 percent less weight than those that did not receive the drug. Additionally, the drug increased aerobic fitness and decreased the rate of obesity and type 2 diabetes in obese, middle-aged mice. Finally, the inhibitor also increased the number of mitochondria in the mice's skeletal muscle. Given that obesity is a risk factor for so many chronic illnesses, the researchers suggest that their findings may help to lower the risk of conditions such as heart disease, cancer, and Alzheimer's disease. The study's lead author comments on the findings: Although we are a long way from developing a similar DNA-PK inhibitor in humans, Dr. Chung suggests that the new study may pave the way for developing an innovative kind of weight loss medication. Dr. Chung also underscores how the study challenges the current societal perceptions around midlife weight gain. This should not discourage people from eating healthfully and exercising, however, adds Dr. Chung. Learn how midlife obesity could accelerate brain aging by 10 years.


News Article | April 19, 2017
Site: www.medicalnewstoday.com

The study is the work of a team at the National Institutes of Health (NIH) in Bethesda, MD, and it is published in the journal Cell Reports. Lead author Dr. Brian Glancy, of the Muscle Energetics Laboratory at NIH's National Heart, Lung, and Blood Institute (NHLBI), and colleagues believe that their findings give important clues on how healthy and diseased heart and skeletal muscle works. Such knowledge, they say, could increase understanding of conditions such as mitochondrial diseases, heart disease, and muscular dystrophy. Muscle cells must provide lots of energy to power movement of muscles that perform a range of functions, from moving the arms and legs to pumping the heart. To supply this energy, muscle cells contain many tiny compartments, or organelles, called mitochondria, which scientists often describe as the "powerhouses" of cells. Mitochondria are specialized organelles that convert sugars, fats, and other nutrients into energy-rich molecules - particularly one known as adenosine triphosphate (ATP). Mitochondria have some unusual features. For example, they have two surrounding membranes and their own genetic code that is separate from that held in the DNA in the cell nucleus. They also divide independently from the cell; their timing and rate of replication is not coupled to that of the cell. To produce ATP, the mitochondria rely on their two membranes: an outer one that has holes large enough for ions to pass through, and an inner one that is less permeable. These, and other differences between the two membranes, allow the mitochondria to sustain a difference in voltage across them that acts as a temporary store of energy (much like a battery) that is essential for the production of ATP, through a process called oxidative phosphorylation. However, after using high-resolution 3-D images to examine mitochondria inside mouse skeletal muscle cells, the same NIH team reported a groundbreaking study, published in 2015, which turned some of the long-held opinions regarding mitochondria on their head: the chemical diffusion of ATP was not the only means of energy distribution in cells. In that study, the team revealed that the electrical energy stored in the voltage across the two membranes of mitochondria was a primary source of energy in the cell and "the dominant pathway for skeletal muscle energy distribution." The study established the idea that the mitochondria act as a "power grid" inside the cell. In the new study, Dr. Glancy and colleagues take the earlier findings further and show that the mitochondrial power grid has inbuilt safety features that allow the cell to continue working if a part of the grid develops a fault. Again, with the help of high-resolution 3-D images and light-activated probes, and working with mouse heart muscle and skeletal muscle cells, the team discovered that the power grids inside these cells comprise subnetworks of mitochondria that are linked through "intermitochondrial junctions," which act in a similar fashion to circuit breakers. The researchers found that this arrangement allows for faulty mitochondria to be "electrically separated from the network in seconds," thus ensuring the integrity of the overall grid so that it can continue to supply the cell with energy. The researchers liken the process to that of the power grid of a city. When lightning strikes, the lights could flicker over the entire city for a second or two, but thanks to the arrangement of circuit breakers and subnetworks, the grid quickly recovers and the power loss is confined to a small part of the network. They conclude: Learn how inflammation can turn mitochondria into toxic factories.


News Article | April 25, 2017
Site: www.eurekalert.org

The search for the genetic determinants of extreme longevity has been challenging, with the prevalence of centenarians (people older than 100) just one per 5,000 population in developed nations. But a recently published study by Boston University School of Public Health and School of Medicine researchers, which combines four studies of extreme longevity, has identified new rare variants in chromosomes 4 and 7 associated with extreme survival and with reduced risks for cardiovascular and Alzheimer's disease. The results, published in the Journals of Gerontology: Biological Sciences, highlight the importance of studying "truly rare survival, to discover combinations of common and rare variants associated with extreme longevity and longer health span," the authors said. The research group, led by Paola Sebastiani, professor of biostatistics the BU School of Public Health (BUSPH), created a consortium of four studies -- the New England Centenarian Study, the Long Life Family Study, the Southern Italian Centenarian Study, and the Longevity Gene Project - to build a large sample of 2,070 people who survived to the oldest one percentile of survival for the 1900 birth year cohort. The researchers conducted various analyses to discover longevity-associated variants (LAVs), and to characterize those LAVs that differentiated survival to extreme age. Their analysis identified new "extreme longevity-promoting variants" on chromosomes 4 and 7, while also confirming variants (SNPs, or single nucleotide polymorphisms) previously associated with longevity. In addition, in two of the datasets where researchers had age-of-onset data for age-related diseases, they found that certain longevity alleles also were significantly associated with reduced risks for cardiovascular disease and hypertension. "The data and survival analysis provide support for the hypothesis that the genetic makeup of extreme longevity is based on a combination of common and rare variants, with common variants that create the background to survive to relatively common old ages (e.g. into the 80s and 90s), and specific combinations of uncommon and rare variants that add an additional survival advantage to even older ages," the authors wrote. They said, however, that while the "yield of discovery" in the study was more substantial than in prior genome-wide association studies (GWAS) of extreme longevity, it remained disappointing, in that the two most significant genotypes discovered "are carried by a very small proportion of the cases included in the analysis," meaning that much of the genetic variability around extreme lifespan remains unexplained. "We expect that many more uncommon genetic variants remain to be discovered through sequencing of centenarian samples," they wrote. "Larger sample sizes are needed to detect association of rare variants. . . and therefore promising associations that miss the threshold for genome-wide significance are important to discuss." BU co-authors on the study include: Stacy Andersen, assistant professor of medicine at BUSM and study manager of the New England Centenarian Study; Thomas Perls, professor of medicine and geriatrics at BUSM and principal investigator of the New England Centenarian Study; and Anastasia Gurinovich, of the BU Bioinformatics Program. The study was supported by funding from the National Institute on Aging, the National Heart Lung Blood Institute, and the William Wood Foundation.

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