Author Interviews, Inflammation, Lipids, University of Pennsylvania / 04.08.2015

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with: Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators. Several aspects of our study design set us apart from what was done in previous studies.
  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.
The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.
Addiction, Author Interviews, Inflammation / 31.07.2015

Prof. Igor Yakymenko Laboratory of Biophysics, Institute of Experimental Pathology, Oncology and Radiobiology NAS of UkraineMedicalResearch.com Interview with: Prof. Igor Yakymenko Laboratory of Biophysics, Institute of Experimental Pathology, Oncology and Radiobiology NAS of Ukraine Medical Research: What is the background for this study? What are the main findings? Prof. Yakymenko: We know a lot about both health effects and metabolic effects of radiofrequency radiation (RFR) today, including mutagenic and carcinogenic effects. For example, epidemiological studies over the world indicate that 5 years of cell phone use 20 min per day increase risk of acoustic neuroma 3 times. Or, for example, 4 years of cell phone use 1 hour or more per day increase risk of some kinds of brain tumors, including glioma, 3-5 times. But it was not understandable the primary mechanisms of such effects. In our study we had analyzed about 100 recent studies on metabolic effects of radiofrequency radiation, including our own experimental data, and demonstrated that oxidative/free radical effects are mandatory feature of RFR exposure of living cells. Moreover, the chronic radiofrequency radiation exposure can produce chronic oxidative stress in living cells as a first step for possible development of bulk of hazardous health effects.
Author Interviews, Genetic Research, Infections, Inflammation, Stanford / 15.05.2015

MedicalResearch.com Interview with: Timothy E Sweeney, MD PhD Resident, General Surgery Postdoc, Khatri Lab, Bioinformatics Stanford University Medical Research: What is the background for this study? What are the main findings? Dr. Sweeney: Sepsis is defined as the presence of systemic inflammation due to infection. Systemic inflammation can be caused from many things, such as trauma, surgery, thrombosis, autoimmunity, etc. It can also be caused by infection. On the other hand, infection does not necessarily cause systemic inflammation, either:  a person can get a minor infection, like strep throat, and not have a systemic response. It's the intersection of severe inflammation (a syndrome called SIRS) with infection that defines sepsis. In general surgery, we frequently see patients after traumatic injury or surgery who are having an inflammatory response (ie, fevers, fast heart rate, high white blood cell count, etc). But it's not clear whether this inflammatory response is a reaction to the trauma or surgery, or whether there might be an infection brewing that is causing the reaction. Identifying the inflammatory response doesn't require many special tests-- it's easy to spot. So we know which patients have inflammation and which do not. What is difficult is determining the root cause of the inflammation, and, in particular, whether there is an infection present that needs treatment with antibiotics. Current diagnostics for infection (not sepsis) are either slow (like blood cultures, which can take 24-72 hours to return) or not highly accurate (like procalcitonin). We sought to define a better test that could specifically differentiate between people with sterile inflammation, and people with inflammation due to infection (sepsis). By integrating gene expression data from multiple publicly available cohorts, we were able to find a set of 82 genes that are significantly differently expressed between these two groups. We then used an algorithm called a greedy forward search to find a subset of 11 genes that were most diagnostic for sepsis.
Author Interviews, Genetic Research, Infections, Inflammation, NYU/NYMC / 07.05.2015

Dr. Ludovic Desvignes. PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical CenterMedicalResearch.com Interview Dr. Ludovic Desvignes PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical Center MedicalResearch: What is the background for this study? Dr. Desvignes: This study is the result of a collaboration at NYU Langone Medical Center, between the laboratories of Dr. Stefan Feske and Dr. Joel Ernst, my mentor. Dr. Feske and colleagues had developed a mouse model of rare, inherited mutations he had identified in infants. These mutations occur in the genes for STIM1 and ORAI1, which are crucial for calcium flux in cells of the immune system. The young patients affected by these mutations suffer from severe, recurrent and chronic infections that often cause death before their first birthday. In particular, some of these patients cannot control infection with BCG, which is a normally innocuous strain of mycobacteria administered to protect against tuberculosis (TB). TB is a chronic infection and one of the leading causes of infection-related death worldwide. Going into this study, Dr. Feske and colleagues knew that without functional calcium channels, immune cells do not function properly. However, they did not fully understand how these channels contribute to immune responses to infectious pathogens in a living organism and in particular, for pathogens that cause chronic infections such as TB. This is why Dr. Ernst and I collaborated with Dr. Feske and provided him with our clinical and research expertise in TB. MedicalResearch: What are the main findings? Dr. Desvignes: Dr. Feske’s mice are genetically engineered to lack STIM1 in a certain type of immune cells, known as T cells or T lymphocytes. We infected these mice with Mycobacterium tuberculosis, the bacterium causing TB. Mycobacterium tuberculosis causes chronic infection by manipulating the immune system even in healthy people. The first very surprising result of our study was that mice lacking calcium flux in T cells handled acute TB fairly well. Only during the chronic phase of infection did they become unable to control mycobacterial growth and developed a strong inflammation in their lungs, which was due to an infiltration by different types of immune cells, including T cells. We discovered that the accumulation of STIM1-deficient T cells in the lungs resulted from the cells’ inability to die, which is a normal mechanism to limit an immune response and prevent excessive inflammation. Another immune control mechanism that failed in the absence of STIM1 is mediated by a subset of T cells called induced regulatory T cells, or iTreg cells. These cells are essential to prevent normal immune responses from going “overboard” by suppressing the functions of other immune cells, including T cells. We found that calcium signals are required for the development of iTreg cells and that their numbers were strongly reduced in the lungs of infected STIM1-deficient mice. We therefore think that the lack of iTreg cells in the absence of STIM1 contributes to the severe lung inflammation in chronic TB. The third finding that really surprised us was that T cells accumulating in the lungs of STIM1-deficient mice produced large amounts of a protein called interferon gamma. While interferon gamma is required to control Mycobacterium tuberculosis, it is also a very potent promoter of inflammation and too much of it can lead to tissue damage. Dr. Feske and colleagues had previously observed that calcium fluxes promote the production of interferon gamma in T cells cultured in vitro and we expected the STIM1-deficient T cells to be defective in the production of that protein. During chronic TB, however, calcium signaling turned out to be not only dispensable for the production of interferon gamma by T cells but it was actually required to limit its production and thus, to control inflammation.
Aging, Author Interviews, Inflammation / 15.02.2015

Dr. Jeremy Van Raamsdonk Laboratory of Aging and Neurodegenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Department of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan, Department of Biology, McGill University, Montreal, Quebec, CanadaMedicalResearch.com Interview with: Dr. Jeremy Van Raamsdon PhD Laboratory of Aging and Neurodk egenerative Disease (LAND), Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, Deptment of Translational Science and Molecular Medicine, Department of Genetics, Michigan State University, East Lansing, Michigan,Dep. of Biology, McGill University, Montreal, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Van Raamsdonk : The free radical theory of aging is one of the most widely accepted theories of aging. This theory suggests that reactive oxygen species (ROS), which are also known as free radicals, cause a type of damage, called oxidative damage, that accumulates over time to cause the functional decline associated with aging. ROS have also been proposed to play a role in many diseases including neurodegenerative disorders such as Parkinson’s disease and Huntington’s disease. However, recent work has demonstrated that ROS are not necessarily detrimental. ROS perform functional roles in the body and thus it is possible to have too little ROS. We previously showed that increasing ROS by decreasing the levels of an antioxidant enzyme called superoxide dismutase (SOD) does not decrease lifespan even when all of the SOD genes are removed. We also showed that in some cases treatment with an antioxidant, such as Vitamin C, can lead to decreased lifespan. This finding is consistent with human clinical trials in which it has not been possible to show a beneficial effect of antioxidants on longevity. In this paper we further examine the relationship between ROS and aging. We use a simple genetic model organism, the worm Caenorhabditis elegans, which has been used extensively in aging research, to determine how location impacts the effect of ROS on lifespan. We used a genetic approach to increase the levels of ROS in different parts of a cell and found that location is crucial in determining the effect of ROS on lifespan. Mildly increasing the levels of ROS in the mitochondria increases lifespan, while increasing ROS in the cytoplasm has the opposite effect of decreasing lifespan.
Author Interviews, Brain Injury, Inflammation / 21.01.2015

Alan I Faden, M.D. David S. Brown Professor in Trauma Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of MedicineMedicalResearch.com Interview with: Alan I Faden, M.D. David S. Brown Professor in Trauma Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Faden: Accumulating clinical and pre-clinical research data indicate that traumatic brain injury (TBI) can lead to chronic progressive neurodegeneration. In this regard, most attention has focused on the connections between TBI and with Alzheimer disease (AD) or Chronic Traumatic Encephalopathy (CTE). However, recent epidemiological studies raise questions about the association between TBI and AD, and CTE is likely a less common end-stage result resulting from complex pathobiological changes. In contrast, both older and newer studies underscore that traumatic brain injury can cause chronic neuroinflammation that leads to chronic neurodegeneration. In contrast to AD and CTE, the latter condition appears to be potentially treatable, even long after injury. Our paper critically assesses the mechanisms and treatment of chronic post traumatic neurodegeneration.
Author Interviews, Breast Cancer, Inflammation / 16.01.2015

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with: Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México MedicalResearch: What is the background for this study? Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.
Author Interviews, Inflammation, Pediatrics, Pediatrics / 06.01.2015

[caption id="attachment_19464" align="alignleft" width="133"]Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark. Prof. Bisgaard[/caption] MedicalResearch.com Interview with: Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Bisgaard: The purpose of this study was to look for a shared risk factor for immunological diseases which make its debut in childhood. During the recent decades a parallel increase in prevalence of immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have been observed in westernized countries. The rate of cesarean delivery has increased in the same period and has previously been associated with the development of some of these diseases. This study takes advantage of the unique and valuable nationwide registry data in Denmark to establish a large population based cohort (2 million term children) with 35 years of follow up (in the period 1977-2012). We found cesarean delivery to be a common risk factor for a range of childhood immunological diseases: asthma, juvenile arthritis, inflammatory bowel diseases, connective tissue disorders, immune deficiencies and leukemia, but with no association to psoriasis, celiac disease, and diabetes type 1.
Author Interviews, Inflammation, Nutrition / 28.11.2014

Joana Alves Dias, MPH Department of Clinical Sciences in Malmö, Lund University Malmö, Sweden MedicalResearch.com Interview with: Joana Alves Dias, MPH Department of Clinical Sciences in Malmö, Lund University Malmö, Sweden Medical Research: What is the background for this study? What are the main findings? Response: The evidence that chronic inflammation may be in the genesis of diseases such as cardiovascular disease, type-II diabetes, and certain types of cancer is increasing. It is suggested that lifestyle factors such as diet, physical activity, smoking, and alcohol consumption could influence the inflammatory state. Instead of focusing on single nutrient effects, we used a hypothesis-driven approach to food pattern studies, and constructed a diet quality index based on the Swedish Nutrition Recommendations and Swedish Dietary guidelines (DQI-SNR). The DQI-SNR consisted of 6 components. Individuals were assigned 0 when not adhering to a recommendation and 1 when adhering, resulting in total scores ranging from 0 to 6. We classified individuals in low (0 or 1 points), medium (2 or 3) and high (4-6 points) diet quality. We explored the association between the index scores and low-grade inflammation. Our study indicates that adherence to a high quality diet is associated with lower systemic inflammation, as measured by several soluble and cellular biomarkers of inflammation, in middle-aged individuals. In other words, adherence to the general nutrition recommendations could help prevent the development of diseases associated with chronic inflammation. The anti-inflammatory effects of Mediterranean-like diets have been studied extensively, but this study focused on the Swedish dietary habits and recommendations for the Swedish population, and reached similar conclusions.
Author Interviews, Gastrointestinal Disease, Inflammation, Metabolic Syndrome / 26.11.2014

Dr. Andrew Gewirtz PhD Professor & Associate Chair Department of Biology Georgia State UniversityMedicalResearch.com Interview with: Dr. Andrew Gewirtz PhD Professor & Associate Chair Department of Biology Georgia State University Medical Research: What is the background for this study? Dr. Gewirtz: 2010 science paper that discovered that loss of toll-like receptor 5 altered gut microbiota to drive metabolic syndrome Medical Research: What are the main findings? Dr. Gewirtz: It is loss of tlr5 on epithelial cells that alters the microbiota to make it more pro-inflammatory that drives metabolic syndrome.
Author Interviews, Inflammation, Nutrition, Vitamin K / 25.03.2014

MedicalResearch.com Interview with Mònica Bulló PhD Human Nutrition Unit Department of Biochemistry & Biotechnology IISPV  School of Medicine Rovira i Virgili University Sant Llorenç, Spain MedicalResearch.com: What are the main findings of the study? Dr Bulló: There is some evidence that different dietary forms of vitamin K could exert varying effects on health, however no study to date has simultaneously evaluated the potential effects of the main vitamin K forms on cancer and cardiovascular mortality. We conducted a prospective, epidemiologic study involving 7,216 elderly subjects at high cardiovascular risk who were followed for about 5 years.The results of the present study show, for the first time that an increase in dietary intake of both forms of vitamin K is related to a lower risk of cardiovascular mortality, cancer mortality or all-cause mortality.
Author Interviews, Inflammation, JAMA, Mental Health Research, PTSD / 12.03.2014

Dr. Dewleen Baker MD Veterans Affairs (VA) San Diego Healthcare System, San Diego, California MedicalResearch.com Interview with: Dr. Dewleen Baker MD Veterans Affairs (VA) San Diego Healthcare System, San Diego, California MedicalResearch.com: What are the main findings of the study? Dr. Baker: The main finding of this study is that a marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.
Aging, CMAJ, Inflammation / 18.09.2013

MedicalResearch.com Interview with: Tasnime Akbaraly  PhD Institut National de la Santé et de la Recherche Médicale Montpellier, France MedicalResearch.com: What are the main findings of the study? Dr. Akbaraly: The aim of this study was to examine the association between chronic inflammation and a range of aging phenotypes, assessed approximately 10 years later in a large British population of men and women  -The Whitehall II Study-. As inflammation characterises a wide range of pathological processes, we considered several aging phenotypes, including cardiovascular disease (fatal and non-fatal), non-cardiovascular mortality and successful aging which encompasses optimal functioning across different physical, mental, and cognitive domains We found that chronic inflammation characterized by high levels of interleukin-6 (>2 pg/mL) twice over the 5-year exposure period nearly halved the odds of successful aging after 10–years of follow-up compared to maintaining low levels of interleukin-6 (<1pg/mL twice over the exposure period). Chronic inflammation was also associated with increased odds of future cardiovascular disease and non-cardiovascular mortality in a dose-response fashion. These associations were found to be independent of socio-economic factors, health behaviours (smoking, physical activity), and conditions such as obesity as well as the use of anti-inflammatory drugs and acute inflammation.