inflammation Tag

25 Nov

Posted at 20:25h in Author Interviews, Genetic Research, Pediatrics
[caption id="attachment_19630" align="alignleft" width="180"]Grant S Schubert MD, PhD Clinical Fellow, Division of Rheumatology Cincinnati Childrens Hospital Dr. Schulert[/caption] MedicalResearch.com Interview Grant S Schulert MD, PhD Clinical Fellow, Division of Rheumatology Cincinnati Childrens Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Schulert: Influenza infection causes millions of illnesses annually, but most of those are relatively mild.  In a subset of cases, patients can become critically ill, even if they are relatively young and healthy.  Several previous reports had observed in these critically ill patients features of a hyperinflammatory syndrome known as HLH (hemophagocytic lymphohistiocytosis) or MAS (macrophage activation syndrome).  This hyperinflammation can be triggered by other infections as well as in a subtype of juvenile arthritis, but there is also a familial form occurring in early childhood with known genetic causes.  Our questions with this study were 1) how often are features consistent with HLH/MAS seen in fatal H1N1 influenza infections and 2) do patients with fatal H1N1 infection have genetic mutations associated with HLH/MAS? Our collaborator Paul Harms, MD, and his team at the Michigan Center for Translational Pathology, University of Michigan Medical School identified 16 cases of fatal H1N1 influenza infection.  Based on their clinical features, between 41-88% of these patients could be categorized as having a hyperinflammatory HLH/MAS.  We then used processed tissue samples from the patients for whole exome genetic sequencing, which reads the entire genetic code of every gene in a person. Five patients carried mutations in genes which cause HLH, and several others carried mutations in genes linked to MAS.  This suggests that there may be genetic risk factors for developing fatal hyperinflammatory syndromes in H1N1 infection.

04 Aug

Posted at 02:26h in Author Interviews, Inflammation, Lipids, University of Pennsylvania
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.

21 Jan

Posted at 01:01h in Author Interviews, Brain Injury, Inflammation
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.

16 Jan

Posted at 13:25h in Author Interviews, Breast Cancer, Inflammation
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.

06 Jan

Posted at 12:00h in Author Interviews, Inflammation, Pediatrics, Pediatrics
[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.

28 Nov

Posted at 21:04h in Author Interviews, Inflammation, Nutrition
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.

13 Sep

Posted at 14:08h in Diabetes, Heart Disease
Carlos F. Sánchez-Ferrer, M.D., Ph.D. Professor of Pharmacology Universidad Autónoma de Madrid, Spain.MedicalResearch.com Interview with: Carlos F. Sánchez-Ferrer, M.D., Ph.D. Professor of Pharmacology Universidad Autónoma de Madrid, Spain. Medical Research: What are the main findings of the study? Dr. Sánchez-Ferrer: We were studying the possible ways of interaction between high glucose levels, which are found in diabetes mellitus, with vascular damage, which is the most common and devastating consequence of this disease. An intriguing fact is that a very strict control of blood sugar in diabetic patients is not sufficient to avoid the development of such diabetes-induced cardiovascular diseases. We think our results can explain why this is happening. Using cultured smooth muscle cells from the main human artery (aorta) in the presence of high concentrations of extracellular glucose, we observed: 1. In the absence of inflammation, excess glucose in the culture fluid didn’t enter the cells. 2. When extra glucose was forced into the cells, no harm was done in the absence of inflammation. 3. When the inflammation-stimulating protein interleukin-1 (IL-1) was introduced, more glucose entered the cells. 4. With IL-1, the glucose entering the cells was metabolized via chemical pathways that spur escalating inflammation, overwhelming the cells’ ability to counteract it. 5. In the presence of the anti-inflammatory drug anakinra, which blocks the activity of IL-1, the deleterious changes didn’t occur.

13 Aug

Posted at 20:15h in Author Interviews, JAMA, Mental Health Research
Dr Golam Khandaker Clinical Lecturer, Department of Psychiatry University of Cambridge MedicalResearch.com Interview with Dr Golam Khandaker Clinical Lecturer, Department of Psychiatry University of Cambridge Medical Research: What are the main findings of the study? Dr. Khandaker: The study shows low grade systemic inflammation may have a role in the pathogenesis of depression and psychotic disorders. Low grade systemic inflammation may also be a common cause for chronic physical and psychiatric illnesses. The study shows that higher serum levels of the circulating inflammatory marker, interleukin 6 (IL-6), in childhood is associated with nearly two-fold increased risk of developing depression and psychotic disorder in young adulthood. This association persisted after taking into account effects of age, sex, social class, ethnicity, body mass index, maternal depression, and past psychological and behavioural problem in the participant. We studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children birth cohort, taking blood samples at age 9 and following up at age 18, to see if they had experienced episodes of depression or . We excluded children with an infection at the time of blood test at age 9 years.

14 Jul

Posted at 00:54h in AHA Journals, Author Interviews, Diabetes, Heart Disease
MedicalResearch.com Interview with: Dr Alex Dregan Lecturer in Translational Epidemiology and Public Health, Division of Primary Care and Public Health Research King's College London, London Medical Research: What are the main findings of the study? Dr. Dregan: Our study showed that chronic inflammation was associated with increased risk of developing cardiovascular disease, specifically type II diabetes and coronary heart disease. The risk of cardiovascular disease increased with the severity of inflammatory disorders. In addition, inflammation also increased the risk of multiple morbidity (two or more cardiovascular diseases).

12 Mar

Posted at 00:41h in Author Interviews, Inflammation, JAMA, Mental Health Research, PTSD
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.

18 Sep

Posted at 22:57h in Aging, CMAJ, Inflammation
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.

28 Aug

Posted at 12:35h in Author Interviews, JCEM, Weight Research
MedialResearch.com Interview with: Dr Catherine M. Phillips Health Research Board Centre for Diet and Health Research Room 4.033, Department of Epidemiology and Public Health Western Gateway Building, University College Cork, Cork, Ireland MedialResearch.com: What are the main findings of the study? Answer: Obesity is associated with increased risk of diabetes and heart disease leading to reduced life expectancy. However in recent years it has been recognized that not all obese individuals are at increased risk – these individuals have been described as being metabolically healthy obese (MHO) in that despite carrying excess weight they do not have the typical abnormal metabolic features associated with obesity such as hypertension, insulin resistance and alterations to their lipid profile. It is not clear what factors determine whether an obese person becomes metabolically healthy or unhealthy. In this study conducted at the Dept. of Epidemiology and Public Health at University College Cork, Ireland, we examined levels of a range of inflammatory markers in 2047 middle-aged Irish adults to investigate to what extent differences between metabolically healthy and unhealthy obese and non-obese male and female adults are explained by inflammatory status. Participants, who were between the ages of 50 and 69, completed lifestyle questionnaires, physical and clinical assessments, and underwent blood testing so their body mass index (BMI), metabolic profiles and inflammatory markers could be determined. We found that, regardless of a person’s BMI, having a favorable inflammatory profile was associated with being metabolically healthy. Specifically metabolically healthy individuals presented with lower levels of complement component 3, C reactive protein, tumour necrosis factor alpha, interleukin 6, plasminogen activator inhibitor-1, reduced white blood cell count and higher adiponectin levels compared to their metabolically unhealthy counterparts.