Reduction In Systemic Inflammation Research Articles

Role of Inhaled Nitric Oxide in the Management of Severe Acute Respiratory Distress Syndrome.

To date, there have been several systematic reviews with meta-analysis that have shown no reduction in mortality with the use of inhaled nitric oxide (iNO) in patients with acute respiratory distress syndrome (ARDS). Importantly, these reports fail to make a distinction between the pediatric and adult patient. The number of adult patients in these reviews are far greater than the number of pediatric patients, which makes it difficult to interpret the data regarding the role of iNO on the pediatric population. Extrapolating data from the adult population to the pediatric population is complicated as we know that physiology and the body’s response to disease can be different between adult and pediatric patients. iNO has been demonstrated to improve outcomes in term and near-term infants with hypoxic respiratory failure associated with pulmonary hypertension. Recently, Bronicki et al. published a prospective randomized control trial investigating the impact of iNO on the pediatric patient population with acute respiratory failure. In this study, a benefit of decreased duration of mechanical ventilation and an increased rate of ECMO-free survival was demonstrated in patients who were randomized to receiving iNO, suggesting that there may be benefit to the use of iNO in pediatric ARDS (PARDS) that has not been demonstrated in adults. iNO has repeatedly been shown to transiently improve oxygenation in all age groups, and yet neonates and pediatric patients have shown improvement in other outcomes that have not been seen in adults. The mechanism that explains improvement with the use of iNO in these patient populations are not well understood but does not appear to be solely a result of sustained improvement in oxygenation. There are physiologic studies that suggest alternative mechanisms for explaining the positive effects of iNO, such as platelet aggregation inhibition and reduction in systemic inflammation. Hence, the role of iNO by various mechanisms and in various age groups warrants further investigation.

Abstract 2614: Surgical weight loss via sleeve gastrectomy, but not a low-fat diet, reverses the pro-tumorigenic effects of obesity

Abstract Background: Obesity is associated with increased incidence of basal-like breast cancer (BLBC), the most aggressive and lethal breast cancer subtype. Epidemiological data is conflicting regarding whether weight loss offers protection against BLBC in obese women; only interventions that typically result in significant sustained weight loss, such as bariatric surgery, produce a consistent anti-cancer benefit. Purpose: We sought to determine the differential effects of surgical and non-surgical weight loss interventions on inflammation, metabolic hormones and tumor burden in a mouse model of pre-menopausal breast cancer. Methods: Mice were fed a low fat control or high fat diet-induced obesity (DIO) regimen for 15 weeks to model chronic obesity. Diet-induced obese mice (n = 75) were randomized to receive either a surgical weight loss intervention (sleeve gastrectomy) or dietary weight loss intervention (switch to low fat control diet), resulting in formerly obese (FOb)-Surg or FOb-Diet mice, respectively. Additionally, a subset of mice remained on the DIO diet (Obese, n = 25), with another subset of normoweight control mice (Con, n = 25) maintained on a low fat diet throughout the study. FOb-Surg and FOb-Diet mice lost a nearly identical amount of weight and body fat; both groups had significantly lower weight and percent body fat than Con. Four weeks after weight stabilized, all mice on study were orthotopically injected with E0771 mammary tumor cells, which model BLBC. Results: At study endpoint, the average tumor weight in FOb-Surg mice was statistically equivalent to normoweight control mice. However, the average tumor weight in FOb-Diet mice was significantly greater than controls and statistically equivalent to the Obese mice. Furthermore, FOb-Surg mice had statistically lower levels of serum interleukin-6 and insulin compared to FOb-Diet, suggesting that in obese mice sleeve gastrectomy, relative to diet-induced weight loss, more effectively reduced obesity-associated inflammation, hyperinsulinemia and mammary tumor growth. Conclusion: Our results suggest that the strong anti-cancer benefits seen with bariatric surgery may be related to a significant reduction in systemic inflammation and growth factor signaling, which did not occur with non-surgical weight loss despite an equivalent amount of weight and body fat loss in FOb-Diet mice. Identifying the mechanisms underlying the protective effects of bariatric surgery against breast cancer could help identify new targets and strategies for breaking the obesity-cancer link. Citation Format: Emily L. Rossi, Laura W. Bowers, Subreen A. Khatib, Laura A. Smith, Steven S. Doerstling, Alfor Lewis, Randy J. Seeley, Stephen D. Hursting. Surgical weight loss via sleeve gastrectomy, but not a low-fat diet, reverses the pro-tumorigenic effects of obesity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2614.

Improvement of the efficiency of treatment in patients with coronary artery disease and metabolic syndrome after percutaneous coronary intervention for acute coronary syndrome without ST-segment elevation.

The paper presents original data on improvement of effectiveness of treatment (reduction of systemic inflammation, stabilization of lipid metabolism, improvment of quality of life) in patients with coronary artery disease (CAD) and metabolic syndrome (MS), who underwent primary percutaneous coronary intervention (PCI) for acute coronary syndrome without ST-segment elevation (ACS nST) by adding quercetin to basic therapy, 40 mg 3 times a day during the 12,07 ± 1,51 months. The reduction of a high sensitive C-reactive proteins (hs-CRP), (2,51 ± 0,93, nmol / L., versus 3,12 ± 0,43, nmol / L.), (p = 0,0007) and low-density lipoproteins (LDL), (4,01 ± 0,36, mmol / L., versus 4,29 ± 0,71, mmol / L.), (p=0,049) in the main group II (n = 33) as compared with the control group I (n=31), respectively,as well as thrombin: 5,96 ± 1,89, ng / mL. in group I as compared with 3,91 ± 1,43, ng / mL. in group II, (p=0,0002) was revealed. High density lipoproteins (HDL) were significantly greater (p = 0,049) in the group II (1,35 ± 0,41, mmol / L.) in comparison with the group I (1,17 ± 0,34, mmol / L.).

Abstract 455: Fimasartan Reduced Carotid Atherosclerosis Progression After Mechanical Injury in ApoE Knockout Mouse

Aim: The beneficial effects of angiotensin receptor blockers (ARBs) in atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan in reducing atherosclerosis progression and systemic inflammation after carotid artery injury in ApoE knockout mouse. Methods: Male ApoE knockout mice were randomly allocated to Group 1 (without carotid artery injury, n =20), Group 2 (without carotid artery injury + fimasartan, n =21), Group 3 (carotid artery injury, n =25) and Group 4 (carotid artery injury + fimasartan, n =24). Fimasartan (3mg/kg in distilled water) was orally injected on daily basis, and left carotid artery injury was induced with 0.014 inch guidewire. At 28 days, hematoxylin & eosin and elastic stains were used to measure cross-sectional atherosclerotic plaque from carotid artery. Moreover, inflammatory markers such as MMP9, IL-6, TNFα and ICAM were analyzed by ELISA, and anti-inflammatory cytokines such as IL-10 was measured in peripheral blood. Results: Histomorphometric staining showed significantly reduced neointimal hyperplasia in Group 2 (2.30±0.66%) compared to Group 1 (12.31±2.97%, p <0.05). In addition, Group 4 (32.03±4.62%) showed significantly reduced neointimal hyperplasia compared to Group 3 (50.06±7.50%, p <0.05). All fimasartan treated groups revealed decreased smooth muscle cell proliferation and CD68+ macrophages in carotid artery. Furthermore, inflammatory cytokines such as MMP9 and IL-6 were significantly lower in Group 4 (0.32±0.02ng/mL and 11.68±2.13pg/mL) compared to Group 3 (0.54±0.13ng/mL and 16.68±3.03pg/mL, p <0.05, respectively). In particular, TNFα and ICAM at were significantly decreased in Group 2 (5.83±2.28pg/mL and 3.76±0.84ng/mL) and Group 4 (7.32±0.95pg/mL and 5.04±1.47ng/mL) compared to Group 1 (6.64±1.34pg/mL and 4.42±0.88ng/mL) and Group 3 (9.28±1.57pg/mL and 6.31±1.60ng/mL, p <0.05, respectively). IL-10 increased significantly in Group 4 (29.20±0.52pg/mL) compared to Group 3 (26.18±1.14pg/mL, p <0.05). Conclusions: Fimasartan reduced neointimal hyperplasia with decreases in macrophages in carotid atherosclerotic plaque and with reductions in systemic inflammation in ApoE knockout mice.

Effects of Surgical vs. Non-Surgical Weight Loss on Mammary Tumor Burden

Abstract Background: Obesity is associated with increased incidence of basal-like breast cancer (BLBC), the most aggressive and lethal breast cancer subtype. Epidemiological data is conflicting on whether weight loss offers protection against BLBC in obese women; only interventions that typically result in significant sustained weight loss, such as bariatric surgery, produce a consistent anti-cancer benefit. Purpose: We sought to determine the differential effects of surgical and non-surgical weight loss interventions on inflammation, metabolic hormones and tumor burden in a mouse model of pre- menopausal breast cancer. Methods: Mice were fed a low fat control (Con) or high fat diet-induced obesity (DIO) regimen for 15 weeks to model chronic obesity. Obese mice were then randomized to continue the DIO diet (Obese) or receive a surgical or diet weight loss intervention, resulting in formerly obese (FOb)-Surg or FOb-Diet, respectively. FOb-Surg mice were subject to sleeve gastrectomy (∼70% of the stomach excised), while FOb-Diet mice received a low fat diet. FOb-Surg and FOb-Diet mice normalized body weight and body fat percentage to levels seen in the Con group. After weights stabilized, all mice were orthotopically injected with E0771 mammary tumor cells, which model BLBC. Results: At study endpoint, the average tumor weight in FOb-Surg mice was statistically equivalent to Con mice that maintained a healthy weight throughout study. However, the average tumor weight in FOb-Diet mice was statistically equivalent to Obese mice, both groups significantly greater than Con mice. Additionally, FOb-Surg had statistically lower serum insulin and interleukin-6 compared to FOb-Diet and Obese mice, suggesting that the sleeve gastrectomy more effectively reduced obesity-associated inflammation. Conclusion: Our results suggest that the anti-cancer benefit seen with bariatric surgery may be related to a significant reduction in systemic inflammation and growth factor signaling, which did not occur with non-surgical weight loss despite an equivalent amount of weight and body fat loss in FOb-Diet mice. Identifying the mechanisms underlying the protective effects of bariatric surgery against breast cancer could help identify new targets and strategies for breaking the obesity-cancer link.

Using Gene Expression Analysis to Examine Changes in Loneliness, Depression and Systemic Inflammation in Lonely Chronically Ill Older Adults.

PurposeThe purpose of this study was to evaluate the effectiveness of LISTEN (Loneliness Intervention) on loneliness, depression, physical health, systemic inflammation, and genomic expression in a sample of lonely, chronically ill, older adults.MethodsThis was a prospective, longitudinal randomized trial of LISTEN, a novel intervention based on theories of narrative and cognitive restructuring to target specific aspects of loneliness. Twenty-three older, lonely, chronically ill adults were recruited from a family medicine clinic in West Virginia. Participants were randomized to two groups, 13 in LISTEN group (Loneliness Intervention) and 10 in attention control (healthy aging education). Participants attended an enrollment session where they completed consent, survey data (including sociodemographics and chronic illness diagnoses), baseline physical measures, and blood sampling for gene expression analysis. After completing the 5 weekly sessions, all participants attended a 12 week post data collection meeting (17 weeks post-baseline) for survey completion, physical measures and blood sampling.ResultsThe results of this study show that the LISTEN intervention improves measures of physical and psychosocial health. Specifically, subjects enrolled in LISTEN showed reductions in systolic blood pressure, as well as decreased feelings of loneliness and depression. These changes may be due, in part, to a reduction in systemic inflammation, as measured by interleukin-2.ConclusionThis study provides support for the use of LISTEN in reducing loneliness in chronically ill, older adults. Further, while some of our results are inconclusive, it provides rationale to expand our study population to evaluate the relationship between loneliness and systemic inflammation. In the future, enhancing knowledge about the relationships among loneliness, chronic illness, systemic inflammation, and gene expression of these particular targets, and how these relationships may change over time with intervention will inform translation of findings to clinical settings.

Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s.

Among patients with HIV infection, changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy (ART) may be related to changes in body composition or biomarkers of inflammation. ACTG A5224s was a substudy of A5202, which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or ritonavir-boosted atazanavir. This analysis explored changes in cystatin C from 0 to 96 weeks. Of the 269 subjects, 85% were male and 66% white non-Hispanics; baseline mean CD4 count was 236 cells per cubic millimeter and cystatin C was 0.89 mg/L. Cystatin C decreased significantly within each arm; however, ritonavir-boosted atazanavir attenuated the beneficial effects of ART on cystatin C compared to EFV. Compared to ABC/3TC, TDF/FTC led to a marginally significant attenuation for percent change analyses only. Higher baseline body mass index and HIV RNA were associated with larger reductions in cystatin C in multivariable models. At baseline, cystatin C was positively correlated with high-sensitivity C-reactive protein (Spearman r = 0.25), interleukin 6 (r = 0.34), soluble intercellular adhesion molecule (r = 0.36), soluble vascular cell adhesion molecule (r = 0.54), tumor necrosis factor α (r = 0.57), and soluble TNF-α receptor I (r = 0.70, all P < 0.001). Reductions in cystatin C from 0 to 96 weeks correlated with reductions in all inflammatory biomarkers (r = 0.39-0.58, P < 0.001) except for high-sensitivity C-reactive protein (r = 0.01, P = 0.89) and IL-6 (r = 0.08, P = 0.24). The beneficial effect of ART on cystatin C concentrations is attenuated by boosted ATV when compared to EFV. Reductions in cystatin C after ART are associated with reductions in systemic inflammation.

Sex differences in the impact of the Mediterranean diet on systemic inflammation

BackgroundSome intervention trials have reported a reduction in systemic inflammation with the Mediterranean diet (MedDiet) while others have observed no effect. Despite the fact that sex differences have been highlighted in the inflammatory regulation, it is still not known whether MedDiet exerts similar effects on systemic inflammation in men and women. The aim of this study was therefore to investigate sex differences in the effects of the MedDiet on high-sensitivity C-reactive protein (hs-CRP).FindingsParticipants were 35 men and 27 premenopausal women (24–53 years) presenting a slightly deteriorated lipid profile. All foods were provided to participants during a 4-week isocaloric MedDiet. At baseline, women had higher hs-CRP concentrations than men (P = 0.03). No sex difference was observed in hs-CRP response to the MedDiet (P for sex-by-time interaction = 0.36), with both men and women experiencing no change (respectively P = 0.62 and P > 0.99). When subgroups were formed according to hs-CRP concentration before the MedDiet phase, men with elevated baseline values (≥2 mg/l) experienced a reduction in hs-CRP over time with the MedDiet (−26.5 %) while an increase was observed in men with lower baseline values (+96.6 %; P for group-by-time interaction = 0.02). This pattern of change was not observed in women.ConclusionsResults from this controlled feeding study suggest that men and women have similar effects from the MedDiet on systemic inflammation. The individual’s overall inflammatory status seems to influence these effects, but only in men.Trial registrationThis clinical trial was registered at www.clinicaltrials.gov as NCT01293344.

The Impact of a Polyphenol Treatment on TNF‐α‐Induced Cytokine Release from C2C12 Myotubes

Tumour necrosis factor –alpha (TNF‐α) promotes skeletal muscle dysfunction and the effects of systemic increases in cytokines can be exacerbated by further local production of pro‐inflammatory cytokines. Increased levels of dietary polyphenols including resveratrol, Epigallocatechin gallate (EGCG) and curcumin are associated with a reduction in systemic inflammation and may therefore alleviate symptoms of muscle dysfunction. We hypothesised that treatment of C2C12 myotubes with TNF‐α would result in increased production of cytokines by muscle and that prior treatment of myotubes with physiological levels of dietary polyphenols would protect against this. C2C12 myotubes were pre‐treated with 1µM or 10 µM of resveratrol, EGCG or curcumin for 24 hours followed by 5ng/ml or 25ng/ml TNF‐α for 24 hours, with appropriate controls. Release of pro‐inflammatory cytokines IL‐6, MCP‐1/CCL2, RANTES/CCL5 and Keratinocyte Chemoattractant (KC) from C2C12 muscle cells was significantly increased in response to 5 and 25ng/ml TNF‐α (p&lt;0.05) compared with untreated cells. Pre‐treatment with 1µM resveratrol significantly reduced the TNF‐α‐induced release of IL‐6, MCP‐1, RANTES/CCL5 and KC from C2C12 cells (p&lt;0.5). These data suggest that resveratrol may be a potent anti‐inflammatory treatment to reduce the local effects of increased systemic TNF‐α in muscle. Funded by BBSRC and the ME Association.

Induction of Heat Shock Proteins in the Therapy of Type 2 Diabetes and Metabolic Syndrome

Induction of Heat Shock Proteins in the Therapy of Type 2 Diabetes and Metabolic Syndrome

Toll-like receptor 4 regulates platelet function and contributes to coagulation abnormality and organ injury in hemorrhagic shock and resuscitation.

Growing evidence indicates that the presence of toll-like receptor 4 (TLR4) on platelets is a key regulator of platelet number and function. Platelets exposed to TLR4 agonists may serve to activate other cells such as neutrophils and endothelial cells in sepsis and other inflammatory conditions. The functional significance of platelet TLR4 in hemorrhagic shock (HS), however, remains unexplored. Using thromboelastography and platelet aggregometry, we demonstrate that platelet function is impaired in a mouse model of HS with resuscitation. Further analysis using cellular-specific TLR4 deletion in mice revealed that platelet TLR4 is essential for platelet activation and function in HS with resuscitation and that platelet TLR4 regulates the development of coagulopathy after hemorrhage and resuscitation. Transfusion of TLR4-negative platelets into mice resulted in protection from coagulopathy and restored platelet function. Additionally, platelet-specific TLR4 knockout mice were protected from lung and liver injury and exhibited a marked reduction in systemic inflammation as measured by circulating interleukin-6 after HS with resuscitation. We demonstrate for the first time that platelet TLR4 is an essential mediator of the inflammatory response as well as platelet activation and function in HS and resuscitation.

SAT0448 Interleukin-1 Dual Variable–Domain Immunoglobulin Reduces Multiple Imflammatory Markers in Knee Osteoarthritis Patients

BackgroundOsteoarthritis (OA) may comprise multiple phenotypes, one of which is inflammation-driven OA. Consequently, a selected subpopulation of OA patients may benefit from optimally targeted anti-inflammatory treatment. Interleukin-1 (IL-1) is a...

Importance of the Kidney, Vessels, and Heart with Administration of β2 Adrenergic Receptor Agonists in Patients Susceptible to Acute Respiratory Distress Syndrome

From the Authors: We thank Drs. Snyder and Johnson for their insightful interest in our recent trial article (1). We agree with them that there are many potentially important nonbronchodilator effects of β-agonists, including stimulation of alveolar fluid clearance, effects upon inflammatory cells, and potentially promoting alveolar epithelial repair responses via MMP-9 (2–5). The wealth of supporting data from translational and animal/preclinical studies drove the hypothesis that β-agonists might work as a therapeutic or preventative agent in patients with or at risk of acute respiratory disease (ARDS). Unfortunately, as has been so often the case with developing new strategies for therapy in ARDS, translation of these findings into clinical benefits has been unsuccessful, with the BALTI-2 study finding an increased risk of death in patients with ARDS treated with intravenous β-agonists (6). In their elegant discussion, Snyder and Johnson suggest that deleterious effects of β-agonists upon the kidney may have counteracted any beneficial effects of β-agonists upon alveolar fluid clearance in patients with ARDS. We agree that the effects of β2-agonists upon renal sodium handling are important to consider. We reported no difference in daily fluid balance in the phase 2 BALTI-1 paper (7) but have no additional unpublished data from BALTI-2 (6) or BALTI-prevention (1) to help shed light on this action. However, we note that when intravenous β2-adrenergic agonists were used for tocolysis during pregnancy, they have been associated with reduced sodium, potassium, and water excretion, leading to a reduced hematocrit and intravascular hypervolemia (8, 9) and development of maternal pulmonary edema (10). Finally, we suggest that, although our BALTI-prevention trial did not reduce the incidence of ARDS, we did demonstrate some findings worthy of future study. We found that inhaled salmeterol resulted in a reduction in systemic inflammation, which resulted in reduced alveolar epithelial barrier dysfunction perioperatively. The magnitude of the effects was not sufficient to prevent postoperative ARDS but did significantly reduce the incidence of reported postoperative pneumonia We suggest, therefore, that salmeterol protected the alveolar epithelium in patients undergoing esophagectomy by reducing inflammatory and epithelial damage during injurious one-lung ventilation. We agree with Snyder and Johnson that combination therapies, targeting different mechanisms implicated in the development of ARDS, are likely to be needed to successfully treat and prevent ARDS.

Reductions in C‐reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training

BackgroundReductions in skeletal muscle mass and increased adiposity are key elements in the aging process and in the pathophysiology of several chronic diseases. Systemic low grade inflammation associated with obesity has been shown to accelerate the age-related decline in skeletal muscle. The aim of this investigation was to determine the effects of 12 months of progressive resistance training (PRT) on systemic inflammation, and whether reductions in systemic inflammation were associated with changes in body composition. We hypothesized that reductions in systemic inflammation following 12 months of PRT in older adults with type 2 diabetes would be associated with reductions in adiposity and increases in skeletal muscle mass.MethodsParticipants (n = 103) were randomized to receive either PRT or sham-exercise, 3 days a week for 12 months. C-reactive protein (CRP) was used to assess systemic inflammation. Skeletal muscle mass and total fat mass were determined using bioelectrical impedance.ResultsTwelve months of PRT tended to reduce CRP compared to sham exercise (β = −0.25, p = 0.087). Using linear mixed-effects models, the hypothesized relationships between body composition adaptations and CRP changes were significantly stronger for skeletal muscle mass (p = 0.04) and tended to be stronger for total fat mass (p = 0.07) following PRT when compared to sham-exercise. Using univariate regression models, stratified by group allocation, reductions in CRP were associated with increases in skeletal muscle mass (p = 0.01) and reductions in total fat mass (p = 0.02) in the PRT group, but not in the sham-exercise group (p = 0.87 and p = 0.32, respectively).ConclusionsWe have shown for the first time that reductions in systemic inflammation in older adults with type 2 diabetes following PRT were associated with increases in skeletal muscle mass. Furthermore, reductions in CRP were associated with reductions in adiposity, but only when associated with PRT. Lifestyle interventions aimed at reducing systemic inflammation in older adults with type 2 diabetes should therefore incorporate anabolic exercise such as PRT to optimize the anti-inflammatory benefits of favorable body composition adaptations.

Reduction in Systemic Inflammation by the PDE4 Inhibitor Roflumilast in Patients With COPD

Reduction in Systemic Inflammation by the PDE4 Inhibitor Roflumilast in Patients With COPD

Impact of weight loss on markers of systemic inflammation in obese Saudi children with asthma

Weight loss studies were conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. To measure the effects of weight loss on markers of systemic inflammation in obese children with bronchial asthma. Eighty obese children with bronchial asthma (42 boys, and 38 girls) with mean age 13.86 ± 3.21 years were divided into two equal groups. The training group received diet regimen, exercise training in addition to the medical treatment for two months, where the control group received the medical treatment only. There was a 17.5%, 15.5%, 22.4%, 14.1% and 15.9% reduction in mean values of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), Leptin and body mass index (BMI) respectively and 38.7 % increase in mean values of adiponectin in the training group. While, there was a 0.7%, 9.0%, 2.8%, 1.6% and 1.2% increase in mean values of TNF-alpha, IL-6, IL-8, Leptin and BMI respectively and 3.9% decrease in mean values of adiponectin in the control group. The mean values of TNF-alpha, IL-6, IL-8, Leptin and BMI was decreased and adiponectin was increased significantly in the training group, however the results of the control group were not significant. Also, there were significant differences between both groups at the end of the study. Weight loss improves markers of systemic inflammation in obese Saudi children with bronchial asthma.

OP0129 Effect of low dose oral prednisolone on symptoms and systemic inflammation in older adults with moderate to severe knee osteoarthritis: A randomized placebo-controlled trial

BackgroundOsteoarthritis (OA), a common disabling condition, is the commonest type of arthritis worldwide. Knee OA is the 4th leading cause of disability in women. Pain is the leading symptom and...

The Effect of Vitamin D Supplementation on Glycemic Control and Body Mass Index in the Obese, Vitamin D Deficient Adult with Type 2 Diabetes Mellitus: A Systematic Review Protocol

The Effect of Vitamin D Supplementation on Glycemic Control and Body Mass Index in the Obese, Vitamin D Deficient Adult with Type 2 Diabetes Mellitus: A Systematic Review Protocol

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes.

Class B Scavenger Receptor Types I and II and CD36 Targeting Improves Sepsis Survival and Acute Outcomes in Mice

Class B scavenger receptors (SR-Bs), such as SR-BI/II or CD36, bind lipoproteins but also mediate bacterial recognition and phagocytosis. In evaluating whether blocking receptors can prevent intracellular bacterial proliferation, phagocyte cytotoxicity, and proinflammatory signaling in bacterial infection/sepsis, we found that SR-BI/II- or CD36-deficient phagocytes are characterized by a reduced intracellular bacterial survival and a lower cytokine response and were protected from bacterial cytotoxicity in the presence of antibiotics. Mice deficient in either SR-BI/II or CD36 are protected from antibiotic-treated cecal ligation and puncture (CLP)-induced sepsis, with greatly increased peritoneal granulocytic phagocyte survival (8-fold), a drastic diminution in peritoneal bacteria counts, and a 50-70% reduction in systemic inflammation (serum levels of IL-6, TNF-α, and IL-10) and organ damage relative to CLP in wild-type mice. The survival rate of CD36-deficient mice after CLP was 58% compared with 17% in control mice. When compensated for mineralocorticoid and glucocorticoid deficiency, SR-BI/II-deficient mice had nearly a 50% survival rate versus 5% in mineralo-/glucocorticoid-treated controls. Targeting SR-B receptors with L-37pA, a peptide that functions as an antagonist of SR-BI/II and CD36 receptors, also increased peritoneal granulocyte counts, as well as reduced peritoneal bacteria and bacterium-induced cytokine secretion. In the CLP mouse sepsis model, L-37pA improved survival from 6 to 27%, reduced multiple organ damage, and improved kidney function. These results demonstrate that the reduction of both SR-BI/II- and CD36-dependent bacterial invasion and inflammatory response in the presence of antibiotic treatment results in granulocyte survival and local bacterial containment, as well as reduces systemic inflammation and organ damage and improves animal survival during severe infections.