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Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. Study Design: Controlled laboratory study. Methods: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography–tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. Results: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P ≤.0001) and docosahexaenoic acid (P ≤.0001) and the pro-resolving lipid mediators 17– and 14–hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P =.0019 and P ≤.0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9–, 11,12–, and 14,15–dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P =.0004, R 2 = 0.251; P =.0002, R 2 = 0.278; and P =.0012, R 2 = 0.214, respectively). Conclusion: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. Clinical Relevance: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Ozone, an allotrope of oxygen, is enjoying an increasing interest in the setting and management of the medical adjunct treatment, which is called, maybe too simplistically, "ozone therapy". Ozone is not a medicine, so the word therapy does not properly fit this gaseous molecule. Like many natural compounds, for example plant flavonoids, even ozone interacts with aryl hydrocarbon receptors (AhRs) and, at low doses, it works according to the paradoxical mechanism of hormesis, involving mitochondria (mitohormesis). Ozone, in the hormetic range, exerts cell protective functions via the Nrf2-mediated activation of the anti-oxidant system, then leading to anti-inflammatory effects, also via the triggering of low doses of 4-HNE. Moreover, its interaction with plasma and lipids forms reactive oxygen species (ROS) and lipoperoxides (LPOs), generally called ozonides, which are enabled to rule the major molecular actions of ozone in the cell. Ozone behaves as a bioregulator, by activating a wide population of reactive intermediates, which usually target mitochondria and their turnover/biogenesis, often leading to a pleiotropic spectrum of actions and behaving as a tuner of the fundamental mechanisms of survival in the cell. In this sense, ozone can be considered a novelty in the medical sciences and in the clinical approach to pharmacology and medical therapy, due to its ability to target complex regulatory systems and not simple receptors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM). Methods: The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined. Results: The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747–0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p <.05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78 mg/L. Conclusion: In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a chronic non-infectious mucosal inflammatory disease caused by an imbalance between reactive oxygen species homeostasis and antioxidant defense systems. Notably, excessive oxidative stress products result in related autoimmune reactions. Further, it activates signaling pathways related to the development of oral lichen planus, as evidenced by the detection of damage to deoxyribonucleic acid, protein, and lipid. Thus, the mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus are numerous and complex. In this review, we first introduce oxidative stress and oxidative products. Then, we summarize the role and possible mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus and present a clinical correlation between oxidative stress and oral lichen planus. Finally, we discuss the current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Vitiligo is a pigmentary disorder resulting from progressive destruction of melanocytes in the skin. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including vitiligo. We aimed to evaluate lipid profile, leptin and C reactive protein (CRP) status among Iranian patients with vitiligo, compared with healthy controls and perused the relationship between abnormal values of these parameters with disease duration and physical characteristics of patients. 40 patients with vitiligo and 40 age-matched and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin and CRP values were recorded and compared. The mean values for nearly all study parameters (except for high-density lipoprotein) were significantly higher in patients with vitiligo, compared with healthy controls, irrespective of age and sex. We could not find any correlation between vitiligo and study parameters, regarding disease severity and extension of lesions; but in patients who have been suffering from vitiligo for more than 5 years, systolic blood pressure, diastolic blood pressure and CRP values were noted to be significantly higher (p<0.001, p=0.003 and p=0.03, respectively). In conclusion, screening of patients with vitiligo in regard to their lipid profile as well as blood pressure should be considered, especially in patients with longer disease duration or those who have other cardiovascular risk factors to prevent morbidity and mortality as a result of developing cardiovascular events. [ABSTRACT FROM AUTHOR]

African American women are more likely to experience preterm birth (<37 completed weeks gestation) compared with White women. African American women are also more likely to live in neighborhoods characterized as disadvantaged (i.e., exhibiting higher rates of vacant housing, poorer property conditions, and more litter and crime) and to experience racial discrimination compared with White women. These chronic stressors have been related to preterm birth (PTB) among African American women. This review focuses on potential stress-related pathways by which neighborhood disadvantage and racial discrimination increase the risk for PTB among African American women. Specifically, we propose cortisol, systemic inflammation, proteome and lipidome profiles, and telomere shortening as potential mediators linking these social determinants of health with PTB among African American women. Examination of these factors and the signaling pathways they contribute to will increase our knowledge of the effects of social determinants of health on PTB for African American women. [ABSTRACT FROM AUTHOR]

Background: Diabetes nephropathy (DN) is a serious diabetic problem that may progress to renal failure. The root of Curcuma longa L., often known as turmeric, provides various health benefits. Bisacurone is a bioactive terpenoid found in small amounts in turmeric that possesses anti-inflammatory and antioxidant properties. The present study focuses on the potential protective effects of bisacurone against DN via reducing renal inflammation, oxidative stress, and apoptosis. Methods: Type 2 diabetes was created in rats by feeding them a high-fat/high-sugar diet for 8 weeks, followed by a low dose of streptozotocin and Bisacurone (50 and 100 μg/kg bisacurone) given for 4 weeks. Results: In diabetic rats, bisacurone reduced hyperglycemia, protected against body weight (BW) loss, lowered renal markers, reduced lipid profile alterations and avoided histological abnormalities. Bisacurone treatment reduced oxidative stress by decreasing malondialdehyde (MDA) levels while enhancing antioxidant defenses through superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. Furthermore, bisacurone treatment activated the renal Nrf2/Keap1 signaling pathway but attenuated the high levels of NFκB p65, TNF-α, IL-1β, IL-6, Cox2, and iNOS. Bisacurone also reduced Bax, caspase-3, caspase-9 and cytochrome c but increased Bcl-2 in the kidneys of diabetic rats. Conclusion: In the present study, bisacurone reduces DN by reducing hyperglycemia, oxidative stress, inflammation, and apoptosis, while also increasing Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

Background: Human dental pulp stem cells (hDPSCs) possess mesenchymal stem cell properties, originating from migrating neural crest cells. hDPSCs have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and ability to differentiate in several cell phenotypes. In this study, we cultured hDPSCs with Y-27632 to observe their biological behaviors changes. Methods: The hDPSCs were separately cultured with Y-27632 (0, 0.156, 0.312, 0.625, 1.25, 2.50, 5, 10, 20, 40 μ m) for 24, 48, 72 h to select the suitable concentration and time using CCK-8. Then, the hDPSCs were cultured with 2.50 μ m Y-27632 for 48 h to analyzed the biological behaviors changes by 5-Ethynyl-2′-deoxyuridine (EdU), plate cloning, transwell, scratch, and Annexin V FITC/PI assays, separately. Additionally, osteogenic calcium nodules and lipid droplets were analyzed using alizarin red staining and oil red O staining, respectively. qRT-PCR was used to analyze the expression of osteogenesis, adipogenesis, stemness maintenance, and inflammation related genes. Results: The hDPSCs proliferation was significantly enhanced after cultured with 2.50 μ m Y-27632 for 48 h, but there was no significant difference in migration and apoptosis. Observation of alkaline phosphatase (ALP) activity, osteogenic and adipogenic differentiation abilities of hDPSCs, Y-27632 treatment clearly decreased the ALP activity and osteogenic differentiation ability, increased the adipogenic differentiation ability. Furthermore, Y-27632 decreased the CD73, CD90, CD105, CD166, TLR4, and NF-κB p65 genes expression, but increased the IL-8 gene expression. Conclusions: The biological behaviors of hDPSCs could be changed when they cultured with Y-27632. [ABSTRACT FROM AUTHOR]

Purpose: The current investigation was carried out to evaluate the efficacy of myricetin in ethanol-induced liver toxicity in Wistar rats. Research Design: Twenty-four rats were randomly divided into four groups with six animals per group. Group-I animals were administered with vehicle (distilled water), Group II, III, and IV were treated orally with sequential (per week) increase in the dose of ethanol (5, 8, 10, and 12 g/kg b wt per week in each group) for 28 days. Myricetin was treated orally to Group-III and IV animals at the respective doses of 25 mg/kg b wt. and 50 mg/kg b wt. Results: Our results showed that myricetin prevented hepatotoxicity by modulating the production of free radicals, ethanol metabolizing enzymes, and inflammatory markers in vivo. Myricetin also helped maintain lipid membrane integrity, oxidant-antioxidant status, and histoarchitecture. Ethanol administration caused elevation in XO, ADH, and CYP2E1 in hepatic tissue, which significantly normalized with myricetin administration. After ethanol administration, there was a steep increase in the hepatotoxicity biomarkers, including ALT, MDA, and AST. The level of cytotoxicity marker LDH also increased after ethanol administration; myricetin administration decreased the level of all these markers. Moreover, myricetin treatment also reduced ethanol-induced inflammatory markers such as NF-κB and IL-6. Conclusion: Findings from the current study demonstrate that myricetin administration prevents alcohol-induced hepatic injury by influencing the metabolism of ethanol, inhibiting oxidative stress, maintaining lipid profile, and suppressing inflammatory markers. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a serious chronic disease in which the oxidant-antioxidant balance is impaired, causing many complications, including hepatopathy. In this study, the effects of short-term and low-dose N-acetylcysteine (NAC) administration on the biochemical, proinflammatory, and oxidative stress parameters in the liver tissue of diabetic rats were investigated. Twenty-four adult male Wistar albino rats weighing approximately 250–300 g were divided into 4 groups (n = 6): Control, Streptozotosin (STZ)-induced diabetes (DM), NAC treatment (60 mg/kg), and STZ-induced diabetes treated with NAC (DM+NAC; 60 mg/kg). NAC treatment was administered intraperitoneally as a single daily dose for 7 days. At the end of the experiment (3 weeks), blood and liver samples were collected for biochemical parameter analysis. Lipid peroxidation, antioxidant parameters, and nitric oxide (NOx) levels were determined by spectrophotometric method. Tissue inflammation parameters were evaluated by ELISA. Lipid peroxidation, proinflammatory cytokines, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values increased significantly with diabetes. NAC treatment significantly decreased serum ALT and AST levels and proinflammatory cytokines in the diabetic group. Liver glutathione (GSH) and NOx levels increased significantly in the DM+NAC group (p < 0.05). While NAC treatment reduced lipid peroxidation in the liver, it improved the inflammatory response and antioxidant status. The beneficial effect of NAC treatment may be due to its antioxidant activity and the resulting increased level of GSH. The results show that low-dose and short-term NAC treatment had a positive effect on oxidative damage and inflammation in liver tissue. NAC can be used as a potential antioxidant in diabetes to prevent hepatopathy. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is associated with an increased risk of cardiovascular disease (CVD). The increased risk of CVD concerns an increased risk of venous thromboembolism (VTE), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), at corresponding relative risks of 2.5, 1.2 and 2.0, respectively, as compared with the general population. Especially young patients under the age of 40 years run a relatively high risk of these complications when compared with the general population. Chronic systemic inflammation causes a hypercoagulable state leading to the prothrombotic tendency characteristic of VTE, and accelerates all stages involved during atherogenesis in ASCVD. Increased awareness of VTE risk is warranted in patients with extensive colonic disease in both ulcerative colitis and Crohn's disease, as well as during hospitalization, especially when patients are scheduled for surgery. Similarly, critical periods for ASCVD events are the 3 months prior to and 3 months after an IBD-related hospital admission. The increased ASCVD risk is not fully explained by an increased prevalence of traditional risk factors and includes pro-atherogenc lipid profiles with high levels of small dense low-density lipoprotein cholesterol particles and dysfunctional high-density lipoprotein cholesterol. Risk factors associated with HF are location and extent of inflammation, female sex, and age exceeding 40 years. A dose-dependent increase of overall CVD risk has been reported for corticosteroids. Immunomodulating maintenance therapy might reduce CVD risk in IBD, not only by a direct reduction of chronic systemic inflammation but possibly also by a direct effect of IBD medication on platelet aggregation, endothelial function and lipid and glucose metabolism. More data are needed to define these effects accurately. Despite accumulating evidence on the increased CVD risk in IBD, congruent recommendations to develop preventive strategies are lacking. This literature review provides an overview of current knowledge and identifies gaps in evidence regarding CVD risk in IBD, by discussing epidemiology, pathogenesis, and clinical management. [ABSTRACT FROM AUTHOR]

Obesity and metabolic syndrome (MetS) are public health problems and are increasing globally. We assessed the differences in lipid profiles through lipid testing, thrombotic and inflammatory parameters, and oxidative stress indexes between overweight and obese patients with MetS in a Turkish adult population. We included 100 obese (body mass index [BMI] >30 kg/m2) patients with MetS (66 women, 34 men, mean age 54.0 ± 10.1 years) and 15 overweight (BMI 25-30 kg/m2) individuals (11 women, 4 men, mean age 50.2 ± 14.5 years) as controls. The group with MetS had significantly higher levels of glycaemia, uric acid, high-sensitivity C-reactive protein, homocysteine, fibrinogen, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, small dense LDL, oxidized LDL, apolipoprotein B (Apo B), lipoprotein (a), small and intermediate high-density lipoprotein (HDL) particles, oxidative stress index, and significantly lower levels of HDL-cholesterol (HDL-C), Apo A, and large HDL particles. In conclusion, obesity with MetS increase atherogenic dyslipidemia and thrombotic, inflammatory and oxidative stress biomarkers. Furthermore, obesity with MetS decreases protective mechanisms of atherosclerosis. We should at least try to prevent overweight individuals from becoming obese with MetS. [ABSTRACT FROM AUTHOR]

Human adenovirus 36 (Ad-36) causes obesity with increased adiposity, in contrast, Ad-36 infection reduces glucose and lipid metabolism; the results, however, are not consistent. In the current study, the effects of Ad-36 infection on glucose and lipid profile and inflammatory markers in Wistar rats were investigated. Sixty male Wistar rats were randomly divided into infected and control groups. Ad-36 virus suspension was injected in the experimental group rats. Blood samples were collected in the beginning and after 12 weeks in both groups. After 12 weeks, a significant improvement was observed in fasting blood glucose, fasting serum insulin, insulin sensitivity, serum triglycerides and total cholesterol in the infected group compared with the non-infected groups. There were no significant differences in inflammatory biomarkers including tumor necrosis factor-α, interleukin 6 and monocyte chemoattractant protein-1 levels between infected and control groups. This study showed that Ad-36 had favorable effects on glycemic and lipid control in infected rats, but inflammatory biomarker levels were similar for 2 groups. Ad-36 infections could potentially be a new way to develop novel antidiabetic and antihyperlipidemic therapeutic agents. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis, like other bacteria belonging to the phylum Bacteroidetes, synthesizes sphingolipids (SLs). However, their exact roles in microbial physiology and their potential role in mediating interactions with their eukaryotic host are unclear. Our working hypothesis for this study was that synthesis of SLs (host-like lipids) affords a mechanism that allows P. gingivalis to persist in homeostasis with its host. In a previous study, we deleted a gene (PG1780 in strain W83) predicted to encode a serine palmitoyl transferase (SPT)-the enzyme that catalyzes the first conserved step in the synthesis of SLs-and we determined that the mutant was unable to synthesize SLs. Here, we characterized the SPT enzyme encoded by PG1780, analyzed the impact of SPT deletion on P. gingivalis gene expression (RNA-Seq analysis), and began to define the impact of SL synthesis on its interactions with host cells. Enzymatic analysis verified that the protein encoded by PG1780 is indeed an SPT. RNA-Seq analysis determined that a lack of SL synthesis results in differential expression of extracytoplasmic function sigma factors, components of the type IX secretion system (T9SS), and CRISPR and cas genes. Our data demonstrate that when human THP1 macrophage-like cells were challenged with the wild type (W83) and the SL-null mutant (W83 ΔSPT), the SL-null strain elicited a robust inflammatory response (elevated IL-1β, IL-6, IL-10, IL-8, RANTES, and TNFα) while the response to the parent strain W83 was negligible. Interestingly, we also discovered that SLs produced by P. gingivalis can be delivered to host cells independent of cell-to-cell contact. Overall, our results support our working hypothesis that synthesis of SLs by P. gingivalis is central to its ability to manipulate the host inflammatory response, and they demonstrate the integral importance of SLs in the physiology of P. gingivalis. [ABSTRACT FROM AUTHOR]

Chronic inflammation coupled with cardiovascular disease (CVD) risk factors influences the progression of atherosclerosis in systemic lupus erythematosus (SLE). High-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) are associated with the risk of CVD in the general population, but their associations with CV risk and disease activity in SLE are unclear. In this cross-sectional study (N = 139 SLE patients, mean age = 45.27 ± 13.18 years), we investigated associations between hs-CRP and Hcy levels and disease activity, damage accrual, and CVD risk in SLE. Disease activity and damage accrual were measured with the SLE Activity Index 2000 (SLEDAI-2K), the Systemic Lupus Erythematosus International Collaborating Clinics Group/American College of Rheumatology damage index (SDI), and anti-double-stranded DNA antibodies (anti-dsDNA). CVD risk factors of obesity, diabetes mellitus, hypertension, blood lipids, and ankle–brachial index were collected. Linear regression analysis and one-way analysis of variance were used to analyze relationships of hs-CRP and Hcy with SLE activity, damage accrual, and CVD risk factors. Results: hs-CRP correlated significantly with SLEDAI-2K (p =.036), SDI (p =.00), anti-dsDNA titers (p =.034), diabetes (p =.005), and obesity (p =.027). hs-CRP and Hcy correlated with triglyceride (TG) levels (p =.032 and p <.001, respectively), TG/high-density lipoprotein cholesterol index (p =.020 and p =.001, respectively), and atherogenic index of plasma (p =.006 and p =.016, respectively). hs-CRP levels >3 mg/L correlated with SDI score (p =.012) and several CVD risk factors. Discussion: Findings suggest SLE patients with elevated hs-CRP and/or Hcy have a higher prevalence of CVD risk factors. [ABSTRACT FROM AUTHOR]

Chronic consumption of diets high in fat leads to obesity and can negatively affect brain function. Rodents made obese by long-term maintenance on a high-fat diet have worse outcome after experimental stroke. High-fat consumption for only three days does not induce obesity but has rapid effects on the brain including memory impairment. However, the effect of brief periods of high-fat feeding or high-fat consumption in the absence of obesity on stroke is unknown. We therefore tested the effect of an acute period of high-fat feeding (three days) in C57B/6 mice on outcome after middle cerebral artery occlusion (MCAo). In contrast to a chronic high-fat diet (7.5 months), an acute high-fat diet had no effect on body weight, adipose tissue, lipid profile or inflammatory markers (in periphery and the brain). Three days of high-fat feeding impaired glucose tolerance, increased plasma glucose and insulin and brain expression of the glucose transporter GLUT- 1. Ischaemic damage was increased (48%) in mice fed an acute high-fat diet, and was associated with a further reduction in GLUT-1 in the ischaemic hemisphere. These data demonstrate that only a brief period of high-fat consumption has a negative effect on glucose homeostasis and worsens outcome after ischaemic stroke. [ABSTRACT FROM AUTHOR]

Background: This paper describes and analyzes the cellular and molecular mechanisms underlying atherosclerosis development. In particular, the roles of monocytes/macrophages, smooth muscle cells, and vascular endothelium in the formation of stable/unstable atheromatous plaques, and the contributions of some processes to atheroma formation.Methods and Results: In this study we analyzed endothelium: function, dysfunction, and involvement into atherogenesis; cell proteins mediating mechanotransduction; proatherogenic role of monocytes; the role of macrophages in the development of unstable atheromatous plaques and smooth muscle cell origin in atherosclerosis. Smooth muscle cell phenotypic switching; their functioning; the ability to retain cholesterol and lipoproteins as well as secretion of pro- and anti-inflammatory molecules and extracellular matrix proteins, their response to extracellular stimuli secreted by other cells, and the effect of smooth muscle cells on the cells surrounding atheromatous plaques are fundamentally important for the insight into atherosclerosis molecular basis.Conclusion: Atheromatous plaque transcriptome studies will be helpful in the identification of the key genes involved in atheroma transformation and development as well as discovery of the new targets for diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days. The migration of inflammatory cells (neutrophils, monocytes, lymphocytes) in the thrombi and injured venous wall, the plasma levels of interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and P-selectin, and local expression of MCP-1 and P-selectin in the venous wall were evaluated by histology, immunohistochemistry, and ELISA examinations. Our data showed that compared with saline and heparin controls, monotherapy of simvastatin and the adjunctive therapy with simvastatin and heparin significantly improved the thrombus resolution and reduced inflammatory cells migration into the venous wall, the release of the inflammatory cell adhesion molecule (P-selectin), inflammatory chemokine (MCP-1) and pleiotropic proinflammatory cytokines (IL-6) into the blood, and the local expression of P-selectin and MCP-1 in the venous wall. Simvastatin targets anti-inflammatory pathways during the resolution phase of a thrombus, providing a therapeutic potential in DVT resolution and post-thrombotic syndrome prevention. [ABSTRACT FROM AUTHOR]

According to recent reports, systemic treatment of rats with methylpalmoxirate (carnitine palmitoyltransferase-1 inhibitor) decreased peroxidation of polyunsaturated fatty acids in brain tissue. This was taken as evidence of mitochondrial β-oxidation in brain, thereby contradicting long-standing paradigms of cerebral metabolism, which claim that β-oxidation of activated fatty acids has minor importance for brain energy homeostasis. We addressed this controversy. Our experiments are the first direct experimental analysis of this question. We fueled isolated brain mitochondria or rat brain astrocytes with octanoic acid, but octanoic acid does not enhance formation of reactive oxygen species, neither in isolated brain mitochondria nor in astrocytes, even at limited hydrogen delivery to mitochondria. Thus, octanoic acid or l-octanoylcarnitine does not stimulate H2O2 release from brain mitochondria fueled with malate, in contrast to liver mitochondria (2.25-fold rise). This does obviously not support the possible occurrence of β-oxidation of the fatty acid octanoate in the brain. We conclude that a proposed inhibition of β-oxidation does not seem to be a helpful strategy for therapies aiming at lowering oxidative stress in cerebral tissue. This question is important, since oxidative stress is the cause of neurodegeneration in numerous neurodegenerative or inflammatory disease situations. [ABSTRACT FROM AUTHOR]

Introduction: Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT. Aim: To follow inflammatory parameters in a cohort of patients with idiopathic DVT. Methods: Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS). Results: The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1. Conclusion: Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT. [ABSTRACT FROM AUTHOR]

Acute or chronic inflammation comprises a highly prevalent type of orofacial pain and is mediated by the generation of endogenous agonists that activate numerous receptors expressed on terminals of trigeminal (TG) nociceptive afferent neurons. One such studied receptor is transient receptor potential vanilloid subtype 1 (TRPV1). TRPV1 is a ligand-gated cation channel that is expressed on a major subclass of nociceptors and is found in many orofacial tissues, including dental pulp. Antagonists to TRPV1 reveal an important role for this channel in mediating hypersensitivity in preclinical models of inflammatory or neuropathic pain. Recent studies have demonstrated that endogenous TRPV1 agonists are generated by oxidation of omega-6 polyunsaturated fatty acids, including both linoleic acid and arachidonic acid. A major mechanism triggering the release of oxidative linoleic acid metabolites (OLAMs) and oxidative arachidonic acid metabolites (OAAMs) is the action of oxidative enzymes. Oxidative enzymes such as cytochrome P450 isozymes are rapidly upregulated in TG neurons after orofacial inflammation and increase the capacity of TG neurons to generate OLAMs. Cytochrome P450 isozymes are also increased in immune cells in irreversibly inflamed human dental pulp, and extracts of this tissue have significantly increased capacity to generate OLAMs. Together, these studies point to a novel pain mechanism involving the enzymatic generation of endogenous OLAM and OAAM agonists of TRPV1. This finding provides a rationale for an entirely new class of analgesics by inhibition of oxidative enzyme activity. [ABSTRACT FROM AUTHOR]

Macrophages (Mφs) play a critical role in the defense against pathogens, orchestrating the inflammatory response during injury and maintaining tissue homeostasis. During these processes, macrophages encounter a variety of environmental conditions that are likely to change their gene expression pattern, which modulates their function. In this study, we found that murine Mφs displayed two different subpopulations characterized by differences in morphologies, expression of surface markers and phagocytic capacity under non-stimulated conditions. These two subpopulations could be recapitulated by changes in the culture conditions. Thus, Mφs grown in suspension in the presence of serum were highly phagocytic, whereas subtraction of serum resulted in rapid attachment and reduced phagocytic activity. The difference in phagocytosis between these subpopulations was correlated with the expression levels of FcγR. These two cell subpopulations also differed in their responses to LPS and the expression of surface markers, including CD14, CD86, scavenger receptor A1, TLR4 and low-density lipoprotein receptor. Moreover, we found that the lipid/cholesterol content in the culture medium mediated the differences between these two cell subpopulations. Thus, we described a mechanism that modulates Mφ function depending on the exposure to lipids within their surrounding microenvironment. [ABSTRACT FROM AUTHOR]

Objectives: Research has identified many factors associated with fibromyalgia (FM), but findings have been inconsistent. This study aimed to investigate changes in levels of nitric oxide (NO), inflammatory markers, lipid profile, and cortisol in normaland overweight patients with FM and controls. Since most patients with FM are overweight, we explored possible changes in these markers according to body mass index (BMI). Methods: This preliminary study was performed on serum samples of women with FM and age-matched controls, grouped according to their BMI: 12 normal-weight patients and 12 controls and 13 overweight patients and 8 controls. Ozone-based chemiluminescence assay was used to measure NO. Inflammatory mediators and cortisol were determined by immunoassay. Lipid profile was measured by a spectrophotometric procedure. Functional capacity was assessed by the fibromyalgia impact questionnaire (FIQ). Results: Normal-weight patients showed higher levels of C-reactive protein (CRP) and apolipoprotein B compared to controls (both p < .05). CRP, apolipoprotein B, and triglycerides were higher in overweight patients versus overweight controls (all p < .05) and in overweight versus normal-weight patients (CRP p < .01; apolipoprotein B, triglycerides p < .05). The other markers were unaffected. Apolipoprotein B (r = .762; p < .05) and NO (r = -.921; p < .05) levels correlated with FIQ score in normal-weight patients. CRP level correlated with FIQ (r = .912; p < .05) in overweight patients. Conclusions: CRP and apolipoprotein B, biomarkers linked to cardiovascular events, may be associated with FM-related dysfunction in normal- and overweight women with FM. Their increased levels in these patients may indicate an increased risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Atherosclerosis is recognized as a chronic inflammatory disease. The aim of this study was to examine the role of urinary trypsin inhibitor (UTI) in inflammation response induced by hyperlipidemia in rabbits.Methods: Thirty rabbits after injury of the right iliac artery endothelium were randomly divided into 3 groups: control group, model group, and UTI group. Iliac arteries were isolated and histology was performed on arterial regions that were injured by balloon after 8 weeks. Neointimal thickness (NT) and neointimal to media radio (N/M) were measured. Blood lipids, interleukin 6, and tumor necrosis factor-α were evaluated. Macrophages were evaluated by immunohistochemical analysis. MicroRNA-181b (miR-181b) was measured by reverse transcriptase-polymerase chain reaction.Results: Urinary trypsin inhibitor therapy decreased serum inflammatory factor levels without significant changes in blood lipids. Compared with model group, UTI reduced macrophage infiltration of iliac artery (13.91 ± 2.03% vs 24.21 ± 8.94%, P < .01). Hyperlipidemia reduced the expression of miR-181b and increased NT and N/M ratio. Systemic administration of UTI rescued miR-181b expression and inhibited neointimal formation.Conclusions: Urinary trypsin inhibitor could reduce neointimal hyperplasia by inhibiting inflammatory response induced by hyperlipidemia and may become a potential antiatherosclerosis supplement. [ABSTRACT FROM AUTHOR]

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS (p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND (p<0.001), iOND (p<0.05) and EarlyMS (p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies (p=0.048; p=0.027). Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS. [ABSTRACT FROM AUTHOR]

South Asians (SAs), in their countries or after migration, are at high risk of coronary artery disease (CAD) and mortality compared to other ethnic groups. It has been shown that >90% of CAD global risk could be attributed to 9 modifiable risk factors (RFs) worldwide. However, these conventional RFs may not fully explain this high risk of CAD among SAs. Therefore, attention has been directed toward nonconventional RFs. In this narrative review, we evaluate the conventional and emerging cardiovascular RFs characterizing SAs. These factors may explain the high morbidity and mortality among SAs. Further prospective studies are urgently needed to set algorithms for the optimal management of these RFs in high-risk populations like SAs. [ABSTRACT FROM PUBLISHER]

Resolvins are potent anti-inflammatory mediators derived from ω-3 fatty acids. Results from our previous studies indicated that resolvin D1 (RvD1) blocks pro-inflammatory responses in salivary glands. Furthermore, RvD1 enhances salivary epithelial integrity, demonstrating its potential use for the restoration of salivary gland function in Sjögren’s syndrome (SS). We investigated whether the RvD1 biosynthetic machinery (e.g., cytosolic phospholipase A2, calcium-independent phospholipase A2, 12/15 and 5-lipoxygenase) is expressed in mouse submandibular glands (mSMG), using qPCR and Western blot analyses. Additionally, we determined the localization of RvD1 biosynthetic machinery in mSMG and human minor salivary glands (hMSG), with and without SS, using confocal microscopy. Finally, we measured RvD1 levels in cell supernatants from mSMG cell cultures and freshly isolated mSMG cells, with and without SS, using ELISA. Our results indicate that: (1) RvD1 machinery is expressed in mouse and human salivary glands; (2) polar distribution of RvD1 biosynthetic machinery is lost in hMSG with SS; (3) RvD1 levels in mSMG cell culture supernatants increased with time; and (4) RvD1 levels in mSMG cell supernatants, with and without SS, were similar. These studies demonstrate that the RvD1 biosynthesis machinery is expressed and functional in salivary glands with and without SS. [ABSTRACT FROM PUBLISHER]

Obesity and type 2 diabetes (T2D) are characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been proposed to promote inflammatory responses. Primary Sjögren’s syndrome (SS) is an autoimmune disease characterized by inflammatory mononuclear cell infiltration and destruction of epithelial cells in the salivary and lacrimal glands. IL-6 production and α-fodrin degradation are increased in salivary gland epithelial cells of patients with primary SS. Although previous studies have shown a link between SS and either dyslipidemia or T2D, little is known about the clinical significance of FFAs in primary SS. Here we report that SFAs, but not unsaturated fatty acids, induced IL-6 production via NF-κB and p38 MAPK activation in human salivary gland epithelial cells. Moreover, palmitate induced apoptosis and α-fodrin degradation by caspase-3 activation. Unlike salivary gland epithelial cells, induction of IL-6 production and the degradation of α-fodrin in response to palmitate were undetectable in squamous carcinoma cells and keratinocytes. Taken together, SFAs induced IL-6 production and α-fodrin degradation in salivary gland epithelial cells, implicating a potential link between the pathogenesis of primary SS and SFAs level in plasma. [ABSTRACT FROM PUBLISHER]

Purpose. This study investigates cardiovascular disease risk factor response in adolescents following introduction of brisk walking into curriculum lessons. Design. Quasi-experimental. Setting. School-based. Subjects. An intervention group consisted of 115 (aged 12.4 ± 0.5 y) year eight participants, and 77 (aged 12.1 ± 1.1 y) year seven and year nine participants formed a control. Intervention. An 18-week cross-curricular physical activity intervention was implemented in one secondary school. Measures. Adiposity variables, blood pressure, lipids, lipoproteins, glucose, insulin, high- sensitivity C-reactive protein, high-molecular-weight adiponectin, aerobic fitness, physical activity behavior, and diet were assessed preintervention and postintervention. Analysis. Dependent and independent t-tests. Results. Prevalence of elevated waist circumference (9.8% vs. 6.9%), systolic blood pressure (3.3% vs. 0%), triglycerides (2.5% vs. 1.2%), and reduced high density lipoprotein cholesterol (3.7% vs. 2.7%) decreased in the intervention group. Significant improvements in high density lipoprotein cholesterol to total cholesterol ratio (mean ± SD: 2% ± 4% [confidence interval (Cl)0.05 = 1% to 2%], t80 = -3.5, p = .001) and glucose (-.1 ± .4 mmol/L [Cl0.05 = -.2% to 0%], t79 3.2, p = .002) were evident for the intervention group. Conclusion. The Activity Knowledge Circuit may prove to be a sustainable, effective, and cost-effective strategy to engage schoolchildren in physical activity on a daily basis. A longer- duration intervention is required to fully understand risk factor response in adolescents. [ABSTRACT FROM AUTHOR]

Background: Nasal polyposis represents the end point of multiple inflammatory pathways and controversy continues as to the exact roles of medical and surgical approaches in the management of nasal polyposis. Methods: A combination of both is often required to manage polyps adequately with surgery and intranasal steroids remaining the mainstay of therapy. Results: Fortunately, new technological advances are making surgery safer and more efficient. In the postoperative period, debridement is effective in reducing the formation of adhesions, and topical medications may play a beneficial role in preventing polyp reformation. Conclusion: Additional investigations into the optimal perioperative medical management is needed to ensure optimal surgical outcomes. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) associates with excess cardiovascular risk and there is a need to assess that risk. However, individual lipid levels may be influenced by disease activity and drug use, whereas lipid ratios may be more robust. A cross-sectional cohort of 400 consecutive patients was used to establish factors that influenced individual lipid levels and lipid ratios in RA, using multiple regression models. A further longitudinal cohort of 550 patients with RA was used to confirm these findings, using generalized estimating equations. Cross-sectionally, higher C-reactive protein (CRP) levels correlated with lower levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol ([HDL-C] P ≤ .015), whereas lipid ratios did not correlate with CRP. The findings were broadly replicated in the longitudinal data. In summary, the effects of inflammation on individual lipid levels may underestimate lipid-associated cardiovascular disease (CVD) risk in RA, thus lipid ratios may be more appropriate for CVD risk stratification in RA. [ABSTRACT FROM PUBLISHER]

We hypothesized that tobacco smoke induces alterations to the 3-OH fatty acids present in lipid A in a manner consistent with a microflora of reduced inflammatory potential. Whole saliva samples and full-mouth clinical periodontal recordings were obtained from persons with (22 smokers; 15 non-smokers) and without (14 smokers; 15 non-smokers) chronic periodontitis. Clear differences in the contributions of multiple saturated 3-OH fatty acid species were noted in the group with disease compared with healthy individuals. Increases in the long-chain fatty acids associated with anaerobic bacterial periodontopathogens, particularly 3-OHCi17.0 (146.7%, relative to controls), were apparent. Significant reductions in the 3-OH fatty acids associated with the consensus (high potency) enteric LPS structure (3-OH-C12.0 and 3-OH-C14.0; 33.3% and 15.8% reduction, respectively) were noted in smokers compared with non-smokers with chronic periodontitis. Thus, smoking is associated with specific structural alterations to the lipid-A-derived 3-OH fatty acid profile in saliva that are consistent with an oral microflora of reduced inflammatory potential. These findings provide much-needed mechanistic insight into the established clinical conundrum of increased infection with periodontal pathogens but reduced clinical inflammation in smokers. [ABSTRACT FROM PUBLISHER]

Hypercholesterolemia and associated cardiovascular complications continue to occur in a great number of people. However, certain coastal populations have lower incidence of cardiovascular and other diseases, which may be attributed to regular intake of seaweeds in their diet. Seaweeds contain sulphated polysaccharides (SPS) which demonstrate a wide spectrum of biomedical properties and are phytochemical analogues of mammalian heparin sulphate. This knowledge served as the major impetus for exploring the therapeutic potential of SPS from the brown algae Sargassum wightii and SPS from Fucus vesiculosus in experimental rats against diet-induced hyperlipidemia and associated inflammatory complications. Adult male Wistar rats were divided into six groups with six rats in each. The control group (group I) was left untreated while group II rats were fed with a high cholesterol diet (CCT diet - normal rat chow with 4% cholesterol, 1% cholic acid and 0.5% thiouracil) for 14 days. Rats in groups III and IV received SPS from S. wightii (SW group) and SPS from F vesiculosus (FV group) (5mg/kg b.wt/day, subcutaneously) during the last 7 days, respectively. Rats in groups V and VI were fed with a high cholesterol diet for 14 days and in addition were given SPS from S. wightii (CCT + SW group) and SPS from F vesiculosus (CCT + FV group) at the weight of 5mg/kg b.wt/day, subcutaneously during the last 7 days, respectively. The adverse effects of hypercholesterolemia were evident from increased levels of serum lipid status and inflammatory complications manifested by augmented levels of plasma tumour necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase (COX-2) and lysosomal enzymes. Treatment with algal SPS considerably restored the above abnormalities. SPS from S. wightii and SPS from F vesiculosus were almost equally effective in mitigating hypercholesterolemia and related inflammatory complications. [ABSTRACT FROM AUTHOR]

Objective: Visfatin is a novel adipokine initially reported to exhibit insulin-mimetic effects that increase insulin sensitivity. Further studies indicate it may also be associated with obesity, serum lipids, and systemic inflammation. At the current time, the role of genetic variation in the visfatin gene (NAMPT) on these parameters is not clear. In the present study, we examined the association between 10 SNPs in NAMPT and insulin resistance, obesity, serum lipids and hsCRP levels. Research design and methods: A total of 1838 subjects (413 men, 1425 women) were recruited from the ongoing CODING Study. All subjects were from the genetically homogenous population of Newfoundland and Labrador, Canada. BMI, waist circumference, waist-to-hip ratio, and body fat percentage (determined using DXA) were measured for all subjects. Serum glucose, insulin, HOMAIR, HOMAβ, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and hsCRP were also determined after a 12-hour fast. Ten SNPs in NAMPT were genotyped using TaqMan validated or functionally tested SNP genotyping assays including rs7789066 (A > G 5' flanking region), rs3801266 (A > G intron), rs6963243 (G > C intron), rs2058539 (A > C intron), rs6947766 (C > T intron), rs4730153 (G > A intron), rs10808150 (G > A intron), rs2098291 (C > T intron), rs10953502 (T > C intron), and rs10953501 (A . G 3' UTR). Results: We observed no significant associations between any of the variants sites and any parameter of insulin resistance, body composition, serum lipids or hsCRP under an additive model with age and gender included as covariates. This was also true when both dominant and recessive models were applied. Conclusions: Our results do not support a significant role for variations in NAMPT with differences in the measured variables in the Newfoundland population. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain (NP) is partially mediated by neuroinflammatory mechanisms, and also modulates local neurogenic inflammation. Dietary lipids, in particular the total amount and relative proportions of polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families, have been reported to modify the threshold for thermal and mechanical allodynia in the partial sciatic nerve ligation model of NP in rats. The effects of dietary lipids on other popular NP models, such as the chronic constriction injury (CCI), have not yet been examined. It is also unknown whether dietary PUFAs exert any effect on the capsaicin (CAP)-induced neurogenic inflammation under control or NP conditions. In this study we investigated these interrelated phenomena in the trigeminal territory, which has been much less explored, and for which not all data derived from limb nerves can be directly applied. Results: We studied the effects of a CCI of the infraorbital nerve (IoN) on the development of mechanical allodynia and CAP-induced plasma extravasation in rats fed either a regular diet (RD), or a modified diet (MD) with much lower total content and ω-3:ω-6 ratio of PUFAs. In rats kept on MD, mechanical allodynia following CCI-IoN was more pronounced and developed earlier. Extravasation was substantially increased in naive rats fed MD, and displayed differential diet-depending changes one and four weeks after CCI-IoN. When compared with basal levels (in naive and/or sham cases), the net effect of CCI-IoN on ipsilateral extravasation was a reduction in the MD group, but an increase in the RD group, effectively neutralizing the original intergroup differences. Conclusion: In summary, PUFA intake reduces CAP-induced neurogenic plasma extravasation in the trigeminal territory, and their removal significantly alters the mechanical allodynia and the plasma extravasation that result from a unilateral CCI-IoN. It is likely that this "protective" effect of dietary lipids is temporary. Also, the presence of contralateral effects of CCI-IoN precludes using the contralateral side as control. [ABSTRACT FROM AUTHOR]

We hypothesized that heme oxygenase (HO)-1, the inducible form of HO, represents an important defense against early oxidative injury in the traumatized spinal cord by stabilizing the blood–spinal cord barrier and limiting the infiltration of leukocytes. To test this hypothesis, we first examined the immunoexpression of HO-1 and compared barrier permeability and leukocyte infiltration in spinal cord-injured HO-1-deficient (+/−) and wild-type (WT, +/+) mice. Heme oxygenase was expressed in both endothelial cells and glia of the injured cord. Barrier disruption to luciferase and infiltration of neutrophils were significantly greater in the HO-1+/− than WT mice at 24 h postinjury (P≤0.019 and =0.049, respectively). We next examined by Western immunoblots the generation of 4-hydroxynoneal (HNE) and malondialdehyde (MDA), major products of lipid peroxidation, in the injured epicenter. There was a significant increase in 10 kDa HNE- and MDA-modified proteins in the HO-1+/− as compared with WT mice (P=0.037 and 0.043, respectively). Finally, we compared the degradation of myelin basic protein (MBP), an indicator of white matter damage, in the HO-1+/− and WT mice by Western immunoblots. There was significantly greater degradation of MBP in the HO-1+/− compared with WT mice (P=0.049). Together, these findings show that HO-1 modulates oxidative stress and white matter injury in the acutely injured spinal cord. This modulation may be partially attributed to the ability of HO-1 to stabilize the blood–spinal cord barrier and limit neutrophil infiltration.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1010–1021. doi:10.1038/sj.jcbfm.9600412; published online 18 October 2006 [ABSTRACT FROM AUTHOR]

The periodontal diseases are infectious diseases caused by predominantly Gram-negative bacteria. However, as our understanding of the pathogenesis of the periodontal diseases grows, it is becoming clear that most of the tissue damage that characterizes periodontal disease is caused by the host response to infection, not by the infectious agent directly. Investigation into the mechanism of action of host-mediated tissue injury has revealed that the neutrophil plays an important role in destruction of host tissues. In this paper, we review the biochemical pathways and molecular mediators that are responsible for regulation of the inflammatory response in diseases such as periodontitis, with a focus on lipid mediators of inflammation. Pro-inflammatory mediators, such as prostaglandins and leukotrienes, are balanced by counter-regulatory signals provided by a class of molecules called lipoxins. The role of lipoxins in the control and resolution of inflammation is discussed, as is the possibility of the development of new therapeutic strategies for the control and prevention of neutrophil-mediated tissue injury in inflammatory diseases like periodontitis. [ABSTRACT FROM AUTHOR]